bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of drug interactions on biotransformation and antiplatelet effect of clopidogrelin vitro
Authors: Zahno Anja , Brecht Karin , Bodmer Michael , Bur Daniel , Tsakiris Dimitrios A , Krähenbühl Stephan
Published: May 2010

BACKGROUND AND PURPOSEThe conversion of clopidogrel to its active metabolite, R‐130964, is a two‐step cytochrome P450 (CYP)‐dependent process. The current investigations were performed to characterizein vitrothe effects of different CYP inhibitors on the biotransformation and on the antiplatelet effect of clopidogrel.

EXPERIMENTAL APPROACHClopidogrel biotransformation was studied using human liver microsomes (HLM) or specific CYPs and platelet aggregation using human platelets activated with ADP.

KEY RESULTSExperiments using HLM or specific CYPs (3A4, 2C19) revealed that at clopidogrel concentrations >10 µM, CYP3A4 was primarily responsible for clopidogrel biotransformation. At a clopidogrel concentration of 40 µM, ketoconazole showed the strongest inhibitory effect on clopidogrel biotransformation and clopidogrel‐associated inhibition of platelet aggregation with IC50values of 0.03 ± 0.07 µM and 0.55 ± 0.06 µM respectively. Clarithromycin, another CYP3A4 inhibitor, impaired clopidogrel biotransformation and antiplatelet activity almost as effectively as ketoconazole. The CYP3A4 substrates atorvastatin and simvastatin both inhibited clopidogrel biotransformation and antiplatelet activity, less potently than ketoconazole. In contrast, pravastatin showed no inhibitory effect. As clopidogrel itself inhibited CYP2C19 at concentrations >10 µM, the CYP2C19 inhibitor lansozprazole affected clopidogrel biotransformation only at clopidogrel concentrations ≤10 µM. The carboxylate metabolite of clopidogrel was not a CYP substrate and did not affect platelet aggregation.

CONCLUSIONS AND IMPLICATIONSAt clopidogrel concentrations >10 µM, CYP3A4 is mainly responsible for clopidogrel biotransformation, whereas CYP2C19 contributes only at clopidogrel concentrations ≤10 µM. CYP2C19 inhibition by clopidogrel at concentrations >10 µM may explain the conflicting results betweenin vitroandin vivoinvestigations regarding drug interactions with clopidogrel.
Therapeutic potential of targeting group III metabotropic glutamate receptors in the treatment of Parkinson's disease
Authors: Duty Susan
Published: May 2010

Current drugs used in the treatment of Parkinson's disease (PD), for example, L‐DOPA and dopamine agonists, are very effective at reversing the motor symptoms of the disease. However, they do little to combat the underlying degeneration of dopaminergic neurones in the substantia nigra pars compacta (SNc) and their long‐term use is associated with the appearance of adverse effects such as L‐DOPA‐induced dyskinesia. Much emphasis has therefore been placed on finding alternative non‐dopaminergic drugs that may circumvent some or all of these problems. Group III metabotropic glutamate (mGlu) receptors were first identified in the basal ganglia a decade ago. One or more of these receptors (mGlu4, mGlu7 or mGlu8) is found on pre‐synaptic terminals of basal ganglia pathways whose overactivity is implicated not only in the generation of motor symptoms in PD, but also in driving the progressive SNc degeneration. The finding that drugs which activate group III mGlu receptors can inhibit transmission across these overactive synapses has lead to the proposal that group III mGlu receptors are promising targets for drug discovery in PD. This paper provides a comprehensive review of the role and target potential of group III mGlu receptors in the basal ganglia. Overwhelming evidence obtained from in vitro studies and animal models of PD supports group III mGlu receptors as potentially important drug targets for providing both symptom relief and neuroprotection in PD.
Protective effect of hydrogen sulphide against 6‐OHDA‐induced cell injury in SH‐SY5Y cells involves PKC/PI3K/Akt pathway
Authors: Tiong Chi Xin , Lu Ming , Bian Jin‐Song
Published: May 2010

BACKGROUND AND PURPOSE Hydrogen sulphide (H2S) is a novel neuromodulator. The present study aimed to investigate the protective effect of H2S against cell injury induced by 6‐hydroxydopamine (6‐OHDA), a selective dopaminergic neurotoxin often used to establish a model of Parkinson's disease for studying the underlying mechanisms of this condition.

EXPERIMENTAL APPROACH Cell viability in SH‐SY5Y cells was measured using MTT assay. Western blot analysis and pharmacological manipulation were employed to study the signalling mechanisms.

KEY RESULTS Treatment of SH‐SY5Y cells with 6‐OHDA (50–200 µM) for 12 h decreased cell viability. Exogenous application of NaHS (an H2S donor, 100–1000 µM) or overexpression of cystathionine β‐synthase (a predominant enzyme to produce endogenous H2S in SH‐SY5Y cells) protected cells against 6‐OHDA‐induced cell apoptosis and death. Furthermore, NaHS reversed 6‐OHDA‐induced loss of tyrosine hydroxylase. Western blot analysis showed that NaHS reversed the down‐regulation of PKCα, ε and Akt and the up‐regulation of PKCδ in 6‐OHDA‐treated cells. Blockade of PKCα with Gö6976 (2 µM), PKCε with EAVSLKPT (200 µM) or PI3K with LY294002 (20 µM) reduced the protective effects of H2S. However, inhibition of PKCδ with rottlerin (5 µM) failed to affect 6‐OHDA‐induced cell injury. These data suggest that the protective effects of NaHS mainly resulted from activation of PKCα, ε and PI3K/Akt pathway. In addition, NaHS‐induced Akt phosphorylation was significantly attenuated by Gö6976 and EAVSLKPT, suggesting that the activation of Akt by NaHS is PKCα, ε‐dependent.

