Energi är grunden för allt mitt arbete. Utan Energi så finns det inget liv. Vad ska jag göra för att få energi och vad ska jag undvika för att inte förlora den? Ett undersökande i hur jag ska gå till väga för att bli lycklig i mitt liv och med min konst. För mig handlar det om att roligt. AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaa………….HAHAHAHA!!!

Inledning: Avslut kan väcka olika känslor. Unga vuxna ska lämna barndomen och tonårstiden för att starta sitt eget vuxenliv. Psykisk ohälsa har ökat bland unga, en del söker psykoterapi, men många hoppar av. För att möjliggöra för fler unga vuxna att fullfölja psykoterapeutisk behandling behöver förståelsen öka kring målgruppens behov. Syfte: Syftet med studien var att undersöka legitimerade psykoterapeuters perspektiv på den avslutande processen i psykodynamisk psykoterapi med unga vuxna. Metod: Kvalitativ metod användes. Semistrukturerade intervjuer genomfördes med fem legitimerade psykoterapeuter. Materialet strukturerades med tematisk analys. Resultat: Kännetecknande för den avslutande processen i terapier med unga vuxna var att det blev individuellt olika; hastiga eller planerade avslut, ibland avhopp. Hur avslutningsprocessen blev var beroende av problematik och personlighetsstruktur snarare än ålder men adolescensens utvecklingsuppgifter och individens anknytningshistoria påverkade. Psykoterapeuter tog ansvar, var uppmärksamma, hjälpte aktivt unga i den avslutande processen. Mentalisering och metakommunikation användes för att begripliggöra avslutet. Diskussion: Resultatet diskuteras utifrån psykoterapeuternas kliniska erfarenheter och förståelse av den avslutande processen med unga vuxna. Betydelsefulla faktorer i deras upplevelser diskuteras i förhållande till teori och tidigare forskning. Vald metod diskuteras och förslag ges till vidare forskning / Introduction: Endings can evoke different emotions. Young adults should leave childhood andadolescence to start their own adult life. Mental illness has increased among young people, some seek psychotherapy, but many drop out. To enable more young adults to complete psychotherapeutic treatment, there is a need to increase understanding of the target group´s needs. Purpose: The purpose of the study was to investigate licensed psychotherapists perspective on the final process of psychodynamic psychotherapy with young adults. Method: Qualitative method was used. Semi structured interviews were conducted with five licensed psychotherapists and the collected material structured with thematic analysis. Results: Characteristic of the final process in therapies with young adults was that it became individually different; hasty or planned endings, sometimes dropout from therapy instead of ending. How the final process became was more dependent on problems and personality structure than age, but the development tasks of the adolescence and the individual's attachment history affected. Psychotherapists took responsibility, were attentive and actively helped young people in the final process. Mentalization and metacommunication were used to comprehend the termination. Discussion: The results were discussed based on the psychotherapists' understanding and clinical experience of the final process with young adults. Significant factors in their experiences are discussed in relation to theory and previous research. The chosen method is discussed, and suggestions are given for further research.

This thesis studies the inter-group variation of the consonant endings among five principal subgroups of the Chaoshan dialect, a branch of the South Min dialect in Eastern Guangdong Province, from the perspective of language contact and horizontal transmission. I conduct a quantitative study to present the synchronic variance of the consonant endings among five Chaoshan subgroups and the diachronic variance from Middle Chinese to modern Chaoshan dialect on a numerical scale. The current literature tends to take the change of the consonant endings as a process of weakening governed by regular rules. My research findings challenge this conventional view. First, the change of the consonant endings from Middle Chinese to five subgroups of modern Chaoshan dialect is irregular, which is an exception to the linguistic laws proposed in the existing literature. Secondly, I find that some characters without consonant endings or with a weakened ending in Chaozhou in the 19th century reverse to have a consonant ending in modern Chaoshan dialect. This reversal contradicts to the weakening hypothesis that regards the change of the consonant endings as a process of simplifying. Finally, my quantitative research shows that Chaozhou dialect in the 19th century in much closer to modern Xiamen dialect than to five subgroups of modern Chaoshan dialect in terms of the relativeness in consonant endings, which is the opposite to the prediction that languages become more and more different and have no consequent contact with other daughter languages after separating from the proto-language. We propose that the actual situation of the consonant endings in different subgroups of the Chaoshan dialect can be better explained from the perspective of language contact and horizontal transmission. The interaction between Han Chinese and non-Han Chinese is the primary reason for the change of the consonant endings of the Chaoshan dialect. Also, the language contact between Chaoshan aborigines and migrants from the Fujian Province leads to the divergence of the consonant endings in different Chaoshan subgroups.Population structure and other social factors determine what phonetic features survive after several times of horizontal transmission.

