bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a stress management course in adult education centres in rural Australia
Authors: Hawkins Kate M. , Reddy Prasuna , Bunker Steve
Published: April 2007

Objective:  To investigate whether attending a six‐week stress management course in a rural adult education centre is effective in reducing participants' levels of stress, anxiety and depression.

Design:  Repeated measures design using self‐report measures of stress, anxiety and depression at commencement and completion of a six‐week stress management course, and six months post‐completion follow up.

Setting and participants:  One hundred and thirty‐two adults (age range 18–73 years) living in a rural community who self‐enrolled in the stress management course at adult education centres.

Intervention:  The course consisted of six weekly group sessions. Each two‐hour session conducted by mental health professionals, included teaching cognitive behavioural strategies targeted at reducing individual symptoms of stress.

Main outcome measures:  Comparative analysis of pre‐ and post‐test and six‐month follow up on measures of stress (Stress Symptom Checklist), anxiety and depression (Hospital Anxiety and Depression Scale).

Results:  Results indicated a significant reduction in stress symptoms (F(7,90) = 34.92, P < 0.001), anxiety and depression (F(3,95) = 87.92, P < 0.001) from course commencement to course completion. These improvements were sustained six months after course completion for stress symptoms (F(11,65) = 22.40, P < 0.001), anxiety and depression (F(5,73) = 41.78, P < 0.001).

Conclusion:  Findings demonstrate the stress management course is an effective community intervention in a rural community. Challenges for future implementation of the program are discussed.
Prevalence of psychological distress, anxiety and depression in rural communities in Australia
Authors: Kilkkinen Annamari , Kao‐Philpot Anna , O'Neil Adrienne , Philpot Benjamin , Reddy Prasuna , Bunker Stephen , Dunbar James
Published: April 2007

Objective:  To describe the prevalence of psychological distress, depression and anxiety in three Australian rural settings and to identify the levels of risk by gender and age.

Design and setting:  Three cross‐sectional surveys in the Greater Green Triangle area covering the south‐east of South Australia (Limestone Coast), and south‐west (Corangamite Shire) and north‐west (Wimmera) of Victoria.

Participants:  A total of 1563 people, aged 25–74 years, randomly selected from the electoral roll.

Main outcome measures:  Psychological distress assessed by the Kessler 10, and anxiety and depression assessed by the Hospital Anxiety and Depression Scale.

Results:  The prevalence of psychological distress was 31% for both men and women with two‐thirds reporting moderate and one‐third high levels of psychological distress. The prevalence of depression and anxiety was approximately 10%. The highest rate of psychological distress, anxiety and depression occurred in the 45–54 years age group. There were no consistent gender or area differences in the prevalence of psychological distress, depression or anxiety.

Conclusions:  A third of the rural population reported psychological distress, with the highest prevalence observed in middle‐aged men and women. Thus, health professionals should attend not only to physical health, but also to mental health status in this age group. It is also important to target prevention strategies at the 20% who reported moderate levels of psychological distress in order to prevent the development of more serious conditions.
headspace: National Youth Mental Health Foundation: Making headway with rural young people and their mental health
Authors: Hodges Craig A. , O'Brien Matthew S. , McGorry Patrick D.
Published: April 2007

Mental health is the number one health issue affecting young people in Australia today, yet only one in four of these young people receive professional help. Approximately 14% of 12‐ to 17‐year‐olds and 27% of 18‐ to 25‐year‐olds experience mental health problems each year. However, many do not have ready access to treatment or are reluctant to seek that help. These issues might be exacerbated in the rural and remote regions of Australia where sociocultural barriers such as stigma, lack of anonymity and logistic difficulties including cost and availability of transport can hinder young people accessing mental health services. headspace: the National Youth Mental Health Foundation has been funded to address these issues. headspace will provide funding for the establishment of communities of youth services across Australia, provide national and local community awareness campaigns and plans, establish a centre of excellence that will identify and disseminate evidence‐based practice in addressing youth mental health issues, and translate findings into education and training programs that are targeted at service providers to work with youth mental health. The communities of youth services will build the capacity of local communities to identify early, and provide effective responses to, young people aged 12–25 years with mental health and related substance use disorders. Specific approaches in rural, regional and remote areas will be developed as well as specific programs to involve young Indigenous people.
Mental health issues and resources in rural and regional communities: An exploration of perceptions of service providers
Authors: Turpin Merrill , Bartlett Helen , Kavanagh David , Gallois Cindy
Published: April 2007

Objective:  To identify service providers' and community organisations' perceptions of the resources available to support people with mental illness and the unmet needs of this client group in rural Queensland.

Design:  An exploratory study was undertaken involving focus group interviews across the study sites.

Setting:  Five regional towns in rural Queensland.

Participants:  Ten to 14 members were recruited for each of the five focus groups. The groups represented a diverse mix of participants including health and community service providers and representatives from community organisations.

Results:  Participants identified gaps in services in relation to health, employment and education, housing and accommodation, transport and social inclusion and health promotion. Inter‐service communication and inappropriate funding models were themes affecting service delivery.

