bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic identification of Mycobacterium tuberculosis by Gaussian mixture models
Authors: FORERO M. G. , CRISTÓBAL G. , DESCO M.
Published: August 2006

Tuberculosis and other kinds of mycobacteriosis are serious illnesses for which early diagnosis is critical for disease control. Sputum sample analysis is a common manual technique employed for bacillus detection but current sample‐analysis techniques are time‐consuming, very tedious, subject to poor specificity and require highly trained personnel. Image‐processing and pattern‐recognition techniques are appropriate tools for improving the manual screening of samples. Here we present a new technique for sputum image analysis that combines invariant shape features and chromatic channel thresholding. Some feature descriptors were extracted from an edited bacillus data set to characterize their shape. They were statistically represented by using a Gaussian mixture model representation and a minimal error Bayesian classification procedure was employed for the last identification stage. This technique constitutes a step towards automating the process and providing a high specificity.
Stress distribution in a post‐restored tooth using the three‐dimensional finite element method
Authors: BOSCHIAN PEST L. , GUIDOTTI S. , PIETRABISSA R. , GAGLIANI M.
Published: August 2006

summary  Clinicians are opting ever more frequently for restorative materials which have an elastic modulus similar to that of dentin when reconstructing endodontically treated teeth. Metallic posts, which are capable of causing dangerous and non‐homogenous stresses in root dentin, are slowly being abandoned. Ideal posts may be those made of various types of fibre (carbon, mineral and glass) and which are adhesively luted into the canal. Among the different methods for evaluating the mechanical behaviour of posts in root canals (progressive loads and photo‐elastic technique) the finite element method (FEM) presents many advantages. The aim of this paper is to evaluate, utilizing three‐dimensional analysis of the finite elements, what the effect of material rigidity, depth of insertion and post diameter could be on the stress distribution in the different components of the single tooth‐post‐core reconstruction unit. The results of the FEM analyses, expressed as the distribution of Von Mises stress values, has allowed us to conclude that (i) fibreglass‐reinforced composite distributes stress better than titanium alloy or stainless steel; (ii) fibreglass‐reinforced composite posts should be inserted as deeply as possible (but maintaining 5–6 mm of gutta‐percha apical seal); (iii) fibreglass‐reinforced composite post diameter does not affect stress distribution, therefore, as much radicular dentin as possible should be preserved.
Structure and reactivity of Trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate
Authors: Dawson Alice , Gibellini Federica , Sienkiewicz Natasha , Tulloch Lindsay B. , Fyfe Paul K. , McLuskey Karen , Fairlamb Alan H. , Hunter William N.
Published: August 2006

The protozoan Trypanosoma brucei has a functional pteridine reductase (TbPTR1), an NADPH‐dependent short‐chain reductase that participates in the salvage of pterins, which are essential for parasite growth. PTR1 displays broad‐spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of antifolates for treatment of trypanosomiasis. Catalytic properties of recombinant TbPTR1 and inhibition by the archetypal antifolate methotrexate have been characterized and the crystal structure of the ternary complex with cofactor NADP+ and the inhibitor determined at 2.2 Å resolution. This enzyme shares 50% amino acid sequence identity with Leishmania major PTR1 (LmPTR1) and comparisons show that the architecture of the cofactor binding site, and the catalytic centre are highly conserved, as are most interactions with the inhibitor. However, specific amino acid differences, in particular the placement of Trp221 at the side of the active site, and adjustment of the β6‐α6 loop and α6 helix at one side of the substrate‐binding cleft significantly reduce the size of the substrate binding site of TbPTR1 and alter the chemical properties compared with LmPTR1. A reactive Cys168, within the active site cleft, in conjunction with the C‐terminus carboxyl group and His267 of a partner subunit forms a triad similar to the catalytic component of cysteine proteases. TbPTR1 therefore offers novel structural features to exploit in the search for inhibitors of therapeutic value against African trypanosomiasis.
Regression stage senile plaques in the natural course of Alzheimer’s disease
Authors: Oide T. , Kinoshita T. , Arima K.
Published: August 2006

Resolution process of cerebroparenchymal amyloid β‐protein (Aβ) deposition has become of increasing interest in the light of recent advance in the Aβ‐vaccination therapy for Alzheimer’s disease (AD). However, the neuropathological features of degraded and disappearing senile plaque remain poorly characterized, especially in the natural course of the disease. To clarify the natural removal processes of Aβ burden in the brain with AD, we devised a triple‐step staining method: Bodian for dystrophic neurites, anti‐glial fibrillary acidic protein for astrocytes, and anti‐Aβ. We thus examined 24 autopsied AD brains. A novel form of senile plaques, termed ‘remnant plaques’, was identified. Remnant plaques were characterized by mesh‐like astroglial fibrils within the entire plaque part, Aβ deposit debris exhibiting weak Aβ immunoreactivity, and only a few slender dystrophic neurites. In remnant plaques, amyloid burden was apparently decreased. The density of remnant plaques increased significantly with disease duration. Dual‐labelling immunohistochemistry revealed many Aβ‐immunoreactive granules in astrocytes and a modest number in microglia, both of which accumulated in senile plaques. We consider amyloid deposits of diffuse and neuritic plaques to be shredded by astrocytic processes from the marginal zone of plaques, and to gradually disintegrate into smaller compartments. Cerebroparenchymal Aβ deposits undergo degradation. After a long‐standing resolution process, diffuse and neuritic plaques may finally proceed to remnant plaques. Astrocytes are actively engaged in the natural Aβ clearance mechanism in advanced stage AD brains, which may provide clues for developing new therapeutic strategies for AD.
Cerebral calpain in fatal falciparum malaria
Authors: Medana I. M. , Day N. P. , Hien T. T. , Mai N. T. H. , Bethell D. , Phu N. H. , Turner G. D. , Farrar J. , White N. J. , Esiri M. M.
Published: August 2006