CONCLUSIONS AND IMPLICATIONS H2S protects SH‐SY5Y cells against 6‐OHDA‐induced cell injury by activating the PKCα, ε/PI3K/Akt pathway.
GSK1562590, a slowly dissociating urotensin‐II receptor antagonist, exhibits prolonged pharmacodynamic activity ex vivo
Authors: Behm DJ , Aiyar NV , Olzinski AR , McAtee JJ , Hilfiker MA , Dodson JW , Dowdell SE , Wang GZ , Goodman KB , Sehon CA , Harpel MR , Willette RN , Neeb MJ , Leach CA , Douglas SA
Published: May 2010

BACKGROUND AND PURPOSE Recently identified antagonists of the urotensin–II (U‐II) receptor (UT) are of limited utility for investigating the (patho)physiological role of U‐II due to poor potency and limited selectivity and/or intrinsic activity.

EXPERIMENTAL APPROACH The pharmacological properties of two novel UT antagonists, GSK1440115 and GSK1562590, were compared using multiple bioassays.

KEY RESULTS GSK1440115 (pKi= 7.34–8.64 across species) and GSK1562590 (pKi= 9.14–9.66 across species) are high affinity ligands of mammalian recombinant (mouse, rat, cat, monkey, human) and native (SJRH30 cells) UT. Both compounds exhibited >100‐fold selectivity for UT versus 87 distinct mammalian GPCR, enzyme, ion channel and neurotransmitter uptake targets. GSK1440115 showed competitive antagonism at UT in arteries from all species tested (pA2= 5.59–7.71). In contrast, GSK1562590 was an insurmountable UT antagonist in rat, cat and hUT transgenic mouse arteries (pKb= 8.93–10.12 across species), but a competitive antagonist in monkey arteries (pKb= 8.87–8.93). Likewise, GSK1562590 inhibited the hU‐II‐induced systemic pressor response in anaesthetized cats at a dose 10‐fold lower than that of GSK1440115. The antagonistic effects of GSK1440115, but not GSK1562590, could be reversed by washout in rat isolated aorta. In ex vivo studies, GSK1562590 inhibited hU‐II‐induced contraction of rat aorta for at least 24 h following dosing. Dissociation of GSK1562590 binding was considerably slower at rat than monkey UT.

CONCLUSIONS AND IMPLICATIONS Whereas both GSK1440115 and GSK1562590 represent high‐affinity/selective UT antagonists suitable for assessing the (patho)physiological role of U‐II, only GSK1562590 exhibited sustained UT residence time and improved preclinical efficacy in vivo.
Is Asia adopting flexicurity?
Authors: VANDENBERG Paul
Published: May 2010

In the face of global competition, many countries are adopting a flexicurity approach to labour regulation, providing employers with greater flexibility to hire and retrench workers while helping workers transition to new jobs. This review of six Asian countries finds that China and the Republic of Korea have enacted such reforms; Singapore and Malaysia provide some ingredients of flexicurity, though no unemployment insurance; India and Sri Lanka have introduced few reforms and continue to rely on an older model of employer‐based security. To support informal workers, the Governments of China, India and Sri Lanka use public works, self‐employment programmes and skills training.
The consequences of job insecurity for employees: The moderator role of job dependence
Authors: SORA Beatriz , CABALLER Amparo , PEIRÓ José María
Published: May 2010

With globalization and increased international competition have come more flexible forms of employment and increased job insecurity. The authors address the impact of perceived job insecurity on employees' work attitudes and intentions. After reviewing relevant research on stress theory and the relationship between job insecurity and its consequences, they test two hypotheses on 942 employees in Spain, namely: first, that job insecurity relates negatively to job satisfaction and organizational commitment and positively to intention to leave; and, second, that job insecurity, economic need and employability interact in the prediction of these outcomes.
The cost of “doing business” and labour regulation: The case of South Africa
Authors: BENJAMIN Paul , BHORAT Haroon , CHEADLE Halton
Published: May 2010

The “Employing Workers” indices compiled from the World Bank's Doing Business (DB) survey for 2006 presented mixed results as to the nature and extent of labour regulation in South Africa. Arguing that these measures – with their narrow focus on legislation – provide only a partial picture, the authors suggest and investigate three possible extensions to the DB framework with the aim of achieving a more realistic representation of labour regulation in practice, namely: “micro‐legislation”, labour market institutions and judicial interpretation. They conclude with a plea for taking account of the crucial importance of these features in the assessment of labour regulation frameworks.
Post‐employment covenants in the United States: Legal framework and market behaviours
Authors: Hannah Richard L.
Published: May 2010