Conclusions:  Specific service issues of housing and transport were identified to be particularly problematic for people with mental illness across all towns. Intersectoral communication and funding models require further research.
EFFECT OF ENALAPRIL TREATMENT ON THE SENSITIVITY OF CARDIOPULMONARY REFLEXES IN RATS WITH MYOCARDIAL INFARCTION
Authors: Andrade TU , Pinto VD , Medeiros ARS , Abreu GR , Moysés MR , Sampaio KN , Bissoli NS
Published: April 2007

The aim of the present study was to evaluate the effect of treatment with enalapril on the sensitivity of cardiopulmonary reflexes 30 days after myocardial infarction in Wistar rats.

Animals were divided into four groups: (i) sham operated, receiving vehicle (SHAM); (ii) infarcted, receiving vehicle (0.9% NaCl; INF); (iii) sham operated, receiving enalapril (SHAME); and (iv) infarcted, receiving enalapril (INFE).

Enalapril was administered at a dose of 10 mg/kg per day. Serotonin (4–32 µg/kg, i.v.) was administered in order to activate the Bezold–Jarisch reflex, which was estimated as the percentage of reduction in heart rate.

The volume‐sensitive cardiopulmonary reflex was induced by saline overload and evaluated as the percentage increase in sodium and volume renal excretion. At the end of the experiments, rats were killed and hearts excised to estimate the size of the infarction. The weight of the kidneys, lungs, liver and cardiac chambers as ratios of bodyweight was used to estimate the extent of hypertrophy.

The results showed an impairment in the sensitivity of the cardiopulmonary reflexes in the INF group compared with the SHAM and SHAME groups. We observed right ventricle and pulmonary hypertrophy, a reduction in mean and systolic arterial pressure and an increase in heart rate in INF animals. In the INFE group, nearly all the parameters were normal compared with the INF group, except for systolic arterial pressure, which was only partially improved.

The main finding of the present study was that treatment with enalapril normalized the sensitivity of the cardiopulmonary reflexes, which could be due, in part, to the reduction of cardiac hypertrophy. The present study provides information about the beneficial effects of the angiotensin‐converting enzyme inhibitors by normalizing the cardiopulmonary reflexes involved with the regulation of volume and sodium, as well as control of arterial pressure and heart rate in infarcted animals.
ACUTE PRESSURE–NATRIURESIS RELATIONSHIP FOLLOWING WITHDRAWAL OF CHRONIC NORADRENALINE INFUSION
Authors: Boesen EI , Anderson WP , Kett MM
Published: April 2007

Pathological changes to the kidney, such as vascular remodelling, have been found in several models of hypertension and may contribute to the maintenance of hypertension or confer susceptibility to redeveloping hypertension after the original prohypertensive stimulus is withdrawn.

To investigate whether noradrenaline‐induced hypertension induces persistent, functionally important changes to the kidney, the acute pressure–natriuresis relationship was characterized in anaesthetized rats under controlled neural and hormonal conditions following chronic (14 days) intravenous infusion of noradrenaline (48 µg/kg per h) or vehicle (0.04 mg/mL ascorbic acid and 0.156 mg/mL NaH2PO4·2H2O in 10 IU/mL heparinized saline).

Conscious mean arterial pressure was significantly elevated by infusion of noradrenaline at 48 µg/kg per h (+10 ± 2 mmHg at Day 14; P < 0.01 vs vehicle group). The acute relationships between arterial pressure and renal blood flow, glomerular filtration rate, Na+ excretion and urine flow were not significantly different between the noradrenaline‐ and vehicle‐infused rats immediately after termination of noradrenaline infusion.

In summary, chronic intravenous noradrenaline infusion did not cause persistent changes in renal function, indicating that, in contrast with many models of hypertension, this model does not induce underlying prohypertensive changes to the kidney.
VASODILATOR EFFECTS OF LEPTIN ON CANINE ISOLATED MESENTERIC ARTERIES AND VEINS
Authors: Mohammed MMJ , Myers DS , Sofola OA , Hainsworth R , Drinkhill MJ
Published: April 2007

Although leptin increases sympathetic nerve activity and blood pressure, its direct action on large arterial rings is to cause relaxation. However, it is the small resistance arteries and veins that are important in blood pressure control. The effects of leptin on these small vessels has not been reported previously in the canine and the effect of leptin on the capacitance vessels is not known.

In the present study, third‐ or fourth‐order canine mesenteric arteries and veins were isolated and placed in a perfusion myograph and preconstricted with noradrenaline. The responses to graded concentrations of leptin were determined and the role of nitric oxide was assessed by administration of NG‐nitro‐l‐arginine methyl ester (l‐NAME), a blocker of nitric oxide synthase.

Leptin induced dose‐related dilatations in both arterial and venous segments. The mean (±SEM) maximum increases in the diameter of the arteries and veins were 25.0 ± 4.8 and 29.9 ± 2.0% of the initial preconstriction, respectively. Relaxations of both arteries and veins were abolished by l‐NAME or by endothelium denudation, although dilatations were still obtained to sodium nitroprusside, a nitric oxide donor.

These results indicate that leptin dilates canine small mesenteric arteries and veins by a mechanism involving endothelial release of nitric oxide. This observation may result in a decrease of peripheral resistance and venous return and, hence, counteract the leptin‐induced neurally mediated vasoconstriction that has been reported previously.
IN VITRO EFFECTS OF ANTIPSYCHOTICS ON HUMAN PLATELET ADHESION AND AGGREGATION AND PLASMA COAGULATION
Authors: Axelsson Stina , Hägg Staffan , Eriksson Andreas C , Lindahl Tomas L , Whiss Per A
Published: April 2007

Several studies suggest an association between venous thromboembolism and the use of antipsychotic drugs, especially clozapine, but the biological mechanisms are unknown. It has been suggested that antipsychotic drugs enhance aggregation of platelets and thereby increase the risk of venous thrombosis. The purpose of the present study was to examine the effects of clozapine and its main metabolite, N‐desmethyl clozapine, as well as olanzapine, risperidone and haloperidol, on platelet adhesion and aggregation and on plasma coagulation in vitro.

