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Unbiased quantitative analysis of macroscopic biological samples demands fast imaging systems capable of maintaining high resolution across large volumes. Here we introduce RAPID (rapid autofocusing via pupil-split image phase detection), a real-time autofocus method applicable in every widefield-based microscope. RAPID-enabled light-sheet microscopy reliably reconstructs intact, cleared mouse brains with subcellular resolution, and allowed us to characterize the three-dimensional (3D) spatial clustering of somatostatin-positive neurons in the whole encephalon, including densely labeled areas. Furthermore, it enabled 3D morphological analysis of microglia across the entire brain. Beyond light-sheet microscopy, we demonstrate that RAPID maintains high image quality in various settings, from in vivo fluorescence imaging to 3D tracking of fast-moving organisms. RAPID thus provides a flexible autofocus solution that is suitable for traditional automated microscopy tasks as well as for quantitative analysis of large biological specimens.
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Encéfalo/anatomía & histología , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Microglía/citología , Microscopía Fluorescente/métodos , Animales , Masculino , RatonesRESUMEN
Massive present-day early-type (elliptical and lenticular) galaxies probably gained the bulk of their stellar mass and heavy elements through intense, dust-enshrouded starbursts--that is, increased rates of star formation--in the most massive dark-matter haloes at early epochs. However, it remains unknown how soon after the Big Bang massive starburst progenitors exist. The measured redshift (z) distribution of dusty, massive starbursts has long been suspected to be biased low in z owing to selection effects, as confirmed by recent findings of systems with redshifts as high as ~5 (refs 2-4). Here we report the identification of a massive starburst galaxy at z = 6.34 through a submillimetre colour-selection technique. We unambiguously determined the redshift from a suite of molecular and atomic fine-structure cooling lines. These measurements reveal a hundred billion solar masses of highly excited, chemically evolved interstellar medium in this galaxy, which constitutes at least 40 per cent of the baryonic mass. A 'maximum starburst' converts the gas into stars at a rate more than 2,000 times that of the Milky Way, a rate among the highest observed at any epoch. Despite the overall downturn in cosmic star formation towards the highest redshifts, it seems that environments mature enough to form the most massive, intense starbursts existed at least as early as 880 million years after the Big Bang.
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AIMS: The aim of this study was to describe the regional profiles of microglial activation in sporadic Creutzfeldt-Jakob disease (sCJD) subtypes and analyse the influence of prion strain, disease duration and codon 129 genotype. METHODS: We studied the amount/severity and distribution of activated microglia, protease-resistant prion protein (PrPSc ) spongiform change, and astrogliosis in eight regions of 57 brains, representative of the entire spectrum of sCJD subtypes. RESULTS: In each individual subtype, the regional extent and distribution of microgliosis significantly correlated with PrPSc deposition and spongiform change, leading to subtype-specific 'lesion profiles'. However, large differences in the ratio between PrPSc load or the score of spongiform change and microglial activation were seen among disease subtypes. Most significantly, atypical sCJD subtypes such as VV1 and MM2T showed a degree of microglial activation comparable to other disease variants despite the relatively low PrPSc deposition and the less severe spongiform change. Moreover, the mean microglial total load was significantly higher in subtype MM1 than in MM2C, whereas the opposite was true for the PrPSc and spongiform change total loads. Finally, some sCJD subtypes showed distinctive regional cerebellar profiles of microgliosis characterized by a high granular/molecular layer ratio (MV2K) and/or a predominant involvement of white matter (MVK and MM2T). CONCLUSIONS: Microglial activation is an early event in sCJD pathogenesis and is strongly influenced by prion strain, PRNP codon 129 genotype and disease duration. Microglial lesion profiling, by highlighting strain-specific properties of prions, contributes to prion strain characterization and classification of human prion diseases, and represents a valid support to molecular and histopathologic typing.
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Encéfalo/patología , Síndrome de Creutzfeldt-Jakob/patología , Gliosis/patología , Microglía/patología , Progresión de la Enfermedad , Humanos , FenotipoRESUMEN
The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.
