bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and echographical control protocol of haemarthrosis in haemophilia patients with inhibitors: evaluation of the efficacy of recombinant factor VIIa in the evolution process (EFFISEVEN protocol)
Authors: QUEROL F. , CORTINA V. , CID A. R. , HAYA S. , AZNAR J. A.
Published: September 2008

Summary.  The intention of the ‘clinical and echographical protocol of evaluation the efficacy of recombinant activated factor VII in the haemarthrosis’ (EFFISEVEN protocol) was to provide an extensive study of the evolution of haemarthrosis, and second, of its repercussions on the degenerative process of joints. The clinical evaluation of haemarthroses and their evolution is based on a well‐established methodology, although very few studies have sought to determine the correlation between pain, mobility and the objective data regarding the haemorrhage. We believe that it is necessary to unify criteria and that the EFFISEVEN protocol may contribute data that improve standards which, in turn, will influence the degenerative process of joints, and consequently affect the quality of life of haemophilia patients with inhibitors. Echographical control of haemarthrosis is an objective method that allows control over how the haemorrhage evolves and also helps in the identification of rebleeding. Therefore, its use adds a new dimension to patient management strategies. Techniques used to monitor recombinant activated factor VII (rFVIIa) treatment require further study, although preliminary results guarantee their efficacy.
The role of rehabilitation and sports in haemophilia patients with inhibitors
Authors: HEIJNEN L.
Published: September 2008

Summary. Treatment of haemophilia patients with inhibitors against factor VIII/IX (FVIII/IX) is still challenging and recurrent haemarthroses cause arthropathy with associated restrictions on participation in physical activities and sports. Rehabilitation is a multidisciplinary approach which includes physiotherapy, occupational therapy, psychology, social work and technical applications like prostheses, orthoses (splints and braces), shoe adaptations, walking aids and adaptations in the house and work situation, but also education. The theoretical principles and practical advice regarding rehabilitation and physiotherapy for both children and adults with haemophilia without inhibitors are highly applicable for patients with inhibitors. Hydrotherapy is useful in the treatment of painful or stiff joints and/or muscles after an acute haemarthrosis, muscle bleeds and chronic arthropathy. In addition, it is of use in cases of chronic synovitis and to start mobilization after long periods of bed rest or during the weaning of a splint. In cases of bleeding and arthropathy, adequate treatment of pain is very important, as are functional exercises. Everyone should be physically active for 30–60 min day−1. Participation in sports is recommended for people with haemophilia, the best sport being swimming. Children should participate in sports appropriate to their size and physical characteristics.
Synoviorthesis in haemophilia patients with inhibitors
Authors: PASTA G. , MANCUSO M. E. , PERFETTO O. S. , SOLIMENO L. P.
Published: September 2008

Summary.  Recurrent bleeding into joints represents the clinical hallmark of haemophilia and, if not adequately treated, it may cause chronic synovitis and degenerative arthropathy. In haemophilia patients with inhibitors, a more severe degree of synovitis is often observed owing to the fact that treatment is more problematic in this setting. The first treatment option of recurrent haemarthroses and/or chronic synovitis is represented by synoviorthesis, both chemical and radioisotopic, with a success rate of approximately 80% for both. However, radioisotopic synoviorthesis should be preferred in inhibitor patients because it makes it possible to obtain complete synovial fibrosis usually in one session, without the need for repeated injections, thus reducing the risk of bleeding complications and concentrate consumption. For all these reasons this procedure should be implemented and supported, particularly in developing countries.
Orthopaedic surgery in haemophilia patients with inhibitors as the last resort
Authors: RODRIGUEZ‐MERCHAN E. C. , QUINTANA M. , JIMENEZ‐YUSTE V.
Published: September 2008

Summary.  Haemophilia patients with inhibitors commonly present much more severe musculoskeletal problems than patients without inhibitors. With haematological advances using recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrate (aPCC), it is now possible to perform orthopaedic procedures in these patients with a high rate of success. In Spain, the healthcare system sets no financial limits for the treatment of haemophilia, and children with haemophilia today have a much better musculoskeletal status than 30 years ago. However, the children of 30 years ago are now adults and are afflicted by severe articular deformities that frequently require the intervention of an orthopaedic surgeon. Our view is that the well‐known concepts of prophylaxis in patients without inhibitors should be followed and applied to patients with inhibitors. In fact, prophylaxis seems to be the only way to prevent the development of haemophilic arthropathy in patients with haemophilia. Until this goal can be achieved, major and minor orthopaedic procedures will be necessary in patients with inhibitors more frequently than in patients without inhibitors.
Mining an Ostrinia nubilalis midgut expressed sequence tag (EST) library for candidate genes and single nucleotide polymorphisms (SNPs)
Authors: Coates B. S. , Sumerford D. V. , Hellmich R. L. , Lewis L. C.
Published: September 2008

Genes expressed in lepidopteran midgut tissues are involved in digestion and Bacillus thuringiensis (Bt) toxin resistance traits. Five hundred and thirty five unique transcripts were annotated from 1745 high quality O. nubilalis larval midgut expressed sequence tags (ESTs). Full‐length cDNA sequence of 12 putative serine proteinase genes and 3 partial O. nubilalis aminopeptidase N protein genes, apn1, apn3, and apn4, were obtained, and genes may have roles in plant feeding and Bt toxin resistance traits of Ostrinia larvae. The EST library was not normalized and insert frequencies reflect transcript levels under the initial treatment conditions and redundancy of inserts from highly expressed transcripts allowed prediction of putative single nucleotide polymorphisms (SNPs). Ten di‐, tri‐ or tetranucleotide repeat unit microsatellite loci were identified, and minisatellite repeats were observed within the C‐termini of two encoded serine proteinases. Molecular markers showed polymorphism at 28 SNP loci and one microsatellite locus, and Mendelian inheritance indicated that markers were applicable to genome mapping applications. This O. nubilalis larval midgut EST collection is a resource for gene discovery, expression information, and allelic variation for use in genetic marker development.
Low level of microsatellite instability in paediatric malignant astrocytomas
Authors: Vladimirova V. , Denkhaus D. , Soerensen N. , Wagner S. , Wolff J. E. A. , Pietsch T.
Published: September 2008