Blood was collected from healthy subjects free of medication. Platelet adhesion to different protein surfaces and aggregation were measured in microplates. The coagulation methods of activated partial thromboplastin time (APTT) and prothrombin time were performed in platelet‐poor plasma.

Clozapine was the only compound that increased platelet adhesion and aggregation and shortened APTT. The effect appeared at therapeutic concentrations and was significant but weak.

This weak effect of clozapine on haemostasis may explain, in part, the association of this compound and venous thromboembolism.
The Bayesian revolution approaches psychological development
Authors: Shultz Thomas R.
Published: April 2007

This commentary reviews five articles that apply Bayesian ideas to psychological development, some with psychology experiments, some with computational modeling, and some with both experiments and modeling. The reviewed work extends the current Bayesian revolution into tasks often studied in children, such as causal learning and word learning, and provides evidence that children's performance can be optimal in a Bayesian sense. There remains much to be done in terms of understanding how representations are created, how development occurs, how Bayesian computation might be neurally implemented, and in reconciling the new work with older evidence that even skilled adults are incompetent Bayesians.
Analysing the Liberal Democrats
Authors: GRAYSON RICHARD S.
Published: April 2007

This article sets the scene for those that follow. It picks out the main themes of each, arguing that the Liberal Democrats could benefit from considering the issues around policy and the nature of political power that arise from the articles. It also argues that debates over relations with other parties are likely to be central to Liberal Democrat politics in the foreseeable future.
Liberal Democrat Policy‐making: An Insider's View, 2000–2004
Authors: BENTHAM CLAIRE
Published: April 2007

Little attention has been paid to the way in which political parties make policy. From the perspective of a former member of party staff, this article explains why the Liberal Democrats have adopted their current procedure, and what the strengths and weaknesses of this are. It pays particular attention to the party's working groups, which produce policy papers, and also focuses on the process for writing manifestos. The article argues that policy‐making should change as the party grows in strength. Shorter conferences with more focused debate would allow delegates the same voice in deciding crucial policies that will form the basis of the next manifesto, but get rid of the fringe debates that attract ridicule in the media. It would also allow parliamentarians more freedom to respond to specific events within the very general policy framework agreed at conference.
‘Meeting the Challenge’? The Liberal Democrats' Policy Review of 2005–2006
Authors: DOREY PETER , DENHAM ANDREW
Published: April 2007

Even before the 2005 election, the Liberal Democrats’ Federal Policy Committee had agreed on the need for a review of party policy, in response both to domestic and international political developments since 2001. Intended to build upon the 2002 policy document ‘It's About Freedom’, 2005 heralded the launch of a Meeting the Challenge policy review, which provided an unprecedented opportunity for party members at all levels to contribute towards the refinement of Liberal Democrat policies and develop a clearer political narrative. This would enable the party to articulate its principles and goals more effectively in the run‐up to the next general election. Through a variety of intra‐party channels, conduits and forums, hundreds of responses from party members, and local and regional Liberal Democrat parties, offered analyses and policy suggestions. On various issues, these revealed ongoing debates between the party's (Orange Book) ‘liberals’ and ‘social democrats’. The outcome of this intra‐party consultation exercise was the 2006 policy document ‘Trust in People’, which was emphatically endorsed at the party's annual conference. This will now provide the framework for further policy development and clarification during the next two years.
The Welsh Liberal Democrats: From Government to Opposition and Then Back Again?
Authors: DEACON RUSSELL
Published: April 2007

For over 50 years from 1945 onwards, the Liberal Party and then the Liberal Democrats were either in decline in Wales or struggling to survive from election to election. Since 1997, however, there has been a steady evolution in the party's electoral and political strength. Over this past decade, the Welsh Liberal Democrats, as a state party, have experienced a change in electoral fortunes that has on occasions put them into national political power well in advance of their federal counterparts in England. As an autonomous state party within a federal structure, the Welsh Liberal Democrats have been able to take like a duck to water to the arrival of devolution in the form of the Welsh Assembly. This article examines how the evolution of the party has occurred and, in particular, the role that has been played by the Welsh Liberal Democrat Assembly Members in Welsh politics. The article also explores not only the strengths but also the weaknesses that still dog the Welsh party as it seeks once more to become a major force in Welsh politics.
Can we trust levelled texts? An examination of their reliability and quality from a linguistic perspective
Authors: Pitcher Brandy , Fang Zhihui
Published: April 2007

Over the past decade in the United States, levelled texts, or ‘little books’ with finely graduated levelling of text difficulty, have regained their status as a literacy staple for beginning readers. Despite their resurgence, questions remain regarding the reliability and quality of these books. In this study, we conducted a detailed analysis of 20 sample texts at levels 5, 10, 15 and 20, from one series of levelled books published in the United States. We found that the levelling system used in this series is not a particularly reliable indicator of text difficulty and that the quality of these books varies considerably between and within levels. We suggest that close attention to text levels could be detrimental in the reader–text matching process. We further recommend that in order to judge and select quality books that answer the needs of their students, teachers become more aware of the various factors influencing text comprehensibility and quality.
A Sociology of Reuse: Deconstructing the Milk Bottle
Authors: Vaughan Paul , Cook Matthew , Trawick Paul
Published: April 2007