In response to fundamental market changes that are giving labour a much more central role in product market competition, employers often seek to extend their control over human capital beyond termination of the employment relationship. Although empirical studies are scarce, the use of restrictive post‐employment covenants is indeed believed to be widespread. But to what extent can employers lawfully restrict the freedom of their former employees? The author examines the criteria that courts in the United States have considered in balancing employers' legitimate economic interests against labour market efficiency and workers' post‐employment freedom and mobility.
Wetland conservation and sustainable use under global change: a tropical Australian case study using magpie geese
Authors: Traill Lochran W. , Bradshaw Corey J. A. , Delean Steven , Brook Barry W.
Published: May 2010

Imminent shifts in environmental parameters due to climatic change might have profound ramifications for wetlands listed under the Ramsar convention. Although the exact mechanisms by which global change will affect these systems are not known, models that simulate component drivers, particularly at a broad spatial scale, can nevertheless allow for more informed conservation decision making. Such general inference is particularly needed for wetlands across the tropics, where less knowledge and fewer resources are available to mitigate the impacts on important conservation sites. Here we develop a case study of wetland loss to sea level rise across tropical north Australia (including Ramsar‐listed sites), and link these to a metapopulation model for a keystone endemic waterbird, the magpie goose Anseranas semipalmata. We projected published models on sea level rise through to the year 2400, and found a non‐linear trajectory of inundation up to 20 m above present levels. Digital elevation models were used to simulate sea level rise and the spatially differentiated loss of wetland habitat used by geese. Range retraction was linked to decline in ecological carrying capacity, and we coupled wetland‐specific habitat loss projections to a spatially explicit demographic metapopulation model. Additionally, we included alternate harvest strategies based on present‐day estimates of indigenous and non‐indigenous offtake of geese, and examined the synergy between wetland loss and hunting on extinction risk. Our results suggest that Australia's once‐abundant and widespread magpie goose will be reduced to a fragmented population of just a few thousand individuals within the next 200–300 yr. Harvest could continue for some time, up to a “tipping point” at around 5% loss of current wetland habitat, after which the decline of geese is rapid. Given the inexorable nature of sea level rise, short‐ to medium‐term conservation of waterbirds across Ramsar wetlands must prepare for adaptive wetland management, such as through buffer‐placement, and ongoing monitoring of harvest.
A randomized controlled trial of positioning treatments in infants with positional head shape deformities
Authors: Hutchison B Lynne , Stewart Alistair W , De Chalain Tristan B , Mitchell Edwin A
Published: May 2010

Background:  Randomized controlled trials of treatment for deformational plagiocephaly and brachycephaly have been lacking in the literature.

Methods:  Infants (n = 126) presenting to a plagiocephaly clinic were randomized to either positioning strategies or to positioning plus the use of a Safe T Sleep™ positioning wrap. Head shape was measured using a digital photographic technique, and neck function was assessed. They were followed up at home 3, 6 and 12 months later.

Results:  There was no difference in head shape outcomes for the two treatment groups after 12 months of follow‐up, with 42% of infants having head shapes in the normal range by that time. Eighty per cent of children showed good improvement. Those that had poor improvement were more likely to have both plagiocephaly and brachycephaly and to have presented later to clinic.

Conclusions:  Most infants improved over the 12‐month study period, although the use of a sleep positioning wrap did not increase the rate of improvement.
Early sexual debut and associated factors among in‐school adolescents in eight African countries
Authors: Peltzer Karl
Published: May 2010

Objective:  This report examines early sexual debut (<age 15) among 15‐year‐old in‐school adolescents in eight African countries.

Participants:  The total sample included 10 070 school children aged 15 years from nationally representative samples from eight African countries.

Methods:  Univariate and multivariate analyses were conducted to assess the relationship between early sexual debut and alcohol, tobacco and other drug use, mental distress, physical activity, protective factors and socioeconomic status variables.

Results:  A total of 27.3% had experienced sexual debut before age 15, 38.1% among boys and 15.8% among girls. Boys and girls with sexual debut at less than age 15 were more likely to report alcohol, tobacco and drug use, truancy, poor parental or guardian connectedness, sedentary behaviour, having been in a physical fight and seriously injured, while for girls, mental distress and poor economic status and for boys, bullied and poor parental or guardian supervision were associated with early coital debut. In multivariable analysis, early sexual debut was among boys associated with currently smoking (OR = 4.45, p = 0.002) and truancy (OR = 2.02, p = 0.007) and, among girls, associated with lower education (OR = 0.22, p = 0.004), ever drunk (OR = 3.94, p = 0.016), having no close friends (OR = 3.36, p = 0.014) and poor parental connectedness (OR = 2.43, p = 0.037).

Conclusion:  The study found a high prevalence of early sexual debut among 15‐year‐olds in eight African countries. Risk factors identified were consistent with problem behaviour theory in which early onset of adolescent sexual behaviour is shared with other problem behaviours. Prevention programmes should broaden sexual health promotion including problem behaviour such as substance use and mental distress for boys and girls in the preteen years, before sexual debut.
Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease
Authors: Kuo Ho‐Chang , Liang Chi‐Di , Wang Chih‐Lu , Yu Hong‐Ren , Hwang Kao‐Pin , Yang Kuender D
Published: May 2010

Objectives:  Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are <5 years old. Intravenous immunoglobulin (IVIG) is the standard therapy for KD. However, many patients with KD still show poor response to initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD.

Methods:  Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG‐responsive and IVIG‐resistant groups. Initial laboratory data before IVIG treatment were collected for analysis.

