999 resultados para PATHOGENETIC IMPLICATIONS
Resumo:
The aim of this thesis research was to gain a better understanding of the emplacement of rapakivi granite intrusions, as well as the emplacement of gold-bearing hydrothermal fluids in structurally controlled mineralizations. Based on investigations of the magnetic fabric, the internal structures could be analysed and the intrusion mechanisms for rapakivi granite intrusions and respectively different deformation stages within gold-bearing shear and fault zones identified. Aeromagnetic images revealed circular structures within the rapakivi granite batholiths of Wiborg, Vehmaa and Åland. These circular structures represent intrusions that eventually build up these large batholiths. The rapakivi granite intrusions of Vehmaa, Ruotsinpyhtää within the Wiborg batholith and Saltvik intrusions within the Åland batholith all show bimodal magnetic susceptibilities with paramagnetic and ferromagnetic components. The distribution of the bimodality is related to different magma batches of the studied intrusions. The anisotropy of magnetic susceptibility (AMS) reveals internal structures that cannot be studied macroscopically or by microscope. The Ruotsinpyhtää and Vehmaa intrusions represent similar intrusion geometries, with gently to moderately outward dipping magnetic foliations. In the case of Vehmaa, the magnetic lineations are gently plunging and trend in the directions of the slightly elongated intrusion. The magnetic lineations represent magma flow. The shapes of the AMS ellipsoids are also more planar (oblate) in the central part of the intrusion, whereas they become more linear (prolate) near the margin. These AMS results, together with field observations, indicate that the main intrusion mechanism has involved the subsidence of older blocks with successive intrusion of fractionated magma during repeated cauldron subsidence. The Saltvik area within the Åland batholith consists of a number of smaller elliptical intrusions of different rapakivi types forming a multiple intrusive complex. The magnetic fabric shows a general westward dipping of the pyterlite and eastward dipping of the contiguous even-grained rapakivi granite, which indicates a central inflow of magma batches towards the east and west resulting from a laccolitic emplacement of magma batches, while the main mechanism for space creation was derived from subsidence. The magnetic fabric of structurally controlled gold potential shear and fault zones in Jokisivu, Satulinmäki and Koijärvi was investigated in order to describe the internal structures and define the deformation history and emplacement of hydrothermal fluids. A further aim of the research was to combine AMS studies with palaeomagnetic methods to constrain the timing for the shearing event relative to the precipitation of ferromagnetic minerals and gold. All of the studied formations are dominated by monoclinic pyrrhotite. The AMS directions generally follow the tectonic structures within the formations. However, internal variations in the AMS direction as well as the shapes of the AMS ellipsoids are observed within the shear zones. In Jokisivu and Satulinmäki in particular, the magnetic signatures of the shear zone core differ from the margins. Furthermore, the shape of the magnetic fabric in the shear zone core of Jokisivu is dominated by oblate shapes, whereas the margins exhibit prolate shapes. These variations indicate a later effect of the hydrothermal fluids on the general shear event. The palaeo-magnetic results reveal a deflection from the original Svecofennian age geomagnetic direction. These results, coupled with correlations between the orientation of the NRM vectors and the magnetic and rock fabrics, imply that the gold-rich hydrothermal fluids were emplaced pre/syntectonically during the late stages of the Svecofennian orogeny.