This article investigates the practice of reuse, the relation between individuals and objects, using as a case study the refillable glass milk bottle. Based on interviews with 22 individuals in mainly rural settings, the study aims to understand what the milk bottle means today to the many people who still use it, and what the socioeconomic and other structures are that sustain this kind of product reuse. The discussion exposes the way that reuse is about both consumption and disposal and is maintained by a web of household practices, revealing the milk bottle as both a site of resistance to supermarkets and a site for the construction of collective and individual identities. We also expose the way that the materiality of the bottle enables myth and trust to be articulated. We conclude that this reuse practice is a form of non‐market mediated exchange, marking reciprocal relations of care and trust.
THE EFFECTS OF LENIENCY PROGRAMS AND FINES ON CARTEL STABILITY
Authors: Chavda Ankur , Jegers Marc
Published: April 2007

Using a stylized oligopoly model, we analyze the effect of cartel deterring fines, taking into consideration exemptions granted to cartel members cooperating with the competition authorities. We conclude that the fines can act as a deterrent to breaking collusive agreements, thus stabilizing the cartel.
CAPITALISTS, WORKERS AND SOCIAL SECURITY
Authors: Michl Thomas R.
Published: April 2007

This paper elaborates an exogenous growth model that nests overlapping generations of workers who save for life cycle reasons with dynastic agents who save for bequest reasons (‘capitalists’). The model overcomes Marglin's objection that the overlapping generations framework requires special assumptions about technology, and it also provides a natural environment to revisit Samuelson's analysis of lump‐sum transfers between generations. The ability of a benevolent planner to improve workers' welfare is severely restricted by the control capitalists exercise over the accumulation process. Prefunding social security assumes renewed significance because it overcomes this restriction.
INTEREST RATE, DEBT, DISTRIBUTION AND CAPITAL ACCUMULATION IN A POST‐KALECKIAN MODEL
Authors: Hein Eckhard
Published: April 2007

In the present paper we extend Lavoie's (Metroeconomica, 1995, vol. 46, pp. 146–177) ‘Minsky–Steindl’ model, building our analysis on a Kaleckian distribution and growth model which has already taken into account distribution effects of interest rate variations on the short‐run equilibrium. Into this model the effects of debt and debt services are explicitly introduced and the effects of interest rate variations on the short‐ and the long‐run equilibrium are derived. It is shown that the effects of interest rate variations on the endogenously determined equilibrium values of the model not only depend on the parameter values in the saving and investment functions but also on the interest elasticity of distribution and on initial conditions with respect to the interest rate and the debt–capital ratio.
IS CORPORATISM FEASIBLE?
Authors: Acocella Nicola , Di Bartolomeo Giovanni
Published: April 2007

This paper investigates the effects of cooperation (corporatism) on macroeconomic performance by considering a rather standard policy game between the government and a monopoly union. We stress the shortcomings of the traditional way used to model cooperation in policy games (the maximization of the weighted sum of players’ preferences), which only approximates the Nash product solution. We find that it is difficult to implement corporatism, although it generally increases social welfare, as it often reduces the union's utility. In particular, we show that an inflation‐neutral union will never find it profitable to cooperate with the government, unless side‐payments are considered. The study of this issue, however, is beyond the scope of this paper.
A comparison of gradient ascent, gradient descent and genetic‐algorithm‐based artificial neural networks for the binary classification problem
Authors: Pendharkar Parag C.
Published: April 2007

Abstract: We compare log maximum likelihood gradient ascent, root‐mean‐square error minimizing gradient descent and genetic‐algorithm‐based artificial neural network procedures for a binary classification problem. We use simulated data and real‐world data sets, and four different performance metrics of correct classification, sensitivity, specificity and reliability for our comparisons. Our experiments indicate that a genetic‐algorithm‐based artificial neural network that maximizes the total number of correct classifications generally fares well for the binary classification problem. However, if the training data set contains inconsistent decisions or noise then the log maximum likelihood maximizing gradient ascent may be the best classification approach to use. The root‐mean‐square minimizing gradient descent approach appears to overfit training data and has the lowest reliability among the approaches considered for our research. At the end of the paper, we provide a few guidelines, including computational complexity, for selection of an appropriate technique for a given binary classification problem.
Categorizing approaches combining rule‐based and case‐based reasoning
Authors: Prentzas Jim , Hatzilygeroudis Ioannis
Published: April 2007

Abstract: Rule‐based and case‐based reasoning are two popular approaches used in intelligent systems. Rules usually represent general knowledge, whereas cases encompass knowledge accumulated from specific (specialized) situations. Each approach has advantages and disadvantages, which are proved to be complementary to a large degree. So, it is well justified to combine rules and cases to produce effective hybrid approaches, surpassing the disadvantages of each component method. In this paper, we first present advantages and disadvantages of rule‐based and case‐based reasoning and show that they are complementary. We then discuss the deficiencies of existing categorization schemes for integrations of rule‐based and case‐based representations. To deal with these deficiencies, we introduce a new categorization scheme. Finally, we briefly present representative approaches for the final categories of our scheme.
A comparison of DEA and the stochastic frontier model using panel data
Authors: Ruggiero John
Published: April 2007