Results:  A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8–562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C‐reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively.

Conclusion:  Pre‐IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD.
Clinico‐pathological spectrum of gallbladder disease in children
Authors: Punia RPS , Garg Shailja , Bisht Bhumika , Dalal Usha , Mohan Harsh
Published: May 2010

Aim:  Because of wide variation in clinico‐pathological spectrum of gallbladder disease in children the world over, the data of gallbladder disease from this stone belt of India were analysed.

Methods:  Children who underwent cholecystectomy over a period of 8 years January 2002–December 2009 were reviewed.

Results:  Out of 7076 cholecystectomies, 56 (0.79%) were in children. Thirty‐nine (69.6%) children were 11–16 years of age. Thirty‐seven (66.07%) children were girls and nineteen (33.9%) were boys. In 12 (21.4%) children, cholecystitis was acalculus. Five (8.9%) children had associated haemolytic disease and 4 (7.1%) children had congenital anomaly in the form of choledochal cyst. Ultrasound findings were available in 44 cases and showed cholelithiasis in 36 cases. Twenty‐two (39.3%) children had mixed cholelithiasis, 8 (14.2%) pigment cholelithiasis, 10 (17.8%) combined cholelithiasis and 4 (7.1%) patients had small concretions. Microscopically, changes of chronic cholecystitis were seen in 98.2% while 1.7% showed acute on chronic cholecystitis. There was single unusual case of cysticercus in the wall of the gallbladder.

Conclusions:  The frequency of gallstone disease is 0.79%. Nonhaemolytic type of cholelithiasis is more common than haemolytic type in this region. Presence of cysticercus in the gallbladder wall in one case was an unexpected finding.
Circulating cardiac troponins levels and cardiac dysfunction in children with acute and fulminant viral myocarditis
Authors: Al‐Biltagi Mohammed , Issa Mona , Hagar Hamdi Abo , Abdel‐Hafez Maher , Aziz Nahla Abdul
Published: May 2010

Objectives:  To study the correlation between cardiac Troponins blood levels and degrees of cardiac dysfunction in children with acute and fulminant viral myocarditis and to study their prognostic role in predicting the outcomes and risk of having dilated cardiomyopathy.

Methodology:  Troponin I & T blood levels were measured in 65 children with acute or fulminant viral myocarditis. The cardiac functions of RV & LV were assessed by Doppler echocardiography.

Results:  The levels of cTnI & CTnT were significantly higher in patients with fulminant myocarditis than in controls and children with acute myocarditis (p < 0.05 & <0.001* respectively). The cardiac functions were significantly impaired in fulminant myocarditis than in acute myocarditis (p < 0.001*). There were negative correlations between the cardiac troponins levels and the cardiac functions measured by echocardiography in children with acute and fulminant myocarditis. There were 3 deaths (7.5%), and 10 (25%) children developed dilated cardiomyopathy in acute myocarditis while there were eight deaths (32%) and one patient (4%) who developed dilated cardiomyopathy in fulminant myocarditis group.

Conclusion:  Cardiac troponins levels can predict the severity of myocarditis and the prognosis on the short‐term level. Fulminant myocarditis was associated with higher levels of both cTn I & cTn T than acute myocarditis. Despite that fulminant myocarditis has a more aggressive course, the risk of developing cardiomyopathy was less than in acute myocarditis.
LmbE proteins from Bacillus cereus are de‐N‐acetylases with broad substrate specificity and are highly similar to proteins in Bacillus anthracis
Authors: Deli Alexandra , Koutsioulis Dimitrios , Fadouloglou Vasiliki E. , Spiliotopoulou Panagiota , Balomenou Stavroula , Arnaouteli Sofia , Tzanodaskalaki Maria , Mavromatis Konstantinos , Kokkinidis Michalis , Bouriotis Vassilis
Published: May 2010

The genomes of Bacillus cereus and its closest relative Bacillus anthracis each contain two LmbE protein family homologs: BC1534 (BA1557) and BC3461 (BA3524). Only a few members of this family have been biochemically characterized including N‐acetylglucosaminylphosphatidyl inositol (GlcNAc‐PI), 1‐d‐myo‐inosityl‐2‐acetamido‐2‐deoxy‐α‐d‐glucopyranoside (GlcNAc‐Ins), N,N′‐diacetylchitobiose (GlcNAc2) and lipoglycopeptide antibiotic de‐N‐acetylases. All these enzymes share a common feature in that they de‐N‐acetylate the N‐acetyl‐d‐glucosamine (GlcNAc) moiety of their substrates. The bc1534 gene has previously been cloned and expressed in Escherichia coli. The recombinant enzyme was purified and its 3D structure determined. In this study, the bc3461 gene from B. cereus ATCC14579 was cloned and expressed in E. coli. The recombinant enzymes BC1534 (EC 3.5.1.‐) and BC3461 were biochemically characterized. The enzymes have different molecular masses, pH and temperature optima and broad substrate specificity, de‐N‐acetylating GlcNAc and N‐acetylchito‐oligomers (GlcNAc2, GlcNAc3 and GlcNAc4), as well as GlcNAc‐1P, N‐acetyl‐d‐glucosamine‐1 phosphate; GlcNAc‐6P, N‐acetyl‐d‐glucosamine‐6 phosphate; GalNAc, N‐acetyl‐d‐galactosamine; ManNAc, N‐acetyl‐d‐mannosamine; UDP‐GlcNAc, uridine 5′‐diphosphate N‐acetyl‐d‐glucosamine. However, the enzymes were not active on radiolabeled glycol chitin, peptidoglycan from B. cereus, N‐acetyl‐d‐glucosaminyl‐(β‐1,4)‐N‐acetylmuramyl‐l‐alanyl‐d‐isoglutamine (GMDP) or N‐acetyl‐d‐GlcN‐Nα1‐6‐d‐myo‐inositol‐1‐HPO4‐octadecyl (GlcNAc‐I‐P‐C18). Kinetic analysis of the activity of BC1534 and BC3461 on GlcNAc and GlcNAc2 revealed that GlcNAc2 is the favored substrate for both native enzymes. Based on the recently determined crystal structure of BC1534, a mutational analysis identified functional key residues, highlighting their importance for the catalytic mechanism and the substrate specificity of the enzyme. The catalytic efficiencies of BC1534 variants were significantly decreased compared to the native enzyme. An alignment‐based tree places both de‐N‐acetylases in functional categories that are different from those of other LmbE proteins.
Influence of Progesterone on Sexual Performance in Male Rats
Authors: Alvarenga Tathiana A. , Andersen Monica L. , Tufik Sergio
Published: May 2010

