Enhanced Transferrin Receptor Expression by Proinflammatory Cytokines in Enterocytes as a Means for Local Delivery of Drugs to Inflamed Gut Mucosa

Therapeutic intervention in inflammatory bowel diseases (IBDs) is often associated with adverse effects related to drug distribution into non-diseased tissues, a situation which attracts a rational design of a targeted treatment confined to the inflamed mucosa. Upon activation of immune cells, transferrin receptor (TfR) expression increases at their surface. Because TfR is expressed in all cell types we hypothesized that its cell surface levels are regulated also in enterocytes. We, therefore, compared TfR expression in healthy and inflamed human colonic mucosa, as well as healthy and inflamed colonic mucosa of the DNBS-induced rat model. TfR expression was elevated in the colonic mucosa of IBD patients in both the basolateral and apical membranes of the enterocytes. Increased TfR expression was also observed in colonocytes of the induced colitis rats. To explore the underlying mechanism CaCo-2 cells were treated with various proinflammatory cytokines, which increased both TfR expression and transferrin cellular uptake in a mechanism that did not involve hyper proliferation. These findings were then exploited for the design of targetable carrier towards inflamed regions of the colon. Anti-TfR antibodies were conjugated to nano-liposomes. As expected, iron-starved Caco-2 cells internalized anti-TfR immunoliposomes better than controls. Ex vivo binding studies to inflamed mucosa showed that the anti-TfR immunoliposomes accumulated significantly better in the mucosa of DNBS-induced rats than the accumulation of non-specific immunoliposomes. It is concluded that targeting mucosal inflammation can be accomplished by nano-liposomes decorated with anti-TfR due to inflammation-dependent, apical, elevated expression of the receptor

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

Conhecimento, aceitabilidade e uso do método billings de planejamento familiar natural El conocimiento, la aceptación y el uso del método Billings de planificación familiar natural Knowledge, acceptability and use of the Billings natural family planning method

Estudo observacional, quantitativo analítico que objetivou verificar o conhecimento, a aceitabilidade e o uso do planejamento familiar natural (PFN) pelos pacientes em um hospital universitário no período de julho a novembro de 2008. Os dados foram coletados utilizando questionário estruturado e analisados através dos Programas Excel e Statistica 8.0. Das 113 mulheres entrevistadas, 70 (62%) aceitavam o método e 1 (0,9%) fazia o uso rotineiro. A aceitação foi maior entre as que desejavam engravidar no futuro quando comparadas aquelas que não desejavam engravidar. A aceitabilidade foi estatisticamente significativa (p=0,0147) entre as 28 (80%) não usuárias de métodos contraceptivos comparadas a 42 (53,8%) com algum método contraceptivo. Fatores como idade, escolaridade, número de filhos vivos e religião não apresentaram associação estatística com a aceitabilidade do PFN. A aceitabilidade do método de ovulação Billings é adequada, porém com pouco uso na prática por falta de informação pelos profissionais da saúde da verdadeira eficácia e aplicabilidade.<br>Estudio observacional, cuantitativo y analítico para verificar el conocimiento, la aceptación y el uso de la planificación familiar natural (PFN) en un hospital universitario en el periodo de julio a noviembre de 2008. Los datos fueron recolectados a través de cuestionario estructurado y analizados mediante los programas Excel e Statistica 8.0. De las 113 mujeres entrevistadas, 70 (62,0%) aceptaron el método y 1 (0,9%) tenían uso rutinario. Aceptación fue mayor entre las que deseaban futuros embarazos en comparación con aquellos que no desean quedar embarazadas. Aceptabilidad fue estadísticamente significativa (p=0,0147) entre 28 (80,0%) no usuarias de anticonceptivos en comparación con 42 (53,8%) con el método anticonceptivo. Factores como edad, escolaridad, número de hijos vivos y religión no se asoció estadísticamente con la aceptación de PFN. Aceptabilidad del método Billings es adecuada, pero con poca utilidad en la práctica por falta de información por parte de profesionales de salud de la efectividad y aplicabilidad.<br>This is an observational, quantitative and analytical study aimed at verifying the knowledge, acceptability and use of natural family planning (NFP) by patients in a university hospital from July to November, 2008. The data were collected using a structured questionnaire and analyzed with the softwares Excel and Statistica 8.0. Of the 113 women interviewed, 70 (62%) accepted the method and 1 (0.9%) used it routinely. Acceptance was higher among those who wished to become pregnant in the future compared to those who did not wish it. Acceptability was statistically significant (p = 0.0147) among the 28 (80%) non-contraceptive users compared to 42 (53.8%) who used some contraceptive method. Factors such as age, education, number of living children and religion were not statiscally associated with the acceptability of NFP. The Billings ovulation method has an adequate acceptability, but has a low actual use because of the lack of information by health professionals of its real effectiveness and applicability

A simplified, non-invasive fecal-based DNA integrity assay and iFOBT for colorectal cancer detection

Neoplasia cells exfoliated from colorectal epithelium have dysfunctional apoptotic mechanisms, thus it is possible to identify high-molecular weight DNA fragments in feces. This prospective single-center study was performed to evaluate the sensitivity and specificity of fecal-based DNA integrity versus immunological fecal occult blood test (iFOBT) and calprotectin for colorectal cancer (CRC) and adenoma detection