Abstract: Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Abstract: he Swift Gamma-Ray Explorer is designed to make prompt multiwavelength observations of gamma-ray bursts (GRBs) and GRB afterglows. The X-ray telescope (XRT) enables Swift to determine GRB positions with a few arcseconds accuracy within 100 s of the burst onset. The XRT utilizes a mirror set built for JET-X and an XMM-Newton/EPIC MOS CCD detector to provide a sensitive broad-band (0.2–10 keV) X-ray imager with effective area of > 120 cm2 at 1.5 keV, field of view of 23.6 × 23.6 arcminutes, and angular resolution of 18 arcseconds (HPD). The detection sensitivity is 2×10−14 erg cm−2 s−1 in 104 s. The instrument is designed to provide automated source detection and position reporting within 5 s of target acquisition. It can also measure the redshifts of GRBs with Fe line emission or other spectral features. The XRT operates in an auto-exposure mode, adjusting the CCD readout mode automatically to optimize the science return for each frame as the source intensity fades. The XRT will measure spectra and lightcurves of the GRB afterglow beginning about a minute after the burst and will follow each burst for days or weeks.

Abstract: We report the discovery of very-high-energy (VHE) γ-ray emission of the binary system PSR B1259−63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13 m Cherenkov telescopes of the HESS experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a γ-ray signal from the binary system was detected with a total significance above 13σ. The flux was found to vary significantly on timescales of days which makes PSR B1259−63 the first variable galactic source of VHE γ-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F0(E/ 1T eV) −Γ with a photon index Γ= 2.7 ± 0.2stat ± 0.2sys and flux normalisation F0 = (1.3 ± 0.1stat ± 0.3sys) × 10 −12 TeV −1 cm −2 s −1 .T his detection of VHE γ-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE γ-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G.

Abstract: Hypericum brasiliense is a medicinal herb containing several compounds with important pharmacological activity. In this study, we investigated the effects of water stress (waterlogging and drought) and temperature (low and high, constant and alternate) on the content of betulinic acid and phenolic compounds (quercetin, rutin, 1,5-dihydroxyxanthone, isouliginosin B) in this species. In general, the water stress increased the levels of all of the compounds analyzed, particularly some of the phenolic compounds. On the other hand, the responses to alternating temperatures varied according to the compound. The results for plants kept in growth chambers indicated that low light intensity might have influenced the levels of the compounds. There was also a reallocation of carbon, with water-stressed plants showing a reduction in growth while the levels of the compounds increased. In the temperature treatments, such an increase was evident only for the phenolic compounds.

Abstract: Rationale: Phosphodiesterase type 5 (PDE5) inhibition has been proposed for the treatment for pulmonary arterial hypertension (PAH). Objective: This study compared adding sildenafil, a PDE5 inhibitor, to conventional treatment with the current practice of adding bosentan, an endothelin receptor antagonist. Methods: Twenty-six patients with PAH, idiopathic or associated with connective tissue disease, World Health Organization (WHO) functional class III, were randomized in a double-blind fashion to receive sildenafil (50 mg twice daily for 4 weeks, then 50 mg three times daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) over 16 weeks. Measurements: Changes in right ventricular (RV) mass (using cardiovascular magnetic resonance), 6-minute walk distance, cardiac function, brain natriuretic peptide, and Borg dyspnea index. Main Results: When analyzed by intention to treat, there were no significant differences between the two treatment groups. One patient on sildenafil died suddenl...

