Regeneração hepática em animais jovens com estenose da veia porta ou ligadura da artéria hepática: estudos histológicos, moleculares e avaliação dos efeitos da insulina e do tacrolimus como agentes regenerativos

INTRODUÇÃO: O transplante hepático é o único tratamento efetivo para uma variedade de doenças hepáticas irreversíveis. No entanto, o número limitado de doadores pediátricos leva ao uso de enxertos hepáticos de doadores adultos, com necessidade de anastomoses vasculares mais complexas. Essas anastomoses tornam-se complicadas pela diferença no calibre dos vasos entre o doador e o receptor, resultando em alterações do fluxo sanguíneo, estenose da anastomose venosa ou arterial e trombose. Os efeitos para regeneração hepática decorrentes da privação do fluxo sanguíneo pela veia porta ou pela artéria hepática não estão completamente elucidados. Experimentalmente, quando um lobo do fígado não recebe o fluxo venoso portal, é observada atrofia deste segmento e hipertrofia do restante do órgão perfundido. Embora existam vários modelos experimentais para estudo da regeneração hepática, poucos são focados em animais em crescimento. Além disso, os efeitos regenerativos de drogas como o tacrolimus e a insulina precisam ser pesquisados, com o objetivo de encontrar um tratamento ideal para a insuficiência hepática ou um método de estimular a regeneração do fígado após ressecções ou transplantes parciais. O objetivo do presente estudo é descrever modelos de regeneração hepática em ratos em crescimento com: 1) ausência de fluxo hepático arterial e 2) redução do fluxo portal. Adicionalmente, o estudo avalia o efeito pró-regenerativo do tacrolimus e da insulina nesses modelos descritos. MÉTODOS: cento e vinte ratos (entre 50 e 100g de peso) foram divididos em 6 grupos, de acordo com o tipo de intervenção cirúrgica: Grupo 1, incisão abdominal sem intervenção hepática; Grupo 2, hepatectomia a 70%; Grupo 3, hepatectomia a 70% + estenose de veia porta; Grupo 4, hepatectomia a 70% + ligadura da artéria hepática; Grupo 5, hepatectomia a 70% + estenose de veia porta + insulina; Grupo 6, hepatectomia a 70% + estenose de veia porta + tacrolimus. Os animais dos grupos 1 ao 4 foram subdivididos em 5 subgrupos de acordo com o momento da morte: 1, 2, 3, 5 e 10 dias após a intervenção cirúrgica. Os animais dos grupos 5 e 6 foram subdividos em 2 subgrupos de acordo com o momento da morte: 2 e 10 dias após a intervenção cirúrgica. Os lobos hepáticos remanescentes foram submetidos à análise histomorfométrica, imuno-histoquímica e molecular. RESULTADOS: Verificou-se que no grupo com hepatectomia a 70% houve recuperação do peso do fígado no terceiro dia com aumento da atividade mitótica, enquanto que no grupo com estenose portal não se observou esse fenômeno (p < 0,001). A insulina e o tacrolimus promoveram aumento do peso do fígado e do índice mitótico. A atividade mitótica foi considerada aumentada nos animais dos grupos hepatectomia, hepatectomia + ligadura da artéria, insulina e tacrolimus; e esse parâmetro estava reduzido no grupo submetido à hepatectomia + estenose portal (p < 0,001). A expressão de interleucina 6 estava presente em todos os animais, sendo significativamente maior nos grupos hepatectomia, hepatectomia + ligadura da artéria e significativamente menor no grupo hepatectomia + estenose portal. Entretanto, a administração de tacrolimus ou insulina recuperou os níveis teciduais de interleucina 6 no grupo com estenose portal. CONCLUSÕES: No presente estudo foi padronizado um modelo simples e facilmente reprodutível para estudar a regeneração hepática em ratos em crescimento com redução do fluxo arterial ou venoso para o fígado. Foi demonstrado que a administração de insulina ou tacrolimus é capaz de reverter os efeitos deletérios da estenose portal na regeneração hepática. A obstrução do fluxo arterial não afetou a capacidade regenerativa hepática

