Sôbre os Élitros de uma espécie Nova de Oontelus do Brasil: (Coleoptera, Malacodermata)

Foram analisados os élitros de uma nova espécie Oontelus e, para comparação, os de Chalepus sanguinicollis ab. axilaris, com o fim de esclarecer a origem das membranas transparentes em forma de janela. As membranas formam-se das epicutículas das duas superfícies do élitro, colads uma a outra por meio de uma massa colaginosa. A espessura em Oontelus é de 0,34 à 0,36 micron, em Chalepus de 4à 4,3 micra. Os dois casos referidos confirmam um exemplo típico de lei da continuidade da cutícula nos tecidos ectodermal, dos insetos, cuja formção - segundo o plano básico da estrutura do corpo - não permite nenhuma interrupção da cutícula.

Estudos anatômicos e histológicos sôbre a subfamília Triatominae (Heteroptera, Reduviidae): X. parte: Espermiohistogênese do Triatoma infestans

No trabalho apresentado, descrevemos a evolução do espérmio maduro de triatoma infestans, iniciando-se a observação das transformações a partir dos espermídeos. Destacamos, em seguida, os principais resultados: 1. A histogênese dos espérmios é subdividida em 6 fases que se superpõem, parcialmente, a respeito do cronismo dos acontecimentos celulares: a) fase de translações (translações dos centríolos, mitocôndrios e do aparelho de GoLGI do pólo apical o pòlo basal da célula). b) Alongamento dos centríolos (formação do filamento axial). c) Alongamento da massa mitocondrial (formação dos fios periféricos). d) Formação do acrosoma (divisão do aparelho de GOLGI em acrosoma e corpo restante, que é eliminado da célula; além disto, translação do acrosoma para o pólo apical). e) Primeira fase de alongamento do núcleo (alongamento do núcleo e condensação da cromatina). f) Segunda fase de alongamento do núcleo (alongamento definitivo do núcleo para formar a cabeça do espérmio). 2. Os centríolos, em Triatoma infestans, podem ser observados, contînuamente, dos estádios da profase (estádio dos cromosomas difusos) até o fim da formação do espérmio. Para esta observação precisamos de cortes finos com, aproximadamente, um micron de espessura. 3. Os centríolos, depois da última divisão de maturação, ficam escondidos no interior do corpo dos restos dos fusos. 4. Não se pode distinguir o centríolo distal do proximal. os dois justapõem-se, um ao lado do outro, sôbre a parede do núcleo. 5. O fio axial tem origem dos dois centríolos, sendo êste um fio duplo. 6. Observamos a transformação dos mitocôndrios em microfibrilas da cauda bem como a de uma parte do aparelho de GOLGI em acrosoma. 7. Depois da condensação da cromatina sôbre a parede do núcleo, formam-se duas saliências longitudinais cromáticas, que são orientadas em espiral com torsão em sentido inverso do relógio. Por isso, o corte transversal do núcleo, fortemente alongado, tem o aspecto de ferradura. 8. O espérmio maduro é composto pelos seguintes elementos, cuja existência é provada, no microscópio eletrônico, por intermédio de cortes e dilacerações: a) Acrosoma (em forma de um cone, ligeiramente curvado). b) Núcleo, formado a "cabeça" do espérmio, sem qualquer estrutura vísivel no seu interior. c) Cone basal do núcleo, formado pelos centríolos. d) Fio axial, composto de duas microfibrilas dos centríolos. e) Oito fios longitudinais mitocondriais, unidos em dois grupos (corpos em forma de vírgula), e incluídos em uma massa homogênea. Cada um dos corpos em forma de vírgula...

Estudos anatômicos e histológicos sôbre a sub-família Triatominae (Heteroptera, Reduviidae): Parte XX: estudo comparado dos estigmas nas espécies mais importantes