Two competing approaches for the measurement of efficiency are the stochastic frontier model and data envelopment analysis (DEA). Previous research has established that the two models applied to cross‐sectional data are both adversely affected by measurement error. While the cross‐sectional stochastic frontier model does not effectively handle statistical noise, panel data models do. This is true because additional information from multiple time periods is incorporated into the estimation. A panel data DEA model that uses averaged data has been shown to effectively smooth out measurement error. In this paper, we compare the panel data models using simulated data.
Simulated Cryptosporidium removal under swimming pool filtration conditions
Authors: Croll B. T. , Hayes C. R. , Moss S.
Published: April 2007

There has been no information available on the removal of Cryptosporidium oocysts or oocyst‐sized particles under the sand filtration conditions normally used for swimming pool water treatment. A pilot sand filtration plant has therefore been constructed at The University of Wales Swansea and operated under swimming pool conditions (25 m/h downflow, 30°C, 1.5 mg/L free chlorine, pH 7.3 to 7.5, alkalinity 120–150 mg/L as calcium carbonate). Removal of fluorescent polystyrene particles of a size range (1–7 μm) similar to the size of Cryptosporidium oocysts (about 5 μm) without added coagulant was less than 50%. Removal of the particles under the operating conditions above but with the addition of either of the coagulants polyaluminium chloride (PAC) or aluminium sulphate was capable of giving better than 99% removal of the particles.
Effects of Rural Medical Financial Assistance in China
Authors: Zhu Ling
Published: April 2007

This paper presents research results from the evaluation of the Medical Financial Assistance (MFA) program, supported by the World Bank, to extremely poor rural residents. It is found that MFA can help to improve the ability of the poor to make use of medical services, and especially their ability to receive services from township clinics. The present study also shows that adoption of the MFA mechanism helps to reduce the impact of disease on the economies of poor families, and prevents the poor afflicted with serious illnesses from being marginalized. However, as the beneficiaries often suffer from serious, complicated and lasting illnesses, the financial assistance is often insignificant in relation to medical expenses. Furthermore, the MFA plays no significant role in restoring a patient's income‐earning ability.
Decomposing Income Inequality and Policy Implications in Rural China
Authors: Yu Lerong , Luo Renfu , Zhang Linxiu
Published: April 2007

Using village data from samples covering 6 provinces, 36 counties and 216 townships, the income inequalities within and between townships in rural China are assessed. The Theil index and the mean logarithmic deviation methods enable us to test income inequality at the township level, and to decompose it into intra‐regional and inter‐regional at county and provincial levels. In the present paper, we also decompose income inequalities between and within the nationally designated poor counties (NDPC). The results show that approximately two‐thirds of the income inequality in rural China would be eliminated if measures and policies were targeted at the county level. This study also confirms the rationale that China's poverty alleviation strategy of focusing on poor counties based on the inequalities between NDPC and non‐NDPC accounts for the most inter‐province inequality.
Emerging Urban Poverty and Effects of the Dibao Program on Alleviating Poverty in China
Authors: Wang Meiyan
Published: April 2007

The present paper describes the current urban poverty situation, examines the factors affecting the probability of a household being in poverty and investigates how the urban minimum living standard guarantee (dibao) program helps poor people to get out of poverty. The targeting efficiency of the urban dibao program is discussed. The present study finds that the poverty rate of households with unemployed workers is much higher than that of households without unemployed workers. The urban dibao program is helpful in reducing poverty rates, but it does not reduce poverty rates too much. The government should place emphasis on helping laid‐off and unemployed workers to become reemployed. The most urgent problem for the dibao program is improving the efficiency of targeting.
High‐dose vitamins E and C supplementation prevents ribavirin‐induced hemolytic anemia in patients with chronic hepatitis C
Authors: Kawaguchi Yasunori , Mizuta Toshihiko , Takahashi Kazuhiro , Iwane Shinji , Ario Keisuke , Kawasoe Hiroaki , Hamaoka Kazuhiro , Eguchi Yuichiro , Yasutake Tsutomu , Shigematsu Hironao , Kawazoe Seiji , Fukushima Noriko , Ozaki Iwata , Fujimoto Kazuma
Published: April 2007

Aim:  In combination therapy using interferon (IFN) and ribavirin for chronic hepatitis C, reduced doses should be used due to ribavirin‐induced hemolytic anemia. The present study aimed to elucidate whether high‐dose vitamins E and C supplementation attenuated ribavirin‐induced hemolytic anemia.

Methods:  Twenty‐one consecutive patients with chronic hepatitis C were enrolled in this study between July 2003 and December 2004, and received high‐dose vitamins E (2000 mg) and C (2000 mg) supplementation, daily, in addition to IFN alfa‐2b and ribavirin combination therapy (vitamins E/C group). Twenty‐one sex‐ and age‐matched patients who received a standard regimen of IFN alfa‐2b and ribavirin for chronic hepatitis C between January 2001 and June 2003 were evaluated as the control group.

Results:  Decrease in hemoglobin level was significantly prevented in the vitamins E and C group compared to that in the control group (P = 0.029). Three (14.3%) patients in the control group discontinued treatment because of anemia, while no treated patient dropped out of the study due to anemia. Sustained virological response was not significantly different between the two groups.

