bluuebunny/crossref_metadata_2025 huggingface dataset:
Prioritizing children's medicines for research: a pharmacoepidemiological study of antiepileptic drugs
Authors: Ackers Ruth , Murray Macey L. , Besag Frank M. C. , Wong Ian C. K.
Published: January 2007

What is already known about this subject

• Recently the European Medicines Agency recommended further research in all newly marketed antiepileptic drugs (AEDs).

• There is no information in the literature about how AEDs are used in children in primary care.

What this study adds

• There is a rapid increase in newer AED prescribing to children and adolescents in UK primary care, while prescribing of conventional AEDs is in decline.

• The uptake of lamotrigine, topiramate and levetiracetam is rapid, and their prescribing is favoured over the conventional AEDs, particularly in adolescents.

• Following concerns about visual field defects with vigabatrin, long‐term safety surveillance of all the newer AEDs is strongly recommended.

Aims

To investigate the prescribing epidemiology, in UK primary care, of newer antiepileptic drugs (AEDs) compared with conventional AEDs and to identify AEDs for further research in response to the European Medicines Agency report on epilepsy.

Methods

Subjects aged 0–18 years, from the UK General Practice Research Database, who were prescribed an AED between 1993 and 2005. Prescribing prevalence and incidence, stratified by age and AED, were calculated.

Results

A total of 7721 subjects were included and 70% were prescribed one drug. Overall prescribing prevalence for all AEDs had increased by 19%. The prevalence (95% confidence interval) of newer AED prescribing had increased fivefold from 0.67 (0.58, 0.76) to 3.20 (3.03, 3.37) per 1000 person‐years. Conversely, the prevalence of conventional AEDs had declined by 17% from 6.63 (6.34, 6.92) per 1000 person‐years to 5.51 (5.28, 5.73). Lamotrigine had 65% of newer AED prescriptions and was the most prescribed newer drug for both the 2–11 years and 12–18 years age groups with prevalences of 1.47 and 2.55 per 1000 person‐years, respectively.

Conclusions

There is a rapid increase in newer AED prescribing to children and adolescents in UK primary care, while prescribing of conventional AEDs is declining. Since 1997, the prevalence of vigabatrin has fallen, coinciding with the UK safety warnings on visual field defects. The uptake of lamotrigine, topiramate and levetiracetam is rapid and as the safety of these drugs has not been established, they should be prioritized for further research. Following concerns with vigabatrin, long‐term safety surveillance of all newer AEDs is strongly recommended.
Melanin pigmentation negatively correlates with plumage preening effort in barn owls
Authors: ROULIN ALEXANDRE
Published: January 2007

According to the handicap principle of sexual selection, colourful ornaments honestly signal absolute quality only if they entail fitness costs. The degree of melanism often covaries positively with aspects of individual quality, and hence melanin‐based coloration should be costly to produce or to maintain in a good shape. This is, however, unlikely because melanin‐based coloration is often strongly heritable and in birds the rate of feather wear decreases with the amount of melanin pigments packed in feathers.

The hypothesis that melanin pigments reduce the cost of maintaining colourful ornaments in a good shape predicts a negative correlation between the degree of melanism and both the size of the uropygial gland that produces preening secretions and the intensity of preening behaviour.

Using a correlative approach, I evaluated these two predictions in the barn owlTyto albain which the body underside varies from immaculate to heavily marked with black spots, a eumelanin‐based trait, and from white to reddish‐brown, a phaeomelanin‐based trait. I correlated plumage traits with preening behaviour in nestlings and with the size and mass of the uropygial gland in dead adults. I also weighed nonornamental wing and tail feathers to assess whether the quality of nonornamental feathers is positively correlated with the degree of melanism of an ornamental plumage trait.

The degree of phaeomelanism was neither associated with preening behaviour nor with the size and mass of the uropygial gland. In line with the two predictions, individuals with more and larger black spots had a lighter uropygial gland and preened less frequently. Because nonornamental wing and tail feathers of spottier individuals were heavier per unit of surface area, the entire plumage of eumelanic individuals may be more robust and in turn require less care than the plumage of nonmelanic conspecifics.

In conclusion, the degree of eumelanism can be associated with aspects of individual quality even if eumelanic ornaments are neither costly to produce nor to maintain in a good shape.
Communicating about haemophilia within the family: the importance of context and of experience
Authors: GREGORY M. , BODDINGTON P. , DIMOND R. , ATKINSON P. , CLARKE A. , COLLINS P.
Published: January 2007

Summary.  This study examines communication within families affected by haemophilia, focusing especially on communication about carrier status. A qualitative study using semi‐structured interviews with family members in the UK revealed recurrent patterns in communication strategies and styles. Participants drew a marked contrast between the nature of communication within the clinic and within the home. In families, it is notable that communication usually occurs within the context of concrete experience of the condition. Noticeable differences existed in families with obligate carriers when compared with families with non‐obligate carrier daughters. In families with affected sons, daughters may have more experience of haemophilia and consequently more understanding of their possible carrier status than in families with an affected father. Families also typically make value judgements and comments on coping strategies when they communicate about the condition. Readiness to receive information is very variable, and depends upon factors such as personality and life stage. Information may seem to be successfully communicated but the recipient may sometimes actually comprehend much less, only understanding more fully later or when the information becomes directly relevant to them. Periodic checking of understanding of different family members, and the provision of written information, may be helpful.
The role of matrix metalloproteinases‐2, ‐7 and ‐9 and β‐catenin in high grade endometrial carcinoma
Authors: Monaghan H , MacWhinnie N , Williams A R W
Published: January 2007

Aims:  To determine the expression of matrix metalloproteinases (MMPs)‐2, ‐7 and ‐9 and β‐catenin in uterine serous carcinoma (USC) and endometrioid endometrial carcinoma (EEC) and to investigate any difference in expression between EEC and USC which might explain the mechanism of invasion and aggressive behaviour of USC.

Methods and results:  Tissue microarrays were created from the viable central part and from the invasive edge of 20 cases of grade 3 EEC and 73 cases of USC. Immunohistochemistry was performed using antibodies to MMPs‐2, ‐7 and ‐9 and β‐catenin. MMPs‐2, ‐7 and ‐9 and β‐catenin were present in both tumour types; there was significantly higher expression of MMPs‐2 and ‐9 in EEC compared with USC and significantly increased expression of MMPs‐2 and ‐9 by carcinoma cells at the invasive edge of USC.

Conclusions:  MMPs‐2, ‐7 and ‐9 and β‐catenin are present in EEC and USC. The increased expression of MMPs‐2 and ‐9 by carcinoma cells at the invasive edge of USC is possibly due to increased binding of MMPs secreted by the stromal cells to carcinoma cells, thus equipping the USC carcinoma cells with proteases for invasion.
Serial analysis of gene expression in the southern cattle tick following acaricide treatment of larvae from organophosphate resistant and susceptible strains
Authors: Guerrero F. D. , Bendele K. G. , Chen A. C. , Li A. Y. , Miller R. J. , Pleasance E. , Varhol R. , Rousseau M.‐E. , Nene V. M.
Published: January 2007

Organophosphate resistant and susceptible tick larvae from laboratory strains of the southern cattle tick, Rhipicephalus (Boophilus) microplus were exposed to low doses of the organophosphate (OP) acaricide, coumaphos. Serial analysis of gene expression (SAGE) was used to analyse differential gene expression in response to OP treatment and to compare the responses of OP‐treated and ‐untreated resistant and susceptible tick larvae. An R. microplus Gene Index was used as an EST database to identify genes which corresponded to SAGE tags whose abundance changed in response to acaricide exposure. Relative quantitative RT‐PCR was used to confirm the differential expression results from the SAGE experiments. Of particular interest is a SAGE tag which corresponds to a cytochrome P450‐like EST in the Gene Index which was more abundant in untreated OP resistant larvae compared to untreated OP susceptible larvae. This SAGE tag was also more abundant in OP resistant larvae treated with OP compared to OP susceptible larvae treated with OP.
Female‐biased expression of odourant receptor genes in the adult antennae of the silkworm, Bombyx mori
Authors: Wanner K. W. , Anderson A. R. , Trowell S. C. , Theilmann D. A. , Robertson H. M. , Newcomb R. D.
Published: January 2007

Olfaction plays an important role in the life history of insects, including key behaviours such as host selection, oviposition and mate recognition. Odour perception by insects is primarily mediated by the large diverse family of odourant receptors (Ors) that are expressed on the dendrites of olfactory neurones housed within chemosensilla. However, few Or sequences have been identified from the Lepidoptera, an insect order that includes some of the most important pest species worldwide. We have identified 41 Or gene sequences from the silkworm (Bombyx mori) genome, more than double the number of published Or sequences from the Lepidoptera.

Many silkworm Ors appear to be orthologs of the 17 published tobacco budworm (Heliothis virescens) Ors indicating that many Or lineages may be conserved within the Lepidoptera. The majority of the Or genes are expressed in adult female and male antennae (determined by quantitative real‐time PCR analysis), supporting their probable roles in adult olfaction. Several Or genes are expressed at high levels in both male and female antennae, suggesting they mediate the perception of common host or conspecific volatiles important to both sexes. BmOrs 45–47 group together in the same phylogenetic branch and all three are expressed at moderate female‐biased ratios, six to eight times higher in female compared to male moth antennae. Interestingly, BmOrs19 and 30 appear to be expressed predominantly in female antennae, opposite to that of the published silkworm pheromone receptors BmOrs 1 and 3 that are specific to male antennae. These results suggest that BmOr19 and 30 may detect odours critical to female behaviour, such as oviposition cues or male‐produced courtship pheromones.
Cloning and expression of a geranylgeranyl diphosphate synthase gene: insights into the synthesis of termite defence secretion
Authors: Hojo Masaru , Matsumoto Tadao , Miura Toru
Published: January 2007

In Nasutitermes takasagoensis, a termite in which soldiers perform specialized chemical defence, Nts19‐1 gene is highly expressed exclusively in soldier head. In this study, two types of transcripts for this gene were obtained, and the full‐length cDNAs were determined by rapid amplification of cDNA ends (RACE). These transcripts were putative homologues of the geranylgeranyl diphosphate (GGPP) synthase gene, involved in the condensation of dimethylallyl diphosphate with isopentenyl diphosphate in the isoprenoid biosynthetic pathway. The genes were thus termed NtGGPPS1. GGPP is a precursor of diterpenes in plants. In situ hybridization localized NtGGPPS1 expression to the epidermal secretory cells of the frontal gland reservoir where many kinds of diterpenes are produced, suggesting that NtGGPPS1 is involved in the biosynthesis of defence secretion.
The relationship between tooth wear, habitat quality and late‐life reproduction in a wild red deer population
Authors: NUSSEY DANIEL H. , METHERELL BONNIE , MOYES KELLY , DONALD ALISON , GUINNESS FIONA E. , CLUTTON‐BROCK TIM H.
Published: January 2007

Molar tooth wear is considered an important proximate mechanism driving patterns of senescence in ungulates but few studies have investigated the causes of variation in molar wear or their consequences for reproductive success.