L'orthographe du français : usages et représentations d'adultes socio-différenciés. Approche pluridisciplinaire.Dans une perspective linguistique, psycholinguistique, sociolinguistique et didactique, qui intègre le plan cognitif et les facteurs sociaux, ce travail de thèse porte sur l'étude de la variation orthographique dans les pratiques et les représentations de l'orthographe du français d'usagers de la langue qui, par obligation professionnelle ou scolaire, écrivent quotidiennement : des scripteurs adultes en cours d'apprentissage (élèves de lycée professionnel) et des scripteurs experts (secrétaires, DRH et futurs enseignants du secondaire).Le questionnement de cette recherche sur l'enjeu social de l'orthographe se centre plus précisément sur la manière dont les usagers de la langue écrite, en difficulté ou en relative sécurité, se construisent des savoirs orthographiques et se représentent l'orthographe ; il pourrait se formuler en ces termes : Face au système complexe de l'écriture du français, quels sont les secteurs de fragilité ou d'insécurité orthographique des scripteurs experts et des scripteurs en difficulté ? En d'autres termes, ces secteurs recouvrent-ils les zones d'instabilité du code graphique ? Quels jugements les scripteurs portent-ils sur l'orthographe et sur leurs pratiques orthographiques, ainsi que sur les propositions d'une nouvelle réforme ?Les objectifs que recouvrent ces questions sont nombreux, cette recherche essaie d'apporter des éléments de réponse sur 1/ la variation orthographique dans les écrits formels afin de déterminer les secteurs de fragilité orthographique des usagers de la langue écrite ; 2/ les patrons ou schémas intériorisés, responsables des variantes orthographiques ; 3/ l'existence d'une demande sociale ou non, de la part des « professionnels » de l'orthographe, en matière d'une réforme orthographique.Somme toute, cette recherche permet de comprendre les difficultés orthographiques d'un certain nombre d'adolescents et d'adultes dans une société où l'on produit de plus en plus d'écrits et où la compétence de lecture et d'écriture est déterminante pour l'insertion sociale et professionnelle. Les analyses tant qualitatives et quantitatives menées ont permis de dégager un profil général de chacun des publics observés au regard des données croisées de leurs compétences orthographiques et de leurs représentations.Enfin, ce travail offre, en ouverture, une réflexion renouvelée sur l'orthographe actuelle et propose des suggestions dans une perspective de formation des enseignants à la variation orthographique - informer des tendances fortes repérées, apporter des outils théoriques pour favoriser les apprentissages. / Uses and Representations of French Spelling in Socially Differentiated Adults.A Multidisciplinary ApproachThis thesis examines orthographic variation from a linguistic, psycholinguistic, sociolinguistic and didactic perspective, integrating both cognitive and social factors. More specifically, it focuses on this variation in the French-spelling practices and representations of language users who use the written medium daily, due to either professional or educational obligations. The users in question are adult writers in the process of learning (sixth form students at a vocational secondary school) and expert writers (secretaries, human resources managers and future secondary school teachers). This research questions the social stakes of spelling, focusing more specifically on 1/ how users of written language, whether they have difficulties or are relatively secure in their uses, build orthographical knowledge and 2/ the representations they have of spelling. The key question could be expressed in the following terms: in the face of the complex French writing system, what are the areas of fragility or orthographical insecurity among expert writers and writers with difficulties? In other words, do these areas overlap with the areas of instability that exist within the French writing system? What judgments do these writers make regarding spelling and their own orthographic practice, and regarding suggestions for a new reform of the spelling system?These questions address a number of aims and this research attempts to provide some answers concerning 1/ spelling variation in formal writing, in order to determine areas of spelling fragility among users of written language; 2/ the internalised patterns or schemas that are responsible for spelling variants; 3/ the existence of social demand for spelling reform on the part of spelling “professionals”. In sum, this study allows an understanding of the spelling difficulties faced by a certain number of adults and adolescents in a society in which more and more written texts are produced and in which competence in reading and writing is a determining factor for social and professional integration. The qualitative and quantitative analyses conducted allow a general profile of each of the groups of writers observed to be drawn up, on the basis of cross-referenced data about their orthographic competence and representations. Finally, this work opens up the perspective of renewed reflection about current spelling and puts forward suggestions for training teachers in orthographic variation i.e. informing them about the strong tendencies identified and providing theoretical tools to foster learning.

