bluuebunny/crossref_metadata_2025 huggingface dataset:
ROLE OF INFLAMMATORY CYTOKINES IN THE EFFECT OF ESTRADIOL ON ATHEROMA
Authors: Gourdy P , Calippe B , Laurell H , Trémollières F , Douin‐Echinard V , Lenfant F , Bayard F , Guery JC , Arnal JF
Published: February 2008

Although hormonal therapy (HT) may increase the risk of coronary heart disease (CHD) and stroke in postmenopausal women, epidemiological studies (protection in premenopausal women) suggest and experimental studies (prevention of fatty streak development in animals) demonstrate a major atheroprotective action of estradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required.

The immuno‐inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Although E2 favours an anti‐inflammatory effect in vitro (cultured cells), it rather elicits a pro‐inflammatory response in vivo involving several subpopulations of the immuno‐inflammatory system, which could contribute to plaque destabilization. The functional role of several cytokines was explored in hypercholesterolemic mice. The atheroprotective effect of E2 was fully maintained in mice deficient in interferon‐g or interleukin‐12, as well as IL‐10. In contrast, the protective effect of estradiol was abolished and even reversed in hypercholesterolemic mice given a neutralizing anti‐transforming growth factor‐b (TGF‐b) antibody. Endothelium is another important target for E2, since it not only potentiates endothelial nitric oxide and prostacyclin production, but also controls trafficking of the populations of the immuno‐inflammatory system.

To conclude, the respective actions of oestrogens on the cell populations involved in the pathophysiology of atherothrombosis may be influenced, among others, by the timing of HT initiation, the status of the vessel wall and, as recently demonstrated the status of the TGF‐b pathway.
ADVANCES IN REDUCING THE BURDEN OF VASCULAR DISEASE IN TYPE 2 DIABETES
Authors: Chalmers John , Joshi Rohina , Patel Anushka
Published: February 2008

The epidemic of diabetes is accelerating and the World Health Organization estimates that the number of people affected worldwide will grow from 171 million in 2000 to 366 million by 2030.

The main causes of death and disability in individuals with type 2 diabetes are macrovascular and microvascular disease, and blood pressure is one of the main determinants of vascular complications in this population.

While randomized trials have demonstrated that blood pressure lowering reduces vascular complications in subjects with type 2 diabetes and hypertension, ADVANCE was designed to determine whether the addition of a fixed combination of perindopril and indapamide, on top of comprehensive and effective cardiovascular treatments and glucose control therapy, would produce further benefits, irrespective of the initial blood pressure.

The blood pressure lowering arm of ADVANCE has demonstrated that the simple addition of the fixed combination of perindopril and indapamide compared to matching placebo, significantly reduces combined macrovascular and microvascular complications by 9%, all‐cause mortality by 14% and cardiovascular death by 18%. It also reduces total coronary events by 14% and all renal events and microalbuminuria by 21%.

Similar benefits were observed in participant sub‐groups characterized by age, sex, baseline blood pressure, previous vascular diseases and concomitant cardiovascular therapy including blood pressure lowering therapy.

Successful implementation of this treatment, with a single combination tablet of perindopril and indapamide, should be practical and affordable in most clinical settings worldwide and has the capacity to save countless lives and to reduce the burden of coronary disease and renal disease burden among millions of people with type 2 diabetes.
CONSTITUTIVE NITRIC OXIDE SYNTHASES IN THE HEART FROM HYPERTROPHY TO FAILURE
Authors: Loyer Xavier , Heymes Christophe , Samuel Jane‐Lise
Published: February 2008

Endogenous myocardial nitric oxide (NO) may modulate the transition from adaptive to maladaptive hypertrophy leading to heart failure. This review summarizes the information on the interrelations between the precise localization of NO synthases (NOS) and their regulatory functions within different compartments of the heart.

In rodent models of pressure overload or myocardial infarction, the three NOS isoforms (NOS1, NOS2, NOS3) were shown to play a neutral, protective, or even adverse role in myocardial remodelling, depending on the NOS activity, the location of each NOS and their regulators.

The analysis of conditions that modulate the expression of NOS1 and NOS3 in the heart according to physiopathological situations, indicated that, beside the level of total NOS activity, unique changes in NO compartmentation secondary to NOS1 or NOS3 subcellular location might be involved in the development of cardiac hypertrophy and failure.

Thus, different circuits in NO‐signalling pathways in myocardium might be activated and this principle is a key to understand contradictions existing in NO biology in the heart. Unravelling the mechanisms behind the NO, NOS and cardiac function is still an ongoing challenge.
ROLE OF ENDOTHELIUM‐DERIVED HYPERPOLARIZING FACTOR IN THE REGULATION OF RADIAL ARTERY BASAL DIAMETER AND ENDOTHELIUM‐DEPENDENT DILATATION IN VIVO
Authors: Bellien Jeremy , Thuillez Christian , Joannides Robinson
Published: February 2008

The role of the balance between nitric oxide (NO) and endothelium‐derived hyperpolarizing factor (EDHF), synthesized by cytochrome epoxygenase and acting through calcium‐activated potassium channels, in the regulation of basal diameter and endothelium‐dependent flow‐mediated dilatation of conduit arteries has been poorly assessed in humans.