Introduction

It has been documented that copulatory experience can alter or improve sexual performance in male rats. However, the hormonal basis and the number of sexual encounters needed for a rat to acquire sufficient performance remains unclear.

Aim

The aim of this study was to examine whether levels of testosterone and progesterone are associated with sexual performance in male rats.

Methods

Adult male Wistar Hannover rats were exposed to a receptive female for 15 minutes every other day for 9 days for acquiring sexual experience.

Main Outcome Measures

After training protocol, rats were scored as low or high sexual performers. Hormonal levels (testosterone and progesterone) were evaluated in both trained and non-trained control groups.

Results

Our results showed that a 9-day training period was not sufficient for some male rats to acquire a good level of sexual performance. While 42.5% of the rats displayed excellent sexual performance during the training sessions, 17.5% showed adequate performance, 7.5% had low sexual activity, and 32.5% of the rats did not display any sexual behaviors whatsoever. Additionally, after 4 days of training, rats with excellent/adequate performance showed a significant decrease in ejaculation latency relative to the first day of training. The rats with low or no sexual activity had lower progesterone levels relative to those displaying the highest sexual performance after 9 days of training. Testosterone, in turn, was also significantly reduced in animals with low/no sexual performance compared with excellent/adequate rats.

Conclusion

In conclusion, progesterone may be a limiting factor to promoting sexual performance in male rats.
Persistent Sexual Dysfunction Impairs Quality of Life after Cardiac Transplantation
Authors: Phan Anita , IsHak Waguih William , Shen Biing-Jiun , Fuess Justin , Philip Kiran , Bresee Catherine , Czer Lawrence , Schwarz Ernst R.
Published: May 2010

Introduction

The impact of sexual dysfunction (SD) on mental and physical health after heart transplantation (HTx) has not been established.

Aim

We investigated the relationship of SD on quality of life (QoL), physical and mental health, and depressive symptoms after HTx.

Main Outcome Measures

We evaluated SD according to the International Index of Erectile Dysfunction and the Female Sexual Function Index. QoL, physical and mental health were assessed using: 1) Short Form 12 Health Survey Questionnaire, 2) Quality of Life Enjoyment and Satisfaction Questionnaire—Short Form, and two depressive symptoms questionnaires: 1) Beck Depression Inventory-II and 2) Quick Inventory Depressive Symptomatology-Self Report.

Methods

We enrolled patients who were greater than 6 months post HTx. Patients unable to read English, had pelvic surgery or trauma, urogenital abnormalities, or sexually inactive were excluded.

Results

Out of 79 subjects that were screened, 33 men and 6 women participated (mean age 61.4+11.4). Response rates were at least 82% for all questionnaires. Overall prevalence of SD was 61%, with 78% of men being affected and 50% of women. There was no significant difference in measures between genders. HTx recipients with SD reported significantly worse QoL on measures of physical health when compared to those without SD. After HTx, patients suffering from SD had significantly worse general health (P = 0.02) and physical health (P = 0.02), including physical functioning (P = 0.01) and physical role limitation (P = 0.01). In contrast, mental health and depressive symptoms after HTx were not significantly different between those with and without SD.