Aim: Microsatellite instability (MSI) has been proposed as a possible mechanism in the development of cancer. The aim of the current study was to determine whether MSI is involved in the pathogenesis of paediatric malignant astrocytomas. Methods: We screened a cohort of 126 high‐grade astrocytoma samples for MSI using a sensitive and precise method of DNA analysis including a panel of five mononucleotide repeats, in combination with immunohistochemistry for DNA mismatch repair (MMR) proteins. Results: We identified low level of MSI (MSI‐L) in four of 126 (3.2%) paediatric malignant astrocytic tumours. To analyse the molecular profile associated with MSI‐L positive tumours, we performed immunohistochemistry for protein expression of hMSH6 and p53 as well as mutational analysis of the K‐ras gene. In MSI‐L paediatric malignant astrocytic tumours we detected retained nuclear expression of hMSH6 protein and strong nuclear accumulation of p53 protein indicating possible mutations of TP53. There was no correlation between K‐ras mutational status and frequency of MSI in this patient population. Conclusion: Our results suggest that the MSI‐L phenotype is associated with p53 accumulation and/or mutations. However, this represents only a small subgroup of paediatric gliomas with possible distinct biological features, and the deficiencies of DNA MMR genes do not play a main role in the tumourigenesis of the majority of paediatric malignant astrocytomas.
Effects of β‐amyloid peptide on the density of M2 muscarinic acetylcholine receptor protein in the hippocampus of the rat: relationship with GABA‐, calcium‐binding protein and somatostatin‐containing cells
Authors: González I. , Arévalo‐Serrano J. , Pérez J. L. , Gonzalo P. , Gonzalo‐Ruiz A.
Published: September 2008

Aims:The deposition of amyloid peptides (Aβ) in the cortex and hippocampus is the primary trigger of Alzheimer's disease (AD). Recent studies also indicated that the M2 subtype of muscarinic acetylcholine receptors (M2mAChR) may be a key molecule involved in cognitive dysfunction. Thus, the purpose of this study was to determine the effects of extracellular deposition of Aβ on the density of M2mAChR in the hippocampus of the rat by M2mAChR‐immunohistochemistry.Methods:Special attention was paid to discerning any interaction between Aβ and M2mAChR in GABA‐, and calcium‐binding protein containing cells by double‐labelling immunohistochemistry. Densitometric analysis of M2mAChR‐immunoreactivity was performed using Scion Image Beta Software. Quantitative analysis of GABA‐, and calcium‐binding protein interneurones containing M2mAChR protein was performed using a NeuroLucida morphometric system.Results:Injections of Aβ into the retrosplenial cortex resulted in a significant reduction in M2mAChR‐immunoreactivity in the CA1 ipsilateral to the Aβ‐injected side as compared with the corresponding hemisphere of non‐treated control animals and with that in the corresponding region of the CA1 in the phosphate‐buffered saline‐injected side. Co‐localization studies showed that the M2mAChR is localized in a subset of GABA‐positive cells of the hippocampus, in cells that contain calcium‐binding proteins, and in a subpopulation of cells that contain the neuropeptide somatostatin.Conclusions:Our findings suggest that Aβ induces a significant reduction in M2mAChR‐immunoreactivity in the CA1 of the hippocampus and a reduction in GABAergic interneurones containing M2mAChR, which may contribute to impairment of GABAergic synaptic transmission in area CA1 of hippocampus.
Involvement of the auditory brainstem system in spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7)
Authors: Hoche F. , Seidel K. , Brunt E. R. , Auburger G. , Schöls L. , Bürk K. , De Vos R. A. , Den Dunnen W. , Bechmann I. , Egensperger R. , Van Broeckhoven C. , Gierga K. , Deller T. , Rüb U.
Published: September 2008

Aims: The spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7) are clinically characterized by progressive and severe ataxic symptoms, dysarthria, dysphagia, oculomotor impairments, pyramidal and extrapyramidal manifestations and sensory deficits. Although recent clinical studies reported additional disease signs suggesting involvement of the brainstem auditory system, this has never been studied in detail in SCA2, SCA3 or SCA7. Methods: We performed a detailed pathoanatomical investigation of unconventionally thick tissue sections through the auditory brainstem nuclei (that is, nucleus of the inferior colliculus, nuclei of the lateral lemniscus, superior olive, cochlear nuclei) and auditory brainstem fibre tracts (that is, lateral lemniscus, trapezoid body, dorsal acoustic stria, cochlear portion of the vestibulocochlear nerve) of clinically diagnosed and genetically confirmed SCA2, SCA3 and SCA7 patients. Results: Examination of unconventionally thick serial brainstem sections stained for lipofuscin pigment and Nissl material revealed a consistent and widespread involvement of the auditory brainstem nuclei in the SCA2, SCA3 and SCA7 patients studied. Serial brainstem tissue sections stained for myelin showed loss of myelinated fibres in two of the auditory brainstem fibre tracts (that is, lateral lemniscus, trapezoid body) in a subset of patients. Conclusions: The involvement of the auditory brainstem system offers plausible explanations for the auditory impairments detected in some of our and other SCA2, SCA3 and SCA7 patients upon bedside examination or neurophysiological investigation. However, further clinical studies are required to resolve the striking discrepancy between the consistent involvement of the brainstem auditory system observed in this study and the comparatively low frequency of reported auditory impairments in SCA2, SCA3 and SCA7 patients.
Cenozoic noncoaxial transtension along the western shoulder of the Ross Sea, Antarctica, and the emplacement of McMurdo dyke arrays
Authors: Rossetti F. , Storti F. , Salvini F.
Published: September 2008