This thesis details my examination of several mechanisms for modulation of neuropeptide release via voltage-dependent and voltage-independent intraterminal signaling in isolated neurohypophysial terminals. The first part of this work characterizes depolarization-induced neuropeptide release in the absence of extracellular calcium. The goal of this project was to examine the relationship between depolarization-induced release of intracellular calcium stores and depolarization-secretion coupling of neuropeptides. We demonstrate that depolarization in the absence of extracellular calcium induced by either High K+ or electrical stimulation induces a rise in [Ca2+]i and subsequent neuropeptide release from Hypothalamic Neurohypophysial System (HNS) terminals. A portion of extracellular calcium-independent neuropeptide release is due to intraterminal calcium, but the remaining depolarization-induced release may be due to calcium-independent voltage-dependent (CIVD) release (Zhang and Zhou, 2002; Zhang et al., 2004; Yang et al., 2005). Nevertheless, our results clearly show that extracellular calcium is notnecessary for depolarization-induced neuropeptide secretion from these CNS terminals. In addition, I investigated the role of internal calcium stores in mediating μ-opioid inhibition of voltage-gated calcium channels (VGCCs). Inhibition of VGCCs via μ-opioid agonists has been shown to reduce neuropeptide release in response to High K+ stimulation of isolated terminals (Bicknell et al., 1985b; Russell et al., 1993; van Wimersma Greidanus and van de Heijning, 1993; Munro et al., 1994; Ortiz-Miranda et al., 2003; Russell et al., 2003; Ortiz-Miranda et al., 2005). My findings show μ-opioid inhibition, of VGCC and High K+-mediated rise in [Ca2+]i, are via a voltage-independent diffusible second-messenger targeting release of calcium from ryanodine-sensitive stores, possibly mediated via the cyclic ADP ribose signaling pathway. Furthermore, I detail a different intracellular messenger pathway mediating the κ-opioid inhibition of VGCC and High K+-mediated rise in [Ca2+]ii. In contrast to the μ-opioid inhibition, κ-receptor activation is coupled to a voltage-dependent membrane-delimited pathway. Inhibition of neuropeptide release via both endogenous and exogenous κ-opioid agonists has been extensively studied (Bicknell et al., 1985a; Nordmann et al., 1986a; Wammack and Racke, 1988; Munro et al., 1994; Ingram et al., 1996; Rusin et al., 1997a). My investigation shows that the κ-inhibition of VGCC is voltage-dependent and is furthermore, relieved within the context of a physiological burst of action potentials (APs). This physiologically-evoked, activity-dependent modulation of VGCC and subsequent release, represents an important mechanism for short-term synaptic plasticity at the level of the terminals. Given the ubiquitous nature of voltage-dependent G-protein signaling in the CNS, our results may prove important in understanding modulatory effects of specific bursting patterns throughout the CNS. In the last 30 years the neurohypophysial system has proven to be an excellent system to study the complexities of depolarization-secretion coupling (DSC). There have been many advances in our understanding of the underlying mechanisms involved and their physiological implications. The current work focuses on two important features of DSC; voltage and calcium. Although in many ways these two are intrinsically linked through VGCC activation, we have found that in isolated HNS terminals that is not always the case. We have further found that when voltage and calcium influx are linked during DSC, modulation by opioids may or may not be linked to activity-dependent relief depending on the opioid receptor activated. This finding has important implications in neuropeptide release during patterned stimulation in vivo. As I will discuss further, many factors play into the complexities of the regulatory mechanisms involving release. As investigations into this remarkable field continue, I hope to have contributed a valuable piece to the puzzle.

A problem with automatic tagging and lexical analysis is that it is never 100 % accurate. In order to arrive at better figures, one needs to study the character of what is left untagged by automatic taggers. In this paper untagged residue outputted by the automatic analyser SWETWOL (Karlsson 1992) at Helsinki is studied. SWETWOL assigns tags to words in Swedish texts mainly through dictionary lookup. The contents of the untagged residue files are described and discussed, and possible ways of solving different problems are proposed. One method of tagging residual output is proposed and implemented: the left-stripping method, through which untagged words are bereaved their left-most letters, searched in a dictionary, and if found, tagged according to the information found in the said dictionary. If the stripped word is not found in the dictionary, a match is searched in ending lexica containing statistical information about word classes associated with that particular word form (i.e., final letter cluster, be this a grammatical suffix or not), and the relative frequency of each word class. If a match is found, the word is given graduated tagging according to the statistical information in the ending lexicon. If a match is not found, the word is stripped of what is now its left-most letter and is recursively searched in a dictionary and ending lexica (in that order). The ending lexica employed in this paper are retrieved from a reversed version of Nusvensk Frekvensordbok (Allén 1970), and contain endings of between one and seven letters. The contents of the ending lexica are to a certain degree described and discussed. The programs working according to the principles described are run on files of untagged residual output. Appendices include, among other things, LISP source code, untagged and tagged files, the ending lexica containing one and two letter endings and excerpts from ending lexica containing three to seven letters.