Abstract: Objectives: The purpose of this study was to evaluate the antimicrobial effect of toluidine blue 0 (TBO), in combination with either a helium/neon (HeNe) laser or a light-emitting diode (LED), on the viability and architecture of Streptococcus mutans biofilms.Methods: Biofilms were grown on hydroxyapatite discs in a constant depth film ferment or fed with artificial saliva that was supplemented with 2% sucrose four times a day, thus producing a typical 'Stephan pH curve'. Photodynamic therapy was subsequently carried out on biofilms of various ages with light from either the HeNe laser or LED using energy densities of between 49 and 294 J/cm(2).Results: Significant decreases in the viability of S. mutansbiofilms were only observed when biofilms were exposed to both TBO and light, when reductions in viability of up to 99.99% were observed with both light sources. Overall, the results showed that the bactericidal effect was light dose-dependent and that older biofilms were less susceptible to photodynamic therapy. Confocal laser scanning microscopy images suggested that lethal photosensitization occurred predominantly in the outermost layers of the biofilms.Conclusions: Photodynamic therapy may be a useful approach in the treatment of dental plaque-related diseases.

Abstract: We report the detection of TeV $\gamma$-rays from the shell-type supernova remnant RX J0852.0-4622 with data of 3.2 h of live time recorded with H.E.S.S. in February 2004. An excess of (700 $\pm$ 60) events from the whole remnant with a significance of 12 $\sigma$ was found. The observed emission region is clearly extended with a radius of the order of 1 degree and the spatial distribution of the signal correlates with X-ray observations. The spectrum in the energy range between 500 GeV and 15 TeV is well described by a power law with a photon index of $\Gamma=2.1 \pm 0.1_{stat} \pm 0.2_{syst}$ and a differential flux at 1 TeV of $\varphi$ 1TEV= (2.1 $\pm 0.2_{stat} \pm 0.6_{syst}) \times 10^{-11} cm^{-2} s^{-1} TeV^{-1}$. The integral flux above 1 TeV was measured to be $\Phi$ (E > 1 TeV) = (1.9 $\pm 0.3_{stat} \pm 0.6_{syst}) \times 10^{-11} cm^{-2} s^{-1}$, which is at the level of the flux of the Crab nebula at these energies. More data are needed to draw firm conclusions on the magnetic field in the remnant and the type of the particle population creating the TeV $\gamma$-rays.

Abstract: The paper ‘A high-velocity ionized outflow and XUV photosphere in the narrow emission line quasar PG1211+143’ was published in Mon. Not. R. Astron. Soc. 345, 705–713 (2003). A re-assessment of the uncertainties in determining spectral features from the XMM– Newton EPIC detectors and an arithmetical error require a revision of the deduced outflow velocities listed in Table 1 of that paper. Fortunately the main findings reported in the paper are unaltered, in particular the detection of absorption lines in both RGS and EPIC spectra with blueshifted wavelengths implying an outflow velocity of ∼ 0.8–1c. The correct version of Table 1 is given here, with details of the absorption lines detected in the EPIC data, together with their pro-

Abstract: The West Siberian Basin (WSB) records a detailed history of Permo-Triassic rifting, extension and volcanism, followed by Mesozoic and Cenozoic sedimentation in a thermally subsiding basin. Sedimentary deposits of Permian age are absent from much of the basin, suggesting that large areas of the nascent basin were elevated and exposed at that time. Industrial seismic and well log data from the basin have enabled extension and subsidence modelling of parts of the basin. Crustal extension (β) factors are calculated to be in excess of 1.6 in the northern part of the basin across the deep Urengoy graben. 1-D backstripping of the Triassic to Cenozoic sedimentary sequences in this region indicates a period of delayed subsidence during the early Mesozoic. The combination of elevation, rifting and volcanism is consistent with sublithospheric support, such as a hot mantle plume. This interpretation accords with the geochemical data for basalts from the Siberian Traps and the West Siberian Basin, which are considered to be part of the same large igneous province. Whilst early suites from Noril'sk indicate moderate pressures of melting (mostly within the garnet stability field), later suites (and those from the West Siberian Basin) indicate shallow average depths of melting. The main region of magma production was therefore beneath the relatively thin (ca. 50–100 km) lithosphere of the basin, and not the craton on which the present-day exposure of the Traps occurs. The indicated uplift, widespread occurrence of basalts, and short duration of the volcanic province as a whole are entirely consistent with published models involving a mantle plume. The main argument against the plume model, namely lack of any associated uplift, appears to be untenable.