Field data on Cenozoic faults and the McMurdo dyke arrays in the Reeves Glacier–Mawson Glacier area, Victoria Land, Antarctica, allow us to support noncoaxial transtensional tectonics along the N–S‐trending western shoulder of the Ross Sea. Dyke injection within a crustal‐scale right‐lateral strike‐slip shear zone is testified by magma filled, tension gash‐like arrangements within some master fault zones, and by the left‐stepping arrangements of dykes in the intrafault zones. The noncoaxiality of deformation is shown by the re‐activation of many dyke walls as right‐lateral strike‐slip faults. This suggests an increase in the strike‐slip component over time along the western shoulder of the Ross Sea. Our data support the relevance of transtensional to strike‐slip tectonics for triggering melting and controlling the geometry and modes of magma emplacement.
Superimposed brittle structures in the late‐orogenic extension of the Northern Apennine: results from the Carrara area (Alpi Apuane, NW Tuscany)
Authors: Ottria G. , Molli G.
Published: September 2008

This paper presents data on the geometric and kinematic features of brittle faults in the Carrara area (Alpi Apuane, NW Tuscany, Italy), providing the first paleostress determination in a key region of the Northern Apennine. Meso‐and microfault analyses point out the presence of brittle structures formed during a polyphase deformation and characterized by an older stage (DS1), with an interfering system of strike slip and normal faulting, followed by the DS2 stage developing normal faults locally showing apenninic trend (NW/SE). As a whole, the brittle structures are related to the late Pliocene–middle Pleistocene evolution of the Thyrrenian side of the Northern Apennine.
Middle Triassic conodonts from northeastern Spain: biostratigraphic implications
Authors: Márquez‐Aliaga A. , Valenzuela‐Ríos J.I. , Calvet F. , Budurov K.
Published: September 2008

The facies development of the Spanish Triassic corresponds to the typical three‐fold subdivision of the Germanic Facies: Buntsandstein, Muschelkalk and Keuper. Two intervals interpreted as epeiric carbonate platforms: lower Muschelkalk (Anisian) and upper Muschelkalk (Ladinian) are recognized during the Middle Triassic of northeastern Spain. These carbonate intervals are separated by one siliciclastic/evaporitic interval interpreted as sabbkha and saline deposits: middle Muschelkalk facies (Lower Ladinian). In northeastern Spain (Catalonian Coastal Ranges), two Middle Triassic sections comprising lower Muschelkalk facies have yielded the following conodont taxa: Paragondolella bulgarica, P. hanbulogi, P. bifurcata, Neogondolella constricta, N. cornuta, N. excentrica and N. basisymmetrica. The conodont sequence allows recognition of the P. bulgarica and N. constricta zones. These results indicate a middle–upper Pelsonian to upper Illyrian age (middle–upper Anisian), and represent the first conodont‐chronostratigraphic approximation for the lower Muschelkalk facies of the western part of the Sephardic Province of the Triassic Tethys Realm.
Oligo‐Miocene granitic magmatism in central Vietnam and implications for continental deformation in Indochina
Authors: Nagy E.A. , Schärer U. , Minh N.T.
Published: September 2008

Two granitoid intrusions within the Bu Khang extensional complex in central Vietnam have been dated by U–Pb and Rb–Sr geochronology. A monazite U–Pb age of 26.0 ± 0.2 (2σ) Myr was obtained for the Bu Khang pluton and 23.7 + 1.6/–1.7 Myr for monazite, allanite and zircon from the Dai Loc intrusion. These ages date crystallization of magmas previously assigned Precambrian to Devonian. Rb–Sr analyses of K‐feldspar and biotite fractions from the samples yield ages of 19.8 ± 0.6 (2σ) Myr and 19.6 ± 0.5 Myr, respectively. The thermal history recorded by the different geochronometers implies an average exhumation rate of ∼2 mm yr−1 corresponding to ∼9 km of unroofing. Magmatism was either (i) induced passively by lithospheric thinning driven by changes in regional tectonic stresses, or (ii) triggered actively by an ascending plume. Tertiary exhumation and magmatism documented elsewhere in Indochina (e.g. Ailao Shan‐Red River and Wang Chao shear zones) favours a regional tectonic cause for extension and granitoid magmatism in the Bu Khang complex. On the other hand, the presence of an upwelling thermal anomaly since at least 35 Ma, causing mantle melting below Indochina, is supported by shear‐wave velocity variations in the mantle, and source geochemistry of both the Bu Khang plutons and the Red River belt intrusions. In either case, Tertiary exhumation of the Bu Khang complex can account for previously undocumented NE–SW‐directed extension, which is required in northern Vietnam to account for structural changes related to the opening of the South China Sea.
X‐ray imaging of uranium in individual fluid inclusions
Authors: Philippot P. , Ménez B. , Simionovici A. , Chabiron A. , Cuney M. , Snigirev A. , Snigireva I.
Published: September 2008

