PubMed · 15705667
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Christopher J M Whitty, Evelyn Ansah, Hugh Reyburn. 2005-02-12. Treating severe malaria.. https://doi.org/10.1136/bmj.330.7487.317
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OBJECTIVES: The objectives of this study were to determine what volume of a microbicide placebo gel is acceptable when applied intrarectally before receptive anal intercourse (RAI); and to evaluate responses to properties of the gel, its application, and its use. STUDY DESIGN: HIV-uninfected men who reported unprotected RAI with serodiscordant or unknown-status partners were enrolled in a volume escalation trial. RESULTS: Up to 35 mL of gel with the physical properties of Femglide (transparent and odorless) was acceptable to the majority of participants. Choice of different levels of viscosity may be needed. For some men, volumes judged acceptable when tried without intercourse were not acceptable when used during sex. Overall, participants reported high intentions to use microbicides when available. Condom use was inconsistent despite advice to use condoms. CONCLUSIONS: Microbicides that would require up to 35 mL of volume to be effective would be acceptable to men who engage in high-risk RAI.
Ulcerative colitis is a chronic and debilitating disease that involves inflammation of the colonic mucosa. Current therapies aim to reduce the symptom burden of ulcerative colitis and maintain disease quiescence. The standard first-line treatment for mild-to-moderate ulcerative colitis is 5-aminosalicylate therapy, which is available in oral and rectal (topical) formulations. While current 5-aminosalicylate formulations are effective in the majority of patients, they are associated with a number of limitations including inconvenient dosing regimens and poor patient acceptability, which may lead to non-compliance with prescribed therapy. A variety of improved delivery mechanisms have been developed in an effort to overcome these limitations. Micropellet formulations and high-dose tablets appear to offer comparable efficacy and tolerability to conventional formulations, although any benefit in terms of long-term patient compliance remains to be proven. Novel methods of delivery, such as those using a combination of hydrophilic and lipophilic matrices, designed to provide once-daily dosing in a high-strength tablet, may offer a significant improvement in the therapy of active and quiescent ulcerative colitis. This review examines the limitations of current 5-aminosalicylate formulations and reports on the evolution of novel oral formulations designed to overcome these limitations, maximize patient compliance during both induction and maintenance of quiescence, and optimize overall clinical outcomes.
BCG rectal administration to newborn and adult mice induced protective immune responses against tuberculosis. BCG reaches the sub-epithelial site and the draining mesenteric lymph nodes (MLNs), and dendritic cells (DC) could be recruited to these sites. Using polarized Caco-2 epithelial cells, we showed that BCG translocates epithelial cells to basolateral compartment. Delayed in newborn BALB/c mice, an important recruitment of CD11c+ DCs, was documented in the rectal lamina propria and the MLNs during the first two weeks after rectal BCG delivery. In MLNs, two major DC subtypes were observed: conventional DCs (cDCs) (B220-) and plasmacytoid DCs (pDCs) (B220+). CIRE, mouse DC-specific intracellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is predominantly expressed on pDCs and at a higher level on pDCs from the adult compared to newborn MLNs. cDCs with a higher capacity to induce the proliferation of naïve CD4+ T cells than pDCs, triggered CD4+ T cells to produce interferon-gamma whereas pDCs triggered them to release interleukin-10. Both DC subtypes equilibrates T cells as a source of microbicidal/microbiostatic signals and those acting as source of counter-inflammatory signals, preventing tissue damage and/or accelerating tissue repair. Thus, rectal delivery of BCG could be a safe and efficient route of vaccination against tuberculosis.