Prostaglandin E2 (PGE2), a byproduct of arachidonic acid metabolism, has been suspected to be involved in tumor promotion. It has been suggested that diet may modulate PGE2 level in organisms thus affecting the implantation and growth of the tumor tissue. PGE2 content was investigated in mice fed ad libitum four types of fatty acid diets: saturated fatty acid diets: a stearic acid and a palmitic acid, and polyunsaturated fatty acid diets: a low fat (safflower 1%) and a high fat diet (safflower 15%). Tumor cells were implanted subcutaneously in mice and harvested when tumors reached .05- 4g. The extracted PGE2 were derivatized and quantified by High Performance Liquid Chromatography (HPLC). The results showed that there is a negative correlation between the level of PGE2 and the size of the tumors. PGE2 level declined as the tumor grew. This suggests that during the early stage of growth the tumor requires higher level of PGE2 to boost its growth. As the tumor becomes more adapted to its environment, it no longer depends on PGE2 to survive. Diet was also seen to be important in tumor suppression. Saturated fatty acid diet (SA-1) showed a suppressive effect on tumor growth. A visual comparison showed that polyunsaturated high fat diet produced more PGE2 than saturated fatty acid. This high level of PGE2 correlate with the highest tumor weights obtained in the Polyunsaturated high fat diet group. / Department of Biology

No description available.

Preterm birth remains a major challenge in obstetrics. It complicates up to 13% of all pregnancies and accounts for approximately 80% of neonatal mortality and morbidity. Bacterial Vaginosis (BV) is associated with a 1.4-fold increased risk of preterm birth. Due to ineffectiveness of antibiotics in preventing preterm labour, probiotics have been proposed to serve as an alternative for treatment of BV and prevention of preterm birth. The objectives of this thesis were to determine 1) the effect of Lactobacillus rhamnosus GR-1 (L. rhamnosus GR-1) supernatant on cytokine profile and prostaglandin (PG)-regulating enzyme expression in lipopolysaccharide (LPS)-stimulated human chorion and placental trophoblast cells from human placentae, 2) the potential signaling pathways through which lactobacilli act and 3) the potential role of immune and placental trophoblast cells in initiating a response to LPS and L. rhamnosus GR-1 treatments. Primary cultures of human placental trophoblast cells were pre-treated with lactobacilli supernatant and then with LPS. In addition, immune cells were removed from cell suspensions using a magnetic purification technique to determine their role in modulating cytokine levels. The expression of pro- and anti-inflammatory cytokines and prostaglandin-regulating enzymes was then determined. We found sex-specific differences in the ability of LPS to increase the output of TNF-α, IL-10, and PTGS2. We also showed that L. rhamnosus GR-1 is able to act through the JAK/STAT and MAPK pathways to increase IL-10 and G-CSF, and independently down-regulates PTGS2 and TNF-α and up-regulates PGDH. The increase in G-CSF and PGDH were only observed in women carrying a female fetus. L. rhamnosus GR-1 may serve as an alternative to antibiotics in preventing some infection/inflammation-mediated cases of preterm birth.

Interleukin-8 is a chemokine which is chemotactic for neutrophils and T-lymphocytes and plays a crucial role in the pathogenesis of inflammatory bowel disease. Intestinal mucosal epithelial cells produce IL-8 in response to pathogens which mediates bidirectional communication between pathogen and host. The objective of this study was to investigate the molecular mechanisms involved in IL-8 gene regulation in T84 human colonic epithelial cells. To determine if IL-8 plays a role in the pathogenesis of intestinal amebiasis, the effect of Entamoeba histolytica on IL-8 gene expression was investigated. E. histolytica secreted components enhanced IL-8 mRNA expression and protein production in the absence of amebae-enterocyte contact. The proinflammatory cytokines IL-1beta and TNF-alpha were not involved in IL-8 protein production. As PGE2 is central in mucosal inflammation, the effect of PGE2 on IL-8 gene expression was determined. Using purified PGE2 and PGE2 receptor agonists, it was shown that PGE2 coupled to the EP4 receptor and triggered cAMP-dependent PKA signaling which upregulated IL-8 mRNA expression at the posttranscriptional level. Elevation of [Ca 2+]i from intracellular Ca2+ stores by A23187 or thapsigargin stimulated IL-8 mRNA transcription and IL-8 protein production through the activation of calcineurin. Moreover, IL-8 3'-UTR had a strong suppressive effect on CAT reporter gene expression in COS7 cells by reducing its mRNA level. A unique fragment (nt 2387-2743) containing AU rich elements was shown to attenuate CAT mRNA expression by destabilizing the transcripts. Secondary structure but not AU rich elements played a major role in CAT mRNA turnover.

Diss. (sammanfattning) Uppsala : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Thesis (Ph.D. in Toxicology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 131-147).