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The extragalactic background light at far-infrared wavelengths comes from optically faint, dusty, star-forming galaxies in the Universe with star formation rates of a few hundred solar masses per year. These faint, submillimetre galaxies are challenging to study individually because of the relatively poor spatial resolution of far-infrared telescopes. Instead, their average properties can be studied using statistics such as the angular power spectrum of the background intensity variations. A previous attempt at measuring this power spectrum resulted in the suggestion that the clustering amplitude is below the level computed with a simple ansatz based on a halo model. Here we report excess clustering over the linear prediction at arcminute angular scales in the power spectrum of brightness fluctuations at 250, 350 and 500 µm. From this excess, we find that submillimetre galaxies are located in dark matter haloes with a minimum mass, M(min), such that log(10)[M(min)/M(â)] = 11.5(+0.7)(-0.2) at 350 µm, where M(â) is the solar mass. This minimum dark matter halo mass corresponds to the most efficient mass scale for star formation in the Universe, and is lower than that predicted by semi-analytical models for galaxy formation.
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Pinus radiata D. Don is a forest tree species native to the Monterey Baja in California. Due to its rapid growth and desirable lumber and pulp qualities, between 1960 and 1980, about 12,000 ha of P. radiata were planted in Sardinia, Italy. The only disease reported on this conifer species has been Diplodia pinea, which causes tip and branch dieback (3). In January 2012, dieback and mortality of 25-year-old radiata pine trees were observed in a reforestation area of about 20 ha located in northern Sardinia (40°43'N, 9°22'E, 600 m a.s.l.). Symptoms included chlorosis, reddish-brown discoloration of the whole crown or dieback starting in the upper crown and progressing downward through the crown, and necrotic bark tissues at root collar. Approximately 25% of the trees were affected. In a first attempt, a Phytophthora species was consistently isolated from the rhizosphere of 23 symptomatic trees, which included necrotic fine roots using oak leaves as bait (4). Afterwards, it was also isolated from phloem samples taken from the margins of fresh lesions at the stem base and upper roots of affected trees using synthetic mucor agar medium (1). Isolation from soil samples of six healthy pine trees randomly selected in the site did not yield any Phytophthora isolate. On carrot agar (CA), Phytophthora colonies were stellate to slightly radiate with limited aerial mycelium. Sporangia were obpiryform, non-papillate, and non-caducous, measuring 46.9 to 51.2 × 29.1 to 32.6 µm (l:b ratio 1.9). Hyphal swellings were formed in chains or clusters; chlamydospores were not observed. These isolates had cardinal temperatures of <5°C, 25°C, and 35°C, respectively. Their morphological and cultural features were typical of Phytophthora cryptogea Pethybridge & Lafferty. They were heterothallic and produced oogonia with amphyginous antheridia when paired with an A2 mating type tester strain of P. cryptogea. This identity was corroborated by sequence analysis of the internal transcribed spacer (ITS) region of the rDNA. BLAST searches showed 99% homology with sequences of P. cryptogea available in GenBank (DQ479410 and HQ697245). The ITS sequence of a representative isolate (PH101) was submitted to GenBank (Accession Nos. KC603895). The strain PH101 was stored in the culture collection of the Department of Agriculture at the University of Sassari. Pathogenicity of isolate PH101 was verified by inoculating five freshly cut logs of radiata pine (1 m long and 15 cm diam.) with a 5-mm agar plug taken from the margin of 4-day-old culture grown on CA (4). The plug was inserted in a 5-mm hole made through the bark with a cork borer. Five control logs were inoculated with sterile CA. All logs were incubated in a growth chamber at 20°C. Phloem lesion sizes were assessed after 1 month and measured 9.7 ± 5.5 cm2 (average ± standard deviation). Control logs had no lesions. The pathogen was re-isolated from the lesions, thus fulfilling Koch's postulates. P. cryptogea has been previously reported in Australia, causing decline of radiata pine trees in wet and flooded soils (2). To our knowledge, this is the first report of P. cryptogea on P. radiata trees in Europe. References: (1) C. M. Brasier and S. A. Kirk. Plant Pathol. 50:218, 2001. (2) M. Bumbieris. Aust. J. Bot. 24:703, 1976. (3) A. Franceschini et al. Informatore Fitopatologico 1:54, 2006. (4) B. Scanu et al. For. Pathol. 43:340, 2013.
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AIM: Childhood obesity is remarkably spreading worldwide, involving both industrialized and low-income countries. Its prevalence, outcome and socioeconomic impact call for the attention of medical community. We conducted a monocentric, open, two-arm, parallel-group study to evaluate the efficacy at reducing appetite and increasing dietary compliance of obese children of Tuberil®, a weight-loss supplement derived from potato and devoid of side effects. METHODS: We recruited participants, children with BMI ≥ 85th, through direct referrals in pediatrician's surgeries. Children were randomized to receive Tuberil® (group A) or nothing (group B), following a chronological order (A-B-A-B). Every child received a nutritionally balanced diet and had to record their appetite and to describe their meals in a diary. RESULTS: Even if we found a significant reduction in BMI, weight and waist circumference in both groups, no statistically significant differences between groups were noted. We did not found any significant differences in appetite between group A and B. CONCLUSION: Our data show that Tuberil® has no efficacy neither in reducing appetite in children nor in increasing dietary compliance. We believe that only a nutritionally balanced diet and our attention in verifying their compliance led to the reduction in BMI, weight and waist circumferences noted in our series.
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Fármacos Antiobesidad/uso terapéutico , Actividad Motora , Obesidad/dietoterapia , Obesidad/tratamiento farmacológico , Preparaciones de Plantas/uso terapéutico , Adolescente , Antropometría , Apetito/fisiología , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , Masculino , Obesidad/psicología , Cooperación del Paciente , Resultado del TratamientoRESUMEN
BACKGROUND: No evidence of disease activity (NEDA) is becoming a gold standard in the evaluation of disease modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS). NEDA-3 status is the absence of relapses, new activity on brain MRI, and disability progression. NEDA-4 meets all NEDA-3 criteria plus lack of brain atrophy. OBJECTIVE: Aim of this study was to investigate the prevalence of two-year NEDA-3, NEDA-4, six-month delayed NEDA-3 (6mdNEDA-3), and six-month delayed NEDA-4 (6mdNEDA-4) in a cohort of patients with RRMS. Six-month delayed measures were introduced to consider latency of action of drugs. METHODS: Observational retrospective monocentric study. All the patients with RRMS starting DMT between 2015 and 2018, and with 2-year of follow-up, were included. Annualized brain volume loss (a-BVL) was calculated by SIENA software. RESULTS: We included 108 patients, the majority treated with first line DMT. At 2-year follow-up, 35 % of patients were NEDA-3 (50 % 6mdNEDA-3), and 17 % NEDA-4 (28 % 6mdNEDA-4). Loss of NEDA-3 status was mainly driven by MRI activity (70 %), followed by relapses (56 %), and only minimally by disability progression (7 %). CONCLUSION: In our cohort 2-year NEDA status, especially including lack of brain atrophy, was hard to achieve. Further studies are needed to establish the prognostic value of NEDA-3 and NEDA4 in the long-term follow-up.
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Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Esclerosis Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Prevalencia , Progresión de la Enfermedad , Recurrencia , AtrofiaRESUMEN
Lentisk (Pistacia lentiscus L., Anacardiaceae) is an evergreen shrub that is widespread over the Mediterranean Region. The species is also cultivated as an ornamental plant in Italy. In August 2008, a survey carried out in a forest nursery in Sardinia (39°57'N, 9°13'E) revealed the presence of symptoms such as wilting and desiccation of foliage associated with root and collar rot on 1- to 3-year-old potted seedlings of lentisk. Approximately 30% of 1,500 potted plants were affected. A Phytophthora sp. was consistently isolated from infected roots on synthetic mucor agar medium. Colonies on carrot agar (CA) were stellate to slightly radiate with low aerial mycelium. Growth occurred from 6 to 38°C, with an optimum around 30°C (mean radial growth rate was 11.8 mm per day). Sporangia were produced abundantly in unsterile pond water; they were nonpapillate, persistent, ellipsoid to obpyriform, (57.8-) 80.5 (-100.5) × (30.2-) 39.3 (-51.5) µm, with a length/breadth ratio of 2.0:1, proliferating internally or externally. Hyphal swellings were spherical to irregular and frequently produced in chains. Chlamydospores were not observed. Isolates were heterothallic and produced oogonia with amphigynous antheridia when paired with A2 mating type of Phytophthora