Disruption of axonal transport may represent a final common pathway leading to neurological dysfunction in cerebral malaria (CM). Calpains are calcium (Ca2+)‐activated cysteine proteases which have been implicated in axonal injury in neurological diseases of various aetiologies. In this study we examined the association between µ‐ and m‐calpain, the specific inhibitor calpastatin, and axonal injury in post mortem brain tissue from patients who died from severe malaria. Calpains were associated with axons labelled for the β‐amyloid precursor protein that detects impaired axonal transport. Elevated levels of calpastatin were rarely observed in injured axons. There were increased numbers of neurones with µ‐calpain in the nuclear compartment in severe malaria cases compared with non‐neurological controls, and increased numbers of glia with nuclear µ‐calpain in CM patients compared with non‐CM malaria cases and non‐neurological controls. There was marked redistribution of calpastatin in the sequestered Plasmodium falciparum‐infected erythrocytes. Responses specific to malaria infection were ascertained following analysis of brain samples from fatal cases with acute axonal injury, HIV encephalitis, and progressive multifocal leucoencephalopathy. Our findings implicate a role for calpains in the modulation of disease progression in CM.
Albino corpus cardiacum extracts induce morphometric gregarization in isolated albino locusts, Locusta migratoria, that are deficient in corazonin
Authors: TANAKA SEIJI
Published: August 2006

Abstract The neuropeptide [His7]‐corazonin, present in the central nervous system and corpus cardiacum, is known to mimic a ‘gregarizing’ effect on phase‐related morphometric ratios (hind femur length/maximum head width and fore wing length/hind femur length) when injected into locusts reared in isolation. However, an albino strain is known to exhibit phase‐specific changes in these ratios in response to rearing density, although it is deficient in [His7]‐corazonin. To examine whether there is a second factor responsible for this phenomenon, perhaps a corazonin‐like factor that has lost its dark‐colour inducing activity, methanol extracts of corpora cardiaca taken from crowd‐reared albino nymphs of Locusta migratoria are injected into isolated‐reared second‐stadium albino nymphs and reared to adults in isolation. The hind femur length/maximum head width and fore wing length/hind femur length ratios are significantly different from those of control oil‐injected counterparts, and shift significantly towards the values typical for crowd‐reared gregarized individuals. The results indicate that the corpora cardiaca contain a factor similar to [His7]‐corazonin, although it has no dark‐colour inducing activity.
Specialized ‘dauciform’ roots of Cyperaceae are structurally distinct, but functionally analogous with ‘cluster’ roots
Authors: SHANE MICHAEL W. , CAWTHRAY GREGORY R. , CRAMER MICHAEL D. , KUO JOHN , LAMBERS HANS
Published: August 2006

When grown in nutrient solutions of extremely low [P] (≤1.0 µm), the sedge Schoenus unispiculatus Benth. (Cyperaceae) develops dauciform roots, which are short and carrot shaped, and produce dense numbers of long root hairs. It has been suggested that dauciform roots of monocotyledonous sedges function to acquire P from nutrient‐poor, P‐fixing soils in a manner similar to that of cluster (proteoid) roots developed by some dicotyledonous species, but without evidence to substantiate this claim. To elucidate the ecophysiological role of dauciform roots, we assessed carboxylate exudation, internal carboxylate and P concentrations and O2 uptake rates during dauciform root development. We showed that O2 consumption was fastest [9 nmol O2 g−1 fresh mass (FM) s−1] and root [P] greatest (0.4 mg P g−1 FM) when dauciform roots were young and rapidly developing. Citrate was the most abundant carboxylate in root tissues at all developmental stages, and was most concentrated (22.2 µmol citrate g−1 FM) in young dauciform roots, decreasing by more than half in mature dauciform roots. Peak citrate‐exudation rates (1.7 nmol citrate g−1 FM s−1) occurred from mature dauciform roots, and were approximately an order of magnitude faster than those from roots of species without root clusters, and similar to those of mature proteoid (cluster) roots of Proteaceae. Both developing and mature dauciform roots had the capacity to acidify (but not alkalinize) the rhizosphere. Anatomical studies showed that epidermal cells in dauciform roots were greatly elongated in the transverse plane; epidermal cells of parent roots were unmodified. Although structurally distinct, the physiology of dauciform roots in sedges appears to be analogous to that of proteoid roots of Proteaceae and Fabaceae, and hence, dauciform roots would facilitate access to sorbed P and micronutrients from soils of low fertility.
Phosphoenolpyruvate carboxylase genes in C3, crassulacean acid metabolism (CAM) and C3/CAM intermediate species of the genus Clusia: rapid reversible C3/CAM switches are based on the C3 housekeeping gene
Authors: VAASEN ANJA , BEGEROW DOMINIK , HAMPP RÜDIGER
Published: August 2006