INTRODUÇÃO: A síndrome de prune belly (PBS) é caracterizada por uma tríade com flacidez da parede abdominal, criptorquidia bilateral e malformações do trato urinário que compreende bexiga de capacidade aumentada, com complacência elevada, hipossensibilidade, hipocontratilidade, com divertículo ou fístula uracal e resíduo pós-miccional elevado. Alguns autores recomendam tratamento clínico, porém outros propõe correção cirúrgica, com reconstrução da via urinária incluindo ureteroplastia e cistoplastia redutoras, orquidopexia e abdominoplastia. Mesmo após a cirurgia, alguns doentes necessitam de cateterismo limpo intermitente. A inervação vesical determina seu funcionamento, mediado por neuroreceptores na junção neuromuscular. Os adrenoreceptores a1 estão relacionados à contratilidade detrusora e o b3 ao seu relaxamento, e certas condições como obstrução infravesical levam à hiperexpressão de receptores a1. O objetivo da presente pesquisa é verificar se no detrusor de doentes com PBS há alteração na densidade de terminações nervosas, hiper ou hipoexpressão de receptores adrenérgicos a1a, a1b, a1d e b3 e proporção anormal dos tecidos muscular e conectivo. MÉTODO Trata-se de estudo retrospectivo de caso-controle que envolveu 14 espécimes de detrusor de doentes com PBS operados entre 1985 a 2005 no Hospital das Clínicas da FMUSP. Dois grupos foram constituídos como controle: 13 fragmentos de bexiga de doentes submetidos à prostatectomia radical no Departamento de Urologia da Universidade de Mainz, com urodinâmica pré-operatória normal (GC1), e cinco fragmentos de bexiga de crianças submetidas à necrópsia no SVOC-USP, sem anomalias neurológicas e de trato urinário. A coloração de van Gieson foi realizada para análise da proporção músculo/tecido conectivo, e a reação imunohistoquímica para os anticorpos policlonais anti-proteína S100 e antiadrenoreceptores a1a, a1b, a1d e b3. A coloração castanho foi considerada evidência da expressão do adrenoreceptor na célula. Cinco a dez imagens digitais foram tomadas por meio de câmara digital e microscopia óptica. Estas foram analisadas pelo programa Adobe Photoshop CS2Ò. A quantidade relativa de receptores foi calculada e a análise estatística realizada pelos testes Kruskal-Wallis e Mann-Whitney. RESULTADOS A média de idade foi de 1,28 ± 1,14 ano no grupo caso (PBS), e de 64 ± 5,22 anos e 1,41 ± 1,11 ano, nos grupos GC1 e GC2, respectivamente. A mediana da relação músculo/tecido conectivo foi de 1,08 para o grupo PBS, 1,59 para o GC1 e para o GC2 de 1,28 (p=0,173). A mediana da proporção S100/tecido muscular foi de 0,21 para o grupo caso (PBS), de 0,20 para o GC1 e para o grupo GC2 de 0,01 (p=0,003). A mediana da relação a1a/tecido muscular foi de 0,06 para o grupo PBS, de 0,16 para o GC1 e para o grupo GC2 de 0,14 (p=0,026). Para a1b, as medianas foram 0,06 no grupo PBS, 0,006 no GC1 e 0,007 no GC2 (p=0,781). No a1d, as medianas foram 0,04 (PBS), 0,04 (GC1) e 0,05 (GC2) (p=0,618). Com relação ao b3, as medianas foram 0,07 no grupo PBS, 0,14 no GC1 e 0,10 no GC2 (p=0,378). CONCLUSÕES Comparando-se fragmentos de detrusor de doentes com PBS e bexigas normais não se observou alteração na densidade de terminações nervosas. Observou-se hipoexpressão do adrenoreceptor a1a, e não houve alteração dos adrenoreceptores a1b, a1d e b3. Também não se observou alteração entre a proporção de tecido muscular e conectivo no detrusor destes doentes. Investigações adicionais, com diferentes métodos e incluindo outros receptores, são necessárias antes de se aplicar esses conhecimentos na prática clínica. / INTRODUCTION: Prune belly syndrome (PBS) is charactherized by a triad of abdominal wall flaccidity, bilateral criptorchidism and urinary tract malformation, that includes a large-capacity bladder, with high detrusor compliance, low sensibility and contractility, associated to urachal diverticulum or fistula and elevated post void residual volumes. Some autors recommend clinical treatment, but others propose surgery correction, with urinary tract reconstruction, including reductive ureteroplasty and cystoplasty, orchidopexy and abdominoplasty. Even after surgery, some patients need intermittent catheterism. The detrusor innervation determines its function, mediated by neuroceptors at the neuromuscular junction. The a1 adrenoceptors are related to detrusor contractility and b3 to relaxation, and some conditions, like infravesical obstruction, lead to a1 adrenoceptor up-regulation. The objective of this work is to verify whether, in the detrusor from patients with PBS, there is altered nerve density, up or down-regulation of a1a, a1b, a1d and b3 adrenergic receptors and if there is an abnormal proportion between muscle and connective tissue. MATERIALS AND METHODS A retrospective case-control study was performed involving 14 detrusor specimens from patients with PBS, who underwent surgical treatment between 1985 an 2005 at University of São Paulo, Medical School Hospital. Two groups were taken as control: 13 bladder fragments from patients who underwent radical prostatectomy at Department