Abstract: Summary The rodent mandible has become a paradigm for studies on the development and evolution of complex morphological structures. We use a combination of geometric and multivariate morphometric methods in order to assess the correspondence between integration patterns and a priori biological models in the context of evolutionary shape divergence in the mandible of rodents of the family Echimyidae. The correlation of shape distances among operational taxonomic units (individuals, species, genera) in separate morphogenetic components allowed the construction of integration matrices among mandible components for data sets corresponding to varying levels of genetic divergence (intergeneric, interspecific, and intrapopulational). The integration matrices were associated with a priori biological (developmental, genetical, modular) models, and the maximum integration axes (singular warps) were compared with realized axes of maximum interspecific variation (relative warps). The integration pattern and intensity were not stable in data sets with different levels of genetic divergence, and the varying functional demands during the ecological radiation in the family were probably responsible for the differences in observed integration patterns. Developmental and genetic models were significantly associated with the interspecific integration patterns observed, suggesting a role for neutral evolution during the evolutionary divergence of mandible shape. However, directional and stabilizing selection were not discarded as processes responsible for the generation of interspecific integration. The choreography of the morphogenetic components in the mandible is highly flexible and the integrated groups of components can be reorganized depending on functional demands during evolutionary shape changes.

Abstract: We have identified a novel motif which consists of the sequence (CCU)n as part of a polypyrimidine-rich tract and permits internal ribosome entry. A number of constructs containing variations of this motif were generated and these were found to function as artificial internal ribosome entry segments (AIRESs) in vivo and in vitro in the presence of polypyrimidine tract-binding protein (PTB). The data show that for these sequences to function as IRESs the RNA must be present as a double-stranded stem and, in agreement with this, rather surprisingly, we show that PTB binds strongly to double-stranded RNA. All the cellular 5′ untranslated regions (UTRs) tested that harbor this sequence were shown to contain internal ribosome entry segments that are dependent upon PTB for function in vivo and in vitro. This therefore raises the possibility that PTB or its interacting protein partners could provide a bridge between the IRES-RNA and the ribosome. Given the number of putative cellular IRESs that could be dependent on PTB for function, these data strongly suggest that PTB-1 is a universal IRES-trans-acting factor.

Abstract: Objectives To compare the success and complication rates of staghorn calculi treated through the upper pole calix, lower/middle calices, and multiple access Methods Between January 1995 and December 2000, the records of 119 patients with staghorn calculi who underwent percutaneous nephrolithotomy were retrospectively reviewed The mean stone burden was 69 cm Of the 119 patients, 16 (134%) had upper pole access, 70 (588%) lower or middle calix access, and 33 (277%) multiple renal access Results The stone-free rate was 800% for those in the lower/middle, 875% for those in the upper pole, and 848% for those in the multiple access group Single access was performed in 723% and multiple access tracts in 277% of patients The average operative time was 868 minutes in the upper pole, 1391 minutes in the lower/middle pole, and 1349 minutes in the multiple access groups Extracorporeal shock wave lithotripsy was used in 42% of patients The overall complication rate was 285% (25% in the upper pole, 214% in the lower/middle, and 454% in the multiple access group) Thoracic complications (pneumothorax and hydrothorax) occurred in 2 patients (17%), but only 1 patient had undergone supracostal access Bleeding requiring blood transfusion was significantly greater in the multiple access group The average hospital stay was 30 days for all patients Conclusions The success of percutaneous treatment of patients with staghorn calculi is highly related to optimal kidney access The supracostal and multiple access approaches can be used, with a slight increase in the incidence of acceptable complications