MY Camelopardalis, a very massive merger progenitor

Context. The early-type binary MY Cam belongs to the young open cluster Alicante 1, embedded in Cam OB3. Aims. MY Cam consists of two early-O type main-sequence stars and shows a photometric modulation suggesting an orbital period slightly above one day. We intend to confirm this orbital period and derive orbital and stellar parameters. Methods. Timing analysis of a very exhaustive (4607 points) light curve indicates a period of 1.1754514 ± 0.0000015 d. High-resolution spectra and the cross-correlation technique implemented in the todcor program were used to derive radial velocities and obtain the corresponding radial velocity curves for MY Cam. Modelling with the stellar atmosphere code fastwind was used to obtain stellar parameters and create templates for cross-correlation. Stellar and orbital parameters were derived using the Wilson-Devinney code, such that a complete solution to the binary system could be described. Results. The determined masses of the primary and secondary stars in MY Cam are 37.7 ± 1.6 and 31.6 ± 1.4M⊙, respectively. The corresponding temperatures, derived from the model atmosphere fit, are 42 000 and 39 000 K, with the more massive component being hotter. Both stars are overfilling their Roche lobes, sharing a common envelope. Conclusions. MY Cam contains the most massive dwarf O-type stars found so far in an eclipsing binary. Both components are still on the main sequence, and probably not far from the zero-age main sequence. The system is a likely merger progenitor, owing to its very short period.

GU Monocerotis: A high-mass eclipsing overcontact binary in the young open cluster Dolidze 25

Context. The eclipsing binary GU Mon is located in the star-forming cluster Dolidze 25, which has the lowest metallicity measured in a Milky Way young cluster. Aims. GU Mon has been identified as a short-period eclipsing binary with two early B-type components. We set out to derive its orbital and stellar parameters. Methods. We present a comprehensive analysis, including B and V light curves and 11 high-resolution spectra, to verify the orbital period and determine parameters. We used the stellar atmosphere code FASTWIND to obtain stellar parameters and create templates for cross-correlation. We obtained a model to fit the light and radial-velocity curves using the Wilson-Devinney code iteratively and simultaneously. Results. The two components of GU Mon are identical stars of spectral type B1 V with the same mass and temperature. The light curves are typical of an EW-type binary. The spectroscopic and photometric analyses agree on a period of 0.896640 ± 0.000007 d. We determine a mass of 9.0 ± 0.6 M⊙ for each component and for temperatures of 28 000 ± 2000 K. Both values are consistent with the spectral type. The two stars are overfilling their respective Roche lobes, sharing a common envelope and, therefore the orbit is synchronised and circularised. Conclusions. The GU Mon system has a fill-out factor above 0.8, containing two dwarf B-type stars on the main sequence. The two stars are in a very advanced stage of interaction, with their extreme physical similarity likely due to the common envelope. The expected evolution of such a system very probably leads to a merger while still on the main sequence.

Cortical Abnormalities in Adults and Adolescents with Major Depression based on Brain Scans from 20 Cohorts Worldwide in the ENIGMA Major Depressive Disorder Working Group

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen’s d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Novel antennal lobe substructures revealed in the small hive beetle Aethina tumida