In this study, we assessed molar tooth wear at death among red deer Cervus elaphus of known age on the Isle of Rum, Scotland.

First molar height showed a decelerating decline with age. In females, the rates of molar wear with age varied with location of home range and individuals experiencing low resource competition showed reduced molar wear. We suggest that this spatial variation in molar wear is related to differences in the availability of high‐quality grazing habitat and levels of resource competition.

There was no evidence that females with more heavily worn molars had reduced reproductive performance late in life or that first molar height was associated with reproductive senescence.
Multispecies conservation planning: identifying landscapes for the conservation of viable populations using local and continental species priorities
Authors: EARLY REGAN , THOMAS CHRIS D.
Published: January 2007

Faced with unpredictable environmental change, conservation managers face the dual challenges of protecting species throughout their ranges and protecting areas where populations are most likely to persist in the long term. The former can be achieved by protecting locally rare species, to the potential detriment of protecting species where they are least endangered and most likely to survive in the long term.

Using British butterflies as a model system, we compared the efficacy of two methods of identifying persistent areas of species’ distributions: a single‐species approach and a new multispecies prioritization tool called ZONATION. This tool identifies priority areas using population dynamic principles (prioritizing areas that contain concentrations of populations of each species) and the reserve selection principle of complementarity.

ZONATION was generally able to identify the best landscapes for target (i.e. conservation priority) species. This ability was improved by assigning higher numerical weights to target species and implementing a clustering procedure to identify coherent biological management units.

Weighting British species according to their European rather than UK status substantially increased the protection offered to species at risk throughout Europe. The representation of species that are rare or at risk in the UK, but not in Europe, was not greatly reduced when European weights were used, although some species of UK‐only concern were no longer assigned protection inside their best landscapes. The analysis highlights potential consequences of implementing parochial vs. wider‐world priorities within a region.

Synthesis and applications. Wherever possible, reserve planning should incorporate an understanding of population processes to identify areas that are likely to support persistent populations. While the multispecies prioritization tool ZONATION compared favourably to the selection of ‘best’ areas for individual species, a user‐defined input of species weights was required to produce satisfactory solutions for long‐term conservation. Weighting species can allow international conservation priorities to be incorporated into regional action plans but the potential consequences of any putative solution should always be assessed to ensure that no individual species of local concern will be threatened.
Environmental correlates of avian diversity in lowland Panama rain forests
Authors: Rompré Ghislain , Douglas Robinson W. , Desrochers André , Angehr George
Published: January 2007

Aim  The composition of communities is known to be influenced by biogeographical history, but also by local environmental conditions. Yet few studies have evaluated the relative importance of the direct and indirect effects of multiple factors on species diversity in rich Neotropical forests. Our study aims to assess drivers of change in local bird species richness in lowland tropical rain forests.

Location  Thirty‐two physiographic subregions along the corridor of the Panama Canal, Panama.

Methods  We mapped the distributions of all forest‐dwelling bird species and quantified the environmental characteristics of all subregions, including mean annual rainfall, topographic complexity, elevational variability, forest age and forest area. Plant species richness, believed to be correlated with structural complexity, was estimated by interpolation through kriging for subregions where data were unavailable.

Results  The study region has a strong rainfall gradient across a short distance (65 km), which is also accompanied by steep gradients in plant and bird species diversity. Path analysis showed that precipitation strongly affected plant species diversity, which in turn affected avian diversity. Forest age and topography affected bird diversity independently of plant diversity. Forest area and its proportion occurring in the largest two fragments of each subregion (habitat configuration) were also positive correlates of bird species richness.

Main conclusions  Our results suggest that plant species richness, known to be influenced in part by biogeographical history and geology, also affects bird species assemblages locally. We provide support for the hypothesis that bird species richness increases with structural complexity of the habitat. Our analysis of the distributions of the region's most disturbance‐sensitive bird species showed that subregions with more rainfall, more complex topography and older forests harboured not only richer communities but also more sensitive species; while subregions with the opposite characteristics usually lacked large fractions of the regional forest bird community and hosted only common, widely distributed species. Results also emphasize the importance of preserving forest diversity from habitat loss and fragmentation, and confirm that larger, continuous forest tracts are necessary to maintain the rich avian diversity in the region.
Biogeography of European land mammals shows environmentally distinct and spatially coherent clusters
Authors: Heikinheimo H. , Fortelius M. , Eronen J. , Mannila H.
Published: January 2007

Aim To produce a spatial clustering of Europe on the basis of species occurrence data for the land mammal fauna.

Location Europe defined by the following boundaries: 11°W, 32°E, 71°N, 35°N.

Methods Presence/absence records of mammal species collected by the Societas Europaea Mammalogica with a resolution of 50 × 50 km were used in the analysis. After pre‐processing, the data provide information on 124 species in 2183 grid cells. The data were clustered using thek‐means and probabilistic expectation maximization (EM) clustering algorithms. The resulting geographical pattern of clusters was compared against climate variables and against an environmental stratification of Europe based on climate, geomorphology and soil characteristics (EnS).

Results The mammalian presence/absence data divide naturally into clusters, which are highly connected spatially and most strongly determined by the small mammals with the highest grid cell incidence. The clusters reflect major physiographic and environmental features and differ significantly in the values of basic climate variables. The geographical pattern is a fair match for the EnS stratification and is robust between non‐overlapping subsets of the data, such as trophic groups.

Main conclusions The pattern of clusters is regarded as reflecting the spatial expression of biologically distinct, metacommunity‐like entities influenced by deterministic forces ultimately related to the physical environment. Small mammals give the most spatially coherent clusters of any subgroup, while large mammals show stronger relationships to climate variables. The spatial pattern is mainly due to small mammals with high grid cell incidence and is robust to noise from other subsets. The results support the use of spatially resolved environmental reconstructions based on fossil mammal data, especially when based on species with the highest incidence.
Prognostic value of plasma soluble P‐selectin and von Willebrand factor as indices of platelet activation and endothelial damage/dysfunction in high‐risk patients with hypertension: a sub‐study of the Anglo‐Scandinavian Cardiac Outcomes Trial
Authors: Varughese G. I. , Patel J. V. , Tomson J. , Blann A. D. , Hughes E. A. , Lip G. Y. H.
Published: January 2007

Background.  Abnormal levels of prothrombotic markers have been described in hypertension, but no such marker has yet been shown to reliably predict cardiovascular outcomes in hypertension. We hypothesized that raised circulating levels of soluble P‐selectin (sP‐sel, an index of platelet activation) and/or von Willebrand factor (vWF, an index of endothelial damage/dysfunction) would predict vascular events in patients treated for cardiovascular risk.

Methods.  We measured vWF and sP‐sel levels by an ELISA in 234 hypertensive participants with no prior cardiovascular events who were participating in the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT). Plasma vWF and sP‐sel levels were related to the subsequent cardiovascular events over a mean (SD) follow‐up period of 59.6 (19) months.

Results.  Plasma sP‐sel was a significant predictor of myocardial infarction (P = 0.03), with the greatest risk amongst those with the highest sP‐sel levels. sP‐sel did not predict cerebrovascular events (P = 0.53) or composite cardiovascular events (P = 0.06). No significant relationships were found between vWF levels and outcomes. There was no relationship to the presence or absence of diabetes mellitus (DM) at baseline or subsequent development of DM during the follow‐up period.

Conclusions.  Among ‘high‐risk’ patients with hypertension, raised levels of sP‐sel (platelet activation) were predictive of myocardial infarction. Levels of vWF (endothelial damage/dysfunction) were not associated with coronary events and neither marker predicted cerebrovascular or composite cardiovascular endpoints. Platelets (or P‐selectin) might represent a target for novel therapies or an adjunctive aid to risk stratification in the setting of hypertension.
Impact of inflammation on epigenetic DNA methylation – a novel risk factor for cardiovascular disease?
Authors: Stenvinkel P. , Karimi M. , Johansson S. , Axelsson J. , Suliman M. , Lindholm B. , Heimbürger O. , Barany P. , Alvestrand A. , Nordfors L. , Qureshi A. R. , Ekström T. J. , Schalling M.
Published: January 2007

Objective.  The lifespan of dialysis patients is as short as in patients with metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA methylation is an important cellular mechanism modulating gene expression associated with ageing, inflammation and atherosclerotic processes.

Design.  DNA methylation was analysed in peripheral blood leucocytes from three different groups of chronic kidney disease (CKD) populations (37 CKD stages 3 and 4 patients, 98 CKD stage 5 patients and 20 prevalent haemodialysis patients). Thirty‐six healthy subjects served as controls. Clinical characteristics (diabetes mellitus, nutritional status and presence of clinical CVD), inflammation and oxidative stress biomarkers, homocysteine and global DNA methylation in peripheral blood leucocytes (defined as HpaII/MspI ratio by the Luminometric Methylation Assay method) were evaluated. CKD stage 5 patients (n = 98) starting dialysis treatment were followed for a period of 36 ± 2 months.

Results.  Inflamed patients had lower ratios of HpaII/MspI, indicating global DNA hypermethylation. Analysis by the Cox regression model demonstrated that DNA hypermethylation (HpaII/MspI ratio <median) was significantly associated with both all‐cause (RR 5.0; 95% CI: 1.7–14.8; P < 0.01) and cardiovascular (RR 13.9; 95% CI: 1.8–109.3; P < 0.05) mortality, even following the adjustment for age, CVD, diabetes mellitus and inflammation.

Conclusion.  The present study demonstrates that global DNA hypermethylation is associated with inflammation and increased mortality in CKD.
Population fragmentation leads to spatial and temporal genetic structure in the endangered Spanish imperial eagle
Authors: MARTÍNEZ‐CRUZ B. , GODOY J. A. , NEGRO J. J.
Published: January 2007

