Gastric mucosal erosions were induced in the glandular stomach of rats by scalding. The incorporation of Thymidine-methyl³-H into desoxyribonucleic acid was used to determine changes in gastric epithelial cell proliferating ability. Total desoxyribonucleic acid per milligram of gastric tissue was also determined. Sampling was done at twenty-four hours, seven days, and fifteen days postburn. Eighty-nine point two percent of rats with a standard 26.5 ± 2% scald burn had developed gastric mucosal erosions by twenty-four hours postburn. Seventeen point eight percent of burned rats had erosions by seven days and the incidence rose to 46.4% by fifteen days postburn. Ten point three percent of control rats in all sampling periods developed erosions. The total desoxyribonucleic acid in the gastric samples did not change significantly in any treatment period nor was it changed by treatment. Uptake of thymidine-methyl³-H was depressed twenty-four hours postburn and renewed so through seven days postburn. The results at the fifteen day sampling were inconclusive. By light microscope, the gastric surface epithelium was lifted from the lamina propria and at times there was complete denudation of this cell layer. The rat is a satisfactory animal model for gross study of mucosal erosions to at least fifteen day postburn. Because of eschar cannibalization inducing variable secretory status, the rat model was not suitable for thymidine uptake studies past seven days postburn. / Surgery, Department of / Medicine, Faculty of / Graduate

The distribution and some of the properties of phosphodiesterase II were studied in homogenates of rat intestinal mucosa in an attempt to elucidate its role in the nucleic acid metabolism of this tissue. In most of the experiments the p-nitrophenyl ester of thymidine 3'-phosphate was used as a substrate for phosphodiesterase. During the work, evidence was accumulated which indicated that phosphodiesterase II of intestine was lysosomal in origin. For instance, when the tissue was suspended (or homogenized) in media of differing tonicity, the phosphodiesterase II activity in the hypotonic preparations increased markedly over a period of 96 hours. Other investigators have shown that this "osmotic activation" is a characteristic of lysosomal enzymes. Subsequently, homogenates of mucosal tissue were fractionated by differential centrifugation and the subcellular fractions obtained were identified by known enzyme markers. The distribution of phosphodiesterase II in the fractions was most similar to that of the marker for lysosomes - acid phosphatase. However a large proportion of the phosphodiesterase II activity, greater than that of acid phosphatase, was found in the supernatant solution remaining after the final high-speed centrifugation step. The highest specific activity for phosphodiesterase II was found in the "light mitochondrial" and "final supernatant" fractions. Similar results were obtained when homogenates or nuclei-free homogenates were fractionated by sucrose density-gradient centrifugation. The distribution patterns of phosphodiesterase II and acid phosphatase were again similar and the particles to which phosphodiesterase II were bound exhibited the highest acid phosphatase activity. An attempt was made to confirm these results by "purifying" lysosomes from intestinal mucosa using a combined differential centrifugation and density-gradient centrifugation technique. During the purification, the specific activities of phosphodiesterase II and acid phosphatase increased parallel with each other and the "purified lysosomal" fractions exhibited the highest specific activities for these enzymes. However the total activities of the two enzymes recovered in the purified fractions were quite small, indicating considerable loss in the discarded soluble fractions. Other workers have shown that homogenization ruptures lysosomes in certain fragile tissues, resulting in high soluble activities of the enzymes contained in these particles. It would seem possible therefore that in intestinal mucosa phosphodiesterase II is located in lysosomes in vivo, since most of its activity was found to be distributed between the lysosomal and soluble fractions of homogenates of this tissue. The phosphodiesterase II of intestine was most active at pH values around neutrality. A second substrate, 2,4-dinitro-phenyl thymidine 3'-phosphate, which was used in only"a few experiments because of its limited availability, was hydrolyzed at a rate faster than that of p-nitrophenyl thymidine 3'-phosphate. Little or no change in the activity of the enzyme was observed in the presence of Mg++, Ca++ or EDTA, but Zn++, Cu++ and Hg++ inhibited markedly. The enzyme was most active at a temperature of 58° and only 27% of the activity was lost on heating the preparation for 1 hour at 55°. The Michaelis constant for the enzyme with p-nitrophenyl thymidine 3'-phosphate was 4.5 x 10(-4) M at 37°, and the activation energy for the phosphodiesterase II catalyzed hydrolysis of the same compound was 14.63 kilocalories/ mole. / Medicine, Faculty of / Biochemistry and Molecular Biology, Department of / Graduate