O objetivo deste estudo foi comparar alterações histológicas induzidas por análogos de prostaglandinas e maleato de timolol na conjuntiva de coelhos. Cinqüenta coelhas da raça Nova Zelândia com idade e peso semelhantes foram divididos em cinco grupos de dez animais. Os olhos esquerdos foram tratados com uma gota diária de bimatoprosta 0,03%, travoprosta 0,004%, latanoprosta 0,005%, maleato de timolol 0,5% ou lágrimas artificiais contendo cloreto de benzalcônio (CBA) durante 30 dias. Os olhos contra-laterais serviram como controles. Realizaram-se biópsias na conjuntiva limbar superior com dimensões de 5 mm x 5 mm no oitavo e trigésimo dias em cinco coelhos de cada grupo. A conjuntiva foi imediatamente fixada com formaldeído a 10% por 24 horas, seguido de coloração por Hematoxilina-Eosina (HE) e Ácido Periódico de Shiff (PAS) e avaliação qualitativa por microscopia óptica. A avaliação histo-morfométrica quantitativa foi realizada usando o programa Image Pro-Plus 4.5. Os parâmetros avaliados foram: infiltrado inflamatório, espessura epitelial, número de células caliciformes, diâmetro e número de vasos sanguíneos. Observou-se leve infiltrado inflamatório focal no tecido conectivo subepitelial nos olhos controle e do grupo CBA, que consistia de aglomerados de linfócitos e raros neutrófilos. Todos os demais grupos exibiram no oitavo e trigésimo dias de tratamento infiltrado inflamatório moderado, composto por linfócitos e neutrófilos, que foi mais denso no grupo tratado com maleato de timolol do que nos grupos dos análogos de prostaglandinas. No trigésimo dia, o grupo que recebeu timolol mostrou aumento da densidade subepitelial de colágeno e aumento estatisticamente significante da espessura epitelial (P=0,004), que não foram observados nos demais grupos. Observou-se um aumento estatisticamente significante do número de vasos no grupo tratado com timolol (P=0,001). O diâmetro vascular no grupo que recebeu travoprosta apresentou aumento estatisticamente significante no oitavo dia de tratamento (P=0,008) e redução no 30º dia (P=0,035). A densidade de células caliciformes aumentou significativamente no grupo que recebeu travoprosta no oitavo dia (P=0,001) e no 30º dia nos grupos tratados com bimatoprosta (P=0,002) e latanoprosta (P=0,009). Conclui-se que, na conjuntiva de coelhos, o número de células caliciformes aumenta com o uso de análogos das prostaglandinas. O estudo sugere que essas drogas, entretanto, induzem menos alterações que o maleato de timolol na conjuntiva de coelhos / The purpose of this study was to compare histological changes induced by prostaglandin analogues and timolol maleate in the rabbit conjunctiva. Fifty New Zealand female rabbits with similar age and weight were divided in five groups of 10 animals. The left eyes were treated with one daily drop of bimatoprost 0,03%, travoprost 0,004%, latanoprost 0,005%, timolol maleate 0,5% or artificial tears containing benzalkonium chloride (BAC) for 30 days. The fellow eyes served as controls. Limbal superior conjunctival biopsies of 5 mm x 5 mm were performed at the 8th and 30th day in five rabbits of each group each time. The conjunctiva was immediately fixed with 10% formaldehyde for 24 hours, followed by Hematoxiline-Eosine (HE) and Periodic Acid Shiff (PAS) staining and optical qualitative microscopic evaluation. Morphohistometric quantitative analyses were conducted using the Image Pro-Plus 4.5 software. The evaluated parameters were: inflammatory infiltrate, epithelial thickness, number of goblet cells, diameter and number of blood vessels. A low level infiltration, consisting of localized clusters of lymphocytes and rare neutrophils, was observed in the subepithelial connective tissue of the control eyes and in the BAC group. At the 8th and 30th day post treatment, all other groups exhibited a diffuse inflammatory infiltrate, composed by lymphocytes and neutrophils, which was denser in the timolol group than in the prostaglandin analogue groups. At the 30th day, the timolol group also showed an increased subepithelial collagen density and a significant increase in epithelial thickness (P=0.004), which was not present in the other groups. A significant increase (P =0.001) in the number of blood vessels was observed in the group treated with timolol. An initial increase in the vascular diameter was observed at the 8th day in the travoprost group (P=0,008) although a significant reduction was observed at the 30th day (P =0,035). The goblet cell density was significantly increased at the 8th day in the group treated with travoprost (P =0.001) and at the 30th day in those treated with bimatoprost (P =0.002) and latanoprost (P =0.009). We conclude that an increase in the number of goblet cell was initially observed with the use of all prostaglandin analogues. This study suggests that these drugs, however, induce fewer changes than timolol maleate in the rabbit conjunctiva

Orientador: João Carlos Pinheiro Ferreira / Coorientador: Milo C. Wiltbank / Resumo: Em ruminantes a luteólise natural é caraterizada pela liberação de vários pulsos de prostaglandina F2alfa (PGF) produzidos pelo útero. A PGF é o hormônio luteolítico, enquanto a prostaglandina E1 (PGE1) é considerada um mediador luteoprotetor. Em estudos anteriores, infusões com doses baixas de PGF no útero com intervalos de 6 horas (h) resultou em regressão do corpo luteo (CL). A proposta deste experimento é desenvolver um modelo para avaliar o efeito de baixas doses de PGE1, também infundidas no lúmen uterino sobre a resposta luteal à PGF intrauterina (IU). Vacas no dia 10 do ciclo estral receberam infusões IU de salina (0,1 ml de salina + 0,1 ml de DMSO), PGE (2 mg de PGE1 em 0,1ml de DMSO) ou PGF (0,25 mg of PGF em 0,1 ml de salina) em intervalos de 6 h em um desenho experimental 2 X 2. Portanto os animais foram agrupados em quatro tratamentos: SALINA (4 infusões de salina; n=5), PGE (4 infusões de PGE1; n=5), PGF (4 infusões de PGF; n=5) e PGE+PGF (4 infusões de PGE1+PGF; n=5). As concentrações plasmáticas de progesterona (P4) foram dosadas por radioimunoensaio e o volume luteal foi determinado por ultrassonografia transretal. As concentrações circulantes de PGFM e PGEM foram dosadas antes e 10 minutos após as primeiras duas infusões. Biopsias luteais foram coletadas de cada vaca 30 minutos após cada infusão para determiner a expressão de genes em resposta a cada tratamento. As concentrações circulantes de PGFM 10 minutos após as infusões foram maiores em vacas que receb... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre