The antiretroviral lectin cyanovirin-N targets well-known and novel targets on the surface of Entamoeba histolytica trophozoites.

Entamoeba histolytica, the protist that causes amebic dysentery and liver abscess, has a truncated Asn-linked glycan (N-glycan) precursor composed of seven sugars (Man(5)GlcNAc(2)). Here, we show that glycoproteins with unmodified N-glycans are aggregated and capped on the surface of E. histolytica trophozoites by the antiretroviral lectin cyanovirin-N and then replenished from large intracellular pools. Cyanovirin-N cocaps the Gal/GalNAc adherence lectin, as well as glycoproteins containing O-phosphodiester-linked glycans recognized by an anti-proteophosphoglycan monoclonal antibody. Cyanovirin-N inhibits phagocytosis by E. histolytica trophozoites of mucin-coated beads, a surrogate assay for amebic virulence. For technical reasons, we used the plant lectin concanavalin A rather than cyanovirin-N to enrich secreted and membrane proteins for mass spectrometric identification. E. histolytica glycoproteins with occupied N-glycan sites include Gal/GalNAc lectins, proteases, and 17 previously hypothetical proteins. The latter glycoproteins, as well as 50 previously hypothetical proteins enriched by concanavalin A, may be vaccine targets as they are abundant and unique. In summary, the antiretroviral lectin cyanovirin-N binds to well-known and novel targets on the surface of E. histolytica that are rapidly replenished from large intracellular pools.

Meaning and methadone: patient perceptions of methadone dose and a model to promote adherence to maintenance treatment.

OBJECTIVES: Methadone maintenance treatment (MMT) effectively reduces illicit opioid use and its negative consequences when patients participate in and adhere to treatment. Patients' participation and adherence may relate to their perceptions about methadone doses and dose adjustments and the meanings that patients associate with treatment. This study assessed patient perceptions about methadone dosing and the meanings associated with methadone treatment to better support patient adherence to and success in MMT. METHODS: We conducted semistructured interviews with 19 patients in an urban MMT program. Interviews were transcribed verbatim and analyzed through an iterative process. RESULTS: Participants' expressed perceptions about methadone doses related to ideas of "comfort" and "function," suggesting a model for determining dose appropriateness and "ideal" methadone dose based on various factors both intrinsic and extrinsic to MMT. Intrinsic factors included those exerting downward pressure on "ideal" methadone dose such as lack of control in treatment, disdain for getting "high," concerns about methadone dependence, and desire to avoid adverse effects; those exerting upward pressure such as concern about withdrawal; and those exerting mixed pressures such as methadone formulations. Extrinsic factors included those exerting downward pressure such as shame about and stigma around MMT; those exerting upward pressure such as medical conditions and medication interactions; and those exerting mixed pressures such as family and peer relationships. CONCLUSIONS: Participants held perceptions about methadone dosing that included considerations beyond typical medical parameters used by physicians and other MMT providers to determine appropriate methadone doses. The model that emerged from our data could help inform MMT providers to support greater patient comfort with methadone doses and dose changes, as well as adherence to and success in MMT.