Orientador: Maria Leticia Cintra, Oslei Paes de Almeida / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-03T15:17:57Z (GMT). No. of bitstreams: 1 Soares_AndresaBorges_M.pdf: 3608623 bytes, checksum: f6bd7c433b9342a1093aad89a2c3c52d (MD5) Previous issue date: 2003 / Resumo: A Doença do Enxerto Contra o Hospedeiro Crônica - DECH ( Graft-versus-host disease cronic- GVHDc) é a maior causa de morbidade e mortalidade em pacientes submetidos a transplante de medula óssea. As alterações clínicas e histopatológicas na cavidade oral podem preceder as manifestações da GVHDc em outros órgãos. O objetivo deste estudo foi avaliar os possíveis fatores associados ao desenvolvimento da doença e as diferenças histopatológicas e imunoistoquímicas entre as alterações de condicionamento e GVHDc, bem como determinar o perfil imunofenotípico predominante das células inflamatórias na GVHDc presentes na mucosa oral e glândulas salivares menores. Foram selecionadas 25 amostras de mucosa labial de pacientes que desenvolveram GVHDc (grupo-experimental) e 16 de pacientes que não desenvolveram GVHDc (grupo controle) nos arquivos do Departamento de Anatomia-Patológica da Faculdade de Ciências Médicas da UNICAMP.As informações clínicas referentes à idade, gênero do receptor, doença de base, tipo de transplante, sexo do doador, compatibilidade do sistema HLA e ABO, presença de infeções virais, desenvolvimento de GVHDa, órgãos afetados na GVHDc, foram obtidas dos prontuários médicos. Foram realizados cortes histológicos do material parafinado, os quais foram corados para HE. Posteriormente, realizou-se estudo imunoistoquímico do infiltrado inflamatório com os seguintes anticorpos: CD68, CD45, CD 4, CD8 e CD20. Idade avançada dos pacientes, transplante de célulastronco-periféricas e presença de infecções virais demonstraram ser fatores de risco para GVHDc. Vacuolização da camada basal, infiltrado linfóide, exocitose, células acidófilas contraídas, divagem focal ou separação entre o epitélio e o conjuntivo são as alterações histológicas que mais diferenciam GVHDc de alterações do condicionamento na mucosa oral. As alterações histopatológicas mais comuns em glândulas salivares menores foram: infiltrado inflamatório linfocitário moderado, fibrose intersticial e diminuição do número de duetos e ácinos. As células predominantes na GVHDc foram linfócitos T citotóxicos, tanto no tecido epitelial, como no tecido conjuntivo e glândulas salivares. Esses resultados indicam que as principais células envolvidas na etiopatogenia da GVHOc na mucosa oral e glândulas salivares menores são os linfócitos T citotóxicos, mas macrófagos e linfócitos auxiliares também participam da patogenia da doença / Abstract: The major cause of morbidity and mortality in patients undergoing allogeneic bone marrow transplantation is graft-versus-host disease (GVHD). The clinical and histological manifestation of oral mucosa can precede other organ involvement in the GVHDc. The aim of our study was to evaluate the predictive risk factors to GVHDc, the histological and immunohistochemical differences between patients with or without GVHDc, as well as to evaluate the immunophenotype of the inflammatory cells in oral mucosa and labial salivary gland. Twenty-five patients who had GVHDc (experimental-group) and 16 patients who had not GVHOc were seected. The data patient, gender, underlying disease, type of transplantation, donor gender, compatibility of the system ABO and HLA, infection diseases, previous GVHDa, organ involved in the GVHOc, were obtained frem the clinical records. The slides were firstly examined in H&E. Immunohistochemical analyses included the following antibodies CD68, CD45, CD4, CD8, CD20. The age of the patients (oldest), type of transplantation and infection disease were found risk factors to GVHDc Hydropic degeneration of the basal cells, apoptotic bodies, Iymphocytic infiltration, and focal or total clivage between epithelial and connective tissue were histological features that could be used to differentiate GVHDc frem chemotherapy effects on oral mucosa. In the labial salivary glands the Iymphocytic infiltration, acinar 1055and fibresis were the main alteration. The predominant cells in GVHDc were CD8 T cells in epithelium, connective tissue as much as in salivary glands / Mestrado / Patologia / Mestre em Estomatopatologia