Abstract: The native fluorescence of paracetamol (PA) in the solid state is demonstrated, allowing the development of a rapid, simple and rugged method for direct analysis of pharmaceutical formulations. It is easily adaptable to any spectrofluorimeter, and no chemical treatment of the sample is needed. The fluorescence measurements ( λ ex = 333 nm; λ em = 382 nm) are performed directly on the powdered sample, the active substance being diluted in lactose, maize starch, poly(vinylpyrrolidone), talc and stearic acid. The influence of the ingredients of PA formulations is discussed. Fluorescence intensity is linearly dependent on PA concentration within the 100–400 mg g −1 range. The analytical frequency is 200 h −1 . Detection and quantification limits were estimated within the 13.0–16.7 and 43.1–55.7 mg g −1 ranges for samples with different ingredient proportions. The method was applied to pharmaceutical formulations and the relative standard deviation of results was n = 20) for all tested ingredient proportions. Results were compared with those obtained by a method recommended by the British Pharmacopoeia and no statistical difference between methods was found at the 95% confidence level.

Abstract: Plasma and serum biomarkers of angiogenesis and activated endothelial cells were evaluated to assess biological activity of PTK787/ZK 222584 (PTK/ZK), a novel oral angiogenesis inhibitor targeting all known vascular endothelial growth factor (VEGF) receptor tyrosine kinases.; Patients with colorectal cancer (CRC) (n=63) were enrolled into two phase I/II dose escalation trials of PTK/ZK in 28-day cycles until discontinuation. Patients with stable disease for > or =2 months were categorized as 'non-progressors'. Plasma markers of angiogenesis, VEGF-A and basic fibroblast growth factor (bFGF), and the serum markers of activated endothelial cells, sTIE-2 and sE-Selectin, were assessed at baseline, and pre-dose on days 1, 8, 15, 22 and 28 of every cycle, with additional assessments 10 h post-dose on days 1 and 15. The percentage change from baseline was subsequently correlated with AUC and C(max) of PTK/ZK on day 1, cycle 1 and clinical outcome.; A dose-dependent increase in plasma VEGF-A and bFGF was observed in the first cycle of PTK/ZK treatment. The correlation of change in plasma VEGF-A with AUC and C(max) was characterized by an E(max) model, suggesting that a change of > or =150% from baseline VEGF-A correlated with non-progressive disease. Change from baseline plasma VEGF-A within the first cycle of treatment was significantly correlated with clinical outcome by logistic regression analysis (P=0.027).; In patients with CRC treated with PTK/ZK, changes in plasma VEGF-A and bFGF demonstrate biological activity of PTK/ZK, may help to establish optimal dose and correlate with outcome.

Abstract: This article presents an investigation of the organization and structures of talk-in-interaction over mobile phone. The analysis is based upon naturally occurring data consisting of a corpus of calls recorded during everyday activities of a young adult. Using these data we reveal a range of sequential phenomena associated with mobile phone usage. Established conversation analytic work on landline telephone conversation is used in order to build a comparative analysis of how actions such as openings, caller–called identity management, and topic introduction are accomplished in mobile vs landline telephone conversation. We first show that, far from revolutionizing the organization of telephone conversation, mobile phone talk retains many of the norms associated with landline phone talk. Subsequently, focusing on those modifications that are identifiable in our data, we show how these are related to aspects of the communicative affordances of mobile phones, orientations to which are observable in the talk of...

Abstract: The aim of this research was to evaluate the effect of the addition of whey protein concentrate (WPC) on the viability of Lactobacillus acidophilus and Bifidobacterium longum and on postacidification throughout the shelf life of fat-free yogurts, and also to analyse the sensory characteristics of the products. Postacidification was not significantly changed by the addition of WPC, but was decreased by Lactobacillus bulgaricus inoculation. WPC did not influence the viability of the lactic acid bacteria ( L. bulgaricus and Streptococcus thermophilus ), but it improved the growth and survival of the microorganisms L. acidophilus and B. longum , especially the former. The panellists did not identify significant differences ( P < 0.05) of the yogurts due to the addition of WPC.