The genus Clusia includes species that exhibit either the C3 or crassulacean acid metabolism (CAM) mode of photosynthesis, or those that are able to switch between both modes according to water availability. In order to screen for species‐specific genetic variability, we investigated the key carboxylase for CAM, phosphoenolpyruvate carboxylase (PEPC). Sequence analysis of DNA isolated from the obligate CAM species, Clusia hilariana, the obligate C3 species, Clusia multiflora, and an intermediate species that can switch between C3 and CAM photosynthesis, Clusia minor, revealed three different isoforms for C. hilariana and one each for the other two species. Sequence alignments indicated that PEPC from the intermediate species had high homology with the C3 protein and with one of CAM plant proteins. These were assumed to constitute ‘housekeeping’ proteins, which can also support CAM in intermediate species. The other two isoforms of the CAM plant C. hilariana were either CAM‐specific or showed homologies with PEPC from roots. Phylogenetic trees derived from neighbour‐joining analysis of amino acid sequences from 13 different Clusia species resulted in two distinct groups of plants with either ‘housekeeping’ PEPC only, or additionally CAM‐related isoforms. Only C. hilariana showed the third, probably root‐specific isoform. The high homology of the PEPC from the intermediate species with the C3 protein indicates that for the reversible transition from the C3 to CAM mode of photosynthesis, the C3 type of PEPC is sufficient. Its expression, however, is strongly increased under CAM‐inducing conditions. The use of the C3 isoform could have facilitated the evolution of CAM within the genus, which occurred independently for several times.
Mosaic maternal uniparental isodisomy for chromosome 7q21‐qter
Authors: Reboul M‐P , Tandonnet O , Biteau N , Belet‐de Putter C , Rebouissoux L , Moradkhani K , Vu PY , Saura R , Arveiler B , Lacombe D , Taine L , Iron A
Published: August 2006

Uniparental disomy (UPD) for several human chromosomes is associated with clinical abnormalities. We report the case of a 2‐year‐old boy with severe intrauterine and post‐natal growth retardation (IUGR/PNGR) and highly variable sweat chloride concentrations. The patient was identified as heterozygous for the F508del mutation of the CFTR (cystic fibrosis transmembrane conductance regulator) gene. Unexpectedly, the signal corresponding to the maternally inherited F508del allele appeared much more intense than the paternally derived wild allele. Molecular analysis including polymorphic marker studies, microsatellites and single‐nucleotide polymorphisms subsequently showed that the boy was a carrier of a de novo mosaic maternal isodisomy of a chromosome 7 segment while there was a biparental inheritance of the rest of the chromosome. This is the first report of a mosaic partial UPD7. The matUPD7 segment at 7q21‐qter extends for 72.7 Mb. The karyotype (550 bands) of our patient was normal, and fluorescence in situ hybridization with probes mapping around the CFTR gene allowed us to rule out a partial duplication. The detection of this chromosomal rearrangement confirms the hypothesis that the 7q31‐qter segment is a candidate for the localization of human imprinted genes involved in the control of IUGR and PNGR. It also emphasizes the importance of searching for UPD7 in severe, isolated and unexplained IUGR and PNGR.
Cord blood transplantation for adults
Authors: Brunstein Claudio G. , Wagner John E.
Published: August 2006

Allogeneic haematopoietic stem cell transplant has become an import tool for the treatment of high risk and advanced haematological diseases. However, allogeneic transplantation has been limited by the availability of suitable related and unrelated donors. The positive results with umbilical cord blood as an alternative source of haematopoietic stem cells for transplantation in the paediatric setting encouraged studies in adult patients. In adults, however, the progress of cord blood transplantation has been slower, in part limited by the limitation of cell dose. We review here the current state of the art on cord blood transplantation for adults, and discuss some of the newer strategies being pursued in order to improve its safety and efficacy.
A population‐based binational register for monitoring long‐term outcome and possible disease concordance among blood donors and recipients
Authors: Edgren G. , Hjalgrim H. , Tran T. N. , Rostgaard K. , Shanwell A. , Titlestad K. , Jakobsson L. , Gridley G. , Wideroff L. , Jersild C. , Adami J. , Melbye M. , Reilly M. , Nyrén O.
Published: August 2006

Background and Objectives  Even with appropriate donor deferrals and advanced screening tests, the risk of disease transmission through blood transfusion cannot be completely disregarded. Efficient monitoring of possible disease transmission between blood donors and recipients should be an important component of a comprehensive haemovigilance system.

Materials and Methods  We assembled the Scandinavian Donations and Transfusions (SCANDAT) database, with data on virtually all blood donors and recipients who have been registered at least once in any of the computerized local blood bank databases in Sweden and Denmark since the start of computerized registration in 1966. The records of these individuals, with their entire computerized donation and/or transfusion histories and all donor‐component‐recipient connections, were linked to nationwide population and health registers to attain essentially complete follow‐up for up to 36 years regarding reproduction, hospital morbidity, cancer, and death.

Results  After data cleaning, the database contained 1 134 290 blood donors who contributed 15 091 280 records of donations and 1 311 079 recipients who received 11 693 844 transfusions. The data quality in the existing data sources was satisfactory. From the data obtained from local blood banks, 4·6%, 1·6%, and 6·4% of the person, donation, and transfusion records, respectively, had to be discarded after review of the legitimacy of recorded values, and comparisons with independent, external databases.

Conclusion  It is possible to use existing computerized data, collected in routine health care, in haemovigilance systems for monitoring long‐term outcome and disease concordance in blood donors and transfusion recipients.
Use of a (proposed) standard protocol to validate Terumo TSCD‐II connections between dissimilar blood bag tubing
Authors: Nightingale M. J. , Lees B. , Biset R. , Mertens W.
Published: August 2006

Background and Objectives  ISO standards for blood bags do not adequately define and control the dimensions of blood bag transfer tubing. This lack of standardization presents potential difficulties when making sterile connections between the wide range of tubing that has evolved in the absence of such standards. We aim to validate the suitability of the TSCD‐II and provide a minimum standard for assessing the suitability of sterile connections (welds) between dissimilar tubing.

Materials and Methods  The Terumo TSCD‐II was used in this study to connect by hermetic welding seven tubing types with a wide range of dimensions from five suppliers. Thirty sterile connections were made between each combination split between dry/dry, wet/wet and dry/wet connections. Welds were assessed for visual defects, by tensile stress test (TST) and pressure tests.

Results  All welds passed visual inspection and pressure tests. All welds had a minimum tensile strength of greater than 40 N and mean of greater than 45 N.

Conclusion  Successful connections have been made between dissimilar tube types and this work does not support the requirement for ‘tight’ tubing dimensional specifications. We have recommended to the ISO Technical Committee 76 Work Group 1 that ISO 3826‐1 be revised and should include a minimum standard validation protocol for joining dissimilar tubing.
Mycological flora of the Hammams, traditional Turkish bath
Authors: Goksugur Nadir , Karabay Oguz , Kocoglu Esra
Published: August 2006

Traditional Turkish baths, Hammams, occupy a prominent place in public health in history and at present. It is well‐known that baths are major sources of fungal skin infections, but according to our knowledge fungal flora of Turkish Hammams was not defined yet. In Bolu, Turkey, two Hammams were open to public and for detecting fungal flora, we collected 209 samples from different part of floors, tools and screened for the fungal pathogens. From floors of the dressing rooms, Trichophyton rubrum and Candida albicans; from slippers T. rubrum, T. mentagrophytes, Epidermophyton floccosum, Candida albicans and C. tropicalis were isolated. While we could not isolate any dermatophyte species and yeasts from the vicinity of the bath windows and walls of baths, Aspergillus spp. and Penicillium spp. were isolated from the same locations. Samples taken from marble floors of baths, central massage platforms (hottest part of the Hammam) and towels did not show any fungal growth. This report reveals that components of the Turkish Hammams have low risk for fungal contamination as a result of frequent cleaning and environmental high temperature. But shared tools like slippers were found to be an important source of fungal contamination.
Tinea capitis due to Trichophyton rubrum in a 3‐month‐old infant
Authors: Valari M. , Stefanaki C. , Karteri G. , Zarkadi E. , Katsambas A.
Published: August 2006

Tinea capitis as a result of Trichophyton rubrum has very rarely been reported in infants. A 3‐month‐old girl with tinea capitis as a result of T. rubrum is reported. Our patient was treated with a 3‐week course of oral fluconazole, which resulted in clearance of the scalp lesion. To our knowledge this case is the first in the literature in which fluconazole was used to treat T. rubrum tinea capitis in children.
The Influence of Pre‐ and Post‐ovulatory Insemination and Early Pregnancy on the Infiltration by Cells of the Immune System in the Sow Oviduct
Authors: Jiwakanon J , Persson E , Dalin A‐M
Published: August 2006

Contents

The aim of this study was to investigate the influence of pre‐ and post‐ovulatory insemination and early pregnancy on the distribution of immune cells in the oviduct. Eighteen sows were pre‐ovulatory and sixteen sows were post‐ovulatory inseminated and slaughtered at different times, 5–6 h after insemination, 20–25 h and approximately 70 h after ovulation, day 11 and day 19. Immediately after slaughter, oviductal samples of three different segments (isthmus, ampulla and infundibulum) were fixed, embedded in plastic resin and stained with toluidine blue or cryofixed and stored in a freezer at −70°C until analysed by immunohistochemistry (pre‐ovulatory inseminated sows) with an avidin–biotin peroxidase method. Quantitative and qualitative examinations of oviductal epithelium and subepithelial connective tissue were performed by light microscopy. After pre‐ or post‐ovulatory insemination, neutrophils were not observed in the oviductal epithelium from any of the segments or groups. The numbers of intraepithelial lymphocytes of all sows as well as CD2‐ and CD3‐positive cells of the pre‐ovulatory inseminated sows were higher in the infundibulum than in the other segments (p ≤ 0.001). In the subepithelial connective tissue of the pre‐ovulatory inseminated sows, significantly higher numbers of lymphocytes (p ≤ 0.001) and plasma cells (p ≤ 0.001) were found in infundibulum than in isthmus. Neutrophils were found mainly in infundibulum, the number approximately 40 h after pre‐ovulatory insemination was significantly higher (p ≤ 0.05) than in the other groups and segments. Significantly higher numbers of CD2 than CD3‐positive cells were found for all groups and segments. In the subepithelial connective tissue of post‐ovulatory inseminated sows, the numbers of lymphocytes was higher (p ≤ 0.001) at day 19 than up to 50 h after insemination and lower (p ≤ 0.001) in isthmus than in ampulla and infundibulum. Neutrophils were found in infundibulum in almost all groups and the number was significantly higher (p ≤ 0.05) in the infundibulum up to 50 h after insemination than in other segments. In the oviductal epithelium, no influence of insemination was found on the presence of phagocytes, i.e. neutrophils and macrophages, but on lymphocytes. In the infundibular connective tissue, pre‐ovulatory insemination had an effect on neutrophil distribution, indicating an active immune response to insemination in the upper segment. Post‐ovulatory insemination changed the oviductal immune cell pattern.
DELAYED PRECONDITIONING VIA ANGIOTENSIN‐CONVERTING ENZYME INHIBITION: PROS AND CONS FROM AN EXPERIMENTAL STUDY
Authors: Marktanner Ralph , Nacke Peter , Feindt Peter , Hohlfeld Thomas , Schipke Jochen D , Gams Emmeran
Published: August 2006

Bradykinin B2receptor activation confers preconditioning from ischaemic injury. In the present study, we tested whether an angiotensin‐converting enzyme (ACE) inhibitor (captopril) could mediate delayed preconditioning and, thus, cardioprotection.