Resumo:
Bullying is characterized by an inequality of power between perpetrator and target. Findings that bullies can be highly popular have helped redefine the old conception of the maladjusted school bully into a powerful individual exerting influence on his peers from the top of the peer status hierarchy. Study I is a conceptual paper that explores the conditions under which a skillful, socially powerful bully can use the peer group as a means of aggression and suggests that low cohesion and low quality of friendships make groups easier to manipulate. School bullies’ high popularity should be a major obstacle for antibullying efforts, as bullies are unlikely to cease negative actions that are rewarding, and their powerful position could discourage bystanders from interfering. Using data from the Finnish program KiVa, Study II supported the hypothesis that antibullying interventions are less effective with popular bullies in comparison to their unpopular counterparts. In order to design interventions that can address the positive link between popularity and aggression, it is necessary to determine in which contexts bullies achieve higher status. Using an American sample, Study III examined the effects of five classroom features on the social status that peers accord to aggressive children, including classroom status hierarchy, academic level and grade level, controlling for classroom mean levels of aggression and ethnic distribution. Aggressive children were more popular and better liked in fifth grade relative to fourth grade and in classrooms of higher status hierarchy. Surprisingly, the natural emergence of status hierarchies in children’s peer groups has long been assumed to minimize aggression. Whether status hierarchies hinder or promote bullying is a controversial question in the peer relations’ literature. Study IV aimed at clarifying this debate by testing the effects of the degree of classroom status hierarchy on bullying. Higher hierarchy was concrrently associated with bullying and predictive of higher bullying six months later. As bullies’ quest for power is increasingly acknowledged, some researchers suggest teaching bullies to attain the elevated status they yearn for through prosocial acts. Study V cautions against such solutions by reviewing evidence that prosocial behaviors enacted with the intention of controlling others can be as harmful as aggression.
Resumo:
The genus Euphorbia comprises about 2000 species ranging from annuals to trees, including C3, C4, and CAM species. Euphorbia species widely studied in agriculture includes E. antiquorum, E. carollata, E. dentata, E. dracunculoides, E. esula, E. geniculata, E. granulata, E. helioscopia, E. heterophylla, E. hierosolymitana, E. hirta, E. maculata, E. microphylla, E. nerifolia, E. piluifera, E. pulcherrima, E. royleana, E. supine, and E. thiamifolia. These species have been reported mainly in field crops/vegetables, orchards, pastures, and rangelands. Euphorbia plants may present allelopathic effect over desirable cereals, pulses, oilseeds, vegetables, forage plants, and nitrifying bacteria, posing a serious threat to livestock production on open range lands through the release of allelochemicals from roots, stems, leaves, and inflorescence in the rhizosphere. Leaves are reported to be more toxic than other plant parts. Competition of Euphorbia spp. against crop plants is the most important crop yield-limiting factor. The critical period for Euphorbia competition with crops is reported to take place between 17 to 70 days after emergence for most crops, depending on root development during the initial crop growth stage, crop height, tillering or branching capacity, whether weeds emerge at the same time as the crop or later after crop emergence; how quickly crop canopy develops and also on Euphorbia species. A yield reduction of 4-85% has been reported in field crops with different Euphorbia species and distinct occurrence densities. Euphorbia species decrease herbage production by 10 to 100% in pasture and rangelands, with many acting as natural insecticide, fungicide, nematidicide, immunopotentiator, or immunosuppressor.
Resumo:
The aims of this study were to investigate the mating system of a fragmented population of the dioecious tropical tree Myracrodruon urundeuva Allemão, using five microsatellite loci and the mixed mating and correlated mating models. The study was conducted in the Estação Ecológica de Paulo de Farias (436 ha), where the population occupies about 142 ha. The mating system was estimated using 514 open-pollinated offspring, collected from 30 seed-trees. Estimates of the multilocus outcrossing rate confirm that the species is dioecious (t m = 1.0). Low levels of mating among relatives were detected in the population (1 - t s = 0.020). The estimate of paternity correlation (r p(m)) indicated that offsprings were composed of mixtures of half-sibs and full-sibs, with the latter occurring at a low frequency (average of 0.148). The estimated coancestry coefficient within families (Θ = 0.147) was larger and the effective population size (Ne(v)) was lower (Ne(v) = 2.98) than expected in progenies from panmictic populations (Θ = 0.125, Ne(v) = 4, respectively). In terms of conservation, the results indicate that to retain an effective population size of 150, is necessary to collect seeds from at least 50 seed-trees.
Resumo:
The data reviewed here suggest the possibility that a global reduction of blood supply to the whole brain or solely to the infratentorial structures down to the range of ischemic penumbra for several hours or a few days may lead to misdiagnosis of irreversible brain or brain stem damage in a subset of deeply comatose patients with cephalic areflexia. The following proposals are advanced: 1) the lack of any set of clinically detectable brain functions does not provide a safe diagnosis of brain or brain stem death; 2) apnea testing may induce irreversible brain damage and should be abandoned; 3) moderate hypothermia, antipyresis, prevention of arterial hypotension, and occasionally intra-arterial thrombolysis may contribute to good recovery of a possibly large subset of cases of brain injury currently regarded as irreversible; 4) confirmatory tests for brain death should not replace or delay the administration of potentially effective therapeutic measures; 5) in order to validate confirmatory tests, further research is needed to relate their results to specific levels of blood supply to the brain. The current criteria for the diagnosis of brain death should be revised.
Resumo:
The role gap junction channels play in the normal and abnormal functioning of the vascular wall is the subject of much research. The biophysical properties of gap junctions are an essential component in understanding how gap junctions function to allow coordinated relaxation and contraction of vascular smooth muscle. This study reviews the properties thus far elucidated and relates those properties to tissue function. We ask how biophysical and structural properties such as gating, permselectivity, subconductive states and channel type (heteromeric vs homotypic vs heterotypic) might affect vascular smooth muscle tone.
Resumo:
Prior customer orientation research has concentrated mainly on studying the economical potential of customer orientation to companies. Service quality research instead has concentrated on emphasizing the evaluation of service quality from the customer’s perspective. This means that the service providers lack important information regarding customer orientation and service quality they would need for managerial purposes such as selecting and training employees. Therefore, there is an emerging need to study how customer orientation and service quality relate to company processes, policies and employees, and this study answers to those calls. The objective of this study was to examine what is the role of sales personnel’s’ customer orientation in quality of service delivery and what features support the development of customer orientation among sales personnel. Also the components customer orientation were studied extensively in order to understand how they relate to service quality. The empiric part of the study was conducted as a qualitative research by interviewing seven sales people from operative, tactical and strategic levels of the case corporation in order to get a broader view for customer orientation. The findings propose that both organizational factors and individual factors are affecting customer orientation construct inseparably. Organizational factors are bundled in this study under standards, support and systems, whereas individual factors are formed of employees’ personal attributes, motivation and self-perceived decision making authority. The findings suggest that in the service delivery process at an operative level, customer orientation appears largely in the employees’ individualistic characteristics. Their social and technical skills and motivation to serve customers are the most identifiable factors for customer orientation and consequently, quality service. However, organizational standards, support and systems are strongly dictating the frames the operative sales people operate in, having an influence on how the employees are experiencing their decision making authority and in the end, customer orientation. When looking at the service delivery process at tactical and strategic levels, customer orientation is affecting mainly in the organizational constructs through setting standards, support and systems. However, tactical and strategic level employees influence the operative level through individual customer orientation components as well. The findings indicate that their emotion and personal interaction skills are affecting the overall service delivery process mainly through supervisor support and motivation of the operative level employees. Based on this study it can be argued that an organization can operate as a facilitator and create certain frames for customer oriented sales behavior through standards, support and systems. However, as the impact of individual customer orientation factors on sales people’s service quality seems decisive, from an organizational perspective it puts pressures on the recruitment.
Resumo:
Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are expressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms by which cytokine signaling affects the function of stress-related neuroendocrine systems are reviewed in this article.