drechsleri and P. cryptogea. Cultural and morphological features were in close agreement with those recently published for Phytophthora sp. "niederhauserii" (4). The rDNA internal transcribed spacer (ITS) sequence (ITS1-5.8S-ITS2) of a representative isolate (LEN1) was submitted to GenBank (Accession No. GU119914) and BLAST searches showed 100% similarity with sequences of P. sp. "niederhauserii" deposited in GenBank (Accession Nos. GQ848201 and EU244850). The strain LEN1 was stored in the culture collection of the Department of Plant Protection at the University of Sassari. Its pathogenicity was verified by inoculating 10 1-year-old lentisk seedlings grown in pots. A mycelial plug (3 to 4 mm2) taken from the margin of a 4-day-old culture grown on CA was put in a shallow wound (~3 mm) made by a sterile scalpel at the root collar of each seedling. All plants were kept in a greenhouse at 25°C in natural daylight. After 20 days, inoculated plants began to show symptoms similar to those observed on naturally infected plants. Five control plants inoculated with sterile CA plugs did not develop any disease symptoms. The pathogen was reisolated from infected tissues, thus fulfilling Koch's postulates. P. sp. "niederhauserii" has not been formally described, however, so far there have been several reports of this species in Europe (1,3). Previously, other Phytophthora spp. were reported associated with lentisk root rot in Italy (2). To our knowledge, this is the first report of P. sp. "niederhauserii" on Pistacia lentiscus and it emphasizes the susceptibility of the Mediterranean species to this new pathogen. References: (1) A. Józsa et al. Plant Pathol. 59:1166, 2010. (2) G. Magnano Di San Lio et al. Micol. Ital. 21:3, 1992. (3) E. Moralejo et al. Plant Pathol. 58:100, 2009. (4) A. Pérez-Sierra et al. Plant Dis. 94:534, 2010.
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Since December 2008, a severe outbreak of ink disease has been observed in a chestnut grove in the Sardinia Region in Italy (40°01'N, 9°13'E, 1,200 m above sea level). Trees have shown symptoms such as microphylly and yellowish foliage as well as necrosis on the main roots and collar. Isolations were made from infected roots and soil using green apples as baits. Small pulp pieces were cut from the lesions that developed in the apples and plated on Phytophthora selective medium (1). In addition to Phytophthora cambivora, another Phytophthora sp. was detected from 60% of 25 symptomatic trees sampled. Colonies subcultured onto carrot agar (CA) were generally appressed and stellate. Growth occurred from 2 to 26°C with an optimum at 20°C (mean radial growth rate of 4.5 mm/day). Sporangia were produced abundantly in unsterile pond water; they were semipapillate, rarely bipapillate, limoniform or ovoid, occasionally caducous with short pedicels (<5 µm), and 35.2 to 58.1 (46.3) × 22.1 to 35.3 (31.9) µm, with a length/breadth ratio of 1.5:1. Catenulate hyphal swellings were frequently present, whereas no chlamydospores were observed. Isolates produced numerous homothallic oogonia with diameters from 23.7 to 31.7 (27.3) µm. Antheridia were predominantly paragynous. Cultural and morphological features were in close agreement with those described for P. pseudosyringae (2). Identity was confirmed by analysis of the internal transcribed spacer region (ITS1-5.8S-ITS2) of rDNA. BLAST searches at GenBank showed 100% identity with reference sequences of P. pseudosyringae (Accession Nos. AY230190 and EU074793). The representative sequence of one P. pseudosyringae strain (CST2A), stored in the culture collection of the Department of Plant Protection-University of Sassari, was submitted to GenBank (Accession No. GU460375). Koch's postulates were fulfilled by inoculating 10 5-month-old chestnut seedlings grown in pots. One shallow cut was made into the bark on the main stem and an agar plug colonized by P. pseudosyringae was inserted beneath the flap. Seedlings were kept at the laboratory at temperatures varying from 16 to 22°C and watered as necessary. After 20 days, extensive, sunken, necrotic lesions measuring 27.2 ± 1.9 mm (mean + standard error) developed around the inoculation sites. Control plants inoculated with sterile CA plugs did not show any disease symptoms. The pathogen was consistently reisolated from infected tissues. P. pseudosyringae has recently been reported as the causal agent of stem necroses on chestnut seedlings in a nursery in Spain (3). To our knowledge, this is the first report of P. pseudosyringae on Castanea sativa in Italy. References: (1) C. M. Brasier and S. A. Kirk. Plant Pathol. 50:218, 2001. (2) T. Jung et al. Mycol. Res. 107:772, 2003. (3) C. Pintos Varela et al. Plant Dis. 91:1517, 2007.