The small hive beetle, Aethina tumida, is an emerging pest of social bee colonies. A. tumida shows a specialized life style for which olfaction seems to play a crucial role. To better understand the olfactory system of the beetle, we used immunohistochemistry and 3-D reconstruction to analyze brain structures, especially the paired antennal lobes (AL), which represent the first integration centers for odor information in the insect brain. The basic neuroarchitecture of the A. tumida brain compares well to the typical beetle and insect brain. In comparison to other insects, the AL are relatively large in relationship to other brain areas, suggesting that olfaction is of major importance for the beetle. The AL of both sexes contain about 70 olfactory glomeruli with no obvious size differences of the glomeruli between sexes. Similar to all other insects including beetles, immunostaining with an antiserum against serotonin revealed a large cell that projects from one AL to the contralateral AL to densely innervate all glomeruli. Immunostaining with an antiserum against tachykinin-related peptides (TKRP) revealed hitherto unknown structures in the AL. Small TKRP-immunoreactive spherical substructures are in both sexes evenly distributed within all glomeruli. The source for these immunoreactive islets is very likely a group of about 80 local AL interneurons. We offer two hypotheses on the function of such structures.

Petrophysical measurement of ODP Leg 122 and 123 samples (Tables 1, 2)

The capillary-pressure characteristics of 22 samples of lithified post-Paleozoic Indian-Ocean carbonates were compared to published data from older carbonate rocks (lower Paleozoic Hunton Group of Texas and Oklahoma). The Indian-Ocean samples are considerably more porous than are the Paleozoic samples, yet all of the Indian-Ocean samples fit readily into a descriptive petrofacies scheme previously established for the Hunton Group. The Indian-Ocean samples may be assigned to four petrophysical facies (petrofacies) based on the shapes of their capillary-pressure curves, their pore-throat-size distributions, their estimated recovery efficiency values (for nonwetting fluids), and the visual characteristics of their pore systems, as observed with a scanning-electron microscope. Petrofacies assignments for the Indian-Ocean samples are as follows. Petrofacies I includes six samples collected from the coarse basal portions of event deposits (primarily turbidites). These samples have large throats, leptokurtic throat-size distributions, low- to moderate recovery efficiency values, concave cumulative-intrusion capillary-pressure curves, and high porosity values. Petrofacies II includes two sedimentologically dissimilar samples that have medium-size throats, platykurtic throat-size distributions, moderate- to-high recovery efficiency values, gently sloping cumulative-intrusion capillary-pressure curves, and high porosity values. Petrofacies III includes two polymictic sandstones and a skeletal packstone that have small throats, polymodal throat-size distributions, moderate recovery efficiency values, gently sloping cumulative-intrusion capillary-pressure curves, and high porosity values. Petrofacies IV includes 11 samples, mostly recrystallized neritic carbonates, that have small throats, leptokurtic throat-size distributions, high recovery efficiency values, convex cumulative-intrusion capillary-pressure curves, and low porosity values. Comparison of petrofacies assignment to core-, thin-section-, and smear-slide data, and to inferred depositional setting, suggests that pore systems in most samples from Holes 765C and 766A result from primary depositional features, whereas pore systems in samples from Hole 761C and one sample from Hole 765C have been strongly influenced by diagenetic processes. For Hole 761C, prediction of petrophysical parameters should be most successful if based on diagenetic facies patterns. By contrast, the distribution of favorable reservoir facies and of permeability barriers in less highly altered rocks collected from Holes 765C and 766A is related to depositional patterns. Recovery efficiency is inversely related to both porosity and median throat size for the present data set. This relationship is similar to that observed for carbonates of the lower Paleozoic Hunton Group and the Ordovician Ellenburger dolomite, but opposite of that observed for some other ancient carbonates. The coarse deposits of the massive basal units of turbidites are petrophysically distinct and form a coherent petrophysical group (Petrofacies I) with substantial reservoir potential. Two samples assigned to Petrofacies I have extremely large throats (median throat size at least 4 ?m, and at least six times that of any other sample) and therefore high permeability values. These two samples come from thin, coarse turbidites that lack or have poorly developed fine divisions and are interpreted to have been deposited on channeled suprafan lobes in a proximal mid-fan setting. The restriction of extremely high permeability values to a single depositional facies suggests that careful facies mapping of deep-sea fans in a deliberate search for such coarse turbidites could dramatically enhance the success of exploration for aquifers or hydrocarbon reservoirs. Such reservoirs should have substantial vertical heterogeneity. They should have high lateral permeability values but low vertical permeability values, and reservoir sections should include numerous thin units having widely differing petrophysical characteristics.