É feito um estudo comparado sôbre a estrutura e o mecanismo dos estigmas de Triatoma vitticeps, Triatoma maculata, Triatoma sórdida, Triatoma brasiliensis, Rhodnius prolines e Panstrongyius megistus com os de Triatoma infestans, anteriormente já tratados. É, assim, elaborada uma tabela comparativa sôbre o tamanho e localização, dos espiráculos torácicos e abdominais, nas espécies citadas. Os estigmas mesotorácicos nas espécies do gênero Triatoma apresentam-se com várias modificações morfológicas, porém, não tão significantes como as encontradas em Panstrongyius megistus e Rhodnius prolixus. Seu mecanismo mostra acentuadas diferenças morfológicas. De um modo geral, os estigmas mesotorácicos possuem uma zona dorsal e outra ventral, que se diferenciam nas diferentes espécies e gêneros. A abertura do átrio para o exterior faz-se, perpendicularmente ao eixo maior do corpo do inseto. Nota-se uma região onde a cutícula é mais espêssa e que serve de base para a implantação dos músculos destinados ao seu funcionamento. O côndilo, que varia quanto à forma, nos diversos Triatomíneos, não é evidenciado nos estigmas metatorácicos. Os espiráculos metatorácicos encontram-se ocultos, totalmente, pelos escleritos do mesotórax e metatórax. O aspecto morfológico do mesmo é semelhante ao do mesotorácico, porém, apresenta algumas diferenças. Os espiraculos abdominais são em número de 8 pares. O 1.º par está situado na região látero-dorsal da membrana intersegmental, entre o tórax e o abdômen. Em Rhodnius prolixus o estigma apresenta-se circundado por zonas esclerosadas, em forma de listas. Nos demais Triatomíneos os escleritos estigmatíferos são semelhantes e menos reforçados. A forma e a estrutura e o mecanismo dêstes estigmas variam em todas as espécies citadas, Encontram-se 3 elementos de proteção à traquéia que se limita com o átrio. São eles: 1) rêde protetora que recobre parcialmente a entrada do estigma, semelhante a um peritrema; 2) côndilo interno que comanda a entrada e saída do ar das traquéias; e 3) falsos espinhos, situados no átrio e que variam de tamanho e espessura nos diferentes Triatomíneos. Finalmente, observa-se o VIII par de estigmas abdominais, cuja forma, mecanismo e localização o diferenciam dos demais. Êste par encontra-se citado por alguns autores, porém, na realidade, sua estrutura só é apresentada no presente trabalho.

Procamallanus brasileiros - parte I (Nematoda, Camallanoidea)

Nessa primeira parte do trabalho referente ao estudo dos Procamallanus brasileiros, os autores propoêm que Spirocamallanus Olsen, 1952, seja aceito apenas como um bom subgênero, baseando-se exclusivamente no aspecto de cápsula bucal. Assi, Spirocamallanus identifica os camalanídeos de cápsula bucal com lâminas espiraladas ou outras estruturas semelhantes, enquanto que Procamallanus se aplicaria aos de cápsula bucal lisa. Quanto às demais subdivisões existentes para o gênero, apoiadas em aspecto e quantidade de espículos, são consideradas resultado de um critério bastante arbitrário para conservarem-se válidas, visto serem os espículos caracteres sujeitos a diversas interpretações por parte dos especialistas, devido à fragilidade que os toma tão sujeitos a modificações no grupo dos camalanídeos. Três espécies são aqui tratadas: Procamallanus (Spirocamallanus) rarus Travassos, Artigas & Pereira, 1928, Procamallanus (Spirocamallanus) pimelodus, e Procamallanus (Spirocamallanus) intermedius. As duas últimas são propostas como novas. Procamallanus (S.) pimelodus é comparada a Procamallanus (Spirocamallanus) olseni Campana-Rouget & Razahihelissoa, 1965, dela se distinguindo, principalmente, por apresentar o rebordo da asa caudal franjado e fortemente musculoso. Procamallanus (S.) intermedius aproxima-se unicamente de Procamallanus (S.) rarus, por apresentar o espículo maior com bifurcação distal e dela se afasta pelo maior número e menor espessura das lâminas espiraladas na cápsula bucal. Para Procamallanus (S.) rarus é apresentada a descrição da fêmea, a redescrição do macho, salientando-se pela primeira vez no gênero, o aspecto singular do espículo maior, aspecto esse também observado ao se lidar com Procamallanus (S.) intermedius, depois de se ter tido acesso ao exemplar tipo e único de Procamallanus (S.) rarus. Foram examinadas 31 amostras de material que faz parte da Coleção Helmintológica do Instituto Oswaldo Cruz.

Limites de distâncias de detecção de caramujos Biomphalaria glabrata marcados com SR-85, usando como absorvedores o ar, a água e areia

Caramujos da espécie Biomphalaria glabrata, vetora da esquistossomose mansônica, podem ser marcados com atividades variáveis de Sr-85 e localizados através dos absorvedores ar, água e reia e de suas várias associações. A atividade a ser incorporada no caramujo será função da espessura, do(s) absorvedor(es), conforme diagramas apresentados, tornando o processo simples, rápido e ecônomico.

The role of Pten in the Hematopoietic System and the Hematopoietic Stem Cells

Résumé Identification, localisation et activation des cellules souches hématopoiétiques dormantes in vivo Les cellules souches somatiques sont présentes dans la majorité des tissus régénératifs comme la peau, l'épithélium intestinal et le système hématopoiétique. A partir d'une seule cellule, elles ont les capacités de produire d'autres cellules souches du même type (auto-renouvellement) et d'engendrer un ensemble défini de cellules progénitrices différenciées qui vont maintenir ou réparer leur tissu hôte. Les cellules souches adultes les mieux caractérisées sont les cellules souches hématopoiétiques (HSC), localisées dans la moelle osseuse. Un des buts de mon travail de doctorat était de caractériser plus en profondeur la localisation des HSCs endogènes in vivo. Pour ce faire, la technique "label retaining assay", se basant sur la division peu fréquentes et sur la dormance des cellules souches, a été utilisée. Après un marquage des souris avec du BrdU (analogue à l'ADN) suivi d'une longue période sans BrdU, les cellules ayant incorporés le marquage ("label retaining cells" LCRs) ont pu être identifiées dans la moelle osseuse. Ces cellules LCRs étaient enrichies 300 fois en cellules de phenotype HSC et, en utilisant de la cytofluorométrie, il a pu être montré qu'environ 15% de toutes les HSCs d'une souris restent dormantes durant plusieures semaines. Ces HSCs dormantes à long terme ne sont probablement pas impliquées dans la maintenance de 'hématopoièse. Par contre, on assiste à l'activation rapide de ces HSCs dormantes lors d'une blessure, comme une ablation myéloide. Elles re-entrent alors en cycle cellulaire et sont essentielles pour une génération rapide des cellules progénitrices et matures qui vont remplacer les cellules perdues. De plus, la détection des LCRs, combinée avec l'utilisation du marqueur de HSCs c-kit, peut être utilisée pour la localisation des HSCs dormantes présentes dans la paroi endostéale de la cavité osseuse. De manière surprenante, les LCRs c-kit+ ont surtout étés trouvées isolées en cellule unique, suggérant que le micro-environement spécifique entourant et maintenant les HSCs, appelé niche, pourrait être très réduit et abriter une seule HSC par niche. Rôles complexes du gène supresseur de tumeur Pten dans le système hématopoiétique La phosphatase PTEN disparaît dans certains cancers héréditaires ou sporadiques humains, comme les gliomes, les cancers de l'utérus ou du sein. Pten inhibe la voie de signalisation de la PI3-kinase et joue un rôle clé dans l'apoptose, la croissance, la prolifération et la migration cellulaire. Notre but était d'étudier le rôle de Pten dans les HSC normale et durant la formation de leucémies. Pour ce faire, nous avons généré un modèle murin dans lequel le gène Pten peut être supprimé dans les cellules hématopoiétiques, incluant les HSCs. Ceci a été possible en croissant l'allèle conditionnelle ptenflox soit avec le transgène MxCre inductible par l'interféron α soit avec le transgène Scl-CreERt inductible par le tamoxifen. Ceci permet la conversion de l'allèle ptenflox en l'allèle nul PtenΔ dans les HSCs et les autres types cellulaires hématopoiétiques. Les souris mutantes Pten développent une splénomégalie massive causée par une expansion dramatiques de toutes les cellules myéloides. De manière interessante, alors que le nombre de HSCs dans la moelle osseuse diminue progressivement, le nombre des HSCs dans la rate augmente de manière proportionnelle. Etrangement, les analyses de cycle cellulaire ont montrés que Pten n'avait que peu ou pas d'effet sur la dormance des HSCs ou sur leur autorenouvellement. En revanche, une augmentation massive du niveau de la cytokine de mobilisation G-CSF a été détéctée dans le serum sanguin, suggérant que la suppression de Pten stimulerait la mobilisation et la migration des HSC de la moelle osseuse vers la rate. Finallement, la transplantation de moelle osseuse délétée en Pten dans des souris immuno-déficientes montre que Pten fonctionnerait comme un suppresseur de tumeur dans le système hématopoiétique car son absence entraîne la formation rapide de leucémies lymphocytaires. Summary Identification, localization and activation of dormant hematopoietic stun cells in vivo Somatic stem cells are present in most self-renewing tissues including the skin, the intestinal epithelium and the hematopoietic system. On a single cell basis they have the capacity to produce more stem cells of the same phenotype (self-renewal) and to give rise to a defined set of mature differentiated progeny, responsible for the maintenance or repair of the host tissue. The best characterized adult stem cell is the hematopoietic stem cell (HSC) located in the bone marrow. One goal of my thesis work was to further characterize the location of endogenous HSCs in vivo. To do this, a technique called "label retaining assay» was used which takes advantage of the fact that stem cells (including HSCs) divide very infrequently and can be dormant for months. After labeling mice with the DNA analogue BrdU followed by a long BrdU free "chase", BrdU "label retaining cells" (CRCs) could be identified in the bone marrow. These CRCs were 300-fold enriched for phenotypic HSCs and by using flow cytometry analysis it could be shown that about 15% of all HSCs in the mouse are dormant for many weeks. Our results suggest that these long-term dormant HSCs are unlikely to be involved in homeostatic maintenance. However they are rapidly activated and reenter the cell cycle in response to injury signals such as myeloid ablation. In addition, detection of LRCs in combination with the HSC marker c-Kit could be used to locate engrafted dormant HSCs close to the endosteal lining of the bone marrow cavities. Most surprisingly, c-Kit+LRCs were found predominantly as single cells suggesting that the specific stem cell maintaining microenvironment, called niche, has limited space and may house only single HSCs. Complex roles of the tumor suppressor gene Pten in the hematopoietic system. The phosphatase PTEN is lost in hereditary and sporadic forms of human cancers, including gliomas, endometrial and breast cancers. Pten inhibits the PI3-kina.se pathway and plays a key role in apoptosis, cell growth, proliferation and migration. Our aim was to study the role of Pten in normal HSCs and during leukemia formation. To do this, we generated a mouse model in which the Pten gene can be deleted in hematopoietic cells including HSCs. This was achieved by crossing the conditional ptenflox allele with either the interferona inducible MxCre or the tamoxifen inducible Scl-CreERT transgene. This allowed the conversion of the ptenflox allele into a pterr' null allele in HSCs and other hematopoietic cell types. As a result Pten mutant mice developed massive splenomegaly due to a dramatic expansion of all myeloid cells. Interestingly, while the number of bone marrow HSCs progressively decreased, the number of HSCs in the spleen increased to a similar extent. Unexpectedly, extensive cell cycle analysis showed that Pten had little or no effect on HSC dormancy or HSC self-renewal. Instead, dramatically increased levels of the mobilizing cytokine G-CSF were detected in the blood serum suggesting that loss-of Pten stimulates mobilization and migration of HSC from the BM to the spleen. Finally, transplantation of Pten deficient BM cells into immuno-compromised mice showed that Pten can function as a tumor suppressor in the hematopoietic system and that its absence leads to the rapid formation of T cell leukemia.