of Urology of Mainz University, with normal urodynamic study prior to the surgery (GC1) and 5 bladder fragments from children submitted to autopsy at SVOC-USP, with no neurological or urinary tract malformation (GC2). Staining was performed using the van Gieson dye to analyse the proportion between muscle and connective tissue, and immunohistochemical reaction was employed, with polyclonal antibodies against S100 protein, as well as a1a, a1b, a1d and b3 adrenoceptors. Brown colour was considered as evidence of adrenoceptor cell expression. Five to ten digital images were captured on an optic microscope with a digital camera. These images were analysed with Adobe Photoshop CS2Ò software. The relative quantity of receptors was calculated and the statistic analysis was done with the Kruskal-Wallis and Mann-Whitney tests. RESULTS Mean age was 1.28 ± 1.14 year in PBS patients, and 64 ± 5.22 yrs. and 1.41 ± 1.11 yrs. in GC1 and GC2, respectively. The median proportion between muscle and connective tissue was 1.08 in PBS, 1.59 in GC1 and in GC2 of 1.28 (p=0.173). The median proportion of S100/muscle area was 0.21 in PBS, 0.20 in GC1 and in GC2 of 0.01 (p=0.003). The median relative quantity of receptors of a1a was 0.06 in PBS, 0.16 in GC1 and 0.14 in GC2 (p=0.026). In a1b, the median values were 0.06 in PBS group, 0.006 in GC1 and 0.007 in GC2 (p=0.781). In a1d, the median values were 0.04 (PBS), 0.04 (GC1) and 0.05 (GC2) (p=0.618). Regarding b3, the median values were 0.07 in PBS, 0.14 in GC1 and 0.10 in GC2 (p=0.378). CONCLUSION Comparing detrusor fragments from patients with PBS and normal bladders, there was no alteration in the density of nerve endings. We observed downregulation of a1a adrenoceptors, but no alteration in the a1b, a1d and b3 receptors. Furthermore, there was no alteration of the proportion between muscle and connective tissue areas. Further investigations, with different methods and including other receptors, are necessary to transfer this knowledge to clinical use.

INTRODUÇÃO: O conhecimento sobre os tipos celulares envolvidos na patogenia da urticária constitui um elemento essencial para a compreensão da fisiopatologia desta doença. Poucos autores têm dado atenção às interações entre mastócitos e dendrócitos da derme na urticária. Os objetivos deste estudo são orientados no sentido de descreverem-se os tipos de degranulação mastocitária na urticária aguda associada a medicamentos, e o de analisarem-se as interações entre dendrócitos da derme e mastócitos. MÉTODOS: Sete doentes com urticária aguda associada com medicamentos foram incluídos neste estudo. Foram obtidas biopsias cutâneas das lesões urticadas e da pele aparentemente normal destes doentes. Os quatorze fragmentos coletados foram divididos em duas partes (28 fragmentos): uma das partes foi enviada para processamento pela coloração de hematoxilina-eosina, para a coloração de Azul de Toluidina e reações de imunoistoquímica com anticorpos anti-CD34, antifator XIIIA (anti- FXIIIa) e antitriptase e o outro fragmento foi processado para uso na microscopia imunoeletrônica, utilizando-se anticorpos para triptase e FXIIIa, além de dupla imunomarcação com ouro com o uso de anticorpos antitriptase e anti-FXIIIa. RESULTADOS: células imunomarcadas com anticorpos anti-CD34 foram observadas de forma esparsa na derme superficial e de forma mais proeminente na derme reticular. Havia múltiplos dendrócitos dérmicos FXIIIa+ na derme superficial e média, dispersos nas regiões subepidérmicas e em torno doa vasos da derme, tanto na pele urticada com na pele aparentemente normal. O número destas células foi similar nos dois grupos de amostras. Não houve diferença estatística entre o número de células triptase-positivas na pele aparentemente normal e na pele urticada, em todos os doentes. Nós observamos mastócitos íntegros na maioria das amostras da pele aparentemente normal. Tanto as amostras de pele aparentemente normal quanto as amostras de pele urticada apresentavam mastócitos em processo de degranulação do tipo anafilático, com inúmeros grânulos extruídos. Após a dupla imunomarcação com ouro, na imuno-microscopia eletrônica de transmissão foram observadas partículas de ouro de 10 nm (FXIIIa) e 15 nm (Triptase) marcando concomitante os grânulos dos mastócitos indicando que tanto a triptase como o FXIIIa encontraram-se presentes nos grânulos destas células. De forma interessante, nós encontramos uma forte evidência de que grânulos contendo tanto FXIIIa, como triptase, extruídos dos mastócitos são fagocitados pelos dendrócitos da derme. CONCLUSÕES: na urticária aguda associada a medicamentos o padrão de degranulação observado foi do tipo anafilático. Este estudo constitui a primeira demonstração da expressão do FXIIIa nos grânulos intracitoplasmáticos e nos grânulos extruídos dos mastócitos, dispersos na matriz extracelular, nos doentes com urticária aguda associada a medicamentos. Outro fato inédito foi a demonstração da fagocitose dos grânulos extruídos dos mastócitos pelos dendrócitos da derme FXIIIa+ / BACKGROUND: The knowledge about the cell types involved in urticaria is an essential element for understanding the pathophysiology of this disease. Few authors have been attempting on interactions among mast cells and dermal dendrocytes in urticaria. The aims of this study are to describe the types of mast cell degranulation in drug-induced acute, besides to analyze the interactions between mast cell and dermal dendrocyte in urticaria. METHODS: Seven patients with drug-induced acute urticaria were enrolled in the study. We token skin biopsies of urticarial lesion and apparently normal skin. The fourteen fragments collected were divided into two parts (28 sections): one to haematoxylin-eosin stain, Toluidine blue stain and immunohistochemisty reactions with anti-CD34, anti-FXIIIa and anti-tryptase antibodies and other part to immunogold electron microscopy using single antibodies to tryptase and FXIIIa, besides double immunogold labelling with anti-tryptase and anti-FXIIIa. RESULTS: immunolabelled CD34+ cells were observed scattered in the superficial dermis and more prominent in the reticular dermis. There were multiple FXIIIa+ dermal dendrocytes in upper and mid dermis, dispersed in subepidermal areas and around blood vessels, both in apparently normal skin and urticarial lesion of drug-induced acute urticaria. The number of these cells was similar in both groups. There was no difference in tryptase positive cells number between apparently normal skin and urticarial lesions, in all patients. We observed intact mast cells in the majority of the sections of the apparently normal skin. Some sections demonstrated a few mast cells in degranulation process, in anaphylactic degranulation type. In urticarial lesions, several mast cells showed degranulation process, in anaphylactic degranulation type. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were seen together over the granules in mast cells indicating that tryptase and FXIIIa are each localized into granules of these cells. Interestingly, we found a strong evidence of than the exocytosed mast cell granules contents both FXIIIa and Tryptase immunolabelled are phagocytised by dermal dendrocytes. CONCLUSIONS: In drug-induced acute urticaria the degranulation pattern of mast cells found was composed by anaphylatic. This is the first report, in acute urtuicaria, concern of the expression of FXIIIa in the cytoplasmic mast cell and in extruded granules into extracellular matrix. Phagocytosis of the extruded mast cell granules by FXIIIa+ dermal dendrocytes in urticaria was observed

INTRODUÇÃO: O conhecimento sobre os tipos celulares envolvidos na patogenia da urticária constitui um elemento essencial para a compreensão da fisiopatologia desta doença. Poucos autores têm dado atenção às interações entre mastócitos e dendrócitos da derme na urticária. Os objetivos deste estudo são orientados no sentido de descreverem-se os tipos de degranulação mastocitária na urticária aguda associada a medicamentos, e o de analisarem-se as interações entre dendrócitos da derme e mastócitos. MÉTODOS: Sete doentes com urticária aguda associada com medicamentos foram incluídos neste estudo. Foram obtidas biopsias cutâneas das lesões urticadas e da pele aparentemente normal destes doentes. Os quatorze fragmentos coletados foram divididos em duas partes (28 fragmentos): uma das partes foi enviada para processamento pela coloração de hematoxilina-eosina, para a coloração de Azul de Toluidina e reações de imunoistoquímica com anticorpos anti-CD34, antifator XIIIA (anti- FXIIIa) e antitriptase e o outro fragmento foi processado para uso na microscopia imunoeletrônica, utilizando-se anticorpos para triptase e FXIIIa, além de dupla imunomarcação com ouro com o uso de anticorpos antitriptase e anti-FXIIIa. RESULTADOS: células imunomarcadas com anticorpos anti-CD34 foram observadas de forma esparsa na derme superficial e de forma mais proeminente na derme reticular. Havia múltiplos dendrócitos dérmicos FXIIIa+ na derme superficial e média, dispersos nas regiões subepidérmicas e em torno doa vasos da derme, tanto na pele urticada com na pele aparentemente normal. O número destas células foi similar nos dois grupos de amostras. Não houve diferença estatística entre o número de células triptase-positivas na pele aparentemente normal e na pele urticada, em todos os doentes. Nós observamos mastócitos íntegros na maioria das amostras da pele aparentemente normal. Tanto as amostras de pele aparentemente normal quanto as amostras de pele urticada apresentavam mastócitos em processo de degranulação do tipo anafilático, com inúmeros grânulos extruídos. Após a dupla imunomarcação com ouro, na imuno-microscopia eletrônica de transmissão foram observadas partículas de ouro de 10 nm (FXIIIa) e 15 nm (Triptase) marcando concomitante os grânulos dos mastócitos indicando que tanto a triptase como o FXIIIa encontraram-se presentes nos grânulos destas células. De forma interessante, nós encontramos uma forte evidência de que grânulos contendo tanto FXIIIa, como triptase, extruídos dos mastócitos são fagocitados pelos dendrócitos da derme. CONCLUSÕES: na urticária aguda associada a medicamentos o padrão de degranulação observado foi do tipo anafilático. Este estudo constitui a primeira demonstração da expressão do FXIIIa nos grânulos intracitoplasmáticos e nos grânulos extruídos dos mastócitos, dispersos na matriz extracelular, nos doentes com urticária aguda associada a medicamentos. Outro fato inédito foi a demonstração da fagocitose dos grânulos extruídos dos mastócitos pelos dendrócitos da derme FXIIIa+ / BACKGROUND: The knowledge about the cell types involved in urticaria is an essential element for understanding the pathophysiology of this disease. Few authors have been attempting on interactions among mast cells and dermal dendrocytes in urticaria. The aims of this study are to describe the types of mast cell degranulation in drug-induced acute, besides to analyze the interactions between mast cell and dermal dendrocyte in urticaria. METHODS: Seven patients with drug-induced acute urticaria were enrolled in the study. We token skin biopsies of urticarial lesion and apparently normal skin. The fourteen fragments collected were divided into two parts (28 sections): one to haematoxylin-eosin stain, Toluidine blue stain and immunohistochemisty reactions with anti-CD34, anti-FXIIIa and anti-tryptase antibodies and other part to immunogold electron microscopy using single antibodies to tryptase and FXIIIa, besides double immunogold labelling with anti-tryptase and anti-FXIIIa. RESULTS: immunolabelled CD34+ cells were observed scattered in the superficial dermis and more prominent in the reticular dermis. There were multiple FXIIIa+ dermal dendrocytes in upper and mid dermis, dispersed in subepidermal areas and around blood vessels, both in apparently normal skin and urticarial lesion of drug-induced acute urticaria. The number of these cells was similar in both groups. There was no difference in tryptase positive cells number between apparently normal skin and urticarial lesions, in all patients. We observed intact mast cells in the majority of the sections of the apparently normal skin. Some sections demonstrated a few mast cells in degranulation process, in anaphylactic degranulation type. In urticarial lesions, several mast cells showed degranulation process, in anaphylactic degranulation type. After double immunogold staining, 10 nm (FXIIIa) and 15 nm (Tryptase) gold particles were seen together over the granules in mast cells indicating that tryptase and FXIIIa are each localized into granules of these cells. Interestingly, we found a strong evidence of than the exocytosed mast cell granules contents both FXIIIa and Tryptase immunolabelled are phagocytised by dermal dendrocytes. CONCLUSIONS: In drug-induced acute urticaria the degranulation pattern of mast cells found was composed by anaphylatic. This is the first report, in acute urtuicaria, concern of the expression of FXIIIa in the cytoplasmic mast cell and in extruded granules into extracellular matrix. Phagocytosis of the extruded mast cell granules by FXIIIa+ dermal dendrocytes in urticaria was observed

INTRODUÇÃO: A síndrome de prune belly (PBS) é caracterizada por uma tríade com flacidez da parede abdominal, criptorquidia bilateral e malformações do trato urinário que compreende bexiga de capacidade aumentada, com complacência elevada, hipossensibilidade, hipocontratilidade, com divertículo ou fístula uracal e resíduo pós-miccional elevado. Alguns autores recomendam tratamento clínico, porém outros propõe correção cirúrgica, com reconstrução da via urinária incluindo ureteroplastia e cistoplastia redutoras, orquidopexia e abdominoplastia. Mesmo após a cirurgia, alguns doentes necessitam de cateterismo limpo intermitente. A inervação vesical determina seu funcionamento, mediado por neuroreceptores na junção neuromuscular. Os adrenoreceptores a1 estão relacionados à contratilidade detrusora e o b3 ao seu relaxamento, e certas condições como obstrução infravesical levam à hiperexpressão de receptores a1. O objetivo da presente pesquisa é verificar se no detrusor de doentes com PBS há alteração na densidade de terminações nervosas, hiper ou hipoexpressão de receptores adrenérgicos a1a, a1b, a1d e b3 e proporção anormal dos tecidos muscular e conectivo. MÉTODO Trata-se de estudo retrospectivo de caso-controle que envolveu 14 espécimes de detrusor de doentes com PBS operados entre 1985 a 2005 no Hospital das Clínicas da FMUSP. Dois grupos foram constituídos como controle: 13 fragmentos de bexiga de doentes submetidos à prostatectomia radical no Departamento de Urologia da Universidade de Mainz, com urodinâmica pré-operatória normal (GC1), e cinco fragmentos de bexiga de crianças submetidas à necrópsia no SVOC-USP, sem anomalias neurológicas e de trato urinário. A coloração de van Gieson foi realizada para análise da proporção músculo/tecido conectivo, e a reação imunohistoquímica para os anticorpos policlonais anti-proteína S100 e antiadrenoreceptores a1a, a1b, a1d e b3. A coloração castanho foi considerada evidência da expressão do adrenoreceptor na célula. Cinco a dez imagens