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Strawberry tree, family Ericaceae, is an evergreen shrub or small tree that grows in the Mediterranean Region. In spring 2009, a survey was conducted to study the fungi associated with canker and branch dieback of strawberry tree in a natural stand located on Caprera Island (41°12'N, 9°27'E), Italy. Fungal isolates obtained from live twigs and branches showing sunken necrotic bark lesions were identified as Diplodia scrobiculata J. de Wet, Slippers & M.J. Wingf. on the basis of morphological features (1). On potato dextrose agar (PDA) at 25°C, D. scrobiculata isolates developed white colonies with appressed mycelium that became dark gray after 4 to 6 days and formed pycnidia after 2 weeks on sterile Pinus radiata needles placed on the PDA surface. The conidia were dark brown with zero to three septa, clavate with truncate base, and measured 31.1 to 41.9 (36.8) × 11.3 to 16.3 (12.6) µm, with a length/width ratio of 2.9 ± 0.1 (mean ± standard error) (n = 50). Identity was confirmed by analysis of the internal transcribed spacer region (ITS1-5.8S-ITS2) of rDNA. BLAST searches in GenBank showed 100% similarity with reference sequences of D. scrobiculata (GenBank Nos. AY160200, EU220438, EU220444, and EU392283). The representative sequence of one D. scrobiculata strain (BL5), stored in the culture collection of the Department of Plant Protection at the University of Sassari, was deposited in GenBank (Accession No. GU722102). Pathogenicity of strain BL5 was tested by stem inoculation on eight 2-year-old strawberry tree seedlings maintained in a greenhouse at 18 to 26°C. A mycelial plug (3 to 4 mm2) taken from the margin of an actively growing colony on PDA was put in a shallow wound (~3 mm) made by a scalpel on the basal part of the stem of each seedling. Four weeks after inoculation, the seedlings displayed dark brown-to-black discoloration, measuring 1.7 ± 0.6 cm (mean ± standard error) of the bark and wood tissues of the stems. The pathogen was successfully reisolated from symptomatic stem tissues, thus fulfilling Koch's postulates. Three control seedlings inoculated with sterile PDA plugs remained asymptomatic. These results demonstrate the active role played by D. scrobiculata in the aetiology of the canker and branch dieback observed on strawberry tree. D. scrobiculata is generally recognized as a weak pathogen of gymnosperms worldwide (2), however, it has recently been reported on olive in Italy (3). To our knowledge, this is the first report of D. scrobiculata on strawberry tree. Currently, further investigations are in progress to determine the possible role of biotic and abiotic factors in the development of this disease. References: (1) J. De Wet et al. Mycol. Res. 107:557, 2003. (2) J. De Wet et al. Mol. Phylogenet. Evol. 46:116, 2008. (3) C. Lazzizera et al. Fungal Divers. 31:63, 2008.
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A survey was carried out in the spring of 2003 to study the fungi associated with declining trees in a cork oak (Quercus suber L.) forest located in Sassari Province, Sardinia, Italy (40°52'N, 9°01'E) at an altitude of 150 m (above sea level). Several isolates obtained from live twigs and branches showing sunken necrotic bark lesions were identified as Fusicoccum parvum Pennycook & Samuels (teleomorph Botryosphaeria parva Pennycook & Samuels). Neither pycnidia nor ascomata were observed on the symptomatic samples collected. On potato dextrose agar (PDA) at 25°C, the isolates developed an aerial and compact mycelium, initially white but becoming gray after 4 to 6 days, and produced pycnidia after 1 month on sterile cork oak twigs placed on the surface of PDA. Conidia from culture were hyaline, ellipsoidal to fusiform, externally smooth, thin walled, nonseptate, 12 to 19 (15.5) × 5.5 to 8.5 (6.5) µm, with length/width ratio of 2.4 ± 0.1 (mean ± standard error). Identity was confirmed by analysis of the nucleotide sequences of the internal transcribed spacer (ITS) from the rRNA repeat and the translation elongation factor 1-alpha (EF1-α), as done elsewhere (1,4). BLAST searches at GenBank showed a high identity with reference sequences (ITS: >99%; EF1-α: 100%). Representative sequences of both regions were deposited at GenBank (ITS: Accession No. DQ487157; EF1-α: Accession No. DQ487158). Pathogenicity tests were carried out on seven 2-year-old cork oak seedlings maintained in a greenhouse at 14 to 26°C with the B. parva strain CBS 119937 obtained in this study. A mycelial plug (3 to 4 mm2) taken from the margin of an actively growing colony on PDA was put in a shallow wound made by a scalpel on the basal part of the stem of each seedling. Sterile PDA plugs were placed into similar wounds on three control seedlings. The inoculation points were wrapped in Parafilm to retain moisture for 1 week. After 4 weeks, all seedlings inoculated with B. parva died and showed a collapse of the stem cortical tissues associated with dark brown discolorations and vascular necrosis measuring 10.9 ± 0.4 cm. No symptoms were visible in the control seedlings. The pathogen was reisolated from all the inoculated seedlings, thus fulfilling Koch's postulates. The results confirm the virulence of this fungus and point to its possible involvement in the aetiology of cork oak decline. B. parva is a cosmopolitan, plurivorous pathogen causing disease in several hosts of economic importance, such as grapevine (3), kiwi (2), and Eucalyptus spp. trees (1). To our knowledge, this is the first report of B. parva causing canker disease on cork oak trees. References: (1) A. Gezahgne et al. S. Afr. J. Bot. 70:241, 2004. (2) S. R. Pennycook and G. J. Samuels. Mycotaxon 24:445, 1985. (3) A. J. L. Phillips. Phytopathol. Mediterr. 41:3, 2002. (4) B. Slippers et al. Mycologia 96:83, 2004.
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Neuroblastoma (NB) is an aggressive pediatric tumor, responsible for 15% of cancer-related deaths in childhood, lacking an effective treatment in its advanced stages. The P2X7 receptor for extracellular ATP was associated to NB cell proliferation and recently emerged as a promoter of tumor engraftment, growth and vascularization. In an effort to identify new therapeutic options for neuroblastoma, we studied the role of P2X7 receptor in NB biology. We first analyzed the effect of P2X7 activation or down-modulation of the main biochemical ways involved in NB progression: the PI3K/Akt/GSK3ß/MYCN and the HIF1α/VEGF pathways. In ACN human NB cells, P2X7 stimulation enhanced PI3K/Akt, while decreasing GSK3ß activity. In the same model, P2X7 silencing or antagonist administration reduced the activity of PI3K/Akt and increased that of GSK3ß, leading to a decrease in cellular glycogen stores. Similarly, P2X7 downmodulation caused a reduction in HIF1α levels and vascular endothelial growth factor (VEGF) secretion. Systemic administration of two different P2X7 antagonists (AZ10606120 or A740003) in nude/nude mice reduced ACN-derived tumor growth. An even stronger effect of P2X7 blockade was obtained in a syngeneic immune-competent neuroblastoma model: Neuro2A cells injected in AlbinoJ mice. Together with tumor regression, treatment with P2X7 antagonists caused downmodulation of the Akt/HIF1α axis, leading to reduced VEGF content and decreased vessel formation. Interestingly, in both experimental models, P2X7 antagonists strongly reduced the expression of the probably best-accepted oncogene in NB: MYCN. Finally, we associated P2X7 overexpression with poor prognosis in advanced-stage NB patients. Taken together, our data suggest that P2X7 receptor is an upstream regulator of the main signaling pathways involved in NB growth, metabolic activity and angiogenesis, and a promising therapeutic target for neuroblastoma treatment.