Lipoxin A4 is a novel estrogen receptor modulator.

Inflammation is intimately linked with naturally occurring remodeling events in the endometrium. Lipoxins comprise a group of short-lived, nonclassic eicosanoids possessing potent anti-inflammatory and proresolution properties. In the present study, we investigated the role of lipoxin A(4) (LXA(4)) in the endometrium and demonstrated that 15-LOX-2, an enzyme necessary for LX biosynthesis, is expressed in this tissue. Our results establish that LXA(4) possesses robust estrogenic activity through its capacity to alter ERE transcriptional activity, as well as expression of estrogen-regulated genes, alkaline phosphatase activity, and proliferation in human endometrial epithelial cells. Interestingly, LXA(4) also demonstrated antiestrogenic potential, significantly attenuating E2-induced activity. This estrogenic activity was directly mediated through estrogen receptors (ERs). Subsequent investigations determined that the actions of LXA(4) are exclusively mediated through ERα and closely mimic those of the potent estrogen 17β-estradiol (E2). In binding assays, LXA(4) competed with E2 for ER binding, with an IC(50) of 46 nM. Furthermore, LXA(4) exhibited estrogenic activity in vivo, increasing uterine wet weight and modulating E2-regulated gene expression. These findings reveal a previously unappreciated facet of LXA(4) bioactions, implicating this lipid mediator in novel immunoendocrine crosstalk mechanisms.