Conclusion:  High‐dose vitamins E and C supplementation prevented ribavirin‐induced hemolytic anemia during combination therapy with ribavirin and IFN alfa‐2b in patients with chronic hepatitis C.
Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma
Authors: Wang Li , Wang Wen‐Liang , Zhang Yong , Guo Shuang‐Ping , Zhang Jing , Li Qin‐Long
Published: April 2007

Aim:  To investigate the roles of epigenetic and genetic alterations of the phosphatase and tensin homologue on chromosome 10 gene (PTEN) in carcinogenesis and the development of hepatocellular carcinomas (HCC).

Methods:  A total of 56 cases of HCC tissues and six liver cell lines were studied for the expression of PTEN by immunohistochemistry and Western blot analysis. The PTEN gene mutations in exon5 and exon8 were detected by a combination of single‐strand conformation polymorphism (SSCP) analysis and DNA sequencing. Methylation‐specific PCR (MSP) was used to identify PTEN promoter methylation.

Results:  Of the 56 cases of HCC, 24 (42.9%) expressed the PTEN protein. All surrounding liver tissues of the hepatoma (32 cases) were positive for PTEN. Of the six cell lines, three liver cancer cell lines showed a low expression of PTEN. Five mutations of 56 HCC samples were detected. All of them were located at intron4. No mutation was found in exon5 and exon8. After MSP analysis, we found nine cases of PTEN promoter methylation in 56 specimens (16.1%). However, no CpG island of PTEN was found to be methylated in all six liver cell lines.

Conclusion:  The level of PTEN protein was altered in part of the HCC. The downregulation of PTEN expression may not be mainly associated with the PTEN mutations, but partly due to PTEN promoter methylation and other epigenetic regulation.
Inhibition of hepatocellular carcinoma growth by antisense oligonucleotides to type I insulin‐like growth factor receptor in vitro and in an orthotopic model
Authors: Lin Ru‐Xian , Wang Zhi‐Yan , Zhang Nin , Tuo Chao‐Wei , Liang Qian‐De , Sun Yu‐Ning , Wang Sheng‐Qi
Published: April 2007

Aim:  The type I insulin‐like growth factor receptor (IGF‐IR) is overexpressed in many tumors including human hepatocellular carcinoma (HCC). It is a critical signaling molecule for tumor cell proliferation and survival. In the present study, IGF‐IR expression was down‐regulated by phosphorothioate antisense oligonucleotides (AS[S]ODN) to evaluate their specific effects on growth of hepatoma cells in vitro and in vivo.

Methods:  HepG2 cells were transfected with different doses of AS[S]ODN, sense [S]ODN, mismatch [S]ODN, or Lipofectin for 72 h, and cell proliferation was analyzed by MTS assay. In vivo, an orthotopic transplant model of HCC was established in nude mice, which were then injected with AS[S]ODN, sense [S]ODN, 5‐fluorouracil or saline. At the endpoint of treatment, the tumors were excised and evaluated.

Results:  Compared to sense and mismatched oligonucleotides, AS[S]ODN targeting to IGF‐IR mRNA significantly inhibited hepatoma cell lines HepG2 proliferation and IGF‐IR expression at both mRNA and protein levels. The in vivo results showed that systemic treatment also resulted in significant inhibition in tumor growth. Tumor growth in mice treated with AS[S]ODN (50 and 75 mg/kg per day) was significantly inhibited (71.81% and 61.74%, respectively) compared to the saline‐treated group (P < 0.01) in a dose‐dependent manner. The antitumor effect of IGF‐IR AS[S]ODN was associated with down‐regulation of IGF‐IR in tumor xenografts. Furthermore, IGF‐IR AS[S]ODN prevented liver recurrence tumor growth and metastasis in the lung, showing a dose‐dependent response. The level of serum α‐fetoprotein in AS[S]ODN‐treated groups was also decreased in a dose‐dependent manner, and a good correlation was observed between tumor volume and serum α‐fetoprotein concentration.

Conclusions:  These data suggest that IGF‐IR AS[S]ODN can effectively and specifically inhibit HCC growth in vitro and in vivo. Blockage of IGF‐IR expression could be a promising therapeutic approach for the management of patients with HCC.
Vitamin K2 inhibits the proliferation of HepG2 cells by up‐regulating the transcription of p21 gene
Authors: Liu Weidong , Nakamura Hideji , Yamamoto Teruhisa , Ikeda Naoto , Saito Masaki , Ohno Masao , Hara Naoki , Imanishi Hiroyasu , Shimomura Soji , Yamamoto Tetsuo , Sakai Toshiyuki , Nishiguchi Shuhei , Hada Toshikazu
Published: April 2007

Aim:  Vitamin K2 has been reported to inhibit the growth of human hepatocellular carcinoma (HCC) in vitro and suppress hepatocarcinogenesis in vivo. However, its inhibitory mechanism has not yet been clarified.

Methods:  Different concentrations of vitamin K2 (30, 10, 1, 0.1 and 0.01 μM) were added to the HCC cell line HepG2 to assess effects on cell growth. The effect of vitamin K2 on cell cycle progression was determined by flow‐cytometric analysis. The expression of cell cycle regulatory proteins p21 and p27 was then examined by Western blot. Whether vitamin K2 regulates the gene expression through action on the p21 promoter region was investigated by luciferase assay.