New Zealand white rabbits received 15 mL infusion of either saline (control group;n = 7) or drugs (0.3 mg/kg captopril (CAP group;n = 7) or 0.3 mg/kg captopril + 0.1 mg/kg HOE 140 (CAPHOE group;n = 7)) via a marginal ear vein over 30 min. After 24 h, hearts were connected to a Langendorff apparatus and buffer perfused. The experimental protocol consisted of 20 min global normothermic hypoxia, followed by 120 min reperfusion.

Compared with baseline, the mean (SEM) contractile state (= dP/dtmax) at 120 min reperfusion was decreased to 42 ± ;23, 72 ± ;16 (*P < 0.05vscontrol) and 49 ± ;22% in the control, CAP and CAPHOE groups, respectively. Early relaxation (= dP/dtmin) was reduced to 55 ± ;28, 73 ± ;15 (*P < 0.05vscontrol) and 52 ± ;19% in the control, CAP and CAPHOE groups, respectively. The estimate for myocardial oxygen consumption (MVO2= rate–pressure product) was decreased to 52 ± ;15, 69 ± ;24 (*P < 0.05vscontrol) and 56 ± ;15% in the control, CAP and CAPHOE groups, respectively. Similarly, coronary flow was decreased in the control, CAP and CAPHOE groups to 49 ± ;20, 67 ± ;18 and 46 ± ;19%, respectively. In contrast, ventricular extrasystoles during reperfusion were significantly elevated in both the CAP and CAPHOE groups (1.3 ± ;0.2 and 1.1 ± ;0.3 /min, respectively) compared with control (0.4 ± ;0.2 /min).

Captopril confers delayed preconditioning against stunning via a B2receptor‐mediated pathway. This pharmacological preconditioning protects against systolic and diastolic stunning, against vascular stunning and preserves cardiac metabolism. In addition to its accepted cardioprotective effects in early preconditioning, captopril should induce delayed preconditioning (e.g. for routine interventional cardiology or in elective cardiac surgery).
PROTECTIVE EFFECTS OF PRAVASTATIN IN MURINE LIPOPOLYSACCHARIDE‐INDUCED ACUTE LUNG INJURY
Authors: Yao Hong‐Wei , Mao Lian‐Gen , Zhu Jian‐Ping
Published: August 2006

The present study was designed to determine whether pravastatin, a 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitor, could attenuate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in BALB/c mice.

Acute lung injury was induced successfully by intratracheal administraiton of LPS (3 mg/g) in BALB/c mice. Pravastatin (3, 10 and 30 mg/kg, i.p.) was administered to mice 24 h prior to and then again concomitant with LPS exposure.

Challenge with LPS alone produced a significant increase in lung index and the wet/dry weight ratio compared with control animals. Pulmonary microvascular leakage, as indicated by albumin content in the bronchoalveolar lavage fluid (BALF) and extravasation of Evans blue dye albumin into lung tissue, was apparently increased in LPS‐exposed mice. Lipopolysaccharide exposure also produced a significant lung inflammatory response, reflected by myeloperoxidase activity and inflammatory cell counts in BALF. Furthermore, histological examination showed that mice exposed to LPS also exhibited prominent inflammatory cell infiltration and occasional alveolar haemorrhage.

Pravastatin (3, 10 or 30 mg/kg, i.p.) produced a significant reduction in multiple indices of LPS‐induced pulmonary vascular leak and inflammatory cell infiltration into lung tissue. Elevated tumour necrosis factor (TNF)‐a levels in lung tissue homogenates of ALI mice were significantly decreased after administration of 10 or 30 mg/kg pravastatin.

These findings confirm significant protection by pravastatin against LPS‐induced lung vascular leak and inflammation and implicate a potential role for statins in the management of ALI. The inhibitory effect of pravastatin was associated with its effect in decreasing TNF‐a.
PRE‐ECLAMPSIA: CONTRIBUTION OF MATERNAL CONSTITUTIONAL FACTORS AND THE CONSEQUENCES FOR CARDIOVASCULAR HEALTH
Authors: Barden Anne
Published: August 2006

Pre‐eclampsia is a serious complication of pregnancy that is potentially life threatening for both the mother and baby. It encompasses a number of abnormalities that may be present in other clinical conditions.

A placenta is essential for the development of pre‐eclampsia and can be important in the pathogenesis of pre‐eclampsia. Normal pregnancy is associated with remodelling of the maternal spiral arteries, which deliver blood to the placental villous space. Remodelling involves invasion by placental cytotrophoblasts that cause the maternal spiral arteries to lose their smooth muscle and become capacitance vessels; this process, known as placentation, is complete by 20 weeks of pregnancy. Poor placentation is associated with small‐for‐gestational‐age fetuses and some cases of pre‐eclampsia. It is thought that poor placentation can result in a hypoxic placenta that releases ‘toxic substances’ into the maternal circulation, contributing to the maternal syndrome. A number of candidate ‘toxic substances’ have been proposed, but none is universally raised in pre‐eclampsia.