Avaliou-se a mucosa de palato duro de indivíduos portadores de síndrome de Apert, atendidos no Hospital de Reabilitação de Anomalias Craniofaciais da Universidade de São Paulo. Doze indivíduos foram submetidos à gengivectomia de tecido exuberante da mucosa palatina para colocação de bandas e acessórios ortodônticos. Os tecidos excisados foram submetidos à análise histológica, morfométrica, histoquímica (PAS, Alcian Blue e Picrossírius) e imunohistoquímica, para observação da proliferação celular com a proteína P63 e identificação de colágeno I e III e decorina. A análise histológica evidenciou epitélio hiperplásico, conjuntivo com áreas de fibras colágenas espessas de trajeto mais linear com fibrócitos em seu interior, áreas com menor número de fibras e marcante presença de fibroblastos, diferente da arquitetura do grupo controle. Os resultados da morfometria não mostraram diferença significativa entre a proporcionalidade dos componentes do tecido conjuntivo nos indivíduos com síndrome de Apert e de indivíduos do grupo controle. Os aspectos histoquímicos evidenciaram que os indivíduos com a síndrome apresentaram maior acúmulo de glicosaminoglicanas em relação ao grupo controle. A coloração de picrossírius, analisada por microscópio confocal e pelo sistema de análise de imagem Image-Pro-Plus evidenciou a presença de fibras colágenas mais espessas nos indivíduos portadores de síndrome de Apert, mas não mostrou diferença significativa entre os dois grupos. A correlação da área ocupada pelas fibras colágenas com a idade dos indivíduos não foi significativa. Os resultados da imunohistoquímica confirmaram a presença de colágeno I e III no tecido Apert, sem evidenciar a atividade proliferativa dos fibroblastos. A maioria dos cortes não evidenciou a imunomarcação para decorina. Conclui-se que o aumento de volume na mucosa palatina em indivíduos portadores de síndrome de Apert é decorrente do crescimento tecidual sem o predomínio de qualquer um dos componentes do tecido conjuntivo, apesar de os indivíduos com a síndrome apresentarem uma arquitetura diferente das fibras colágenas e maior acúmulo de glicosaminoglicanas. / The aim of this study was to evaluate the oral mucosa of patients with Apert syndrome attended at the Hospital of Rehabilitation and Craniofacial Anomalies. The gingivectomy was realized in twelve patients with gingival lateral swellings targeting orthodontic accessories. The specimens were submitted for histological, morphometric, histochemistry (PAS, Alcian Blue, picrossirius) and immunohistochemistry analysis to evaluate cell proliferation with P63 protein, and identification of the collagens I and III and decorin. The histological analysis showed a hyperplasic epithelium, areas of thick collagen fibers in the connective tissue with inactive fibroblasts, different that revealed in the control group. The proportion of the components of the connective tissue between the Aperts syndrome and the control groups wasnt statistical significant. The histochemicals features showed a high concentration of glycosaminoglycans in the connective tissue of Aperts syndrome compared with that revealed in the control group. The picrossírius stained, in the confocal microscope and in the Image Pro-Plus system showed the presence of dense collagen fibers in the Aperts syndrome group, but the statistical analysis wasnt significant between the both groups. The correlation between the collagen area and the age of the patients wasnt statistically significant. The analyses in the Apert syndrome group confirmed the presence of type -I and -III collagen and no proliferative activity of fibroblasts. The decorin staining was absent in almost all the specimens. We conclude that in Aperts syndrome gingival lateral swellings is a secondary outcome and is independent of a increase in the connective tissue components; the collagen fibers, and the glycosaminoglycans gathering found in the Apert syndrome patients were structurally different.