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Neuroblastoma/metabolismo , Receptores Purinérgicos P2X7/fisiología , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones Desnudos , Trasplante de Neoplasias , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Traditionally, the stomach is regarded as two functional unit regions: 1) a proximal portion mainly involved in receptive relaxation and emptying of liquids; and 2) a distal portion that grinds, mixes and empties solids. Manometric and radioisotopic studies have been employed to construct such a physiological model. More recently, ad hoc designed studies have led to the identification of other factors that contribute to the regulation of gastric emptying. Antral, intestinal and pyloric motility, fundic tone and antropyloroduodenal coordination appear to be all involved in the regulation of gastric emptying. Nowadays, no single technique can simultaneously measure those parameters. Gastroduodenal manometry can be regarded as the most advanced technique, in studying gastrointestinal motility. Nevertheless, fundic tone, which is an important determinant of gastric emptying, cannot be concurrently recorded.
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Duodeno/fisiología , Vaciamiento Gástrico/fisiología , Manometría , Estómago/fisiología , Motilidad Gastrointestinal/fisiología , HumanosRESUMEN
Mesenteric cysts are uncommon abdominal masses in children. They occur most frequently in the small bowel mesentery and often contain chylous fluid. These cysts may be multilocular, grow to huge proportions and are believed to be caused by obstructed, malformed, ectopic lymphatic tissue. The patients' clinical presentations is dependent on cyst size, location and related complications such as partial or complete bowel obstruction, perforation, peritonitis, volvulus and malignant degeneration. Surgical resection is the treatment of choice. Ultrasound and CT are the most valuable modalities for evaluating mesenteric cysts.
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Neoplasias Abdominales/diagnóstico , Linfangioma/diagnóstico , Quiste Mesentérico/diagnóstico , Neoplasias Abdominales/complicaciones , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Linfangioma/complicaciones , Quiste Mesentérico/etiologíaRESUMEN
This article presents a case of a young, otherwise asymptomatic male patient with a parotid gland enlargement. The initial clinical history did not reveal any risk factors related with HIV infection. A fine needle aspiration biopsy of the lesion showed a benign cystic lymphoepithelial lesion of the parotid gland. This once unusual lesion of the salivary gland has been recently associated with infection by the human immunodeficiency virus (HIV) and is presently encountered with increased frequency in the clinical practice. The knowledge of the association between these two entities led, in this case, to the diagnosis of HIV infection in an otherwise asymptomatic patient. Early detection of HIV infection is of vital importance since it has been demonstrated that prompt treatment of these patients with AZT slows down the progression of the disease.
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Síndrome de Inmunodeficiencia Adquirida/diagnóstico , Linfocele/diagnóstico , Enfermedades de las Parótidas/diagnóstico , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/patología , Adulto , Biopsia con Aguja , Humanos , Linfocele/complicaciones , Linfocele/patología , Masculino , Enfermedades de las Parótidas/complicaciones , Enfermedades de las Parótidas/patología , Glándula Parótida/diagnóstico por imagen , Glándula Parótida/patología , Tomografía Computarizada por Rayos XRESUMEN
A specific, sensitive and reliable gas chromatography-mass spectrometry (GC-MS) technique for detection of sympathomimetic amines following urinary extraction is proposed. Amphetamine, phentermine, ephedrine, mephenorex, methylphenidate, benzphetamine, clobenzorex and internal standard (fenfluramine) are extracted from urines at pH 7.0 using elution by chloroform-isopropanol on C18 cartridges. Derivatization followed by GC-MS analysis allows identification of these drugs founded on relative retention times and mass spectra. The quantitation limit for derivatizable drugs was found to be 200 ng/ml and 500 ng/ml for underivatizable drugs.
Asunto(s)
Doping en los Deportes , Simpatomiméticos/orina , Anfetaminas/orina , Benzfetamina/orina , Fenfluramina/análogos & derivados , Fenfluramina/orina , Cromatografía de Gases y Espectrometría de Masas , HumanosRESUMEN
Fetal stem cells transplants depend on nucleated cells from fetal blood. This study was a prospective randomized trials to compare the collection of fetal blood by gravity into a bag containing anticoagulant, before and after delivery of the placenta. The obstetric and the newborn characteristics in the two group were not significantly different. The mean volume of fetal blood collected while the placental was still in utero was 74.93+/-7.1 ml as against 35.78+/-3.6 ml for collection of fetal blood after delivery of the placenta.