Results:  Vitamin K2 inhibited the growth of HepG2 cells dose‐dependently, and its inhibitory rate reached approximately 50% at the dose of 30 μM after 96 h treatment. After treatment with vitamin K2, the proportion of cells in G0–G1 phase increased, and in S phase decreased. Apoptotic cells were not detected. The expression of cell cycle regulatory protein p21 was induced by vitamin K2 treatment, but p27 was not. By the luciferase assay, vitamin K2 significantly activated the promoter of p21. Knock‐down of p21 by siRNA reversed the growth inhibition of HepG2 cells by vitamin K2.

Conclusions:  The findings suggest that vitamin K2 suppresses the proliferation of HCC cells by blocking the cell cycle G1/S progression through the transcriptional induction of p21.
Continuous normothermic hemihepatic vascular inflow occlusion over 60 min for hepatectomy in patients with cirrhosis caused by hepatitis B virus
Authors: Wen Tianfu , Chen Zheyu , Yan Lunan , Li Bo , Zeng Yong , Wu Guochang , Zheng Guangqi
Published: April 2007

Aim:  To evaluate the safety of remnant liver in cirrhotic patients who had undergone irregular hepatectomy with continuous normothermic hemihepatic vascular inflow occlusion for over 60 min.

Methods:  A group of 133 cirrhotic patients who had hepatitis B virus accompanied by hepatocellular carcinoma and had undergone irregular hepatectomy by hemihepatic vascular inflow occlusion was studied. According to the time of hemihepatic vascular inflow occlusion, patients were assigned either to the control group, treatment60 group, or treatment90 group. The quantity of blood loss and blood transfusion, routine liver biochemistry and postoperative complications were retrospectively analyzed.

Results:  The data showed that there were no significant differences in postoperative complications between the three groups. Compared to the preoperative day, the levels of aspartate transaminase (AST), alanine transaminase (ALT), prothrombin time (PT) and serum bilirubin on postoperative days 1 and 3 were significantly increased in all three groups and the levels of albumin and platelet were significantly decreased on postoperative day 1. Duration of hospital stay and the levels of ALT and AST on postoperative days 1, 3 and 7 were higher in the treatment90 group than in the control group and treatment60 group (P < 0.05). However, no significant differences were displayed in the length of hospital stay and the levels of AST, ALT, PT, albumin, platelet count and serum bilirubin on postoperative days 1, 3 and 7 between the control group and the treatment60 group (P > 0.05).

Conclusion:  Hemihepatic vascular inflow occlusion over 60 min is a possible method for irregular hepatectomy in patients with cirrhosis caused by the hepatitis B virus. However, caution must be exercised in utilizing this method where the time of vascular occlusion is over 90 min.
Sensitivity of Monkey B Virus (
Cercopithecine herpesvirus
1) to Antiviral Drugs: Role of Thymidine Kinase in Antiviral Activities of Substrate Analogs and Acyclonucleosides
Authors: Focher Federico , Lossani Andrea , Verri Annalisa , Spadari Silvio , Maioli Andrew , Gambino Joseph J. , Wright George E. , Eberle Richard , Black Darla H. , Medveczky Peter , Medveczky Maria , Shugar David
Published: April 2007

Herpes B virus (B virus [BV]) is a macaque herpesvirus that is occasionally transmitted to humans where it can cause rapidly ascending encephalitis that is often fatal. To understand the low susceptibility of BV to the acyclonucleosides, we have cloned, expressed, and characterized the BV thymidine kinase (TK), an enzyme that is expected to “activate” nucleoside analogs. This enzyme is similar in sequence and properties to the TK of herpes simplex virus (HSV), i.e., it has a broad substrate range and low enantioselectivity and is sensitive to inhibitors of HSV TKs. The BV enzyme phosphorylates some modified nucleosides and acyclonucleosides and
l
enantiomers of thymidine and related antiherpetic analogs. However, the potent anti-HSV drugs acyclovir (ACV), ganciclovir (GCV), and 5-bromovinyldeoxyuridine were poorly or not phosphorylated by the BV enzyme under the experimental conditions. The antiviral activities of a number of marketed antiherpes drugs and experimental compounds were compared against BV strains and, for comparison, HSV type 1 (HSV-1) in Vero cell cultures. For most compounds tested, BV was found to be about as sensitive as HSV-1 was. However, BV was less sensitive to ACV and GCV than HSV-1 was. The abilities of thymidine analogs and acyclonucleosides to inhibit replication of BV in Vero cell culture were not always proportional to their substrate properties for BV TK. Our studies characterize BV TK for the first time and suggest new lead compounds, e.g., 5-ethyldeoxyuridine and pencyclovir, which may be superior to ACV or GCV as treatment for this emerging infectious disease.
Statistical Methods for Establishing Quality Control Ranges for Antibacterial Agents in Clinical and Laboratory Standards Institute Susceptibility Testing
Authors: Turnidge John , Bordash Gerry
Published: April 2007