The fragmentation of a population may have important consequences for population genetic diversity and structure due to the effects of genetic drift and reduced gene flow. We studied the genetic consequences of the fragmentation of the Spanish imperial eagle (Aquila adalberti) population into small patches through a temporal analysis. Thirty‐four museum individuals representing the population predating the fragmentation were analysed for a 345‐bp segment of the mitochondrial control region and a set of 10 nuclear microsatellite loci. Data from a previous study on the current population (N = 79) were re‐analysed for this subset of 10 microsatellite markers and results compared to those obtained from the historical sample. Three shared mitochondrial haplotypes were found in both populations, although fluctuations in haplotype frequencies and the occurrence of a fourth haplotype in the historical population resulted in lower current levels of haplotype and nucleotide diversity. However, microsatellite markers revealed undiminished levels of nuclear diversity. No evidence for genetic structure was observed for the historical Spanish imperial eagle population, suggesting that the current pattern of structure is the direct consequence of population fragmentation. Temporal fluctuations in mitochondrial and microsatellite allelic frequencies were found between the historical and the current population as well as for each pairwise comparison between historical and current Centro and historical and current Parque Nacional de Doñana nuclei. Our results indicate an ancestral panmictic situation for the species that management policies should aim to restore. A historical analysis like the one taken here provides the baseline upon which the relative role of recent drift in shaping current genetic patterns in endangered species can be evaluated and this knowledge is used to guide conservation actions.
Foliar resistance of cacao (Theobroma cacao) to Phytophthora palmivora as an indicator of pod resistance in the field: the effect of light intensity and time of day of leaf collection
Authors: Tahi G. M. , Kébé B. I. , Sangare A. , Cilas C. , Eskes A. B.
Published: January 2007

Resistance of cacao leaves to Phytophthora palmivora was studied with regard to the time of leaf collection (morning, afternoon) and the degree of exposure of the leaves to light in the field (low, medium and high). The efficiency of leaf disc inoculations in predicting field resistance of nine clones was compared with that of detached and attached pod inoculations. Significant effects were observed, with leaves exposed to high light intensity and collected early in the afternoon showing highest susceptibility. The effect of time of leaf collection was reduced when leaves were stored overnight and leaf discs prepared and inoculated the following day, as compared to inoculations on the day of collection. Interactions between the main factors were significant, though less substantial than the clone effects. The most significant correlations with pod resistance (r = 0·70 to 0·97) were obtained for leaves collected early in the morning and exposed to intermediate shade conditions in the canopy. For other treatments, the correlations with pod resistance were still positive (r = 0·23 to 0·83) but often not significant. Pod inoculations in the laboratory were better correlated with field resistance (r = 0·92) than pod inoculations in the field (r = 0·72). Detached pod inoculations were also better correlated with leaf disc inoculations than those of attached pods. The results confirm the validity of laboratory inoculations of leaves and pods to assess field resistance to Phytophthora. Standardization of the leaf disc test is essential to obtain reliable results.
Original article: Grass pollen symptoms interfere with the recollection of birch pollen symptoms – a prospective study of suspected, asymptomatic skin sensitization
Authors: Assing K. , Bodtger U. , Poulsen L. K. , Malling H. J.
Published: January 2007

Background:  Asymptomatic skin sensitization (AS) is a risk factor for the development of allergic symptoms. A meticulous definition of this condition requires a systematic assessment of clinical symptoms before inclusion.

Objective:  To examine the concordance between retrospective assessment of seasonal allergic symptoms and prospective seasonal symptom registration among subjects with AS.

Methods:  On the basis of a population survey, autumn 2002, including skin prick tests (positive if ≥3 mm) and a screening questionnaire, 87 subjects with AS to birch and/or grass pollen, birch and/or grass pollen allergic symptomatic subjects (n = 63) and healthy controls (n = 40) were included in January to March 2003, completed diary cards on symptom and medication use during the relevant seasons 2003, and were examined at follow up in autumn 2003. Allergy: positive SPT and symptoms ≥ seven diary days.

Results:  Eleven AS subjects (birch: n = 10) subsequently developed allergic symptoms, yet nine admitted, at follow up, to have had symptoms before inclusion, or even denied pollen‐related symptoms despite a significant diary. Compared with AS subjects sensitized to grass pollen, AS subjects sensitized to birch pollen had significantly larger skin prick reactions and more often and severe pollen symptoms.

Conclusion:  In the context of double‐sensitization, retrospective symptom assessment is not a reliable method for ensuring that subjects classified, as asymptomatically skin sensitized, are truly, asymptomatic. This matter should be considered in studies on allergy development.
Induction of tumor necrosis‐α, p38 and JNK in the spinal cord following acute heart injury in the rat model
Authors: Dai R.‐P. , Xu J.‐M , Tao L.‐J. , Li L. , Li Z.‐P. , Zhang J.‐Y.
Published: January 2007

Background:  It is still not known whether the spinal cytokine signaling pathways are involved in the pathophysiologic mechanism of the acute phase of heart disease. This study examines the expression pattern of tumor necrosis factor‐α (TNF‐α) and its two related mitogenic‐activated protein kinases, p38 and Jun‐N‐terminal kinase (JNK), in the spinal cord in response to acute cardiac injury (ACI).

Methods:  The ACI rat model was established by intra‐myocardial injection of formalin. At the indicated times after the establishment of ACI, the thoracic segments of the spinal cord were harvested and Western blot was performed to determine the expression of TNF‐α, p38 and JNK. The localization of the cytokine and the kinases was determined by immunohistochemistry and double immunofluorescence.

Results:  In response to ACI, TNF‐α protein was up‐regulated and reached a peak level at 6 h after ACI. The up‐regulated TNF‐α was distributed in all the laminae in the spinal cord and mainly localized in the neurons, as determined by immunohistochemistry and double immunofluorescence. In response to ACI, p38 and JNK were also up‐regulated in the spinal cord. The expression profiles of p38 and JNK were similar to that of activated TNF‐α following ACI.