Although the placenta is necessary for the development of pre‐eclampsia, the extent to which placental abnormalities contribute to the condition varies. It is becoming apparent that maternal constitutional factors may also be important in this syndrome. Underlying hypertension, diabetes and obesity strongly predispose to pre‐eclampsia. However, a continuum of risk may exist for blood pressure, bodyweight, glucose and lipids, which, in combination with each other and some degree of placental abnormalities, may lead to the development of pre‐eclampsia.

The present review will focus on the maternal constitutional factors that define the metabolic syndrome and examine their contribution to pre‐eclampsia and the long‐term consequences for cardiovascular health.
OBESITY IN CHILDHOOD AND CARDIOVASCULAR RISK
Authors: Burke Valerie
Published: August 2006

Childhood obesity is increasing worldwide and is associated with an increase in cardiovascular risk factors in childhood.

In children, obesity is associated with hypertension, impaired vascular function, dyslipidaemia, atheroma, the metabolic syndrome, type 2 diabetes, systemic inflammation and oxidative stress. Greater risk is associated with clustering of risk factors.

Obesity tracks from childhood to adult life and predicts adverse levels of risk and an increase in cardiovascular end‐points.

Adults who were obese as children have higher rates of obesity and its sequelae: greater intima–media thickness, left ventricular hypertrophy and atherosclerosis. There is greater all‐cause and cardiovascular mortality, as well as a greater risk of stroke, in long‐term follow‐up of obese children.

Genetic and environmental factors contribute to familial aggregation of obesity, with parental obesity as a strong predictor of obesity in children. However, clustering of adverse health‐related behaviours is seen in such families.

Adverse behaviours (smoking, poor dietary choices, less physical activity and greater alcohol intake) also cluster in individuals, suggesting the need for multimodal interventions.

Recognition of families at risk offers opportunities for prevention of obesity in children and decreasing risk in parents.
EXERCISE IS GOOD FOR YOUR BLOOD PRESSURE: EFFECTS OF ENDURANCE TRAINING AND RESISTANCE TRAINING
Authors: Fagard RH
Published: August 2006

Although several epidemiological studies have not observed significant independent relationships between physical activity or fitness and blood pressure, others have concluded that blood pressure is lower in individuals who are more fit or active. However, longitudinal intervention studies are more appropriate for assessing the effects of physical activity on blood pressure.

Previously, we have performed meta‐analyses of randomized controlled trials involving dynamic aerobic endurance training or resistance training. Inclusion criteria were: random allocation to intervention and control; physical training as the sole intervention; inclusion of healthy sedentary normotensive and/or hypertensive adults; intervention duration of at least 4 weeks; availability of systolic and/or diastolic blood pressure; and publication in a peer‐reviewed journal up to December 2003.

The meta‐analysis on endurance training involved 72 trials and 105 study groups. After weighting for the number of trained participants, training induced significant net reductions of resting and day time ambulatory blood pressure of 3.0/2.4 mmHg (P < 0.001) and 3.3/3.5 mmHg (P < 0.01), respectively. The reduction of resting blood pressure was more pronounced in the 30 hypertensive study groups (‐6.9/‐4.9) than in the others (‐1.9/‐1.6; P < 0.001 for all). Systemic vascular resistance decreased by 7.1% (P < 0.05), plasma noradrenaline by 29% (P < 0.001) and plasma renin activity by 20% (P < 0.05). Bodyweight decreased by 1.2 kg (P < 0.001), waist circumference by 2.8 cm (P < 0.001), percentage body fat by 1.4% (P < 0.001) and the Homeostatic Model Assessment (HOMA) index of insulin resistance by 0.31 units (P < 0.01). High‐density lipoprotein–cholesterol increased by 0.032 mmol/L (P < 0.05).

Resistance training has been less well studied. A meta‐analysis of nine randomized controlled trials (12 study groups) on mostly dynamic resistance training revealed a weighted net reduction of diastolic blood pressure of 3.5 mmHg (P < 0.01) associated with exercise and a non‐significant reduction of systolic blood pressure of 3.2 mmHg (P = 0.10).

In conclusion, dynamic aerobic endurance training decreases blood pressure through a reduction of systemic vascular resistance, in which the sympathetic nervous system and the renin–angiotensin system appear to be involved, and favourably affects concomitant cardiovascular risk factors. In addition, the few available data suggest that resistance training is able to reduce blood pressure.
A TELEOLOGICAL VIEW OF OBESITY, DIABETES AND HYPERTENSION
Authors: Landsberg Lewis
Published: August 2006

The current worldwide epidemic of obesity and its major complications, namely type 2 diabetes and hypertension, is well documented. The present mini‐review develops the thesis that ‘thrifty’ metabolic traits, evolved in the setting of intermittent famine, contribute to the obesity pandemic.

These thrifty traits, namely a decreased capacity for dietary thermogenesis and an increased resistance to insulin‐mediated glucose uptake in skeletal muscle, would prolong survival during famine but predispose to obesity and diabetes in the face of abundance. The regulation of dietary thermogenesis by the sympathetic nervous system also explains the well‐established association between obesity and high blood pressure.

These observations provide a deep‐seated rationale for the efficacy of lifestyle interventions in the treatment of obesity and its complications and may also provide a predicate for the development of new therapeutic strategies aimed at neutralizing the impact of these thrifty traits. Such strategies may entail, for example, therapeutic agents that enhance metabolic rate during low‐energy diets, thereby reversing the physiological impediment imposed by suppression of the sympathetic nervous system.
EXERCISE AND BLOOD PRESSURE: APPLYING FINDINGS FROM THE LABORATORY TO THE COMMUNITY SETTING
Authors: Cox Kay L
Published: August 2006

During the 1980s, there was growing epidemiological evidence that aerobic training lowered blood pressure (BP). Early intervention studies had not always supported this conclusion. Such studies were limited by methodological shortcomings. Few studies had used normotensive individuals or women alone.