Cruciferous vegetables and cancer risk in a network of case-control studies.

Background Cruciferous vegetables have been suggested to protect against various cancers, though the issue is open to discussion. To further understand their role, we analyzed data from a network of case-control studies conducted in Italy and Switzerland. Patients and methods The studies included a total of 1468 cancers of the oral cavity/pharynx, 505 of the esophagus, 230 of the stomach, 2390 of the colorectum, 185 of the liver, 326 of the pancreas, 852 of the larynx, 3034 of the breast, 367 of the endometrium, 1031 of the ovary, 1294 of the prostate, 767 of the kidney, and 11 492 controls. All cancers were incident, histologically confirmed; controls were subjects admitted to the same network of hospitals as cases for a wide spectrum of acute nonneoplastic conditions. Results The multivariate odds ratio (OR) for consumption of cruciferous vegetables at least once a week as compared with no/occasional consumption was significantly reduced for cancer of the oral cavity/pharynx (OR = 0.83), esophagus (OR = 0.72), colorectum (OR = 0.83), breast (OR = 0.83), and kidney (OR = 0.68). The OR was below unity, but not significant, for stomach (OR = 0.90), liver (OR = 0.72), pancreatic (OR = 0.90), laryngeal (OR = 0.84), endometrial (OR = 0.93), ovarian (OR = 0.91), and prostate (OR = 0.87) cancer. Conclusion This large series of studies provides additional evidence of a favorable effect of cruciferous vegetables on several common cancers.

Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4).

OBJECTIVE: To compare the expression of the prostaglandin (PG) E(2) transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A(4) (LXA(4)) in endometriotic epithelial cells. DESIGN: Molecular analysis in human samples and a cell line. SETTING: Two university hospitals and a private clinic. PATIENT(S): A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy. INTERVENTION(S): Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies. MAIN OUTCOME MEASURE(S): Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE(2) was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA). RESULT(S): MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA(4) attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE(2) metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA(4) treatment inhibited extracellular PGE(2) release. CONCLUSION(S): We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA(4) in endometriotic epithelial cells.

Contrast ultrasound: a simple-to-use phase-shifting medium offers saline infusion sonography-like images.

OBJECTIVE: To test the ability of a novel phase-shifting medium (PSM) to provide sustained distension of the uterine cavity and produce saline infusion sonography (SIS)-like images in a simplified contrast ultrasound procedure. DESIGN: Prospective pilot feasibility trial of a new diagnostic procedure, contrast ultrasound. SETTING: Clinical reproductive endocrine and infertility unit of regional teaching hospital. PATIENT(S): Twenty-six asymptomatic infertile women (group I) and 27 women presenting with dysfunctional uterine bleeding (DUB) who were scheduled for exploratory surgery (group II). INTERVENTION(S): All women who were temporarily on oral contraceptive first had a regular pelvic ultrasound followed by the intrauterine instillation of up to 3 mL PSM, using a regular insemination catheter, after which all instruments were removed and a regular ultrasound was performed again. RESULT(S): In all 53 women, intrauterine instillation of 1-3 mL PSM resulted in a 3-7 mm uterine distension, sufficient to produce SIS-like images of the uterine cavity that lasted 7-10 min. Contrast ultrasound revealed an endometrial polyp in 3 asymptomatic women of group I. In group II. 12 of 14 women (86%) whose vaginal ultrasound were positive or dubious had positive findings with contrast ultrasound; 9 of 12 patients whose vaginal ultrasounds were negative also had positive contrast ultrasound findings. All the positive and negative findings of contrast ultrasound made in group II were confirmed anatomically (sensitivity and specificity of 100%), whereas the correlation for standard vaginal ultrasound was markedly lower at 57.1% and 85.7%, respectively. Most patients (46 of 53) reported no discomfort during or after the procedure, and 7 women described the procedure as mildly uncomfortable. CONCLUSION(S): Contrast ultrasound, a novel simple diagnostic procedure conducted after intrauterine instillation of 1-3 mL PSM using a simple plastic catheter, delivered SIS-quality images in asymptomatic (group I) and symptomatic (group II) patients while retaining the simplicity of standard ultrasound. We therefore foresee broad application of contrast ultrasound for sensitive and specific assessment for uterine pathologies in the physician's office.

Caracterización de las células madre neoplásicas en el cáncer de endometrio

El carcinoma de endometrio (CE) es el tumor maligno más frecuente del tracto genital femenino en países desarrollados. Durante los últimos años, ha ganado firmeza la hipótesis de que el origen de los tumores se encuentra en la transformación de células indiferenciadas multipotenciales denominadas células madre somáticas (CMS) en células madre neoplásicas (CSC). Estudios recientes han observado la existencia de células madre en endometrios murinos y humanos; el presente proyecto pretende identificar, aislar, cultivar y caracterizar las CSC endometriales y estudiar los mecanismos moleculares responsables de su transformación. Nuestros resultados muestran que diferentes lineas celulares de cancer de endometrio expresan factores de célula indiferenciada. Un trabajo más extenso con la línea celular Ishikawa muestra la capacidad de estas células para crecer como esferas, diferenciarse a otros linajes y resistir al tratamiento radioterapéutico. Los resultados obtenidos nos permiten pensar que la línea Ishikawa es un buen modelo para el estudio de las CSC endometriales, aunque se necesitaría ampliar el estudio para ser concluyente.

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.

Lipoxin A4 Is A Novel Estrogen Receptor Agonist

Lipoxins (LXs), are endogenously produced eicosanoids, which possess potent antiinflammatory and proresolution bioactivities. The role of LXs in the endometrium is unknown. Our initial observations showed LXA4 enhanced estrogen receptor (ER)-mediated transcriptional activation in Ishikawa endometrial epithelial cells. Furthermore, we demonstrated that LXA4 possesses robust estrogenic activity through its capacity to alter cellular proliferation as well as the expression of estrogen-regulated genes implicated in cancer development. Interestingly, LXA4 also demonstrated antiestrogenic potential in that it attenuated E2-mediated cellular proliferation, consistent with the effects of a partial ER agonist. Subsequent studies revealed that these actions of LXA4 were directly mediated by ERa and appear to closely mimic those of the potent estrogen, 17b-Estradiol (E2). Using competitive radioligand binding assays, we confirmed that this lipid binds ER. We additionally demonstrated this estrogenic activity of LXA4 in mouse uterus in vivo using a uterotrophic assay and the expression of E2- dependent genes as readouts. Taken together our results establish a dual capacity of LXA4 to modulate estrogenic activity in the endometrium. These findings highlight a previously unappreciated paradigm in LXA4-mediated activities and reveal novel immunoendocrine crosstalk mechanisms. Disclosure of interest: None declared.

Diabetes mellitus and cancer risk in a network of case-control studies.

Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without-adjusted for major identified confounding factors for the cancers considered through logistic regression models-were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer. [Table: see text] [Table: see text].

Estudo da Energia da Banda de Condução em Células Solares Sensibilizadas por Complexos de Ruténio

Um dos grandes desafios do nosso tempo é o aproveitamento da energia solar e outras fontes de energias renováveis para promover um desenvolvimento sustentável em grande escala. Para além da inocuidade face ao meio ambiente, a eficiência e os reduzidos custos de produção das células solares sensibilizadas por corante (DSSC, do inglês dye-sensitized solar cells) continuam a atrair considerável interesse tanto académico como comercial. Em 1991, Grätzel e O’Regan deram um enorme avanço no desenvolvimento das DSSC, utilizando um material de eléctrodo com elevada área superficial, filmes semicondutores nanocristalinos de TiO2 com espessura na ordem dos mícrons Nas células fotovoltaicas o corante sensibilizador (S) adsorvido na camada de TiO2 vai absorver a radiação solar e transfere o electrão fotoexcitado para o semicondutor (SC), formando um par de cargas separadas. O sensibilizador oxidado é regenerado pelo mediador redox existente na solução de electrólito. Uma vez efectuado o trabalho através do circuito externo, o electrão volta para o contra eléctrodo onde reduz o dador de electrão oxidado, completando o ciclo. Desta maneira, a luz é convertida em electricidade sem transformação química permanente