Fungal Burden, Early Fungicidal Activity, and Outcome in Cryptococcal Meningitis in Antiretroviral-Naive or Antiretroviral-Experienced Patients Treated with Amphotericin B or Fluconazole

Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa.
Clinical Infectious Diseases (Impact Factor: 9.42). 08/2007; 45(1):76-80. DOI: 10.1086/518607
Source: PubMed

ABSTRACT In a prospective observational study of 54 patients with human immunodeficiency virus-associated cryptococcal meningitis, the early fungicidal activity of amphotericin B (1 mg/kg/day) was significantly greater than that of fluconazole (400 mg/day). Compared with antiretroviral therapy-naive patients, patients developing cryptococcal meningitis while already receiving antiretroviral therapy had lower baseline fungal burdens and a longer median duration of survival, but there were no differences observed in fungal clearance, cerebrospinal fluid proinflammatory cytokines, or 10-week mortality.

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    ABSTRACT: Cryptomonad algae (cryptophyte algae), originated from a eukaryotic host cell and a eukaryotic endosymbiont by secondary endosymbiosis, are unicellular biflagellate, freshwater or marine, eukaryotic algae, unique among flagellate algae in having phycobiliproteins (Cr-phycoerythrin or Cr-phycocyanin) as photosynthetic accessory pigments. An eyespot is found only in some species (e.g. Chroomonas coerulea) although most of the cryptomonad species are phototactic. Cryptomonad phototaxis may be exclusively positive (Cryptomonas sp. CR-1, cryptomonas rostratiformis and Chroomonas nordstedtii) or exclusively negative (Chroomonas coerulea) or positive at low fluence rates and negative at higher fluence rates (Cryptomonas maculata) or diaphototactic, i.e. orienting perpendicular to the direction of the light beam (Cryptomonas sp. S2). Action spectroscopy for positive phototaxis in Cryptomonas sp. CR-1 led to the discovery of its very unique yellow-light sensing with an action peak in the yellow light region at ca. 560 nm, which was later confirmed in the action spectrum for positive phototaxis in cryptomonas rostratiformis and Chroomonas nordstedtii, together with a new action peak at 460 nm (the former showing also a UV peak at 280 nm), strongly suggesting that the photoreceptor mediating positive phototaxis is common among these species, and not phycobilins. Analyses using repeated pulses of stimulus light showed that light is sensed by the ventral side of Cryptomonas sp. CR-1 cells. The striking similarity of the action spectra for photoaccumulation and light-induced membrane depolarization in the ciliate Paramecium with that for the cryptomonad phototaxis seems to suggest considerable common nature of their unidentified photoreceptors. Analyses of phototactic responses of Cryptomonas sp. CR-1 cells to intermittent light stimuli with variable light durations and dark intervals revealed a striking dark interval dependence, suggesting also considerable similarity in the photoreceptor-signal transduction processes between cryptomonads and the green alga Chlamydomonas, in which retinal-binding protein(s) are supposed to work as the photoreceptor(s) for its green-light sensing phototaxis, suggesting that a dark interval dependence of phototaxis is theoretically expected on the basis of kinetic analyses of the photoreceptor current. The presence of Ca2+ is crucially needefor phototactic orientation and antagonized by K+ ions, consistently with other phototactic organisms such as Chlamydomonas, Euglena and Paramecium. The ecological significance of cryptomonad phototaxis is demonstrated, in general accordance with other algae, as the means for the cells to locate themselves in photosynthetically advantageous light habitats and to avoid harmful strong light or UV radiation both horizontally and vertically. The molecular identification of the photoreceptor pigment(s) as well as the understanding of the ecological and biochemical meanings of the UV-sensing in Cryptomonas is a challenging subject of future studies.
  • Current Fungal Infection Reports 12/2010; 4(4):197-199. DOI:10.1007/s12281-010-0036-4