Abstract: PSORS1 is the major susceptibility locus for psoriasis vulgaris (PV) and lies within an approximately 200 kb segment of the major histocompatibility complex on chromosome 6p21.3. Alleles of candidate genes in this region including human leukocyte antigen (HLA)-C, α-helical coiled coil rod (HCR), and corneodesmosin (CDSN) show association with early-onset PV. Late-onset psoriasis (LOP) is defined as a disease with onset after 40 y of age and is typically sporadic. We assessed the role of PSORS1 in genetic susceptibility to LOP. Genotyping for HLA-C alleles and seven single nucleotide polymorphisms (SNP) within the genes HCR and CDSN was performed in LOP (n=145) and normal controls (n=309). Statistical analysis of allelic frequencies included calculation of odds ratio and χ2 comparisons. LOP demonstrated only a weak association to PSORS1 alleles HLA-Cw*6 (p=0.037), CDSN*5 (p=0.041), HCR*WC (p=0.013), and HCR SNP +325 (p=0.038). Patients with age of onset for psoriasis of 50 y or above provided no evidence of association with any of these alleles. These data suggest that the study cohort may include a number of subjects who harbor PSORS1 predisposition to early-onset psoriasis and yet do not present with disease by the age of 40 y. Thus this study demonstrates that PSORS1 is not a major inherited risk factor in the pathogenesis of LOP. These data suggest that the exclusion of LOP subjects from case–control studies will aid further delineation of the PSORS1 locus. Future genome-wide studies will be required to identify loci conferring risk for late-onset disease.

Abstract: Univ Estadual Paulista Julio Mesquita Filho, Dept Microbiol & Immunol, BR-18618000 Botucatu, SP, Brazil

Abstract: : The invertebrate benthos, especially the micro- and mesofaunal components, of the Brazilian seas is still poorly known Relatively few species have been recorded, reflecting the lack of research in this field The intertidal zone, to depths of about 20 m, has been studied the most, and there the numbers of endemic species are relatively high The diversity of demersal and pelagic fishes is similar among the major marine regions, and endemism is typically low (<5%) and restricted to reef species Surveys in southeastern Brazil (depths of up to 2000 m) have recorded more than 1300 species of benthic animals, of which the Porifera, Cnidaria, Sipuncula, Gastropoda, Bivalvia, Scaphopoda, Polychaeta, Crustacea, Ophiuroidea, Bryozoa, and Brachiopoda were the most abundant or frequent Excepting the molluscs, decapods (brachiurans), cirripeds, and echinoderms, the faunas of salt marshes, coral reefs, and islands remain poorly known Marine and estuarine demersal teleosts include 617 species in 26 orders and 118 families Just over half the species (337) are Perciformes Overexploitation, for food and by the aquarium fish trade, habitat degradation and destruction, alien species introductions, pernicious tourism, and pollution are the principal threats to Brazil's marine biodiversity The Ministry of the Environment lists 34 threatened and 10 overexploited or at risk of being overexploited benthic species Fishes officially listed as threatened include 15 species of sharks and rays and 7 teleosts Another six elasmobranchs and 27 teleosts are currently or potentially being overexploited Conservation of marine biodiversity in Brazil is still broadly inadequate despite existing legislation and several protected areas The number and size of marine protected areas are insufficient, and some still lack management plans or have yet to receive the appropriate measures and infrastructure to make them effective Fisheries administration and management is still precarious and in many areas lacks effective participation of local communities Major conservation initiatives include the identification of keys areas for biodiversity conservation, surveys, intensified monitoring of fisheries, environmental education, and the creation and improved management of protected areas Resumen: Los invertebrados bentonicos, especialmente los componentes micro y mesofaunicos, de los mares brasilenos son poco conocidos Se han registrado pocas especies relativamente, lo que refleja la carencia de investigacion en este campo La zona intermareas hasta profundidades de casi 20 m es la mas estudiada, y el numero de especies endemicas es relativamente alto La diversidad de peces demersales y pelagicos es similar en las regiones marinas principales, y el endemismo es tipicamente bajo (<5%) y esta restringido a especies arrecifales En muestreos en el sureste de Brasil (profundidades hasta 2000 m) se han registrado mas de 1300 especies de animales bentonicos, de las cuales fueron mas abundantes y frecuentes Porifera, Cnidaria, Sipuncula, Gastropoda, Bivalvia, Scaphopoda, Polychaeta, Crustacea, Ophiuroidea, Bryozoa y Brachiopoda Las faunas de marismas, arrecifes coralinos e islas permanecen poco conocidas, excepto por los moluscos, decapodos (braquiuros) cirripedios y equinodermos Los telesoteos demersales marinos y estuarinos incluyen 617 especies en 26 ordenes y 118 familias Un poco mas de la mitad de especies (337) son Perciformes Las principales amenazas a la biodiversidad marina brasilena son la sobreexplotacion, para alimento y el comercio de peces de acuario, la degradacion y destruccion del habitat, la introduccion de especies exoticas, el turismo pernicioso y la contaminacion El Ministerio del Ambiente enlista a 34 especies bentonicas amenazadas y 10 sobreexplotadas o en riesgo de serlo Los peces enlistados oficialmente como amenazados incluyen 15 especies de tiburones y rayas y 7 de teleosteos Otras seis especies de elasmobranquios y 27 de teleosteos estan siendo sobreexplotados actual o potencialmente La conservacion de la biodiversidad marina en Brasil aun es considerablemente inadecuada a pesar de la legislacion existente y varias areas protegidas El numero y tamano de areas marinas protegidas es insuficiente, algunas aun carecen de planes de manejo o no han recibido las medidas e infraestructura adecuadas para hacerlas efectivas La administracion y gestion de pesquerias todavia es precaria y carece de la participacion efectiva de comunidades locales en muchas areas Las principales iniciativas de conservacion incluyen la identificacion de areas clave para la conservacion de biodiversidad, muestreos, monitoreo intensivo de pesquerias, educacion ambiental y la creacion y mejor administracion de areas protegidas