Resumo:
Extensive neuronal cell loss is observed in Alzheimer's disease. Laminin immunoreactivity colocalizes with senile plaques, the characteristic extracellular histopathological lesions of Alzheimer brain, which consist of the amyloid ß (Aß) peptide polymerized into amyloid fibrils. These lesions have neurotoxic effects and have been proposed to be a main cause of neurodegeneration. In order to understand the pathological significance of the interaction between laminin and amyloid, we investigated the effect of laminin on amyloid structure and toxicity. We found that laminin interacts with the Aß1-40 peptide, blocking fibril formation and even inducing depolymerization of preformed fibrils. Protofilaments known to be intermediate species of Aß fibril formation were also detected as intermediate species of laminin-induced Aß fibril depolymerization. Moreover, laminin-amyloid interactions inhibited the toxic effects on rat primary hippocampal neurons. As a whole, our results indicate a putative anti-amyloidogenic role of laminin which may be of biological and therapeutic interest for controlling amyloidosis, such as those observed in cerebral angiopathy and Alzheimer's disease.
Resumo:
Metastasis is a multistep cascade initiated when malignant cells penetrate the tissue surrounding the primary tumor and enter the bloodstream. Classic studies indicated that blood platelets form complexes around tumor cells in the circulation and facilitate metastases. In other work, the anticoagulant drug heparin diminished metastasis in murine models, as well is in preliminary human studies. However, attempts to follow up the latter observation using vitamin K antagonists failed, indicating that the primary mechanism of heparin action was unrelated to its anticoagulant properties. Other studies showed that the overexpression of sialylated fucosylated glycans in human carcinomas is associated with a poor prognosis. We have now brought all these observations together into one mechanistic explanation, which has therapeutic implications. Carcinoma cells expressing sialylated fucosylated mucins can interact with platelets, leukocytes and endothelium via the selectin family of cell adhesion molecules. The initial organ colonization of intravenously injected carcinoma cells is attenuated in P-selectin-deficient mice, in mice receiving tumor cells pretreated with O-sialoglycoprotease (to selectively remove mucins from cell surfaces), or in mice receiving a single dose of heparin prior to tumor cell injection. In each case, we found that formation of a platelet coating on cancer cells was impeded, allowing increased access of leukocytes to the tumor cells. Several weeks later, all animals showed a decrease in the extent of established metastasis, indicating a long-lasting effect of the short-term intervention. The absence of obvious synergism amongst the three treatments suggests that they all act via a common pathway. Thus, a major mechanism of heparin action in cancer may be inhibition of P-selectin-mediated platelet coating of tumor cells during the initial phase of the metastatic process. We therefore suggest that heparin use in cancer be re-explored, specifically during the time interval between initial visualization of a primary tumor until just after definitive surgical removal.
Resumo:
In this paper, the topology of cortical visuotopic maps in adult primates is reviewed, with emphasis on recent studies. The observed visuotopic organisation can be summarised with reference to two basic rules. First, adjacent radial columns in the cortex represent partially overlapping regions of the visual field, irrespective of whether these columns are part of the same or different cortical areas. This primary rule is seldom, if ever, violated. Second, adjacent regions of the visual field tend to be represented in adjacent radial columns of a same area. This rule is not as rigid as the first, as many cortical areas form discontinuous, second-order representations of the visual field. A developmental model based on these physiological observations, and on comparative studies of cortical organisation, is then proposed, in order to explain how a combination of molecular specification steps and activity-driven processes can generate the variety of visuotopic organisations observed in adult cortex.
Resumo:
Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II) appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS). ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration ([Ca2+]i), a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.
Resumo:
The epidemiology of hepatitis A virus (HAV) infection is shifting from high to intermediate endemicity in Brazil, resulting in increased numbers of susceptible individuals and a greater potential for the emergence of outbreaks. Universal vaccination against HAV has been recommended for children, but updated sero-epidemiological data are necessary to analyze the level of natural immunity and to identify candidates for preventive measures. In addition, more molecular studies are necessary to characterize the genotypes involved in HAV infections and outbreaks. Sera from 299 school children (5-15 years old) and 25 school staff members, collected during an outbreak of HAV at a rural public school in June 2000, were tested for IgM and total anti-HAV antibodies (ELISA). Viral RNA was amplified by RT-PCR from anti-HAV IgM-positive sera and from 19 fecal samples. Direct nucleotide sequencing of the VP1/2A region was carried out on 18 PCR-positive samples. Acute HAV infection was detected by anti-HAV IgM in 93/299 children and in 3/25 adult staff members. The prevalence of total anti-HAV antibodies in IgM-negative children under 5 years of age was only 10.5%. HAV-RNA was detected in 46% IgM-positive serum samples and in 16% stool samples. Sequence analysis showed that half the isolates belonged to subgenotype IA and the other half to IB. On the basis of these data, mass vaccination against HAV is recommended without prevaccination screening, especially for children before they enter school, since nearly 90% of the children under 5 years were susceptible. Molecular characterization indicated the endemic circulation of specific HAV strains belonging to subgenotypes IA and IB.