A mucosite induzida por quimioterapia e radioterapia representa um dos principais efeitos colaterais indesejáveis no tratamento do câncer. A dor associada à mucosite, dificulta a mastigação, a deglutição e freqüentemente é causa de interrupção temporária do tratamento e de atraso na recuperação do paciente. Ela se manifesta por eritema generalizado e/ou lesões ulcerativas na mucosa bucal, laringe e no trato gastrointestinal. O grupo estudado foi composto por 33 pacientes com câncer de cólon com idades entre 28 e 66 anos, 15 mulheres e 18 homens. Noventa e nove ciclos de quimioterapia foram analisados. O esquema de tratamento utilizado foi uma combinação da droga antineoplásica 5-fluorouracil, com o agente modulador ácido folínico. Idade, gênero, fluxo salivar antes e durante o tratamento foram associados à ocorrência de mucosite OMAS e mucosite WHO, tanto para pacientes com fluxo salivar normal quanto para pacientes com fluxo salivar reduzido. Também foram analisados os sítios de maior ocorrência das lesões e o tamanho das lesões em relação aos fluxos normais e reduzidos. A partir dessas associações obtivemos os seguintes resultados: os pacientes com fluxo salivar reduzido antes e durante a quimioterapia desenvolveram mais mucosite OMAS e WHO em comparação com os pacientes com fluxo normal. Os pacientes com fluxo salivar reduzido tiveram mais ulceração, considerando qualquer tamanho de lesão. A semimucosa do lábio inferior e as bordas laterais de língua foram os sítios em que ocorreram a maior incidência de ulceração e as úlceras de maior severidade. / Mucositis induced by chemotherapy and radiotherapy represents one of most undesirable side effects in the cancer treatment. The pain associated to mucositis raise difficulties to patients ability to chew and swallow and frequently causes temporary interruption of treatment and delay in patient recovery. It presents itself as redness and/or ulcerative sores in the soft tissues of the mouth, throat and gastrointestinal tract. The studied group was composed by 33 patients with colon cancer with ages between 28 and 66 years, 15 women and 18 men Ninety nine cycles of chemotherapy were analyzed. A combination of 5-fluorouracil, with folinic acid was used. Age, gender, salivary flow before and during treatment were associated to the occurrence of OMAS and WHO mucositis for patients with normal and reduced salivary flow. Size and sites of ulceration occurrence were also analyzed. The following results were found: the patients with reduction of salivary flow, before and during chemotherapy developed more OMAS and Who mucositis comparing to normal flow patients. Patients with reduced flow also had more ulceration and the mucosal surfaces of inferior lips and the lateral borders of tongue were the sites with more severe ulceration rates.