Exercise training is an attractive lifestyle strategy in the prevention of hypertension. In our studies in men, vigorous intensity cycling did not lower resting BP.

Vigorous exercise reduces day time ambulatory BP and, in combination with calorie restriction, had a synergist effect to reduce night‐time and 24 h BP.

Exercise is a positive and effective adjunct to other lifestyle measures in the prevention of hypertension. Adherence to either supervised or unsupervised moderate‐intensity exercise is sufficient to reduce BP in the short and long term.

Further studies need to be performed to evaluate the clinical significance and mechanisms for the increase in resting BP observed in older women.

Older individuals with hypertension should be monitored when taking up a swimming programme.

Exercise induced changes in BP seen in the laboratory are also observed in the community setting.
FISH OILS, PHYTOSTEROLS AND WEIGHT LOSS IN THE REGULATION OF LIPOPROTEIN TRANSPORT IN THE METABOLIC SYNDROME: LESSONS FROM STABLE ISOTOPE TRACER STUDIES
Authors: Watts GF , Chan DC , Ooi EMM , Nestel PJ , Beilin LJ , Barrett PHR
Published: August 2006

Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is characterized by high plasma concentrations of triglyceride‐rich and apolipoprotein (apo) B‐containing lipoproteins, with depressed concentrations of high‐density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very‐low density lipoprotein (VLDL) apoB‐100, decreased catabolism of apoB‐containing particles and increased catabolism of HDL apoA‐I particles.

Nutritional interventions may favourably alter lipoprotein transport in the metabolic syndrome. We review our collaborative studies, using stable isotopes and compartmental modelling, of the kinetic effects of fish oils, plant sterols (phytosterols) and weight reduction on the dyslipoproteinaemia in this disorder.

Fish oil supplementation diminished hepatic secretion of VLDL‐apoB and enhanced conversion of VLDL to low‐density lipoprotein (LDL)‐apoB, without altering catabolism.

Plant sterols (phytosterols) did not have a significant effect on plasma concentrations of lipids and lipoprotein or the kinetics of apoB and apoA‐I.

Modest weight reduction optimally decreased plasma triglyceride and LDL–cholesterol via reduction in hepatic apoB secretion and reciprocal upregulation of LDL catabolism.

The scope and potential of future studies using stable isotope tracers is discussed.
RELATIONSHIP BETWEEN ARTERIAL STIFFNESS AND GLUCOSE METABOLISM IN WOMEN WITH METABOLIC SYNDROME
Authors: Nestel Paul
Published: August 2006

Cardiovascular risk factors associated with the metabolic syndrome affect vascular functions adversely. The aim of the present study was to assess the relationship between parameters of glucose homeostasis and arterial stiffness in women with characteristics of the metabolic syndrome.

Twenty post‐menopausal women participated in a cross‐sectional study in which systemic arterial compliance (SAC) and plasma glucose, lipids and glycosylated haemoglobin (HbA1c) were measured while subjects were maintained on a diet high in fibre, raised in protein and reduced in saturated fat.

Regression analysis suggested that mean ( SD) fasting glucose of 5.9 ± 1.7 mmol/L, glucose levels 2 h after a 75 g glucose load of 6.8 ± 3.6 mmol/L, systolic blood pressure of 131 ± 12 mmHg and HbA1c of 5.3 ± 1.7% predicted SAC negatively. The following correlations were obtained between SAC and: (i) fasting glucose: R = ‐0.49, P = 0.028; (ii) 2 h glucose level post‐glucose load: R = ‐0.42, P = 0.064; (iii) HbA1c: R = ‐0.42, P = 0.056; and (iv) systolic blood pressure: R = ‐0.55, P = 0.012.

Relationships between SAC and fasting glucose and systolic blood pressure were significantly independent of each other. There was no evidence of relationships between SAC and any plasma lipid parameter (other than a trend in relation to plasma triglyceride), bodyweight or waist circumference.

In conclusion, in post‐menopausal women with metabolic syndrome, fasting plasma glucose and systolic blood pressure, and possibly HbA1c and the 2 h glucose post‐glucose load, predicted increased arterial stiffness.
Complications and diagnostic difficulties arising from biliary self‐expanding metal stent insertion before definitive histological diagnosis
Authors: Ayaru Lakshmana , Kurzawinski Tom R , Shankar Ariun , Webster George JM , Hatfield Adrian RW , Pereira Stephen P
Published: August 2006

Background:  Self‐expanding metal bile duct stents provide good palliation for inoperable malignant disease. However, problems may arise if metal stents are inserted before definitive histological diagnosis. The aim of this study was to evaluate the outcome of such patients.

Methods:  A retrospective case note review was conducted of patients referred to a tertiary pancreaticobiliary center between 1992 and 2004 in whom a metal bile duct stent was inserted for presumed unresectable malignant disease before definitive histological diagnosis.