The spatial distribution of major (K, Ca, Mn, Fe) and trace elements (Ti, Cr, Cu, As, Br, Rb, Sr, Zr, Pb, Th, U) were determined in individual fluid inclusions from quartz veins of the Streltsov uranium deposit, Russia, using synchrotron radiation X‐ray fluorescence (SXRF). The analyses were performed on the beamline ID‐22 Micro‐FID (Fluorescence, Imaging, Diffraction) of the European Synchrotron Research Facility (ESRF, Grenoble, France). Fluorescence X‐ray maps of single fluid inclusions show a relatively homogeneous distribution of most elements throughout the inclusion, whereas Fe and, to a lesser extent, Sr display highly localized count rates. This observation argues for the presence of minute, optically invisible, compounds that are precipitated inside the inclusion. Simple model calculations indicate that relatively diluted solutions (10–100 ppm U) trapped at geologically relevant temperatures (e.g. 250 °C) would precipitate submicron sized particles. These particles would be highly reactive to the photon flux but not necessarily visible under the microscope. These results indicate that third‐generation synchrotron light source can be a powerful technique to study the physical processes undergone by the fluid. When combined with chemical data, this technique can help to clarify fluid transport properties in natural systems.
Sr‐Nd‐Pb isotope ratios, geochemical compositions, and 40Ar/39Ar data of lavas from San Felix Island (Southeast Pacific): Implications for magma genesis and sources
Authors: Haase K.M. , Mertz D.F. , Sharp W.S. , Garbe‐Schönberg C.‐D.
Published: September 2008

We present the first trace element and age data combined with new Sr, Nd, and Pb isotope ratios on lavas from San Felix Island in the Southeast Pacific. A 40Ar/39Ar plateau age of 421 ± 18 ka implies young intraplate volcanic activity in this region relative to the ∼22 Ma old volcanism on the neighbouring Easter seamount chain (ESC). The incompatible element compositions of the San Felix magmas are similar to those of EM1‐type basalts from Gough, although the isotopic compositions differ. San Felix formed some 20 Ma after the ESC plume affected the plate in this region but no chemical signature of the ESC material is observed in the young volcanic rocks. The composition of the San Felix basalts indicates a mantle source containing old continental lithospheric material from either metasomatized mantle or recycled sediments, which ascends in a weak mantle plume.
Genetic Diversity within an Italian Population of Forest Armillaria gallica Isolates as Assessed by RAPD‐PCR Analysis
Authors: Gatto Angela , Sicoli Giovanni , Luisi Nicola
Published: September 2008

The genus Armillaria includes harmful fungal pathogens that cause root rot and wood decay in a broad range of host plants throughout the world. The aim of this study was to detect, by means of Random amplified polymorphic DNA‐polymerase chain reaction (RAPD‐PCR) markers, the level of intraspecific variability within isolates of an Armillaria gallica population sampled from a Quercus spp. stand located in Gravina in Puglia, southern Italy. UPGMA cluster analysis of RAPD profiles generated by decamer primers grouped the isolates in subclusters demonstrating relatively low intraspecific genetic variability. Moreover, RAPD pattern analysis yielded clusters which did not correspond to the groups discriminated by vegetative compatibility tests performed by a previous investigation on the same population. The findings of this research pose the question of whether somatic incompatibility, which involves an undefined number of genes and alleles per gene, might still be considered an effective tool for the epidemiological studies of A. gallica, whereas molecular analyses are more useful for assessing genomic variation within the species.
Changes in Phenolics, Polyphenol Oxidase and its Isoenzyme Patterns in Relation to Resistance in Taro against Phytophthora colocasiae
Authors: Sahoo Manas Ranjan , Kole Paresh Chandra , Dasgupta Madhumita , Mukherjee Archana
Published: September 2008

The effect of Phytophthora leaf blight disease, caused by Phytophthora colocasiae Raciborski, on the accumulation of phenolics and polyphenol oxidase (PPO) activity in ex vitro plants was studied in three resistant (DP‐25, Duradim and Jhankri) and one susceptible (N‐118) genotypes of taro [Colocasia esculenta (L). Schott]. The inoculation of taro leaves with P. colocasiae spores resulted in a quantitative change in both biochemical parameters and induction of PPO isoforms in resistant genotypes. The amount of phenolics was increased owing to blight by 68.02%, 58.87%, 52.67% and 11.50% in DP‐25, Duradim, Jhankri and N‐118, respectively. The per cent increase in PPO under stress over non‐stress condition was also highest in DP‐25 (49.14%) followed by Duradim (41.56%), Jhankri (40.55%) and N‐118 (17.08%). The resistant genotypes showed higher activity of PPO as compared with susceptible ones, which was reflected through its banding pattern in isoenzyme analysis, detecting four different isoforms. The intensity of the bands was higher in the resistant genotypes than in susceptible N‐118. The appearance of high intensity bands and/or reduction in the intensity of particular isoform(s) in the zymograms of all the three resistant taro genotypes studied, led to the apparent conclusion of linking PPO isoenzyme expression with blight resistance in taro. The blight incidence (per cent leaf infection and leaf area infection) was lower in the resistant genotypes than in susceptible, N‐118. The yield reduction owing to blight was below 20% in DP‐25, Jhankri and Duradim, while the same was more than 40% in N‐118. The phenolics and PPO activity was negatively correlated with disease incidence and yield reduction owing to blight. Based on the results of disease incidence, biochemical contents and yield, the pattern of stress tolerance was DP‐25 > Duradim > Jhankri > N‐118. The studied parameters, i.e. phenolics and PPO could be used as biochemical markers for leaf blight stress tolerance studies in taro.
A Quantitative Polymerase Chain Reaction Assay for the Detection of Polyscytalum pustulans, the Cause of Skin Spot Disease of Potato
Authors: Lees A. K. , Sullivan L. , Cullen D. W.
Published: September 2008