Holocene depositional history of the Burdekin River delta of northeastern Australia: A model for a low-accommodation, highstand delta

The Burdekin River of northeastern Australia has constructed a substantial delta during the Holocene (delta plain area 1260 km2). The vertical succession through this delta comprises (1) a basal, coarse-grained transgressive lag overlying a continental omission surface, overlain by (2) a mud interval deposited as the coastal region was inundated by the postglacially rising sea, in turn overlain by (3) a generally sharp-based sand unit deposited principally in channel and mouth-bar environments with lesser volumes of floodplain and coastal facies. The Holocene Burdekin Delta was constructed as a series of at least thirteen discrete delta lobes, formed as the river avulsed. Each lobe consists of a composite sand body typically 5-8 m thick. The oldest lobes, formed during the latter stages of the postglacial sea-level rise (10-5.5 kyr BP), are larger than those formed during the highstand (5.5-3 kyr BP), which are in turn larger than those formed during the most recent slight sea-level lowering and stillstand (3-0 kyr BP). Radiocarbon ages and other stratigraphic data indicate that inter-avulsion period has decreased through time coincident with the decrease in delta lobe area. The primary control on Holocene delta architecture appears to have been a change from a pluvial climate known to characterize the region 12-4 kyr BP to the present drier, ENSO-dominated climate. In addition to decreasing the sediment supply via lower rates of chemical weathering, this change may have contributed to the shorter avulsion period by facilitating extreme variability of discharge. More frequent avulsion may also have been facilitated by the lengthening of the delta-plain channels as the system prograded seaward. Copyright © 2006, SEPM (Society for Sedimentary Geology).

Segmental lung lobe torsion in a 7-week-old Pug

Case summary: A 7-week-old, intact female Pug was referred with an acute history of expiratory dyspnea, tachypnea, and pyrexia. Radiologic evaluation revealed bilateral pleural effusion and a poorly demarcated area of soft tissue opacity cranial to the heart. The presence of air bronchograms in the cranial lung lobes suggested alveolar parenchymal pathology consistent with pulmonary edema, congestion, or cellular infiltration. Exploratory thoracotomy revealed a segmental torsion of the left cranial lung lobe. The affected lobe was removed and the puppy recovered uneventfully. Unique information: Lung lobe torsion tends to occur more frequently in mature large breed dogs at a mean age of 3 years. The age, breed, and segmental nature of the torsion in the reported case are contrary to most of the previously documented cases of lung lobe torsion. To the authors' knowledge, this is the first report of lung lobe torsion in a 7-week-old dog.

Synaptogenesis in the mushroom body calyx during metamorphosis in the honeybee Apis mellifera: An electron microscopic study

The goals of this study are to determine relationships between synaptogenesis and morphogenesis within the mushroom body calyx of the honeybee Apis mellifera and to find out how the microglomerular structure characteristic for the mature calyx is established during metamorphosis. We show that synaptogenesis in the mushroom body calycal neuropile starts in early metamorphosis (stages P1-P3), before the microglomerular structure of the neuropile is established. The initial step of synaptogenesis is characterized by the rare occurrence of distinct synaptic contacts. A massive synaptogenesis starts at stage P5, which coincides with the formation of microglomeruli, structural units of the calyx that are composed of centrally located presynaptic boutons surrounded by spiny postsynaptic endings. Microglomeruli are assembled either via accumulation of fine postsynaptic processes around preexisting presynaptic boutons or via ingrowth of thin neurites of presynaptic neurons into premicroglomeruli, tightly packed groups of spiny endings. During late pupal stages (P8-P9), addition of new synapses and microglomeruli is likely to continue. Most of the synaptic appositions formed there are made by boutons (putative extrinsic mushroom body neurons) into small postsynaptic profiles that do not exhibit presynaptic specializations (putative intrinsic mushroom body neurons). Synapses between presynaptic boutons characteristic of the adult calyx first appear at stage P8 but remain rare toward the end of metamorphosis. Our observations are consistent with the hypothesis that most of the synapses established during metamorphosis provide the structural basis for afferent information flow to calyces, whereas maturation of local synaptic circuitry is likely to occur after adult emergence.