Abstract: Background: Aging is characterized by a decline in the postural control performance, which is based on a coherent and stable coupling between sensory information and motor action. T

Abstract: OBJECTIVE. The purpose of this study was to evaluate the prevalence of the reversed halo sign in pulmonary paracoccidioidomycosis.MATERIALS AND METHODS. The high-resolution CT scans (1- or 2- mm collimation scans) of 148 consecutive patients with proven pulmonary paracoccidioidomycosis were reviewed to determine the prevalence of the reversed halo sign in these patients. The reversed halo sign was defined as central ground-glass opacity surrounded by a crescent or ring of consolidation. The images were reviewed by two radiologists who reached a decision by consensus.RESULTS. A reversed halo sign was found in 15 patients (10%), including 13 men and two women ranging in age from 20 to 58 years (mean, 48 years). Three patients had only one reversed halo sign, one had two lesions, and the remaining had multiple lesions. The size of the sign ranged from 10 to 50 mm (average, 20 mm). In two cases the reversed halo sign was the only finding on CT. The most common associated findings seen in the remaining 13 pati...

Abstract: Background Recently published trials addressing the pharmacological management of hypertension have reported an increase in new-onset diabetes mellitus when comparing certain older and newer treatment regimens. Thiazide-type diuretics (thiazides) and beta-blockers have been individually implicated, but these drugs are frequently combined, and the magnitude of risk associated with their combined use has not been quantified. Methods and results Randomized control trials were retrieved that: (i) featured stepped treatment to manage hypertension; (ii) compared initial treatment using a thiazide or beta-blocker (older drug) with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker or calcium antagonist (newer drug); (iii) assessed cardiovascular outcomes; (iv) reported new-onset diabetes; and (v) provided at least 1-year follow-up. A meta-analysis of available trials indicated that patients exposed to treatment regimens combining thiazides and beta-blockers are at greater risk of developing diabetes than regimens avoiding this combination of drugs (risk ratio for alternative therapy 0.81, 95% confidence interval 0.77-0.86). Current data cannot inform reliably about the risks associated with individual older drugs because of similar overall exposures in patients starting on newer and older drugs. Interpretation and implications The results suggest that the routine combined use of a thiazide with a beta-blocker should be questioned in the early management of hypertension, particularly in patients who are at increased risk of developing new-onset diabetes. In such patients, the increased risk of developing diabetes may exceed the benefit of blood pressure lowering.