Skin spot disease of potato caused by the pathogen Polyscytalum pustulans is likely to become more important with the withdrawal of 2‐aminobutane as a fungicide, and new methods of control will need to be found. As part of a disease control strategy, it will be necessary to study the disease in more detail, to utilize host resistance and to identify stocks where problems are likely to arise. Existing methods for the detection and quantification of P. pustulans are time‐consuming and require specific expertise. Real‐time PCR assays have been developed for many pathogens of potato and have subsequently been used as tools for the study of the epidemiology and control of disease. The development of a real‐time PCR assay for the detection and quantification of P. pustulans is described. The specificity of the assay was demonstrated and detection was shown to be reliable at levels as low as 20–250 fg/μl DNA, (equivalent to 60–680 pg DNA/g) in soil and on symptomless tubers at attogram (ag) levels. These values are in line with previously developed tests.
ANGIOTENSIN II‐MEDIATED VASODILATION IS REDUCED IN ADULT SPONTANEOUSLY HYPERTENSIVE RATS DESPITE ENHANCED EXPRESSION OF AT2 RECEPTORS
Authors: Ognibene DT , Oliveira PRB , Marins de Carvalho LCR , Costa CA , Espinoza LA , Criddle DN , Tano T , Soares de Moura R , Resende AC
Published: September 2008

The vasodilator action of angiotensin (Ang) II has not yet been demonstrated in spontaneously hypertensive rats (SHR), nor have any possible changes in this response during the development of hypertension.

In the present study, the vasodilator effect of AngII was evaluated in the rat isolated, preconstricted mesenteric arterial bed (MAB) from 6‐ (young) and 24‐week‐old (adult) SHR and compared with effects on MAB from age‐matched normotensive rats (control).

Angiotensin II (10–300 nmol) induced vasodilation in noradrenaline (NA)‐preconstricted MAB that was greater in vessels from young compared with adult rats in both the control and SHR groups. Angiotensin II‐induced vasodilation was reduced by the angiotensin AT2 receptor antagonist PD 123319 (10 µmol/L), the angiotensin‐(1–7) receptor antagonist A779 (1 µmol/L) and the bradykinin B2 receptor antagonist HOE‐140 (0.01 µmol/L), but not by the AT1 receptor antagonist losartan (30 µmol/L). Expression of AT2 receptors was weak in vessels from adult control rats compared with that in young control rats, whereas in young SHR AT2 receptor expression was increased compared with that in young control rats. This increased expression of AT2 receptors was maintained in adult SHR and there was no significant difference in AT2 receptor expression between young and old SHR.

The findings of the present suggest that AngII induces an AT2 receptor‐mediated vasodilator effect in the MAB via activation of angiotensin‐(1–7) and bradykinin receptors, an action that is reduced in adult control rats and adult SHR. In adult control rats, the attenuated response of AngII is probably due to endothelial dysfunction and reduced expression of AT2 receptors, whereas in adult SHR it is associated with endothelial dysfunction alone. Increased expression of AT2 receptors in SHR may represent a counteracting response for modulating blood pressure.
MicroRNA‐320 EXPRESSION IN MYOCARDIAL MICROVASCULAR ENDOTHELIAL CELLS AND ITS RELATIONSHIP WITH INSULIN‐LIKE GROWTH FACTOR‐1 IN TYPE 2 DIABETIC RATS
Authors: Wang XH , Qian RZ , Zhang W , Chen SF , Jin HM , Hu RM
Published: September 2008

The aim of the present study was to determine the role of myocardial microvascular endothelial cells (MMVEC) in impaired angiogenesis of type 2 diabetic Goto‐Kakizaki (GK) rats.

A microRNA (miRNA) microarray was used to assess miRNA expression in MMVEC from GK and Wistar rats. Upregulation of miRNA‐320 was observed in MMVEC from GK rats using real‐time reverse transcription–polymerase chain reaction (RT‐PCR).

So far, nine miRNAs have been reported to target angiogenic factors and/or receptors, including kinase insert domain containing receptor (Flk‐1), insulin‐like growth factor 1 (IGF‐1) and insulin‐like growth factor 1 receptor (IGF‐1R). The predicted genes targeted by miR‐320 include Flk‐1, IGF‐1 and IGF‐1R. Western blot analysis and RT‐PCR were used to analyse the protein and mRNA expression, respectively, of the putative genes IGF‐1 and IGF‐1R. The expression of IGF‐1 and IGF‐1R proteins decreased significantly in diabetic MMVEC. However, the expression of IGF‐1 mRNA increased rather than decreased. The mRNA expression of IGF‐1R did not differ significantly between diabetic and control MMVEC.

Transfection of an miR‐320 inhibitor into MMVEC from GK rats confirmed that miR‐320 impaired angiogenesis. The proliferation and migration of diabetic MMVEC improved after transfection of the miR‐320 inhibitor. In addition, the miR‐320 inhibitor significantly increased the expression of IGF‐1 protein, but had no effect on the expression of IGF‐1R.

Eleven miRNAs were upregulated in MMVEC from GK rats compared with those in Wistar rats: let‐7e, miR‐129, miR‐291‐5p, miR‐320, miR‐327, mir‐333, miR‐363–5p, miR‐370, miR‐494, miR‐503 and miR‐664.