Quality control (QC) ranges for antimicrobial agents against QC strains for both dilution and disk diffusion testing are currently set by the Clinical and Laboratory Standards Institute (CLSI), using data gathered in predefined structured multilaboratory studies, so-called tier 2 studies. The ranges are finally selected by the relevant CLSI subcommittee, based largely on visual inspection and a few simple rules. We have developed statistical methods for analyzing the data from tier 2 studies and applied them to QC strain-antimicrobial agent combinations from 178 dilution testing data sets and 48 disk diffusion data sets, including a method for identifying possible outlier data from individual laboratories. The methods are based on the fact that dilution testing MIC data were log normally distributed and disk diffusion zone diameter data were normally distributed. For dilution testing, compared to QC ranges actually set by CLSI, calculated ranges were identical in 68% of cases, narrower in 7% of cases, and wider in 14% of cases. For disk diffusion testing, calculated ranges were identical to CLSI ranges in 33% of cases, narrower in 8% of cases, and 1 to 2 mm wider in 58% of cases. Possible outliers were detected in 8% of diffusion test data but none of the disk diffusion data. Application of statistical techniques to the analysis of QC tier 2 data and the setting of QC ranges is relatively simple to perform on spreadsheets, and the output enhances the current CLSI methods for setting of QC ranges.
Genome Sequence of a Clinical Isolate of
Campylobacter jejuni
from Thailand
Authors: Poly Frédéric , Read Timothy , Tribble David R. , Baqar Shahida , Lorenzo Maria , Guerry Patricia
Published: April 2007

Campylobacter jejuni
CG8486, which belongs to the HS4 complex, was isolated from a patient with inflammatory diarrhea in Thailand. This strain caused a diarrheal disease in ferrets comparable to that caused by
C. jejuni
strain 81-176, but it was much less invasive for epithelial cells in vitro than 81-176. Complete genome sequencing of CG8486 revealed a 1.65-Mb genome that was very similar to the other two published genomes of clinical isolates of
C. jejuni
, the genomes of 81-176 and NCTC 11168, with a limited number of CG8486-specific genes mapping outside the hypervariable carbohydrate biosynthesis loci. These data suggest that the genes required for induction of inflammatory diarrhea are among the genes shared by CG8486 and 81-176 but that either major changes in the carbohydrate loci and/or more subtle changes in other genes may modulate virulence.
Assessment of the Kinetics ofTreponema pallidumDissemination into Blood and Tissues in Experimental Syphilis by Real-Time Quantitative PCR
Authors: Salazar Juan C. , Rathi Asha , Michael Nelson L. , Radolf Justin D. , Jagodzinski Linda L.
Published: April 2007

Little is known about the size and kinetics of treponemal burdens in blood and tissues during acquired or experimental syphilitic infection. We used real-time quantitative PCR to measureTreponema pallidumDNA levels in rabbits infected intratesticularly with the prototype Nichols strain. At the outset, we performed a series of in vitro blood spiking experiments to determine the effect of blood processing procedures on the distribution of treponemes in various blood components.T. pallidumDNA levels in plasma and whole blood were approximately 10-fold higher than those in serum and more than 200-fold greater than those in peripheral blood mononuclear cells (PBMCs). Ten rabbits were inoculated intratesticularly with doses of treponemes ranging from 4 × 107to 2 × 108organisms. In five rabbits,T. pallidumDNA levels were measured sequentially in serum, plasma, whole blood, and PBMCs until sacrifice at peak orchitis, at which time brain, kidney, liver, spleen, and testicles were harvested; blood and organs were also harvested at orchitis from the other five rabbits.T. pallidumDNA was detected in plasma within 24 h postinfection. Treponeme levels in whole blood and blood components increased significantly with the development of peak orchitis. Overall, levels in serum and PBMCs were lower than those in plasma and whole blood; this disparity was particularly marked at early time points. Significantly greater numbers of spirochetes were found in the spleen than in liver, kidney, or brain tissue at the time of sacrifice. Our findings highlight the remarkable capacity ofT. pallidumto disseminate from the site of infection to blood and tissues, and they identify the spleen as a prime target for treponemal invasion.
Identification of a
Campylobacter jejuni
Protein That Cross-Reacts with Cholera Toxin
Authors: Albert M. John , Haridas Shilpa , Steer David , Dhaunsi Gursev S. , Smith A. Ian , Adler Ben
Published: April 2007

The question of whether
Campylobacter jejuni
produces a cholera toxin-like toxin (CTLT) has been controversial. The objective of this study was to identify the factor that cross-reacts with CT from
C. jejuni
. Filtrates of
C. jejuni
grown in four different liquid media reported to promote CTLT production were tested by Chinese hamster ovary (CHO) cell elongation assay and for reactivity with CT antibody using GM1 ganglioside enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Protein sequence was determined by matrix-assisted laser desorption ionization-time of flight (MALDI TOF-TOF). Filtrates from seven reference strains reported to produce CTLT and from 80 clinical strains were negative in the CHO cell assay, but those from three reference strains and 16 clinical strains were positive by GM1 ELISA. All strains tested, including
C. jejuni
NCTC 11168, which does not contain a CT gene homologue, possessed a 53-kDa protein which reacted with CT antibody by immunoblotting. This band was identified as the major outer membrane protein, PorA, of
C. jejuni
. CT antibody reacted by immunoblotting with a recombinant PorA, but antibody to the recombinant PorA did not react with CT. Our results indicate that
C. jejuni
does not produce a functional CTLT, but the reactivity of PorA with CT antibody would lead to the erroneous conclusion that
C. jejuni
produces a functional CTLT.