Abstract: Because infants are more susceptible to the adverse effects of mycotoxins, this work was carried out to determine aflatoxin M(1) (AFM(1)) and ochratoxin A (OA) in milk from the Human Milk Bank of the Southern Regional Hospital, Sao Paulo, Brazil. Analytical methods were first established and evaluated. The methods involved the extraction of AFM(1) with methanol and OA with 1% aqueous sodium bicarbonate solution and methanol, clean-up with immunoaffinity columns having antibodies specific for each mycotoxin and quantification by high performance liquid chromatography (HPLC) with fluorescence detection. The method established for AFM(1) had mean recovery percentages of 94, 77 and 82% and coefficients of variation of 17.5, 3.4 and 4.2% at 0.01, 0.03 and 0.05 ng ml(-1), respectively. For the OA method, the corresponding values were 84, 84 and 75% for recovery and 14.1, 3.7 and 4.0% for the coefficient of variation. The limit of quantification for both methods was 0.01 ng ml(-1). Of a total of 50 samples analysed, only one was contaminated with AFM1, at 0.024 ng ml(-1), and two with OA, at 0.011 and 0.024 ng ml(-1). Although the incidence observed was low, it is recommended that the study be extended to other milk banks of the city of Sao Paulo.

Abstract: The purpose of this prospective study was to determine the clinicopathological significance of necrotic areas demonstrated by rapid-bolus contrast-enhanced computed tomography (CT) in patients with biochemically predicted severe pancreatitis. Although CT necrosis occurred significantly more frequently in patients with clinically severe (ten of 12) compared with mild (seven of 20) pancreatitis (P less than 0.025), seven of 17 (41 per cent) patients with CT necrosis developed clinically mild pancreatitis and six of ten (60 per cent) patients with clinically severe pancreatitis and CT necrosis recovered with conservative management. The site and extent of CT necrosis did not correlate with disease severity. Fine-needle aspiration cytology, operative and post-mortem findings and endoscopic retrograde cholangiopancreatography examinations all strongly suggested that CT necrosis represents true pancreatic necrosis. We conclude that the finding of CT necrosis is not in itself an indication for operative intervention, but that rapid-bolus contrast-enhanced dynamic CT greatly facilitates the planning and execution of surgical therapy.

Abstract: Following our previous description of the serotonin transporter (SERT) acting as a conduit to 5-hydroxytryptamine (5-HT)-mediated apoptosis, specifically in Burkitt's lymphoma, we now detail its expression among a broad spectrum of B cell malignancy, while exploring additional SERT substrates for potential therapeutic activity. SERT was readily detected in derived B cell lines with origins as diverse as B cell precursor acute lymphoblastic leukemia, mantle cell lymphoma, diffuse large B cell lymphoma, and multiple myeloma. Concentration and timecourse kinetics for the antiproliferative and proapoptotic activities of the amphetamine derivatives fenfluramine (an appetite suppressant) and 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") revealed them as being similar to the endogenous indoleamine. A tricyclic antidepressant, clomipramine, instead mirrored the behavior of the selective serotonin reuptake inhibitor fluoxetine, both being effective in the low micromolar range. A majority of neoplastic clones were sensitive to one or more of the serotonergic compounds. Dysregulated bcl-2 expression, either by t(14;18)(q32;q21) translocation or its introduction as a constitutively active transgene, provided protection from proapoptotic but not antiproliferative outcomes. These data indicate a potential for SERT as a novel anti-tumor target for amphetamine analogs, while evidence is presented that the seemingly more promising antidepressants are likely impacting malignant B cells independently of the transporter itself.