Radial artery diameter and flow (echotracking coupled to Doppler) were measured in healthy volunteers under basal conditions and during flow‐mediated dilatation induced by hand skin heating, in the presence of saline and inhibitors of NO‐synthase, NG‐monomethyl‐L‐arginine (L‐NMMA), calcium‐activated potassium channels, tetraethylammonium (TEA) and cytochrome epoxygenases, fluconazole, infused alone and in combination. Mean wall shear stress, the flow‐mediated dilatation stimulus, was calculated and taken as cofactor into statistical analysis.

Under basal conditions, the radial artery diameter was not affected by L‐NMMA and fluconazole infused alone but was decreased by TEA, the combinations of L‐NMMA + fluconazole and, to a greater extent, L‐NMMA + TEA. During heating, radial artery diameter increased with temperature in all cases. This increase in diameter, compared with saline, was reduced by L‐NMMA, TEA, fluconazole and to a greater extent, by L‐NMMA + TEA and L‐NMMA + fluconazole.

These data show that EDHF is involved in balance with NO in the regulation of basal diameter and endothelium‐dependent dilatation of human peripheral conduit arteries. The alteration of this balance could play a major role in the physiopathology of the endothelial dysfunction, in particular during essential hypertension.
Post‐natal hearing loss in universal neonatal hearing screening communities: Current limitations and future directions
Authors: Hutt Nicole , Rhodes Christine
Published: February 2008

Abstract:  Universal hearing screening has dramatically improved outcomes for babies born with detectable hearing abnormalities; yet there are some infants who develop significant hearing problems after passing a neonatal screen. There is much conjecture as to the number and the characteristics of infants with post‐natal hearing losses; yet evidence suggests that many children may be affected, and that a large proportion have no discoverable cause. Currently, screening programmes use lists of risk factors to enrol babies into surveillance programmes. This practice is problematic because audiological follow‐ups are expensive and under‐utilised, and parental disclosure is often inaccurate. The large databases from universal neonatal programmes could inform the development of effective, evidence‐based practice and policy for the detection and intervention of children who develop post‐natal hearing losses.
A report of supratentorial leptomeningeal hemangioblastoma and a literature review
Authors: Takeuchi Hiroaki , Hashimoto Norichika , Kitai Ryuhei , Kubota Toshihiko
Published: February 2008

Hemangioblastomas of the CNS are solid or cystic vascular‐rich tumors, most common in the cerebellum, less frequent in the brainstem or spinal cord, and rare in supratentorial locations with meningeal involvement. We document a case in a 58‐year‐old man who presented with about 2 months history of motor weakness and speech dysfunction. The tumor was a heterogeneously enhanced dural‐based tumor with high vascularity and perifocal edema in the left frontal lobe. The tumor was completely removed followed by embolization and preoperative radiotherapy. Histologic examination revealed a hemangioblastoma with features resembling angiomatous meningioma. Immunohistochemistry for epithelial membrane antigen (EMA) and S100 may be helpful to make differential diagnosis. Electron microscopic investigation is essential to differentiate between meningiomas and other leptomeningeal tumors.
Variation in sexual reproduction in Taxus cuspidata Sieb. & Zucc
Authors: ALLISON TABER D. , SHIMIZU TATEMI , OHARA MASASHI , YAMANAKA NORIKAZU
Published: February 2008

Male and female strobilus production and seed production were measured in multiple years in three natural populations of Taxus cuspidata in Japan. Our goal was to record variation in these parameters among individuals, among populations, and from year to year in this species, which is defined as dioecious. We also wished to determine whether cosexual individuals occurred in the sampled T. cuspidata populations. Male and female strobilus production varied significantly among male and female individuals, respectively, and individuals had significant annual variation in male and female strobilus production. Significant variation in male and female strobilus production was also recorded in comparisons among T. cuspidata populations. In some populations, males were significantly larger than females, but this result was not consistently observed. No cosexual individuals were recorded in any of the populations studied. Correlations among reproductive variables and measured vegetative characters were generally non‐significant at all sites and in most years, with a few exceptions. When compared with other Taxus species, strobilus ratios in T. cuspidata were less male biased (2.3 male strobili per female strobilus in T. cuspidata versus 8.7 and 7.0 male strobili per female strobilus in Taxus brevifolia and Taxus canadensis, respectively). Seed production efficiency was comparable to T. brevifolia, but less than half of that recorded for T. canadensis, the only species of the genus that has individuals that are typically cosexual.
Pathogens promote plant diversity through a compensatory response
Authors: Bradley Devon J. , Gilbert Gregory S. , Martiny Jennifer B. H.
Published: February 2008

Pathogens are thought to promote diversity in plant communities by preventing competitive exclusion. Previous studies have focussed primarily on single‐plant, single‐pathogen interactions, yet the interactions between multiple pathogens and multiple hosts may have non‐additive impacts on plant community composition. Here, we report that both a bacterial and a fungal pathogen maintained the diversity of a four‐species plant community across five generations; however, significant interactions between the pathogens resulted in less plant diversity when the two pathogens were present than when the fungal pathogen was present alone. Standard models predict that pathogens will maintain plant diversity when they cause a disproportionate loss of fitness in the dominant plant species. In our experiment, however, pathogens maintained plant diversity because the rare species produced more seeds through a compensatory response to pathogen infection. Finally, we found that the influence of pathogens on maintaining plant diversity was 5.5 times greater than the influence of nutrient resource heterogeneity. Pathogens may be a major factor in maintaining plant diversity, and our findings emphasize the importance of investigating the roles of pathogens in natural plant communities.
Localized prostate cancer: can we better define who is at risk of unfavourable outcome?
Authors: Joniau Steven , Van Poppel Hein
Published: February 2008

Prostate cancer encompasses a biological continuum from a slow‐growing indolent tumour to a highly aggressive and potentially fatal form. A major challenge faced daily by physicians is to identify men with localized prostate cancer who are at high risk of dying from the disease, in order to maximize disease control and survival, without overtreating men who are likely to die from comorbidities. Treatment selection in patients with localized prostate cancer should be guided not only by patient‐related factors (e.g. age and comorbidities), but also by cancer‐related parameters (clinical stage, biopsy grade and preoperative prostate‐specific antigen [PSA]) that enable patients to be classified as low, intermediate, or high risk for unfavourable outcomes. Surgery alone will only cure a fraction of high‐risk patients. Instead these patients typically need a pro‐active multimodal approach comprising a combination of surgery, radiotherapy and/or hormonal deprivation. The place of chemotherapy in the adjuvant or neoadjuvant setting in this patient group needs to be evaluated in clinical trials.
Effect of regulatory oversight on the association between internal governance characteristics and audit fees
Authors: Boo El’fred , Sharma Divesh
Published: February 2008

We examine the relationship between internal governance, external audit monitoring and regulatory oversight for a sample comprising industrial companies and financial/utility companies subject to additional industry‐specific regulation. Our results indicate that the association between audit fees and board/audit committee independence and size are weaker for regulated companies. These observations are consistent with the notion that regulatory oversight partially substitutes the external audit as a monitoring mechanism. However, boards/audit committees with more multiple directorships demand a more extensive audit in the presence of regulatory oversight to protect their reputation capital. Our study enhances our understanding of the complex relationships among the major corporate governance elements.
Is international trust performance predictable over time? A note
Authors: Fletcher Jonathan , Marshall Andrew
Published: February 2008

We examine whether past return measures have any significant predictive ability for future returns of UK unit trusts with international equity objectives. We find significant positive persistence between the past return performance of the trust relative to its investment sector and future trust returns relative to its sector. This result holds at short‐run and long‐run return horizons. The persistence is stronger in trusts that perform well relative to their sector. Our findings suggest that the past return performance of the trust relative to their sector provides a useful guide to future return performance relative to their sector.
Relationship between franking credits and the market risk premium: a reply
Authors: Gray Stephen , Hall Jason
Published: February 2008

We have previously documented an inconsistency between the dividend yield implied by the Officer (1994) model with standard Australian regulatory parameters and actual dividend yields of Australian companies. We have shown that, within the Officer framework, this inconsistency can be resolved by setting the assumed value of franking credits (γ) to zero, consistent with the practice of Australian firms and independent valuation experts. Truong and Partington (2008) and Lally (2008) recognize this same inconsistency and propose alternate ways of resolving it. In this paper, we demonstrate that these proposals are outside the Officer framework. The standard set of regulatory parameters cannot be resolved with observed dividend yields within the Officer framework. Whichever method is used to resolve the inconsistency, the effect will be an increase in the estimated after‐tax cost of equity.
The cost of obesity in Hong Kong
Authors: Ko G. T. C.
Published: February 2008

Obesity is now being considered a rapid growing economic burden on the healthcare system of many countries. These costs should include expenditure on prevention, as well as the investigation and treatment of obesity and its related problems. Accurate information on the cost of obesity in Hong Kong is lacking so we analysed the annual hospital discharges in a representative district hospital in Hong Kong. The estimated hospitalization costs in Hong Kong' public hospitals were HK$ 2.29 billion (US$ 0.29 billion) in 1998 and HK$ 3.36 billion (US$ 0.43 billion) in 2002 accounting for 8.2–9.8% of total public expenditure on health in Hong Kong. Based on the likelihood ratio of diabetes, hypertension and dylsipidaemia related to obesity in Hong Kong Chinese (defined as body mass index ≥25 kg m−2) the estimated proportion of these conditions attributable to obesity are 10–20%. In addition, significant amounts of money are being spent by the public on obesity self management schemes of no proven benefit. In 2005, 5.5% of Hong Kong's total population was consuming proprietary drugs for obesity or its related conditions. To properly assess the overall costs of obesity, other indirect costs should also be considered such as economic losses on sick leave because of obesity and its related conditions.
Childhood obesity and its health consequence in China
Authors: Li Y. , Yang X. , Zhai F. , Piao J. , Zhao W. , Zhang J. , Ma G.
Published: February 2008

Analyses of data from the representative 2002 National Nutrition and Health Survey were used to assess the likelihood of metabolic complications of overweight and obesity in Chinese children aged 7–17 years. Chinese criteria for body mass index classification were used for overweight and obesity with the 75th percentile US adolescent values for waist circumferences and all the metabolic criteria for blood pressure, lipids, fasting glucose established for US adolescents. Diabetes in 7–12‐year‐olds was 0.2% and 0.4% in children aged 12–18 years. Prevalences of dyslipidaemia (61.9%), hypertriglyceridaemia (18.2%) and low high‐density lipoprotein cholesterol (56.1%) were high and 16.0% of 15–18 years had hypertension. The overall prevalence of the metabolic syndrome was 3.3% with more than half the children having at least one metabolic abnormality and 19.8% having at least two. All the metabolic parameters were significantly elevated in the overweight and obese children except high‐density lipoprotein cholesterol. These data emphasize the marked sensitivity of Chinese children to the metabolic complications of overweight and obesity and amplify the need for early preventive measures.
Childhood obesity and adverse health effects in Hong Kong
Authors: Chan C.
Published: February 2008

Hong Kong soon became aware of the importance of ensuring the optimum growth of their children with growth standards for Hong Kong being set out in 1962. By 1972 it was already clear that childhood obesity was emerging as a problem and increasing in prevalence and by 1987 an international workshop on nutrition, held in Hong Kong, was being alerted to this issue. Then 10 years later obesity featured as a major issue in the programme of the Asian Congress of Pediatrics with the local contributors highlighting the evidence already available in Hong Kong of the wide range of metabolic, cardiovascular, physical and psychological complications of obesity in the local community. The school health service was given a prominent role and there are now guidelines not only in relation to the standards of school lunches but also for the need to enhance the physical activity of children and involve a new educational community wide approach as part of a major co‐coordinated effort within Hong Kong. Professional and community workers together with the government now have a comprehensive determination to tackle the challenge of obesity prevention. So Hong Kong intends to play a major role in the international response to the formation of the Global Alliance for the prevention of obesity and its associated chronic diseases.
Leisure‐time physical activity alone may not be a sufficient public health approach to prevent obesity – a focus on China
Authors: Bauman A. , Allman‐Farinelli M. , Huxley R. , James W. P. T.
Published: February 2008

Much small‐scale research has identified the role of physical activity in obesity prevention. This is the ‘energy expenditure’ side of the energy balance equation. Although around half an hour of daily moderate‐intensity physical activity is required for cardiovascular health and disease prevention, the quantum of physical activity required for obesity prevention and weight loss is around 60–90 minutes per day. This amount of physical activity is difficult to achieve through leisure time physical activity (LTPA) alone, and additional energy expenditure is needed in the domains of active transport, occupation activity and in domestic settings. Modeling of 24‐hour energy expenditures demonstrate the need for ‘active living’, namely energy expenditure over and above that due to LTPA, for weight loss and obesity prevention. The consequences of this for developing countries such as China are the need to focus on preventing the declines in energy expenditure attributable to urbanization, industrialization, and motor vehicle dependence. These will pose policy challenges in the developing world, if they are to be taken seriously as obesity prevention strategies.
Interventions in local communities and work sites through Physical Activity and Nutrition Programme
Authors: Togami T.
Published: February 2008

The altered Japanese lifestyle with inactivity and dietary fat increases, together with a rapidly ageing society, has led to obesity and chronic diseases, which present major challenges. Center of Health Promotion, International Life Sciences Institute Japan – ILSI Japan CHP – has therefore initiated Project PAN (Physical Activity and Nutrition) to develop and implement sustainable programmes for physical activity and dietary change. One programme, TAKE10!®, is for the elderly and the other is LiSM10!® (Lifestyle Modification 10), which develops and implements a comprehensive programme of physical exercise and diet/nutrition education in work sites for at‐risk adults over 40 years. The elderly intervention approach was evaluated over 1 year in 1400 elderly people 65 years old and over in a local community in 2002–2003. Behavioural changes were observed with more physical exercise and more meat, fish and shellfish, eggs and milk consumption. Maximum walking speed was maintained regardless of age, and several physiological parameters improved. The LiSM10!® involves screening at‐risk adults followed by their setting their own objectives with regular face‐to‐face counselling by experts and systems for family and work site support. An intervention study was conducted in five manufacturing plants during 2001–2003. Both of the programmes, TAKE10!® and LiSM10!®, have been shown to be an effective way of creating behavioural changes, and the LiSM10!® programme in particular can control obesity and lifestyle‐related disease. Therefore, ILSI Japan CHP is promoting, with business support, both programmes as a sustainable population intervention for adults.
Evaluation of a classroom‐based physical activity promoting programme
Authors: Liu A. , Hu X. , Ma G. , Cui Z. , Pan Y. , Chang S. , Zhao W. , Chen C.
Published: February 2008

The purpose of the present study was to evaluate the effect of the Happy 10 programme on the promotion of physical activity, physical growth and development of primary school students, and on obesity control and prevention. Two similar primary schools from one district of Beijing, China were selected, one as an intervention school and the other as a control school. A Happy 10 programme was implemented at least once every school day in the intervention school for two semesters, whereas no intervention was adopted in the control school. The information on energy expenditure and duration of physical activity was collected by a validated 7‐day physical activity questionnaire. Height and weight were measured by the trained investigators following standardized procedure. Energy expenditure and intensity of each Happy 10 session were measured by a physical activity monitor. The average energy expenditure and duration of total physical activity per day among students in the intervention school increased significantly from 15.0 to 18.2 kcal kg−1 and 2.8 to 3.3 h, respectively, whereas the figures significantly decreased in the control school. There was a significant difference in change of weight and body mass index between girls in the intervention and control school (2.4 kg vs. 4.6 kg; 0.47 kg m−2 vs. 0.66 kg m−2). The prevalence of overweight and obesity in the intervention school decreased by 0.4–5.6%, as compared with the increase by 0.6–4.5% in the control school. The average energy expenditure and intensity per 10‐min session ranged from 25.0 to 35.1 kcal and from 4.8 to 6.2 kcal kg−1 h−1, respectively, in grades 1–5. The Happy 10 programme provides a useful strategy to promote physical activity among school children, and also plays a positive role in building up physical growth and development of girls.
Demonstrative clefts and double cleft constructions in spontaneous spoken English*
Authors: Calude Andreea S.
Published: February 2008

Abstract. The current paper reports on the grammatical structure and discourse role of demonstrative clefts found in spontaneous, spoken language. Constructions such asthat’s what I thinkorthis is where he’s coming from, previously placed under the umbrella of reversed wh‐clefts, are shown to exhibit significant differences from these. The inspection of 200,000 words of informal conversation excerpts from the Wellington Spoken Corpus of New Zealand English (WSC) shows that demonstrative clefts constitute the most frequent cleft type in the spoken data. The deictic properties of their cleft constituents, their distinctive function in discourse and prevalence in this linguistic medium set them apart from other cleft types. The paper also discusses a related construction, termed here double cleft, which exhibits syntactic un‐integratedness, as inthat’s what you’re supposed to do is restandthis is where he went is Auckland.It is hoped that the findings presented here will contribute to existing knowledge of the grammatical constructions used by speakers of New Zealand English and English worldwide, and to our understanding of the barriers that have to be crossed in the teaching and learning of spoken language.
Miller and Modigliani, Predictive Return Regressions and Cointegration*
Authors: Alessandri Piergiorgio , Robertson Donald , Wright Stephen
Published: February 2008

This paper investigates the use of alternative measures of dividend yields to predict US aggregate stock returns. Following Miller and Modigliani [Journal of Business (1961), Vol. 34, pp. 411–433] we construct a cashflow yield that includes both dividend and non‐dividend cashflows to shareholders. Using a data set covering the course of the 20th century, we show in a cointegrating vector autoregression framework that this measure has strong and stable predictive power for returns. The weak predictive power of standard measures of the dividend yield is explained by the strong rejection of the implied cointegrating and causality restrictions on the impact of non‐dividend cashflows.
Alban Berg’s Piano Sonata, Op. 1: a Landmark in Early Twentieth‐Century Music
Authors: Forte Allen
Published: February 2008

Eventually published in 1926, the Piano Sonata, Op. 1, was completed in 1908, the year after Berg terminated his formal studies with Arnold Schoenberg, and first performed in Vienna in 1911. Berg's decision to assign the first opus number in his compositional canon to this piece was highly significant, since it clearly indicated the status that he accorded to such extraordinary music. The Sonata is one of the most expressive instrumental compositions of the early twentieth century – comparable, for example, to works by Debussy such as L’isle joyeuse (1904) and Bartók's Sonata for piano (1926). The present article situates the work in its contemporary context, illuminating points of theoretical significance as they relate to the composer's ongoing creative development and distinctive musical language.
Redox modulation of homomeric ρ1 GABAC receptors
Authors: Calero Cecilia I. , Calvo Daniel J.
Published: February 2008

The activity of many receptors and ion channels in the nervous system can be regulated by redox‐dependent mechanisms. Native and recombinant GABAA receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABAC receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABAρ1 receptors expressed in Xenopus laevis oocytes. The reducing agents dithiothreitol (2 mM) and N‐acetyl‐l‐cysteine (1 mM) potentiated GABA‐evoked Cl− currents recorded by two‐electrode voltage‐clamp, while the oxidants 5‐5′‐dithiobis‐2‐nitrobenzoic acid (500 μM) and oxidized dithiothreitol (2 mM) caused inhibition. The endogenous antioxidant glutathione (5 mM) also enhanced GABAρ1 receptor‐mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABAρ1 receptors was strongly dependent on the GABA concentration; dose–response curves for GABA were shifted to the left in the presence of reducing agents, whereas oxidizing agents produced the opposite effect, without changes in the maximal response to GABA and in the Hill coefficient. Our results demonstrate that, similarly to GABAA receptors and other members of the cys‐loop receptor superfamily, GABAC receptors are subjected to redox modulation.
Light affects mitochondria to cause apoptosis to cultured cells: possible relevance to ganglion cell death in certain optic neuropathies
Authors: Osborne Neville N. , Li Guang‐Yu , Ji Dan , Mortiboys Heather J. , Jackson Sandra
Published: February 2008

Retinal ganglion cell axons within the globe are laden with mitochondria that are unprotected from light (400–760 nm) impinging onto the retina. Light can be absorbed by mitochondrial enzymes such as cytochrome and flavin oxidases causing the generation of reactive oxygen species, and we have suggested this may pose a risk to ganglion cell survival if their energy state is compromised, as may be so in glaucoma or in Leber’s Hereditary Optic Neuropathy. Here, we demonstrate that light (400–760 nm) provokes apoptosis in cultured retinal ganglion‐5 cells, and that this effect is enhanced in low serum, and attenuated by various antioxidants. Apoptosis is shown to be caspase independent, involving reactive oxygen species generation and the activation of poly(ADP‐ribose) polymerase‐1 and apoptosis‐inducing factor. We further show that light‐induced apoptosis requires the participation of the mitochondrial respiratory chain. This was demonstrated by culturing fibroblasts (BJhTERT cells) in ethidium bromide for 40 days to deplete their mitochondrial DNA and perturb their mitochondrial respiratory chain function (BJhTERT rh0 cells). Only BJhTERT cells, with intact mitochondrial respiratory chain function were affected by light insult. Finally, we show that exposure of anaesthetized pigmented rat eye to white, but not red light, causes changes in the expression of certain retinal mRNAs (neurofilament light, Thy‐1 and melanopsin) and optic nerve proteins (neurofilament light and tubulin), suggesting that ganglion cell survival is affected. Our findings support the proposal that the interaction of light, particularly the blue component, with intra‐axonal ganglion cell mitochondria may be deleterious under certain circumstances, and suggest that reducing the light energy impinging upon the retina might benefit patients with certain optic neuropathies.
Contribution of perospirone and risperidone to reduce delirium in senile patients
Authors: USHIJIMA Michikazu , YOKOYAMA Shin , SUGIYAMA Eiko , AMANO Naoji
Published: February 2008

Background:  Serotonin–dopamine antagonists (SDAs) inhibit dopaminergic transmission in the mesolimbic system less than in the nigrostriatal dopaminergic pathway, which relates to the extrapyramidal side‐effects of these drugs. The SDAs seem to have an adequate receptor binding profile for the management of the behavioral and psychiatric symptoms of dementia. However, clinicians are discouraged from prescribing SDAs for elderly patients because of an advisory statement from the US Food and Drug Administration that warns about an increased mortality rate among elderly patients treated with atypical antipsychotics.

Methods:  We conducted a retrospective study involving 16 elderly patients (mean age 84.9 years; range 67–94 years) with delirium who were treated with one of two SDAs, namely perospirone (4–12 mg/day) or risperidone (1–2 mg/day). The time‐course of their psychiatric symptoms was assessed using subcategories of the Delirium Rating Scale (DRS) before treatment and on Days 10 and 24 of treatment.

Results:  Total DRS scores were significantly decreased from baseline in both treatment groups. Both agents led to significant improvements from baseline in psychomotor behavior and lability of mood. Of interest, perospirone decreased hallucinations and delusions and improved sleep–awake cycle disturbances compared with baseline. No serious side‐effects were seen with either drug.

Conclusions:  Both perospirone and risperidone are effective in the management of delirium in elderly patients. The improvement in the sleep–awake cycle with perospirone may be derived from its short pharmacological half‐life.
Conversion pseudodementia in the elderly: A review of the literature with case presentation
Authors: PERITOGIANNIS Vaios , ZAFIRIS Spiros , PAPPAS Dimitrios , MAVREAS Venetsanos
Published: February 2008

Few data exist in the literature regarding conversion pseudodementia. The knowledge results from case reports and case series that describe a syndrome characterized by cognitive impairment, regression and physical dependency. In elderly patients, this condition can cause serious diagnostic problems and, occasionally, discrimination from dementia is awkward. The reported case assembles all the characteristic traits of conversion pseudodementia. The development of the symptomatology, the diagnostic approach and the difficulties of management and treatment of conversion pseudodementia are discussed. The authors also provide a review of the international literature; certain conclusions and proposals are presented.
Long‐term effect of donepezil for Alzheimer's disease: Retrospective clinical evaluation of drug efficacy in Japanese patients
Authors: KUMAGAI Ryo , MATSUMIYA Michiko , TADA Yuko , MIYAKAWA Koichi , ICHIMIYA Yosuke , ARAI Heii
Published: February 2008

Background:  Alzheimer's disease (AD) is common in the Japanese population. In 1999, donepezil was authorized in Japan for the treatment of AD. However, because the time since donepezil was authorized is relatively short, there are few reports regarding the long‐term effects of donepezil in Japanese AD patients.

Methods:  In the present study, the clinical features of 72 AD patients treated at Juntendo University Urayasu Hospital were examined retrospectively in order to examine the long‐term effects of donepezil. Sixty‐two AD patients had been administrated donepezil. The effect of donepezil was evaluated using the Revised Hasegawa Dementia Scale (HDS‐R). In patients with increased points on the HDS‐R after 6 months, treatment was regarded as effective, whereas patients in whom there was no change in points on the HDS‐R were classified as ‘no change’; finally, in patients with decreased points on the HDS‐R after 6 months, treatment was regarded as non‐effective.

Results:  The duration of medication was divided into four groups: (i) 6 months (16 cases; 26%); (ii) 1 year (16 cases; 26%); (iii) 2 years (13 cases; 21%); and (iv) more than 3 years (11 cases; 18%). Donepezil treatment was stopped in six patients (10%) because of adverse effects. Thus, the 56 patients who continued with donepezil treatment were categorized as follows: treatment was effective in 27 cases (48%), no change was found in five cases (9%) and, in 24 cases (43%), donepezil treatment was found to be non‐effective. Differences in treatment efficacy were not related to sex, apolipoprotein E genotype or medical history. Comparative studies for the age of onset of AD and points of the HDS‐R before administration of donepezil suggest that donepezil tended to be effective in patients in whom AD developed at 71–80 years of age and with 16–20 points of the HDS‐R. In patients in whom donepezil was effective, cognition returned to the state before treatment 2 years later. However, the marked degradation of points on the HDS‐R was not seen in these cases. Conversely, the long‐term consequences for patients in whom donepezil was not effective after 6 months were similar to those for patients not treated with donepezil.

Conclusion:  Donepezil improved the dementia symptoms in patients in whom it was effective over the long term. We suggest that the presence of drug efficacy after 6 months is an indicator that long‐term treatment with donepezil is warranted. In particular, donepezil was effective in cases with mild to moderate AD.
Long‐Term Episodic Memory in Children with Attention‐Deficit/Hyperactivity Disorder
Authors: Skowronek Jeffrey S. , Leichtman Michelle D. , Pillemer David B.
Published: February 2008

Twenty‐nine grade‐matched 4th–8th‐grade males, 12 with attention‐deficit/hyperactivity disorder (ADHD) (age M= 12.2 years, SD= 1.48), and 17 without (age M= 11.5, SD= 1.59), completed two working memory tasks (digit span and the Simon game) and three long‐term episodic memory tasks (a personal event memory task, story memory task, and picture recognition task). In line with clinical observations, children with ADHD performed worse than peers on all working memory tasks, but performed as well as or better than peers on long‐term episodic tasks, demonstrating particularly detailed memory for personally experienced past events. Participants' parents also completed questionnaires about their children's memories in daily life. Parents rated children with ADHD lower than children without ADHD on working and semantic memory (e.g., remembering names, spelling, and math), but rated them as high or higher on memory for events. Implications for theory and educational practice are discussed.
Defibrillation Coil Reversal: A Rare Cause of Abnormal Noise and Inappropriate Shocks
Authors: JEEVANANTHAM VINODH , LEVINE ETHAN , BUDZIKOWSKI ADAM S. , SHAH ABRAR H. , DAUBERT JAMES P.
Published: February 2008

We report a rare case of inadvertent reversal of the defibrillator shock coils during generator change which then resulted in both intermittent, recurrent “noise” on both the rate sensing and the shock electrogram leads and multiple inappropriate shocks.
Kiitricha minuta n. sp., a Peculiar Hypotrichous Ciliate (Ciliophora, Spirotrichea) from the Yellow Sea
Authors: XU KUIDONG , LEI YANLI , CHOI JOONG KI
Published: February 2008

ABSTRACT. The morphology and infraciliature of a new ciliate, Kiitricha minuta n. sp., isolated from the Yellow Sea, were investigated using live observation and protargol impregnation. Kiitricha minuta represents a third member of the rarely known order Kiitrichida. It is unique in the subclass Hypotrichia in having many rows of small uniform cirri along the right side of the body and the dorsal kineties composed of dikinetids, most of which bear two cilia. Kiitricha minuta n. sp. is ovoid and measures about 60 × 45 μm in vivo. It has a huge buccal cavity occupying about 80% of the body length, numerous body extrusomes, one macronucleus and two micronuclei, 27–27 adoral membranelles, 9–12 frontoventral cirral rows, a submarginal row of 7–9 cirri, 6 or 7 transverse cirri, and roughly 7–9 dorsal kineties. This new species differs distinctly from its only congener Kiitricha marina by its smaller size (60 μm vs. 80–150 μm), the presence of body extrusomes (vs. absent), the different macronuclear pattern (one vs. two nodules), and the lower number of frontoventral cirral rows (9–12 vs. 21–26), which terminate at the anterior two‐thirds of body (vs. extend to the posterior). The new term “submarginal cirral row” is introduced to distinguish from the marginal cirral row in typical hypotrichs sensu lato. Based on our new observations and the literature, an improved diagnosis for the genus Kiitricha is provided and its phylogenetic importance is discussed.
Assessing the Contribution of Foraminiferan Protists to Global Ocean Carbonate Production1
Authors: LANGER MARTIN R.
Published: February 2008

ABSTRACT. Larger symbiont‐bearing foraminifera are prominent and important producers of calcium carbonate in modern tropical environments. With an estimated production of at least 130 million tons of CaCO3 per year, they contribute almost 5% of the annual present‐day carbonate production in the world's reef and shelf areas (0–200 m) and approximately 2.5% of the CaCO3 of all oceans. Together with non‐symbiont‐bearing smaller foraminifera, all benthic foraminifera are estimated to annually produce 200 million tons of calcium carbonate worldwide. The majority of foraminiferal calcite in modern oceans is produced by planktic foraminifera. With an estimated annual production of at least 1.2 billion tons, planktic foraminifera contribute more than 21% of the annual global ocean carbonate production. Total CaCO3 of benthic and planktic foraminifera together amounts to 1.4 billion tons of calcium carbonate per year. This accounts to almost 25% of the present‐day carbonate production of the oceans, and highlights the importance of foraminifera within the CaCO3 budget of the world's oceans.
Polypodium leucotomos extract inhibits glutathione oxidation and prevents Langerhans cell depletion induced by UVB/UVA radiation in a hairless rat model
Authors: Mulero Miquel , Rodríguez‐Yanes Esperanza , Nogués María Rosa , Giralt Montserrat , Romeu Marta , González Salvador , Mallol Jordi
Published: February 2008