Conclusions

After HTx a high prevalence of SD remains among both men and women. Patients with SD had worse general and physical health but not depressive symptoms when compared to those without SD. The contributing factors may be more related to physical rather than psychological causes.
THE DETERMINANTS OF EMPLOYMENT: A SECTORAL ANALYSIS FOR TURKEY
Authors: AYDINER‐AVSAR Nursel , ONARAN ÖZlem
Published: May 2010

This paper analyzes the effects of wages, openness, and demand on employment in the private manufacturing industry in Turkey based on panel data for the period of 1973–2001. The wage elasticity of employment increases after trade liberalization. Nevertheless, output elasticity of labor demand is higher than wage elasticity in the total manufacturing sector for the whole estimation period, and in the high‐ and medium‐skilled sectors in the post‐1980 period. Trade effects, after controlling for output, seem to have a low economic significance. The positive effects of exports on the labor intensity of production are low or are offset by labor saving effects of foreign trade, particularly in the high‐ and medium‐skilled sectors. On the other hand, there is some evidence of a negative import effect in the low‐skilled sectors, whereas in the high‐ and medium‐skilled group a complementary relation between domestic labor and imported inputs dominates the effects.
BORDER BARRIERS IN AGRICULTURAL TRADE AND THE IMPACT OF THEIR ELIMINATION: EVIDENCE FROM EAST ASIA
Authors: CHANG Kuo‐I , HAYAKAWA Kazunobu
Published: May 2010

We investigate the impact of the elimination of import tariffs and nontariff policy barriers (NTPBs) on agricultural trade in a notional East Asian Free Trade Agreement using a Global Trade Analysis Project (GTAP)‐based computable general equilibrium model. The investigation is divided into two parts. We first measure the NTPBs by employing a widely used method derived from the literature on border effects. Then, by adding into the GTAP database our estimates on the NTPBs, which the original GTAP database by its nature does incorporate, we compute the impact of the entire elimination of policy barriers (the complete reduction of import tariffs and NTPBs) on GDP. The result shows that there are remarkable differences between the effect of abolition of import tariffs and that of entire elimination of all import barriers.
WELFARE GAINS OF AID INDEXATION IN SMALL OPEN ECONOMIES
Authors: DHASMANA Anubha
Published: May 2010

Foreign‐aid flows to poor, aid‐dependent economies are highly volatile and pro‐cyclical. Shortfalls in aid coincide with shortfalls in GDP and government revenues. This increases the consumption volatility in aid dependent countries, thereby causing substantial welfare losses. This paper finds that indexing aid flows to exogenous shocks, like a change in the terms of trade, can significantly improve the welfare of an aid‐dependent country by lowering its output and consumption volatility. Compared to the benchmark specification with stochastic aid flows, indexation of aid flows to terms‐of‐trade shocks can reduce the cost of business‐cycle fluctuations in the recipient country by 4% of permanent consumption. Moreover, use of indexed aid can allow donors to reduce the aid flows by 3% without lowering the level of welfare in the recipient country.
Evaluation of the weight‐increasing effects of biphasic analog and regular NPH insulin mixtures in patients with Type 2 diabetes mellitus
Authors: TEMİZEL Mustafa , MERT Meral , BOZBEY Celal , ARMAN Yücel , CEVIZCI Ertan , ALTINTAŞ Nejat , ÇETIN ÖLEK Ali
Published: May 2010

Background:  Weight gain is a significant problem in diabetic patients in terms of worsening glycemic control, increasing diabetic and cardiovascular morbidity and mortality, and contributing to social and psychological problems. In the present study, we evaluated the effects of a biphasic analog and regular NPH insulin mixtures on weight gain in patients with Type 2 diabetes mellitus (T2DM) over 1 year.

Methods:  Group I consisted of 71 patients (29 men and 42 women) being treated with analog mixtures (insulin lispro 75/25 mix and biphasic insulin aspart 70/30 mix) twice daily; Group II consisted of 69 patients (23 men and 46 women) being treated with a regular insulin mixture (70/30) twice daily. Starting weight, body mass index, HbA1c, and hypoglycemic episodes were evaluated after 6 and 12 months.

Results:  Weight gain in Group I at 6 and 12 months was 1.41 ± 2.70 and 2.08 ± 3.74 kg, respectively. In Group II, weight gain at 6 and 12 months was 1.5 ± 3.0 and 2.29 ± 3.85 kg, respectively. Intragroup comparisons indicated that, for both groups, weight gain at 6 and 12 months differed significantly from the starting weight. However, no significant differences in weight gain were found between the two groups (P > 0.05).

Conclusions:  The weight‐increasing effects of an analog mixture of insulin and the NPH regular mixture of insulin appear to be similar. This should be taken into account when determining the type of insulin to use in treating T2DM patients.
Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa
Authors: Wakabayashi Taku , Sawa Miki , Gomi Fumi , Tsujikawa Motokazu
Published: May 2010

Purpose:  To assess and correlate fundus autofluorescence (FAF) characteristics with photoreceptor morphology and functional features in eyes with retinitis pigmentosa (RP).

Methods:  Thirty‐four eyes of 17 patients with RP were examined. We compared FAF images obtained by confocal scanning laser ophthalmoscopy with Spectral‐domain optical coherence tomography (SD‐OCT) and retinal function assessed by microperimetry.

Results:  Normal FAF surrounded by a ring of increased FAF at the macular area was detected in 32 (94%) eyes. The diameter of the normal FAF was correlated significantly with the preserved area of the photoreceptor inner segment and outer segment (IS/OS) junction on SD‐OCT (R = 0.939, p < 0.001). The area outside the ring was associated with loss of IS/OS junction and external limiting membrane (ELM). The ring of increased FAF demarcated the border between the central retina with preservation of the IS/OS junction and ELM, and the adjacent eccentric retina with loss of these bands. In two eyes of one patient, there was no preservation of normal FAF at the macula and the photoreceptor IS/OS junction was not detected on SD‐OCT. The mean retinal sensitivity derived from microperimetry was correlated significantly with the area of normal FAF (R = 0.929, p = 0.007) and the preserved area of the IS/OS junction (R = 0.851, p = 0.032). Ten eyes had progressive reduction in size of the normal FAF inside the ring accompanied by decreased area of preserved IS/OS during 3.1 years.