Abstract: Peripheral tuberculous lymphadenopathy is the commonest form of extrapulmonary tuberculosis. Sixty-seven patients with peripheral tuberculous lymphadenopathy who presented to general surgeons and underwent lymph node biopsy between 1979 and 1989 are reviewed. Fifty-four patients (81 per cent) were of Indian subcontinent ethnic origin and 13 (19 per cent) were of white ethnic origin. The sites most commonly affected were the cervical lymph nodes. Biopsy specimens obtained by open operation were sent for microbiological examination in all but 13 cases, of whom seven were patients of white ethnic origin. Tuberculous lymphadenopathy remains an important differential diagnosis of cervical lymphadenopathy and it is essential that peripheral lymph node biopsies are examined both histologically and microbiologically.

Abstract: Aims/hypothesis To assess the involvement of the AGE-specific receptor (AGER, also known as RAGE) axis and nuclear factor kappa-B (NFKB, also known as NF-kappaB) activation in the development of lacrimal gland and tear film dysfunction in diabetes, the present study evaluated: (1) lacrimal gland and tear film alterations in diabetic rats; and (2) the expression of AGE, AGER and NFKB in ocular tissues of normoglycaemic and diabetic rats.

Abstract: The aim of this study was to investigate the microbial composition of necrotic root canals using culture methods and microarray technology. Twenty uniradicular teeth with radiographic evidence of periapical bone loss and with no previous endodontic treatment were selected for this study. For molecular diagnosis a DNA chip with 20 different species-specific, 16S-rDNA-directed catcher probes was used. The microorganisms most frequently detected by the DNA chip were: Micromonas micros, Fusobacterium nucleatum ssp., Tannerella forsythia, Treponema denticola, Veillonella parvula, Eubacterium nodatum, Porphyromonas gingivalis, Actinomyces odontolyticus, and Streptococcus constellatus. As expected, additional important bacterial taxa were found by culture analysis, but microorganisms such as T. forsythia and T. denticola could not be identified. In conclusion, microarrays may provide significant additional information regarding the endodontic microbiota by detecting bacterial species that are otherwise difficult or impossible to culture.

Abstract: It is clear that leukotrienes mediate inflammatory response; new aspects of leukotriene function have recently been described. In this study, we demonstrate that leukotrienes are key chemical mediators in the control of parasite burdens in mice infected with Strongyloides venezuelensis. High leukotriene levels were detected in the lungs and small intestines of Swiss mice. In infected Swiss mice treated with MK886, a leukotriene synthesis inhibitor, numbers of adult worms, and eggs/g/feces were greater than in infected-only animals. The MK886 treatment inhibited leukotriene B4 production in the lungs and small intestines, albeit on different postinfection days. Similarly, parasite burdens and eggs/g/feces were greater in 5-lipoxygenase−/− mice than in wild-type animals. These observation were confirmed by histopathological study of the duodena. We subsequently observed significant lower numbers of eosinophils and mononuclear cells in the blood, peritoneal cavity fluid, and bronchoalveolar lavage fluid of Swiss mice treated with MK886. In the lung parenchyma of infected animals, MK886 significantly inhibited synthesis of IL-5 at the beginning of infection, whereas levels of IL-12 increased progressively throughout the postinfection period. However, levels of leukotriene C4, PGE2, TNF-α, IL-3, IL-4, IFN-γ, and IL-10 were comparable between the treated and untreated groups. Nevertheless, IgE and IgG1 (but not IgG2a) synthesis was also significantly inhibited by MK886 administration. Therefore, in S. venezuelensis-infected mice, adult worm and egg burdens are leukotriene dependent. These findings indicate potential immunostimulatory strategies involving leukotriene administration, and may serve as an alert to physicians treating Strongyloides stercoralis-infected patients presenting asthma-like symptoms because use of 5-lipoxygenase inhibitors may worsen the infection.