Made available in DSpace on 2014-06-11T19:30:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T19:19:33Z : No. of bitstreams: 1 castilho_ec_dr_botfm.pdf: 693976 bytes, checksum: bbfa4da3f523001acac2d23b6b1ac73b (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Justificativa: as lesões da mucosa traqueal em contato com o balonete do tubo traqueal são proporcionais à pressão exercida pelo balonete e ao tempo de exposição. Objetivo: estudar as eventuais lesões da mucosa do segmento traqueal em contato com o balonete do tubo traqueal insuflado com volume de ar suficiente para se obter a pressão de “selo” para impedir vazamento durante ventilação artificial, ou com a pressão “crítica” de 25 cm H2O. Método: dezesseis cães foram submetidos à anestesia venosa com pentobarbital sódico e ventilação com fluxo total de gases frescos de 2 L.min-1. Os cães foram distribuídos aleatoriamente em dois grupos de acordo com a pressão no balonete de grande volume do tubo traqueal (Portex Blue-Line, Inglaterra): G1 (n=8) balonete insuflado até a obtenção da pressão mínima de “selo” necessária para impedir vazamento de ar durante a respiração artificial; G2 (n=8) balonete insuflado até atingir a pressão de 25 cm de H20. A medida da pressão do balonete foi realizada por meio de manômetro digital (Mallinckrodt, EUA) no início do experimento (controle) e após 60, 120 e 180 minutos. Após osacrifício dos cães, foram feitas biópsias nas áreas traqueais adjacente ao tubo traqueal para análise à microscopia óptica (MO) e microscopia eletrônica de varredura (MEV). Resultados: à MO, evidenciaram-se mínimas alterações em ambos os grupos, mais significantemente em G1, em duas áreas da parede anterior da traquéia: uma em contato com o balonete (BB1) e outra abaixo do tubo traqueal (BP1) (p=0,002). À MEV as alterações não foram significantemente diferente nos grupos (p>0,30), mas ocorreram lesões mais intensas nas áreas de contato com o balonete nos dois grupos (p<0,05). Conclusões: no cão, nas condições experimentais empregadas... / Background: The lesions of the tracheal mucosa in contact with the endotracheal tube cuff are proportionally related to the intracuff pressure and to the time of exposition. Objective: the aim of this work was to study the development lesions of tracheal mucosa in contact with the endotracheal tube cuff inflated to reach the “sealing” pressure in order to avoid leaking during the artificial ventilation or with the “peak” inflation pressure of 25 cm H2O. Methods: sixteen dogs were submitted to intravenous anesthesia with pentobarbital sodium and ventilation with total flow of fresh gases of 2 L.min-1. The dogs were randomly distribuited into two experimental groups according to the pressure in the high volume cuff of the endotracheal tube (Portex Blue Line, Inglaterra): G1 (n=8) the cuff was inflated in order to reach the sealing minimum pressure to avoid air leaking during the artificial respiration; G2 (n=8) the cuff was inflated to reach the pressure of 25 cm H2O. The intracuff pressure was measured with a digital manometer (Mallinckrodt, EUA) at the beginning of the experiment (control) and after 60, 120 and 180 minutes. The animals were sacrificied and biopsies were perfomed from the areas of the trachea adjacent the endotracheal tube to be analysed by light microscopy (LM) and scanning electronic microscopy (SEM). Results: The light microscopy showed mild and similar alterations in both groups. However G1 revealed alterations most frequently in two different areas of trachea anterior wall: one lesion in direct contact with the cuff (BB1) and the other lesion just below the tracheal tube (BP1) (p=0.002). The scanning electronic microscopy also showed similar alterations in both groups (P>0.30), with more. Conclusions: In the dog, considering the experimental conditions used... (Complete abstract, click electronic address below)

"April 2004" / Bibliography: leaves 121-142. / xviii, 142, [19] leaves : ill. (some col.), plates (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Attempts to build a complete understanding of the cellular mechanisms associated with gastrointestinal mucositis through investigations of the effects throughout the gastrointestinal tract of chemotherapeutic agents Methotrexate and Irinotecan, the possible ameliorating potential of the cytokine Interleukin-11 in reducing the side effects of chemotherapy, the expression of pro- and anti-apoptopic proteins and transcription factors along the gastrointestinal tract in normal human patients and the time-course of development of oral mucositis in human patients. Suggests that the entire gastrointestinal tract follows a similar pattern of development of mucositis. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2004

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (M.S.)--University of Michigan, 1954.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.