A passive reflect array with dual-feed microstrip patch elements

The design, development, and testing of an X-band 137-element passive reflect away capable of incorporating active devices such as transistor amplifiers is presented. In order to avoid grating lobes in the radiation pattern, the interelement spacing is minimized using dual-feed aperture-coupled patch antenna elements. Far-field radiation pattern results are presented and compared with the predicted radiation patterns. (C) 1999 John Wiley & Sons, Inc.

Growth of experimentally reconstructed thalli of the lichen Parmelia conspersa

The centres of thalli of Parmelia conspersa (Ehrh. ex Ach.) Ach. were removed, the major lobes were separated from each other and from the substratum, and then the lobes were glued back together in their original configuration. The mean radial growth, the pattern of seasonal growth, and the degree of variation in growth between lobes of the reconstructed thalli, were similar to those of control thalli. When lobes were removed from thalli and glued apart from one another, the pattern of seasonal growth and the degree of variation in lobe growth were unaffected, but annual growth rates were reduced compared with lobes reconstructed into a thallus. Glueing the lobes together in a different configuration and constructing thalli in which each lobe came from a different ‘donor’ thallus did not influence the mean radial growth of the lobes or the degree of variation in lobe growth. These results suggest that although major lobes of P. conspersa are influenced by the proximity of their neighbours there is little chemical exchange between them. In addition, some thalli may form as a result of the fusion of lobes or propagules derived from different individuals. Copyright © 1984, Wiley Blackwell. All rights reserved

Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex--a study in ten patients

OBJECTIVE: To determine the distribution of the pathological changes in the neocortex in multiple-system atrophy (MSA). METHOD: The vertical distribution of the abnormal neurons (neurons with enlarged or atrophic perikarya), surviving neurons, glial cytoplasmic inclusions (GCI) and neuronal cytoplasmic inclusions (NI) were studied in alpha-synuclein-stained material of frontal and temporal cortex in ten cases of MSA. RESULTS: Abnormal neurons exhibited two common patterns of distribution, viz., density was either maximal in the upper cortex or a bimodal distribution was present with a density peak in the upper and lower cortex. The NI were either located in the lower cortex or were more uniformly distributed down the cortical profile. The distribution of the GCI varied considerably between gyri and cases. The density of the glial cell nuclei was maximal in the lower cortex in the majority of gyri. In a number of gyri, there was a positive correlation between the vertical densities of the abnormal neurons, the total number of surviving neurons, and the glial cell nuclei. The vertical densities of the GCI were not correlated with those of the surviving neurons or glial cells but the GCI and NI were positively correlated in a small number of gyri. CONCLUSION: The data suggest that there is significant degeneration of the frontal and temporal lobes in MSA, the lower laminae being affected more significantly than the upper laminae. Cortical degeneration in MSA is likely to be secondary to pathological changes occurring within subcortical areas.

Lobe interactions within the thallus margin and the maintenance of symmetry in the lichen Parmelia conspersa (Ehrh. ex Ach.)Ach.