Conclusions:  This study shows that cardiac injury can induce the activation of spinal TNF‐α, p38 and JNK. The activated spinal cytokine signaling may contribute to disease progression in the acute phase of cardiac injury in clinical practice.
Regional Anesthesia Surveillance System: first experiences with a quality assessment tool for regional anesthesia and analgesia
Authors: Schulz‐Stübner S. , Kelley J.
Published: January 2007

Background:  The incidence of complications related to regional anesthesia and analgesia is hardly known and estimates are based on extrapolation from controlled trials, insurance registries and retrospective chart reviews and only a few attempts of prospective data collection have been made. We designed a surveillance system for regional anesthesia for easy and reliable data acquisition.

Methods:  A list of definitions of complications and quality indicators of interest was created and introduced in a single institution. Data are collected within the hospital information system and by individual reports of complications from trained reporters in the Acute Pain Service. A data cross‐check is performed by the Surveillance coordinator.

Results:  We present complications rates for 9790 catheter days and 4547 punctures for continuous neuraxial and peripheral nerve blocks between October 2003 and January 2006. Most complications were related to catheter dislocation and ‘wet taps’. Serious complications such as neurologic deficits, bleeding complications and infections were rare. Data quality reached 98% reliability of complication coding.

Discussion:  This is the description of a prospective regional anesthesia surveillance system, which currently allows longitudinal analysis of performance parameters at a single institution and will provide data about the incidences of complications related to regional anesthesia and analgesia in the future.
FUNCTIONAL IMPAIRMENT OF CARDIAC TRANSIENT OUTWARD K+ CURRENT AS A RESULT OF ABNORMALLY ALTERED CELLULAR ENVIRONMENT
Authors: Du Zhimin , Chaoqian Xu , Shan Hongli , Lu Yanjie , Ren Nanqi
Published: January 2007

Physiological functions of cardiac cells require a normal cellular environment. Under pathological conditions, there is a loss of normal cellular environment due to metabolic perturbations and other abnormalities. To test the hypothesis that cellular environmental stresses can create an electrophysiological substrate for electrical disorders in the heart, we investigated the effects of hypoxia, acidosis and ischaemia on transient outward K+ current (Ito) in single canine ventricular myocytes.

The Ito was studied because it plays a critical role in initiating cardiac repolarization and, thereby, arrhythmias. It was found that Ito was significantly depressed by some 30% under hypoxic conditions relative to that in a normal cellular environment with normal Tyrode's solution.

Acidosis created by lowering the pH of the external solution from 7.4 to 7.2 produced a substantial (approximately 35%) reduction of the Ito amplitude.

A marked impairment of Ito function was consistently observed in ischaemic hearts in the canine coronary artery ligation model, with an approximate 30% decrease in the size of Ito.

Importantly, the impairment of Ito under these environmental stresses was largely reversible following restoration to normal conditions.

The results of the present study suggest that Ito is susceptible to changes in the cellular environment and the functional impairment of Ito under environmental stresses contributes to arrhythmias under relevant pathological conditions of the heart.
ANGIOTENSIN II‐INDUCED GROWTH OF VASCULAR SMOOTH MUSCLE CELLS IS ASSOCIATED WITH MODULATION OF CELL SURFACE AREA AND PLATELET‐DERIVED GROWTH FACTOR RECEPTOR EXPRESSION
Authors: Kuma Sosei , Oki Eiji , Onohara Toshihiro , Komori Kimihiro , Maehara Yoshihiko
Published: January 2007

Excessive growth of vascular smooth muscle cells (VSMC) can lead to critical problems in the treatment of some vascular diseases. Recent studies suggest a connection between this abnormal growth of VSMC and the octapeptide hormone angiotensin (Ang) II. However, the growth‐promotive potential of AngII on VSMC is unclear.

Using the novel AngII inhibitor E4177 and an original animal model, we confirmed that AngII does function in abnormal growth of VSMC induced after transplantation of vein grafts in an animal model.

Furthermore, using a primary culture of human aortic smooth muscle cells (HASMC), we found that AngII augmented the growth of HASMC in a serum‐dependent manner and induced enlargement of the cell surface area in HASMC, both effects being nullified by E4177. The latter effect of AngII was associated with an increase in the expression level of platelet‐derived growth factor (PDGF) receptors. In specimens obtained from the animal model, PDGF receptors were highly expressed.

These data obtained in vitro and in vivo imply that AngII has the potential to promote growth of VSMC and suggest that this growth promotion may be mediated by enlargement of the cell surface area.
ACUTE CORONARY LIGATION IN THE DOG INDUCES TIME‐DEPENDENT TRANSITIONAL CHANGES IN MITOCHONDRIAL CRISTA IN THE NON‐ISCHAEMIC VENTRICULAR MYOCARDIUM
Authors: McLachlan Craig Steven , Almsherqi Zakaria A , Chua Kerin Sze Yi , Liew Yu Ying , Low Chwee Wah , Deng Yuru
Published: January 2007

The aim of the present study was to examine, in the dog myocardium, the incidence of zig‐zag mitochondrial cristae over time in the non‐ischaemic posterior wall, following an acute anterior wall infarct.

Changes within the myocardial mitochondrial crista membrane in dogs were investigated following acute left anterior descending coronary artery ligation. Transmyocardial biopsy samples were taken serially from the posterior non‐ischaemic wall in the same dog. Changes in heart mitochondrial cristae were examined by transmission electron microscopy prior to coronary ligation (control) and 40 min and 2, 4, 6 and 24 h postinfarction.

