Abstract
Candida adherence is implicated in the pathogenesis of oral candidosis. Adhesion to buccal epithelial cells (BEC), germ tube (GT) formation, and relative cell surface hydrophobicity (CSH) are colonization attributes of candidal pathogenicity. Candida dubliniensis (C.dubliniensis) is allied with recurrent oral candidosis, which can be treated with nystatin, amphotericin B, ketoconazole, and fluconazole. Due to the diluent effect of saliva and the cleansing effect of the oral musculature in the oral cavity C.dubliniensis isolates undergo brief and sequential exposure to antifungal agents during therapy. Thus, in the present study, we evaluated the adhesion to BEC, GT formation, and the CSH of oral isolates of C.dubliniensis following brief and sequential exposure to nystatin, amphotericin B, ketoconazole, and fluconazole. After determining the minimum inhibitory concentration (MIC) of the aforementioned drugs, 20 oral isolates of C.dubliniensis were briefly (1h), and sequentially (10days) exposed to subcidal concentrations of these drugs. Following drug removal, adhesion to BEC, GT formation, and CSH of these isolates were determined. The percentage reduction of adhesion to BEC, GT formation, and CSH of the isolates following exposure to antifungal agents were as follows: nystatin: 53.55%, 33.98%, and 29.83% (P<0.001); amphotericin B: 53.84%, 36.23%, and 28.97% (P<0.001); ketoconazole: 37.43%, 20.51%, and 16.49% (P<0.001); and fluconazole: 8.93% (P<0.001), 1.6%, and 0.63% (P>0.05). Brief and sequential exposure of C.dubliniensis to antifungal agents would continue to wield an antifungal effect by altering its adhesion attributes, and elucidate possible pharmacodynamics by which antifungal agents might operate in modulating candidal adherence.
Highlights
In neurons most pre-synaptic proteins are synthesized in the soma and are transported long distances to reach their site of action
In vivo pulse chase labeling experiments identified two major forms of anterograde axonal transport: a fast component (FC) associated with vesicular organelles moving between 50–200 mm/day and a slow component of cytoskeletal and cytoplasmic proteins moving 0.2– 10 mm/day, which can be further subdivided into slow component a (SCa) and slow component b (SCb)
Dynein Preferentially Accumulates in Distal Axons throughout Development As an important first step, we wanted to characterize the distribution of cytoplasmic dynein in our model system of primary hippocampal neurons isolated from the dynein-GFP knockin mouse
Summary
In neurons most pre-synaptic proteins are synthesized in the soma and are transported long distances to reach their site of action. The transit of new axonal and synaptic constituents via slow transport can take up to a year for cells with extended axons such as human motor neurons. At least three times the amount of protein is delivered to pre-synapses by slow compared to fast transport (Garner and Mahler, 1987), making this the major protein delivery system. Instantaneous velocities for neurofilaments are similar to those measured for vesicular cargos, but overall transport rates are dominated by long off-track times in a ‘‘stop and go’’ model for transport (Brown et al, 2005)
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