This study determined whether the radial growth of lobes of the foliose lichen Parmelia conspersa (Ehrh. ex Ach.)Ach. was influenced by the radial growth and morphology of their closest neighbours and whether such interactions influence thallus symmetry. The radial growth and morphology of a sample of adjacent lobes from six thalli was measured. Positive correlations were observed between radial growth and lobe width in three thalli and with the degree of bifurcation of the lobe in two thalli. Negative correlations between the radial growth of adjacent lobes were observed in four thalli suggesting that faster growing lobes may inhibit the growth of their neighbours.Lobes glued next to individual lobes had no signifiacnt effect on the radial growth of wide or narrow lobes. Lobes glued 1-2 mm in front of their neighbours exhibited an intital phase of increased radial growth and then a phase of slower growth. Radial growth decreased when the lobes were glued 2 mm behind their neighbours and these lobes were essentially eliminated by the growth of the adjacent lobes. The data suggest that lobe interactions may incresae lobe growth variation within a thallus. However, the decrease in radial growth of lobes which protrude from the margin and the elimination of slower growing lobes may help to maintain thallus symmetry.

Neuropathological heterogeneity in Alzheimer's disease:A study of 80 cases using principal components analysis

Three hypotheses have been proposed to explain neuropathological heterogeneity in Alzheimer's disease (AD): the presence of distinct subtypes ('subtype hypothesis'), variation in the stage of the disease ('phase hypothesis') and variation in the origin and progression of the disease ('compensation hypothesis'). To test these hypotheses, variation in the distribution and severity of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in 80 cases of AD using principal components analysis (PCA). Principal components analysis using the cases as variables (Q-type analysis) suggested that individual differences between patients were continuously distributed rather than the cases being clustered into distinct subtypes. In addition, PCA using the abundances of SP and NFT as variables (R-type analysis) suggested that variations in the presence and abundance of lesions in the frontal and occipital lobes, the cingulate gyrus and the posterior parahippocampal gyrus were the most important sources of heterogeneity consistent with the presence of different stages of the disease. In addition, in a subgroup of patients, individual differences were related to apolipoprotein E (ApoE) genotype, the presence and severity of SP in the frontal and occipital cortex being significantly increased in patients expressing apolipoprotein (Apo)E allele ε4. It was concluded that some of the neuropathological heterogeneity in our AD cases may be consistent with the 'phase hypothesis'. A major factor determining this variation in late-onset cases was ApoE genotype with accelerated rates of spread of the pathology in patients expressing allele ε4.

Lobe growth variation and the maintenance of symmetry in foliose lichen thalli

The aim of this study was to determine how thallus symmetry could be maintained in foliose lichens when variation in the growth of individual lobes may be high. Hence, the radial growth of a sample of lobes was studied monthly, over 22 months, in 7 thalli of Parmelia conspersa (Ehrh. Ex Ach.) Ach. And 5 thalli of P. glabratula ssp fuliginosa (fr. ex Duby) Laund. The degree of variation in the total radial growth of different lobes within a thallus over 22 months varied between thalli. Individual lobes showed a fluctuating pattern of radial growth from month to month with alternating periods of fast and slow growth. Monthly variations in radial growth of different lobes were synchronized in some but not in all thalli. Few significant correlations were found between the radial growth of individual lobes and total monthly rainfall or shortwave radiation. The levels of ribitol, arabitol and mannitol were measured in individual lobes. All three polyols varied significantly between lobes within a thallus suggesting that variations in algal phostosynthesis and in the partitioning of fungal polyols may contribute to lobe growth variation. The effect on thallus symmetry of lobes which grew radially either consistently faster or slower than average was studied. Slow growing lobes were overgrown, and gaps in the perimeter were eliminated by the growth of neighbouring lobes, in approximately 7 to 9 months. However, a rapidly growing lobe, with its neighbours removed on either side, continued to grow radially at the same rate as rapidly growing control lobes. The results suggested that lobe growth variation results from a combination of factors which may include the origin of the lobes, lobe morphology and the patterns of algal cell division and hyphal elongation in different lobes. No convincing evidence was found to suggest that exchange of carbohydrate occurred between lobes which would tend to equalize their radial growth. Hence, the fluctuating pattern of lobe growth observed may be sufficient to maintain a degree of symmetry in most thalli. In addition, slow growing lobes would tend to be overgrown by faster growing neighbours thus preventing the formation of indentations in the thallus perimeter.