digitais foram tomadas por meio de câmara digital e microscopia óptica. Estas foram analisadas pelo programa Adobe Photoshop CS2Ò. A quantidade relativa de receptores foi calculada e a análise estatística realizada pelos testes Kruskal-Wallis e Mann-Whitney. RESULTADOS A média de idade foi de 1,28 ± 1,14 ano no grupo caso (PBS), e de 64 ± 5,22 anos e 1,41 ± 1,11 ano, nos grupos GC1 e GC2, respectivamente. A mediana da relação músculo/tecido conectivo foi de 1,08 para o grupo PBS, 1,59 para o GC1 e para o GC2 de 1,28 (p=0,173). A mediana da proporção S100/tecido muscular foi de 0,21 para o grupo caso (PBS), de 0,20 para o GC1 e para o grupo GC2 de 0,01 (p=0,003). A mediana da relação a1a/tecido muscular foi de 0,06 para o grupo PBS, de 0,16 para o GC1 e para o grupo GC2 de 0,14 (p=0,026). Para a1b, as medianas foram 0,06 no grupo PBS, 0,006 no GC1 e 0,007 no GC2 (p=0,781). No a1d, as medianas foram 0,04 (PBS), 0,04 (GC1) e 0,05 (GC2) (p=0,618). Com relação ao b3, as medianas foram 0,07 no grupo PBS, 0,14 no GC1 e 0,10 no GC2 (p=0,378). CONCLUSÕES Comparando-se fragmentos de detrusor de doentes com PBS e bexigas normais não se observou alteração na densidade de terminações nervosas. Observou-se hipoexpressão do adrenoreceptor a1a, e não houve alteração dos adrenoreceptores a1b, a1d e b3. Também não se observou alteração entre a proporção de tecido muscular e conectivo no detrusor destes doentes. Investigações adicionais, com diferentes métodos e incluindo outros receptores, são necessárias antes de se aplicar esses conhecimentos na prática clínica. / INTRODUCTION: Prune belly syndrome (PBS) is charactherized by a triad of abdominal wall flaccidity, bilateral criptorchidism and urinary tract malformation, that includes a large-capacity bladder, with high detrusor compliance, low sensibility and contractility, associated to urachal diverticulum or fistula and elevated post void residual volumes. Some autors recommend clinical treatment, but others propose surgery correction, with urinary tract reconstruction, including reductive ureteroplasty and cystoplasty, orchidopexy and abdominoplasty. Even after surgery, some patients need intermittent catheterism. The detrusor innervation determines its function, mediated by neuroceptors at the neuromuscular junction. The a1 adrenoceptors are related to detrusor contractility and b3 to relaxation, and some conditions, like infravesical obstruction, lead to a1 adrenoceptor up-regulation. The objective of this work is to verify whether, in the detrusor from patients with PBS, there is altered nerve density, up or down-regulation of a1a, a1b, a1d and b3 adrenergic receptors and if there is an abnormal proportion between muscle and connective tissue. MATERIALS AND METHODS A retrospective case-control study was performed involving 14 detrusor specimens from patients with PBS, who underwent surgical treatment between 1985 an 2005 at University of São Paulo, Medical School Hospital. Two groups were taken as control: 13 bladder fragments from patients who underwent radical prostatectomy at Department of Urology of Mainz University, with normal urodynamic study prior to the surgery (GC1) and 5 bladder fragments from children submitted to autopsy at SVOC-USP, with no neurological or urinary tract malformation (GC2). Staining was performed using the van Gieson dye to analyse the proportion between muscle and connective tissue, and immunohistochemical reaction was employed, with polyclonal antibodies against S100 protein, as well as a1a, a1b, a1d and b3 adrenoceptors. Brown colour was considered as evidence of adrenoceptor cell expression. Five to ten digital images were captured on an optic microscope with a digital camera. These images were analysed with Adobe Photoshop CS2Ò software. The relative quantity of receptors was calculated and the statistic analysis was done with the Kruskal-Wallis and Mann-Whitney tests. RESULTS Mean age was 1.28 ± 1.14 year in PBS patients, and 64 ± 5.22 yrs. and 1.41 ± 1.11 yrs. in GC1 and GC2, respectively. The median proportion between muscle and connective tissue was 1.08 in PBS, 1.59 in GC1 and in GC2 of 1.28 (p=0.173). The median proportion of S100/muscle area was 0.21 in PBS, 0.20 in GC1 and in GC2 of 0.01 (p=0.003). The median relative quantity of receptors of a1a was 0.06 in PBS, 0.16 in GC1 and 0.14 in GC2 (p=0.026). In a1b, the median values were 0.06 in PBS group, 0.006 in GC1 and 0.007 in GC2 (p=0.781). In a1d, the median values were 0.04 (PBS), 0.04 (GC1) and 0.05 (GC2) (p=0.618). Regarding b3, the median values were 0.07 in PBS, 0.14 in GC1 and 0.10 in GC2 (p=0.378). CONCLUSION Comparing detrusor fragments from patients with PBS and normal bladders, there was no alteration in the density of nerve endings. We observed downregulation of a1a adrenoceptors, but no alteration in the a1b, a1d and b3 receptors. Furthermore, there was no alteration of the proportion between muscle and connective tissue areas. Further investigations, with different methods and including other receptors, are necessary to transfer this knowledge to clinical use.