Conclusion:  FAF appears to reflect the integrity of the photoreceptor layer. It may serve as a secondary outcome measure for novel therapeutic strategies for RP.
SURVEY ON VIOLENCE AND AGGRESSION PREVENTION AND MANAGEMENT STRATEGIES IN EUROPEAN RENAL UNITS
Authors: Zampieron Alessandra , Saraiva Maria , Pranovi Rebecca , Laskari Anastasia , Buja Alessandra
Published: May 2010

Goals: This descriptive survey aims to explore strategies for the prevention and management of violence and aggression in renal units in 12 European countries.

Method: The convenience sample consisting of dialysis, nephrological and transplantation units in European countries was used. A questionnaire, developed with the collaboration of National Associations, was used. Data were analysed using STATA software. A preliminary descriptive variable analysis was performed followed by a verification of the association between variables; values of p < 0.002 were considered statistically significant.

Results: A total of 436 completed questionnaires were received (participation rate: 22%). Written policies and procedures regarding violence and aggression are present in 18% of units. Educational strategies are available in less than 20% of units. Incidents are prevented by security staff (48%) or pharmacological treatment (66%). Incident reporting is mandatory for any violent and aggressive behaviour in 66% of units. There are differences between European countries.

Discussion and conclusion: Violence and aggression prevention and management strategies are not widely implemented throughout Europe. The dissemination of information on the prevention and management of violence and aggression is vital.
CORRELATION OF PERISCREEN STRIP RESULTS AND WHITE CELL COUNT IN PERITONEAL DIALYSIS PERITONITIS
Authors: Fan Stanley , Lane Catherine , Punzalan Sally
Published: May 2010

Introduction: Monitoring of peritoneal dialysis (PD) peritonitis can be difficult for visually impaired patients. PeriScreen strips measure leukocyte esterase activity and this might be a useful objective test that can be performed by patients at home. Methods: A prospective study of 138 episodes of peritonitis was undertaken. Effluent samples were analysed for white cell count (WCC) and PeriScreen score on days 3 and 5. Co‐morbidity data were collated from these patients. Results: Effluent WCC and PeriScreen results were found to correlate with the gold standard assessment of microbiology WCC count. A positive PeriScreen result on day 5 predicted that the episode of peritonitis would relapse after treatment with a sensitivity of 80% but with a poor specificity of 45%. Patients who cleared or relapsed their peritonitis could not be differentiated based on their burden of co‐morbidity, Karnofsky scores, age, dialysis vintage or infective organism. Conclusion: PeriScreen strip analysis correlated with microscopic WCC of PD. However, analysis of PD effluent on day 5 of treatment is not a good test to risk stratify patients for relapsing peritonitis.
CARDIAC REHABILITATION FOR PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Byrne Gobnait , Murphy Fiona
Published: May 2010

Cardiac Rehabilitation programmes are an integrated part of the total care of the patient and are delivered by a multidisciplinary team. Cardiac Rehabilitation is usually organised in four phases and has shown to reduce the morbidly and mortality associated with cardiac disease. Chronic Kidney Disease patients who are at risk of, or already have, Cardiovascular Disease should be monitored, educated and managed through close working relationships between the renal and cardiac multidisciplinary teams. One mechanism by which this may be achieved is through the use of cardiac rehabilitation programmes.
VENTRICULAR ARRHYTHMIAS AND SUDDEN DEATH IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Green Darren , Roberts Paul R.
Published: May 2010

One in four dialysis patients will die suddenly. Most do not fall into the high‐risk categories that are associated with sudden death in the general population. The cause of sudden death in the dialysis population is unknown. It may be related to factors associated with chronic kidney disease (CKD) itself, for example, inflammation, vascular stiffness, left ventricular hypertrophy, coronary artery disease, electrolyte/fluid abnormalities or autonomic dysfunction. Studies of patients with implantable cardioverter defibrillators have shown that patients with CKD are more likely to use their devices for ventricular arrhythmias but in spite of this still have a high associated mortality. Until a comprehensive risk stratification strategy is understood, minimising risk by good control of basic parameters such as fluid balance, electrolytes and blood pressure, along with careful assessment of all patients for evidence of coronary artery disease and heart failure is the mainstay of management of the CKD patient.
THE IMPORTANCE OF RENIN‐ANGIOTENSIN BLOCKADE IN PATIENTS WITH CARDIO‐RENAL DISEASE
Authors: Benavente David , Chue Colin D. , Ferro Charles J.
Published: May 2010

The existence of the renin–angiotensin–aldosterone system was first postulated over 100 years ago. Following the identification of all the major components, came the discovery of their potential pathogenicity in cardiovascular and renal disease. The introduction of drugs that inhibit the synthesis or actions of this system has prompted a number of trials that have largely shaped how cardiovascular and renal disease is managed today. The continued discovery of yet more components of this system promises to further our understanding of its influence on disease processes and herald the development of more highly selective drugs, ensuring that the renin–angiotensin–aldosterone system will continue to be a key area of interest for many years to come.
SCREENING FOR CARDIOVASCULAR DISEASE IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE
Authors: Sharma Rajan
Published: May 2010