The results indicate that upregulation of miR‐320 in MMVEC from GK rats may be responsible for the inconsistency between the expression of IGF‐1 protein and mRNA and therefore related to impaired angiogenesis in diabetes. Transfection of an miR‐320 inhibitor may be a therapeutic approach for the treatment of impaired angiogenesis in diabetes.
DIVERSITY OF GLUTATHIONE S‐TRANSFERASE OMEGA 1 (A140D) AND 2 (N142D) GENE POLYMORPHISMS IN WORLDWIDE POPULATIONS
Authors: Takeshita Haruo , Fujihara Junko , Takastuka Hisakazu , Agusa Tetsuro , Yasuda Toshihiro , Kunito Takashi
Published: September 2008

Glutathione S‐transferase class omega (GSTO) 1 and 2 are members of the glutathione‐S‐transferase family, which uses glutathione in the process of the biotransformation of drugs, xenobiotics and oxidative stress. Associations with the age‐at‐onset of Alzheimer's and Parkinson's diseases have been shown in the genetic polymorphism of GSTO1 and GSTO2.

In the present study, the frequencies of GSTO1*A140D and GSTO2*N142D in Ovambos (n = 163), Turks (n = 194), Mongolians (n = 243) and Japanese (n = 102) were investigated and compared with findings from other studies. Detection of these single nucleotide polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism analysis.

The allele frequencies of these polymorphisms in Ovambos, Turks, Mongolians and Japanese were 0.040, 0.085, 0.128 and 0.108, respectively, for GSTO1*A140D and 0.583, 0.219, 0.173 and 0.216, respectively, for GSTO2*N142D. Ovambos showed the lowest allele frequency of GSTO1*A140D. Conversely, Africans, including Ovambos, showed higher allele frequencies of GSTO2*N142D than Caucasians and Asians.

The existence of a certain genetic heterogeneity in the worldwide distribution of these two polymorphisms is revealed in the present study.
METHODS FOR STUDYING THE PHYSIOLOGY OF KIDNEY OXYGENATION
Authors: Evans Roger G , Gardiner Bruce S , Smith David W , O’Connor Paul M
Published: September 2008

An improved understanding of the regulation of kidney oxygenation has the potential to advance preventative, diagnostic and therapeutic strategies for kidney disease. Here, we review the strengths and limitations of available and emerging methods for studying kidney oxygen status.

To fully characterize kidney oxygen handling, we must quantify multiple parameters, including renal oxygen delivery (DO2) and consumption (VO2), as well as oxygen tension (Po2). Ideally, these parameters should be quantified both at the whole‐organ level and within specific vascular, tubular and interstitial compartments.

Much of our current knowledge of kidney oxygen physiology comes from established techniques that allow measurement of global kidney DO2and VO2, or local tissuePo2. When used in tandem, these techniques can help us understand oxygen mass balance in the kidney.Po2can be resolved to specific tissue compartments in the superficial cortex, but not deep below the kidney surface. We have limited ability to measure local kidney tissue DO2and VO2.

Mathematical modelling has the potential to provide new insights into the physiology of kidney oxygenation, but is limited by the quality of the information such models are based on.

Various imaging techniques and other emerging technologies have the potential to allowPo2mapping throughout the kidney and/or spatial resolution ofPo2in specific renal tissues, even in humans. All currently available methods have serious limitations, but with further refinement should provide a pathway through which data obtained from experimental animal models can be related to humans in the clinical setting.
Using a surveillance system to identify and treat newly acquired hepatitis C infection
Authors: Walsh Nick , Lim Megan , Hellard Margaret
Published: September 2008

Background and Aim:  Hepatitis C treatment uptake in Australia is low. We describe the rate of acute hepatitis C treatment in the Australian state of Victoria by linking the centralized passive notifications system for hepatitis C with the Australian Trial in Acute Hepatitis C (ATAHC), a nationwide clinical trial aimed at providing people with newly acquired hepatitis C with 24 weeks' pegylated interferon monotherapy.

Methods:  Mandatory notifications of clinical or laboratory evidence of hepatitis C were further investigated for evidence of newly acquired infection. Followed‐up individuals were then screened for eligibility for the ATAHC study (which included documented hepatitis C antibody positivity within the previous 6 months) and offered acute hepatitis C treatment if this was the case. We examined the first 18 months of the recruitment.

Results:  A total of 4591 hepatitis C cases were notified with 414 (9%) of these flagged as being potentially newly acquired. Through follow‐up of doctors and patients, 160 of these were confirmed as newly acquired; 87 of these 160 (54%) were potentially eligible for ATAHC and were referred to ATAHC researchers. Fourteen (16%) were successfully enrolled in ATAHC. Eight individuals commenced acute hepatitis C treatment during this period.

Conclusion:  The use of hepatitis C surveillance system has been successful in identifying cases of newly acquired hepatitis C which are often difficult to identify in a clinical setting. In addition, marginalized patients who may otherwise never have been referred to a clinic are able to access hepatitis C treatment and specialist services. Despite this, only eight out of 87 eligible individuals (9%) began acute hepatitis C treatment.
Epidemiological study of hepatitis E virus infection in the general population of Okinawa, Kyushu, Japan
Authors: Toyoda Kazuhiro , Furusyo Norihiro , Takeoka Hiroaki , Murata Masayuki , Sawayama Yasunori , Hayashi Jun
Published: September 2008

Background and Aim:  The aim of this study was to investigate the prevalence of hepatitis E virus (HEV) infection in the general population of Japan by determining presence of the antibody to HEV (anti‐HEV).

Methods:  The prevalence of HEV infection was determined by positivity of serum antibody to HEV (anti‐HEV).

Results:  On retrospective analysis, a significant decrease in anti‐HEV prevalence was found in Okinawa healthy residents from 1995 (15.8%) to 2005 (5.5%) (P < 0.0001). In 2005, the anti‐HEV prevalence was significantly higher in Okinawa wild boar hunters (25.3%) than in the residents (male 7.7% and female 4.1%) (P < 0.0001). A significant difference was found in the history of consumption of undercooked or raw boar meat between anti‐HEV positive and negative hunters (100% vs 64.3%) (P = 0.0018).