Abstract:  In this report, we have addressed the effect of oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL) on the deleterious effects of ultraviolet radiation (UVR) on the levels of epidermal and plasmatic antioxidants in hairless rats. We have found that pretreatment with PL effectively reduced glutathione oxidation in both blood and epidermis, suggesting a potent systemic antioxidant effect. In addition, PL inhibited UVR‐mediated Langerhans cell (LC) depletion. Our results demonstrate the efficacy of PL as an oral antioxidant and photoimmunoprotective agent and support its employment as a complement to topical sunscreens.
Bioactive molecules from the Blue Lagoon: in vitro and in vivo assessment of silica mud and microalgae extracts for their effects on skin barrier function and prevention of skin ageing
Authors: Grether‐Beck Susanne , Mühlberg Kathrin , Brenden Heidi , Felsner Ingo , Brynjólfsdóttir Ása , Einarsson Sigurbjörn , Krutmann Jean
Published: February 2008

Abstract:  Bathing in the Blue Lagoon, a specific geothermal biotope in Iceland has been known for many years to be beneficial for human skin in general and for patients with psoriasis and atopic dermatitis in particular. The scientific rationale for this empirical observation, however has remained elusive. We now report that extracts prepared from silica mud and two different microalgae species derived from the Blue Lagoon are capable of inducing involucrin, loricrin, transglutaminase‐1 and filaggrin gene expression in primary human epidermal keratinocytes. The same extracts also affects primary human dermal fibroblasts, because extracts from silica mud and one type of algae inhibited UVA radiation‐induced upregulation of matrix metalloproteinase‐1 expression and both algae, as well as silica mud extracts induced collagen 1A1 and 1A2 gene expression in this cell type. These effects were not restricted to the in vitro situation because topical treatment of healthy human skin (n = 20) with a galenic formulation containing all three extracts induced identical gene regulatory effects in vivo, which were associated with a significant reduction of transepidermal water loss. In aggregate, these results suggest that the bioactives in Blue Lagoon have the capacity to improve skin barrier function and to prevent premature skin ageing. These observations explain at least some of the beneficial effects of bathing in the Blue Lagoon and provide a scientific basis for the use of Blue Lagoon extracts in cosmetic and/or medical products.
Screening of urocanic acid isomers in human basal and squamous cell carcinoma tumors compared with tumor periphery and healthy skin
Authors: Decara Juan Manuel , Aguilera José , Abdala Roberto , Sánchez Purificación , Figueroa Félix L. , Herrera Enrique
Published: February 2008

Abstract:  Trans‐urocanic acid is a major chromophore for ultraviolet (UV) radiation in human epidermis. The UV induces photoisomerization of trans‐urocanic acid (tUCA) form to cis‐urocanic acid (cUCA) and has been reported as an important mediator in the immunosuppression induced by UV. This immunomodulation has been recognized as an important factor related to skin cancer development. This is the first time that UCA isomers have been measured in epidermis of skin biopsies from patients with squamous cell carcinoma (SCC) and with basal cell carcinoma (BCC) and compared with the tumor periphery and biopsies of healthy photoexposed and non‐photoexposed skin as controls. The UCA isomers were separated and quantified by high performance liquid chromatography. Analysis of UCA in healthy skin showed significant increase in total UCA content in non‐photoexposed body sites compared with highly exposed skins. In contrast, the percentage of cUCA was higher in photoexposed body sites. Maximal levels of cUCA were found in cheek, forehead and forearm and lower levels in abdomen and thigh. No differences were found in total UCA concentration between the tumor samples and healthy photoexposed skin. However, differences were found in relation between isomers. Higher levels of cUCA were detected in SCC biopsies (44% of total UCA) compared with samples of BCC and that of healthy photoexposed skin (30%). These results suggest that the UV radiation exposure, a main factor in development of SCC can be mediated, apart from direct effect to cells (DNA damage), by immunosuppression pathways mediated by high production of cUCA.
Safety in paediatric clinical trials – a 7‐year review
Authors: Sammons HM , Gray C , Hudson H , Cherrill J , Choonara I
Published: February 2008

Aim: The safety of clinical trials in children has not been previously studied. We aimed to identify how safety is monitored and the extent of adverse drug reactions (ADRs).

Methods: A literature review of the Medline Database for therapeutic clinical trials involving oral and intravenous medicines in children from 1996 to 2002. Papers were read to determine the safety monitoring and the presence of adverse events (AEs) or ADRs.

Results: Seven hundred thirty‐nine trials were identified. Thirteen (2%) had safety monitoring committees (SMCs). Five hundred twenty‐three (71%) trials reported AEs and 151 (20%) of these trials reported a serious AE. ADRs were present in 270 (36.5%) trials, with 80 (11%) of trials having a moderate or severe ADR. Six clinical trials were terminated early because of significant drug toxicity. All of these had SMCs. There were deaths in 83 (11%) trials. In the majority of trials, mortality was thought to be unrelated to the investigational drug; however, in two trials mortality was higher in the treatment group.

Conclusions: About 11% of trials have a moderate or severe ADR. All paediatric clinical trials should have a SMC.