Cardiovascular disease remains the major cause of mortality and morbidity in patients with advanced chronic kidney disease (CKD) and after renal transplantation. The mechanisms for cardiotoxicity are multiple. Identifying high‐risk patients remains a challenge. Given, the poor long‐term outcome of dialysis patients who do not receive renal transplantation and the lower supply of donor kidneys relative to demand, optimal selection of renal transplantation candidates is crucial. This requires a clear understanding of the validity of cardiac tests in this patient group. This paper explores the strengths and weaknesses of currently available diagnostic tools in patients with advanced CKD. Echocardiography is very useful for the detection of cardiomyopathy and prognosis. Stress echocardiography, myocardial perfusion imaging and coronary angiography are the best tools for the assessment of coronary artery disease. All predict outcome. No single gold standard investigation exists. At present, there is not an optimal technique for predicting sudden cardiac death in this patient group. Ultimately, the choice of cardiac test will always be determined by patient preference, local expertise and availability.
THE ASSOCIATION OF CHRONIC KIDNEY DISEASE‐MINERAL BONE DISORDER AND CARDIOVASCULAR RISK
Authors: Eddington Helen , Kalra Philip A.
Published: May 2010

Chronic kidney disease‐mineral bone disorder (CKD‐MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as ‘renal osteodystrophy’ or ‘renal bone disease’. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.
LIPIDS IN CHRONIC KIDNEY DISEASE
Authors: Lewis David , Haynes Richard , Landray Martin J.
Published: May 2010

Patients with chronic kidney disease (CKD) develop premature cardiovascular disease. In the general population (without CKD), there are strong associations between cholesterol fractions and the risk of coronary disease and weaker associations with stroke. Randomised trials in the general population demonstrate that lowering blood cholesterol (chiefly with a statin) reduces the risk of vascular events. Patients with CKD differ significantly from the general population. They have markedly disturbed lipid metabolism manifesting as elevated triglyceride concentrations, reduced HDL cholesterol concentrations and a preponderance of small, dense LDL particles that are potentially more atherogenic; the observed association between lipids and vascular disease is bizarre, and is confounded by co‐morbidity; the nature of the vascular disease appears less strongly associated with classical atherosclerosis. Randomised trials are required to determine the relevance of blood lipids to the development of vascular disease in CKD patients, but the results of such studies have been inconclusive to date. CKD patients are at risk of end‐stage renal disease. Lipids may be involved in the progression of renal disease. Modifying them may delay the progression of CKD. The current data are based on effects on markers of progression (e.g. proteinuria). The ongoing SHARP (Study of Heart and Renal Protection) trial should provide reliable information about the effects of statins on both vascular and renal risk.
CARDIO‐RENAL SYNDROMES
Authors: Goh Ching Yan , Ronco Claudio
Published: May 2010

‘Cardio‐Renal syndromes’ (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time‐frame and simultaneous cardiac and renal co‐dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF‐ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF‐CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.
PRACTICAL MANAGEMENT OF DIET AND LIFESTYLE INTERVENTIONS FOR PEOPLE WITH DIABETES OR CARDIOVASCULAR DISEASE
Authors: Symes Fiona , Sutton Debbie
Published: May 2010

Increased collaboration between the vascular specialities is clearly leading to increased understanding of the interrelationships between the different disease states and how each impacts and influences the other. This advantage will be reflected in improved patient care if the practical outputs of this growing knowledge are carefully implemented at service level. This article outlines how the aspects of diet and lifestyle associated with vascular‐related disease complement, contrast and in some cases contradict each other. It gives information and guidelines as to how the expertise of dietitians working in the different specialist areas might usefully be shared to be of maximum advantage to all patients.
Tyrosine phosphatase TpbA of Pseudomonas aeruginosa controls extracellular DNA via cyclic diguanylic acid concentrations
Authors: Ueda Akihiro , Wood Thomas K.
Published: May 2010

Inactivating the tyrosine phosphatase TpbA of Pseudomonas aeruginosa PA14 induces biofilm formation by 150‐fold via increased production of the second messenger cyclic diguanylic acid (c‐di‐GMP). Here, we show the tpbA mutation reduces extracellular DNA (eDNA) and that increased expression of tpbA increases eDNA; hence, eDNA is inversely proportional to c‐di‐GMP concentrations. Mutations in diguanylate cyclases PA0169, PA4959 and PA5487 and phosphodiesterase PA4781 corroborate this trend. The tpbA mutation also decreases cell lysis while overexpression of tpbA increases cell lysis. To further link c‐di‐GMP concentrations and eDNA, the gene encoding phosphodiesterase PA2133 was overexpressed which increased eDNA and decreased biofilm formation by decreasing c‐di‐GMP. Furthermore, the effect of the tpbB mutation along with the tpbA mutation was examined because loss of TpbB restored the phenotypes controlled by enhanced c‐di‐GMP in the tpbA mutant. The tpbA tpbB double mutations restored eDNA to that of the PA14 wild‐type level. These findings suggest that c‐di‐GMP, rather than TpbA, controls eDNA. Hence, TpbA acts as a positive regulator of eDNA and cell lysis by reducing c‐di‐GMP concentrations.