Conclusions:  In conclusion, the anti‐HEV prevalence has decreased in the residents of this area, but HEV infection has continued at a high rate in the hunters through the custom of eating undercooked or raw boar meat.
Endoscopic ultrasound guided fine needle aspiration of solid pancreatic lesions: Performance and outcomes
Authors: Fisher Leon , Segarajasingam Dev Shankar , Stewart Colin , Deboer W Bastiaan , Yusoff Ian Fuad
Published: September 2008

Background and Aim:  We report our single‐centre experience with endoscopic ultrasound guided fine needle aspiration (EUS‐FNA) of solid pancreatic lesions with regard to clinical utility, diagnostic accuracy and safety.

Methods:  We prospectively reviewed data on 100 consecutive EUS‐FNA procedures performed in 93 patients (54 men, mean age 60.6 ± 12.9 years) for evaluation of solid pancreatic lesions. Final diagnosis was based on a composite standard: histologic evidence at surgery, or non‐equivocal malignant cytology on FNA and follow‐up. The operating characteristics of EUS‐FNA were determined.

Results:  The location of the lesions was pancreatic head in 73% of cases, the body in 20% and the tail in 7%. Mean lesion size was 35.1 ± 12.9 mm. The final diagnosis revealed malignancy in 87 cases, including adenocarcinomas (80.5%), neuroendocrine tumours (11.5%), lymphomas (3.4%) and other types (4.6%). The FNA findings were: 82% interpreted as malignant cytology, 1% as suspicious for neoplasia, 1% as atypical, 7% as benign process and 9% as non‐diagnostic. No false‐positive results were observed. There was a false‐negative rate of 5%. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 94.3%, 100%, 100%, 72.2% and 95%, respectively. In 23 (88.5%) of 26 aspirated lymph nodes malignancy was found. Minor complications occurred in two patients.

Conclusions:  Our experience confirms that EUS‐FNA in patients with suspected solid pancreatic lesions is safe and has a high diagnostic accuracy. This technique should be considered the preferred test when a cytological diagnosis of a pancreatic mass lesion is required.
Emergence of adefovir‐resistant mutants after reversion to YMDD wild‐type in lamivudine‐resistant patients receiving adefovir monotherapy
Authors: Kwon Hyeok Choon , Cheong Jae Youn , Cho Sung Won , Choi Jae Myoung , Hong Sun Pyo , Kim Soo‐Ok , Yoo Wang Don
Published: September 2008

Background:  To evaluate the effect of reversion to YMDD wild‐type on emergence of adefovir (ADV)‐resistant mutation and antiviral activity of ADV in lamivudine (LAM)‐ resistant patients.

Methods:  We determined YMDD mutations and ADV‐resistant mutations before and every 3 months during ADV monotherapy in 33 LAM‐resistant patients using the restriction fragment mass polymorphism (RFMP) method.

Results:  Reversion to pure YMDD wild‐type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV‐resistant mutations at 48 weeks of therapy. Adefovir‐resistant mutants emerged in all patients after reversion to YMDD wild‐type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild‐type HBV (−3.1 log10 copies/mL vs−3.4 log10 copies/mL, P > 0.05).

Conclusions:  ADV‐resistant mutations emerged after reversion to YMDD wild‐type in LAM‐resistant patients who received ADV monotherapy. Thus, ADV add‐on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance.
Is there yet any place for reagent strips in diagnosing spontaneous bacterial peritonitis in cirrhotic patients? An accuracy and cost‐effectiveness study in Brazil
Authors: De Araujo Alexandre , De Barros Lopes Antônio , Trucollo Michalczuk Matheus , Stifft Jonathas , Nardelli Enzo , Escobar Gabriela , Rossi Gabriela , Álvares‐da‐Silva Mário Reis
Published: September 2008

Background:  Diagnosis of spontaneous bacterial peritonitis (SBP) is currently based on ascitic cell counting, but there is a need for a more simple and rapid diagnostic tool. The objectives of this study are to evaluate the accuracy of reagent strips in diagnosing SBP and compare their costs with total and differential cell counts.

Patients and Methods:  71 cirrhotic in‐ and outpatients were consecutively included (159 samples). Spontaneous bacterial peritonitis was defined as neutrophil cells ≥ 250/µL. The cutoff values for each reagent strip were defined by a receiver operating characteristic (ROC) curve. Sensitivity (S), Specificity (Sp), Positive and Negative Predictive Values (PPV and NPV), Accuracy (Ac) and cost‐effectiveness (US$) in comparison to cell count exam were calculated.

Results:  Spontaneous bacterial peritonitis was diagnosed in 17 patients (23.9%), 11 of them with positive culture (64.7%). The best cutoff points found in ROC curves were 1+ for Multistix 10 SG and ca. 75 for Choiceline 10 (Multistix 10 SG S = 80%, Sp = 98.5%, PPV = 90.9%, NPV = 96.2%, Ac = 95%; Choiceline 10 S = 76.9%, Sp = 97.7%, PPV = 87%, NPV = 95.6%, Ac = 94%). In terms of cost‐effectiveness by cost/accuracy, cell count was 41.5, Multistix 10 SG 0.57, and Choiceline 10, 0.19 (P < 0.001).