In control hearts, 90% of mitochondrial cristae had a lamelliform appearance. Following infarction, there were twotransitional states with respect to mitochondrial cristae, the first characterized by undulating lamelliform cristae that are also found in 10% of control samples and a second transitional state that was zig‐zag and reached a maximum between 6 and 24 h after infarction.

In conclusion, an undulating lamelliform crista pattern is present in the non‐ischaemic wall of the acute infarcted dog and we hypothesize that this may be an intermediate from, between ‘normal’ lamelliform and ‘abnormal’ zig‐zag cristae.
CHOLESTEROL, STATINS AND CANCER
Authors: Brown Andrew J
Published: January 2007

The link between cholesterol and cardiovascular disease is well‐established. Emerging evidence is now forging a tantalizing link between cholesterol and cancer.

Results from a number of case‐control studies have indicated that the commonly prescribed cholesterol‐lowering drugs, the statins, may reduce the risk of certain cancers, although this area certainly remains controversial.

Herein, the recent literature examining statins and cancer is reviewed briefly and the relationship between a key cholesterol homeostatic pathway and signalling pathways that are involved in carcinogenesis is discussed. In particular, how the sterol‐regulatory element binding protein, Akt and Hedgehog pathways may converge in cancer is reviewed.
CARDIOPROTECTIVE EFFECTS OF A NON‐ALCOHOLIC EXTRACT OF RED WINE DURING ISCHAEMIA AND REPERFUSION IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Fantinelli Juliana C , Mosca Susana M
Published: January 2007

We reported recently the cardioprotection conferred by a non‐alcoholic extract of Cabernet‐Sauvignon red wine (RWE) against alterations derived from ischaemia and reperfusion in normotensive rats. The aim of the present study was to assess the effects of RWE on ischaemia/reperfusion injury in hearts isolated from spontaneously hypertensive rats (SHR).

After stabilization, rat isovolumic perfused hearts were exposed to a 20 min global ischaemic period followed by 30 min reperfusion in the absence (ischaemic control (IC) hearts) or presence of RWE infused prior to ischaemia and early in reperfusion. In other hearts, NG‐nitro‐l‐arginine methyl ester (l‐NAME), an inhibitor of nitric oxide synthase, was administered prior to RWE infusion (l‐NAME + RWE).

Left ventricular developed pressure (LVDP), dP/dtmax and left ventricular end‐diastolic pressure (LVEDP) were used to assess myocardial function.

At the end of reperfusion, LVDP and dP/dtmax decreased to 47 ± 9 and 46 ± 9% of baseline values, respectively, in IC. Treatment with the RWE significantly improved systolic postischaemic recovery (LVDP = 85 ± 8%; dP/dtmax = 83 ± 5%) and attenuated the increase in LVEDP (23 ± 6 and 53 ± 8 mmHg in RWE and IC, respectively; P < 0.05).

In the l‐NAME + RWE group, l‐NAME completely abolished the systolic and diastolic protection induced by RWE (LVDP = 44 ± 13%; dP/dtmax = 43 ± 13%; LVEDP = 60 ± 10 mmHg).

These data are the first demonstration that a non‐alcoholic extract of Cabernet‐Sauvignon red wine protects SHR hearts from systolic and diastolic alterations induced by ischaemia and reperfusion through a nitric oxide‐dependent mechanism.
EFFECTS OF SHRIMP (MACROBRACIUM ROSENBERGII)‐DERIVED CHITOSAN ON PLASMA LIPID PROFILE AND LIVER LIPID PEROXIDE LEVELS IN NORMO‐ AND HYPERCHOLESTEROLAEMIC RATS
Authors: Hossain Shahdat , Rahman Azizur , Kabir Yearul , Shams Ali Ahmed , Afros Fahmida , Hashimoto Michio
Published: January 2007

The effects of chitosan (CS) derived from the exoskeleton of the shrimp Macrobracium rosenbergii on bodyweight, plasma lipid profile, fatty acid composition, liver lipid peroxide (LPO) levels and plasma levels of glutamate pyruvate transaminase (GPT) were determined in normocholesterolaemic (NC) and hypercholesterolaemic (HC) Long Evans rats.

The NC rats were fed a diet containing 2% CS and the HC rats were fed a diet containing 2 and 4% CS for 8 weeks. Chitosan significantly reduced bodyweight gain only in HC + 4% CS rats compared with HC rats, but not in NC + 2% CS or HC + 2% CS rats.

Chitosan reduced plasma total cholesterol in the HC + 2% CS, HC + 4% CS and NC + 2% CS rats; however, low density lipoprotein–cholesterol decreased only in the first two groups. High‐density lipoprotein–cholesterol (HDL‐C) increased in the HC + 4% CS rats by 24% compared with the HC + 2% CS group and by 30% compared with HC rats; however, HDL‐C did not increase in the NC + 2% CS group compared with NC rats. The level of plasma triglycerides decreased significantly only in HC + 2% CS rats compared with HC rats.

Chitosan significantly decreased plasma levels of arachidonic acid in the HC + 2% CS and HC + 4% CS groups, with a concurrent increase in the molar ratio of total unsaturated fatty acid (TUFA) to total saturated fatty acid (TSFA).

Moreover, CS increased liver LPO levels without affecting plasma levels of GPT. Liver LPO levels were positively correlated with the TUFA/TSFA molar ratio.