Results:  There were 21 patients identified. Final diagnoses were: group 1, benign disease (n = 3); group 2, resectable malignancy (n = 2); group 3, unresectable malignancy (n = 12); and group 4, diagnosis remains uncertain (n = 4). During a follow‐up of 22, 38 and 111 months, the patients in group 1 had one, eight and five episodes of stent occlusion. In group 2, both patients underwent pancreaticoduodenectomy for ampullary carcinoma, 2 and 6 months after presentation. In group 3, the median time to a confirmed malignant diagnosis was 2 months (range 1–27 months). In group 4, a median of two biopsies (range 1–4) were negative for malignancy, during a median follow up of 13 months (range 3–46). Overall in eight patients, the metal stents caused artifacts on computed tomography and/or were associated with tissue in‐growth making the differentiation between benign and malignant disease difficult.

Conclusion:  These cases indicate that metal bile duct stent insertion before definitive histological diagnosis can be problematic. A proportion of cases will have benign strictures and in others the confirmation of malignancy may be made more difficult.
Evaluation of solitary and scattered esophageal varices according to infrared endoscopy and endoscopic ultrasonography
Authors: Tsujigami Koji , Okamura Seisuke , Fukuda Tamotsu , Ichikawa Soichi , Nakasono Masahiko , Okita Yoshio , Muguruma Naoki , Ito Susumu
Published: August 2006

Background and Aim:  The aim of this study was to clarify the etiology and clinical significance of solitary and scattered esophageal varices by evaluating their hemodynamics and other characteristics using infrared endoscopy and endoscopic ultrasonography.

Methods:  The study group comprised 44 lesions of these two related types detected in 28 patients by visible‐light endoscopy. Infrared endoscopy was used to characterize blue‐black coloration before and after rapid intravenous injection of indocyanine green (2 mg/kg). During endoscopic ultrasonography, depth within the esophagus and echo patterns of these varices were characterized.

Results:  Diameters of these varices were significantly smaller in lesions more strongly staining by infrared endoscopy. Lesion diameter was significantly smaller in varices showing homogeneous low echogenicity than in those showing mixed echogenicity. Lesions showing homogeneous high echogenicity stained most weakly followed in turn by lesions with mixed echogenicity and finally those showing homogeneous low echogenicity.

Conclusion:  Indocyanine green injection was useful for infrared observation of the hemodynamics of solitary and scattered esophageal varices, as was endoscopic ultrasonography in defining the location and morphology of these lesions. Varices with larger diameters stained more persistently when hemodynamics were evaluated by infrared endoscopy, and often showed a mixture of low and high echogenicity by endoscopic ultrasonography. These observations suggest that blood flow in the varices is slowed, and that the risk of hemorrhage increases with increased diameter especially with uniform enhancement and uniform echogenicity.
Gene expression profiling in whole liver of bile duct ligated rats: VEGF‐A expression is up‐regulated in hepatocytes adjacent to the portal tracts
Authors: Tanaka Atsushi , Tsuneyama Kohichi , Mikami Masaki , Uegaki Satoko , Aiso Mitsuhiko , Takikawa Hajime
Published: August 2006

Background and Aim:  It would be of clinical importance to clarify molecular mechanisms of cholangiocytes proliferation for the treatment of intractable cholestatic diseases. The aim of this study was to elucidate gene expression profiling in the whole liver of bile duct ligated (BDL) rats using microarray analysis. In addition, the localization and time course of up‐regulated expression of vascular endothelial growth factor (VEGF) was investigated.

Methods:  Male Sprague‐Dawley rats were used. The whole liver was removed from BDL and sham‐operated rats at day 2 after the procedure, and microarray analysis was performed using an array on which 3757 rat cDNA clones spotted. The up‐regulation of VEGF expression was investigated by RT‐PCR using livers at day 1, 2, 4 and 7, and immunoblotting and immunohistochemistry at day 2.

Results:  Marked proliferation of bile ducts was observed in livers of BDL rats. By microarray analysis, 38 up‐regulated and 17 down‐regulated transcripts were detected in whole liver of the BDL rat. The expression of VEGF‐A was significantly elevated in the BDL rats at day 2; the VEGF‐A/GAPDH ratio was 4.030 ± 2.493 in BDL rats and 1.159 ± 0.125 in sham‐operated rats (P = 0.0330). The up‐regulation of VEGF‐A expression was maximal at day 2. Immunoblotting also demonstrated up‐regulated expression of VEGF‐A at the protein level. Immunostaining of VEGF revealed that the expression was evident in hepatocytes adjacent to the portal tracts, and scarcely observed in hepatocytes at the centrilobular area or cholangiocytes.

Conclusion:  Gene expression profiling in the whole liver of the BDL rats revealed 38 up‐regulated and 17 down‐regulated transcripts. In addition, the up‐regulated expression of VEGF was mainly observed in hepatocytes surrounding to the portal tracts.
Meaning‐making in the aftermath of sudden infant death syndrome
Authors: Krueger Guenther
Published: August 2006

The reconstruction of meaning in the aftermath of sudden infant death syndrome (SIDS) is part of the grieving process but has to date been poorly understood. Earlier theorists including Freud, Bowlby and Kübler‐Ross provided a foundation for what occurs during this time using stage theories. More recent researchers, often using qualitative techniques, have provided a more complex and expanded view that enhances our knowledge of meaning reconstruction following infant loss. This overview of representative contemporary authors compares and contrasts them with the longstanding models that are being supplanted within the emerging field of thanatology. Understanding parental reactions within this new framework can help healthcare professionals in dealing with those affected by SIDS and provide a more empathic and sensitive approach to individual differences. Parents’ own accounts of their post‐SIDS experience are consistent with these newer theories. Comprehending how parents cope and reconstruct their lives is an important element in providing appropriate psychological support services.