Conclusion:  Reagent strips are a useful tool for diagnosing SBP in cirrhotic patients, but they have some limitations. Strips are especially indicated when total and differential cell counts are not quickly available or sometimes unavailable. They are also indicated as screening test in emergency rooms to anticipate the diagnosis of SBP and allow its early treatment. It's an interesting option in developing countries.
The alteration of enterochromaffin cell, mast cell, and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors
Authors: Lee Kwang Jae , Kim Yeong Bae , Kim Jang Hee , Kwon Hoek Chun , Kim Dong Kyu , Cho Sung Won
Published: September 2008

Background/Aims:  Psychological factors and subtle histopathological changes have been implicated in irritable bowel syndrome (IBS). The aims of the present study were to investigate whether the numbers of enterochromaffin (EC) cells, mast cells, and lamina propria T lymphocytes are altered in IBS, and evaluate the relationship of such alterations with psychological factors.

Methods:  Forty‐two consecutive IBS patients (M : F = 17:25, mean age 48 years) fulfilling the Rome III criteria and twelve asymptomatic healthy controls underwent rectal biopsy. Immunostaining was performed for EC cells, mast cells, and lamina propria T lymphocytes.

Results:  The IBS group included five post‐infectious (PI) IBS and 37 non‐PI IBS patients. Significantly more EC cells, mast cells and lamina propria T lymphocytes were observed in PI IBS patients. Mast cells significantly increased in non‐PI IBS‐D (diarrhea) patients, but not in non‐PI IBS‐C (constipation) and non‐PI IBS‐M (mixed) patients. Enterochromaffin cell numbers were not significantly altered in non‐PI IBS patients. Anxiety and depression scores did not differ between IBS patients with and without abnormal increase in EC cell or mast cell counts, defined as more than the mean of controls + 2 standard deviations. Enterochromaffin cell, mast cell, or lamina propria T lymphocyte numbers were poorly correlated with anxiety and depression scores in the IBS group.

Conclusions:  Enterochromaffin cells, mast cells, and lamina propria T lymphocytes significantly increase in PI IBS, whereas only mast cells significantly increase in non‐PI IBS‐D. Such histopathological changes do not seem to be directly associated with psychological factors.
Perindopril attenuates tubular hypoxia and inflammation in an experimental model of diabetic nephropathy in transgenic Ren‐2 rats
Authors: WIGGINS KATHRYN J , TIAUW VICTORIA , ZHANG YUAN , GILBERT RICHARD E , LANGHAM ROBYN G , KELLY DARREN J
Published: September 2008

Background:  Renal hypoxia plays a role in the development of diabetic nephropathy, and may be mediated by overactivity of the renin‐angiotensin‐aldosterone system (RAAS). In this study the localization of cellular hypoxia in an experimental model of diabetic nephropathy was assessed, and the effect of the angiotensin‐converting enzyme inhibitor perindopril on hypoxia evaluated.

Methods:  Female Sprague–Dawley rats heterozygous for the Ren‐2 gene were randomized to three groups (n = 8 per group) – controls, diabetes or diabetes + perindopril. Diabetes was induced by injection of streptozotocin at 6 weeks of age. Perindopril was administered at a dose of 2 mg/kg daily from 6 weeks. Subjects were culled after 16 weeks. Areas of tissue hypoxia were localized using immunohistochemistry to detect pimonidazole uptake.

Results:  Diabetic rat kidneys were characterized by increases in tubulointerstitial collagen deposition compared with controls. Tubular hypoxia was significantly greater in diabetic rats, indicated by a 2.5‐fold increase in the proportional area of pimonidazole immunostaining (P < 0.001). Immunohistochemical staining for pimonidazole co‐localized with osteopontin, and was associated with higher numbers of ED‐1‐positive cells (macrophages) within the tubulointerstitium. Treatment with perindopril ameliorated structural changes of diabetic nephropathy and reduced the amount of pimonidazole and ED‐1 immunostaining to levels similar to that of controls.

Conclusion:  In diabetic Ren‐2 rats the development of diabetic nephropathy was associated with tubular hypoxia. Co‐localization of osteopontin with hypoxic cells suggests that tubular hypoxia may be involved in the pathogenesis of diabetic nephropathy. The degree of hypoxia and fibrosis was attenuated by treatment with perindopril.
Corticospinal inhibition of transmission in propriospinal‐like neurones during human walking
Authors: Iglesias Caroline , Nielsen Jens Bo , Marchand‐Pauvert Véronique
Published: September 2008

It is crucial for human walking that muscles acting at different joints are optimally coordinated in relation to each other. This is ensured by interaction between spinal neuronal networks, sensory feedback and supraspinal control. Here we investigated the cortical control of spinal excitation from ankle dorsiflexor afferents to quadriceps motoneurones mediated by propriospinal‐like interneurones. During walking and tonic contraction of ankle dorsiflexors and knee extensors while standing [at matched electromyography (EMG) levels], the effect of common peroneal nerve (CPN) stimulation on quadriceps motoneurones was tested by assessing averaged and rectified EMG activity, H‐reflexes [evoked by femoral nerve (FN) stimulation] and motor evoked potentials (MEPs) produced by transcranial magnetic stimulation (TMS). The biphasic EMG facilitation (CPQ‐reflex) produced by isolated CPN stimulation was enhanced during walking, and when CPN stimulation was combined with FN or TMS, the resulting H‐reflexes and MEPs were inhibited. The CPQ‐reflex was also depressed when CPN stimulation was combined with subthreshold TMS. The peripheral (in CPN and FN) and corticospinal volleys may activate inhibitory non‐reciprocal group I interneurones, masking spinal excitations to quadriceps motoneurones mediated by propriospinal‐like interneurones. It is proposed that the enhanced CPQ‐reflex produced by isolated CPN stimulation during walking cannot be fully explained by an increase in corticospinal and peripheral inputs, but is more likely caused by central facilitation of the propriospinal‐like interneurones from other sources. The corticospinal control of non‐reciprocal group I interneurones may be of importance for reducing reflex activity between ankle dorsiflexors and quadriceps during walking when not functionally relevant.