Resumo:
cDNA microarray is an innovative technology that facilitates the analysis of the expression of thousands of genes simultaneously. The utilization of this methodology, which is rapidly evolving, requires a combination of expertise from the biological, mathematical and statistical sciences. In this review, we attempt to provide an overview of the principles of cDNA microarray technology, the practical concerns of the analytical processing of the data obtained, the correlation of this methodology with other data analysis methods such as immunohistochemistry in tissue microarrays, and the cDNA microarray application in distinct areas of the basic and clinical sciences.
Resumo:
Intracranial aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition requiring immediate neurocritical care. A ruptured aneurysm must be isolated from arterial circulation to prevent rebleeding. Open surgical clipping of the neck of the aneurysm or intra-arterial filling of the aneurysm sack with platinum coils are major treatment strategies in an acute phase. About 40% of the patients suffering from aSAH die within a year of the bleeding despite the intensive treatment. After aSAH, the patient may develop a serious complication called vasospasm. Major risk for the vasospasm takes place at days 5–14 after the primary bleeding. In vasospasm, cerebral arteries contract uncontrollably causing brain ischemia that may lead to death. Nimodipine (NDP) is used to treat of vasospasm and it is administrated intravenously or orally every four hours for 21 days. NDP treatment has been scientifically proven to improve patients’ clinical outcome. The therapeutic effect of L-type calcium channel blocker NDP is due to the ability to dilate cerebral arteries. In addition to vasodilatation, recent research has shown the pleiotropic effect of NDP such as inhibition of neuronal apoptosis and inhibition of microthrombi formation. Indeed, NDP inhibits cortical spreading ischemia. Knowledge of the pathophysiology of the vasospasm has evolved in recent years to a complex entity of early brain injury, secondary injuries and cortical spreading ischemia, instead of being pure intracranial vessel spasm. High NDP levels are beneficial since they protect neurons and inhibit the cortical spreading ischemia. One of the drawbacks of the intravenous or oral administration of NPD is systemic hypotension, which is harmful particularly when the brain is injured. Maximizing the beneficial effects and avoiding systemic hypotension of NDP, we developed a sustained release biodegradable NDP implant that was surgically positioned in the basal cistern of animal models (dog and pig). Higher concentrations were achieved locally and lower concentrations systemically. Using this treatment approach in humans, it may be possible to reduce incidence of harmful hypotension and potentiate beneficial effects of NDP on neurons. Intracellular calcium regulation has a pivotal role in brain plasticity. NDP blocks L-type calcium channels in neurons, substantially decreasing intracellular calcium levels. Thus, we were interested in how NDP affects brain plasticity and tested the hypothesis in a mouse model. We found that NDP activates Brain-derived neurotrophic factor (BDNF) receptor TrkB and its downstream signaling in a reminiscent of antidepressant drugs. In contrast to antidepressant drugs, NDP activates Akt, a major survival-promoting factor. Our group’s previous findings demonstrate that long-term antidepressant treatment reactivates developmental-type of plasticity mechanisms in the adult brain, which allows the remodeling of neuronal networks if combined with appropriate rehabilitation. It seems that NDP has antidepressant-like properties and it is able to induce neuronal plasticity. In general, drug induced neuronal plasticity has a huge potential in neurorehabilitation and more studies are warranted.