The present study suggests that dietary CS decreases the atherogenic lipid profiles of both NC and HC rats and reduces the bodyweight gain of HC rats.
FIBRIN D‐DIMER FRAGMENTS ENHANCE INFLAMMATORY RESPONSES IN MACROPHAGES: ROLE IN ADVANCING ATHEROSCLEROSIS
Authors: Zhou Dong , Yang Peng‐Yuan , Zhou Bin , Rui Yao‐Cheng
Published: January 2007

Fibrin D‐dimer is considered a consistent and independent marker of the risk of cardiovascular disease in population studies, as well as being related to atherosclerosis severity in patients. However, the role of fibrin D‐dimer in macrophage‐derived foam cell formation during atherogenesis remains unclear.

In the present study, using microarray techniques, we determined the effects of 100 ng/mL fibrin D‐dimer fragments on macrophage cell function in atherosclerosis by investigating the expression levels of 128 genes related to the atherosclerotic pathophysiological processes.

The results showed that 27 genes were enhanced by D‐dimer fragments to over twofold of control. These 27 genes belonged to six groups and included adhesion molecules, extracellular molecules, molecules related to lipid transport and metabolism, cell growth and proliferation molecules, transcription regulators and genes responsive to stress. We proceeded to determine the expression levels of five of these genes (intercellular adhesion molecule‐1, matrix metalloproteinase‐9, oxidized low‐density lipoprotein receptor 1, vascular endothelial growth factor A and peroxisome proliferator‐activated receptor α) using SYBR real‐time polymerase chain reaction. The results confirmed gene upregulation, similar to the results obtained with the microarray, following treatment with D‐dimer.

Therefore, the present study provides direct evidence regarding the pro‐atherosclerotic role of D‐dimer in macrophage function, which is mainly to enhance the inflammatory response during macrophage‐derived foam cell formation.
AMINO ACID AND FATTY ACID COMPOSITION OF AN AQUEOUS EXTRACT OFCHANNA STRIATUS(HARUAN) THAT EXHIBITS ANTINOCICEPTIVE ACTIVITY
Authors: Zakaria ZA , Mat Jais AM , Goh YM , Sulaiman MR , Somchit MN
Published: January 2007

The present study was performed in order to determine the amino acid and fatty acid composition of an aqueous extract of the freshwater fishChanna striatus, obtained by soaking (1 : 2, w/v) fresh fillets overnight in a chloroform : methanol (2 : 1, v/v) solvent, to elucidate the mechanism responsible for its antinociceptive activity and to clarify the relationship between the presence of the amino and fatty acids and the expected activity.

The aqueous extract was found to contain all amino acids with the major amino acids glycine, alanine, lysine, aspartic acid and proline making up 35.77 ± 0.58, 10.19 ± 1.27, 9.44 ± 0.56, 8.53 ± 1.15 and 6.86 ± 0.78% of the total protein, respectively.

In addition, the aqueous extract was found to have a high palmitic acid (C16 : 0) content, which contributed approximately 35.93 ± 0.63% to total fatty acids. The other major fatty acids in the aqueous extract were oleic acid (C18 : 1), stearic acid (C18 : 0), linoleic acid (C18 : 2) and arachidonic acid (C20 : 4), contributing 22.96 ± 0.40, 15.31 ± 0.33, 11.45 ± 0.31 and 7.44 ± 0.83% of total fatty acids, respectively.

Furthermore, the aqueous extract was demonstrated to possess concentration‐dependent antinociceptive activity, as expected, when assessed using the abdominal constriction test in mice.

It is concluded that the aqueous extract ofC. striatuscontains all the important amino acids, but only some of the important fatty acids, which are suggested to play a key role in the observed antinociceptive activity of the extract, as well as in the traditionally claimed wound healing properties of the extract.
DIFFERENTIAL GROWTH INHIBITION AND INDUCTION OF APOPTOSIS BY GOSSYPOL BETWEEN HCT116 AND HCT116/BAX−/– COLORECTAL CANCER CELLS
Authors: Zhang Manchao , Liu Hongpeng , Tian Zhenkun , Huang Jenny , Remo Mylene , Li Q Quentin
Published: January 2007

Bax is a very important pro‐apoptosis molecule. HCT116/Bax−/– cells do not express the pro‐apoptosis Bcl‐2 family member, Bax. In the present study, the anticancer effects of gossypol on HCT116 and HCT116/Bax−/– cells were compared in terms of inhibition of cell growth, inhibition of colony formation and induction of apoptosis.

Following treatment with concentrations more than 20 µmol/L gossypol, only slight differences (not signficant) were seen between HCT116 and HCT116/Bax−/– cells in terms of the inhibition of cell growth and induction of apoptosis. No difference was seen in the inhibition of colony formation. Gossypol had no effect at concentrations < 2 µmol/L. The only effective concentration of gossypol to result in differences between HCT116 and HCT116/Bax−/– cells was 5 µmol/L. However, even at this concentration, Bax deficiency did not result in complete abolition of gossypol‐induced growth inhibition or apoptosis. Exposure of cells to 5 µmol/L gossypol for 24 h did not cause any significant difference in the activation of caspase 2 between HCT116 and HCT116/Bax−/– cells; however, activation of caspase 3, 8 and 9 was significantly elevated in HCT116 cells, with the effect on caspase 3 activation being the greatest, compared with HCT116/Bax−/– cells.

These findings suggest that the contribution of Bax to gossypol‐induced growth inhibition and apoptosis is dose dependent and that gossypol‐induced apoptosis requires activation of caspase 3, 8, and 9.