The surface plasmon polariton-enhanced Raman spectra of size-selected C 16 , C 18 , and C 20 clusters isolated in nitrogen matrices are presented along with the calculated vibrational frequencies for the ring and linear chain isomers. The Raman spectra, recorded at a range of excitation wavelengths from 457.9 to 670 nm, show strong resonance enhancement for the three clusters. The calculated vibrational frequencies for ring and linear chain isomers and the cage and bowl structures for C 20 are compared to the experimental frequencies. Systematic shifts in the series of peaks in the 200 cm Ϫ1 region for C 16 , C 18 , and C 20 suggest that the observed isomers have the same geometry, thereby ruling out the bowl and cage isomers for C 20 . The measured spectra appear to be most consistent with the linear chain isomer. This high-energy isomer may be produced during neutralization of the deposited cluster ions.
Intravaginal rings releasing tenofovir (TFV) or its prodrug, tenofovir disoproxil fumarate (TDF), are being evaluated for HIV and herpes simplex virus (HSV) prevention. The current studies were designed to determine the mechanisms of drug accumulation in human vaginal and immune cells. The exposure of vaginal epithelial or T cells to equimolar concentrations of radiolabeled TDF resulted in over 10-fold higher intracellular drug levels than exposure to TFV. Permeability studies demonstrated that TDF, but not TFV, entered cells by passive diffusion. TDF uptake was energy independent but its accumulation followed nonlinear kinetics, and excess unlabeled TDF inhibited radiolabeled TDF uptake in competition studies. The carboxylesterase inhibitor bis-nitrophenyl phosphate reduced TDF uptake, suggesting saturability of intracellular carboxylesterases. In contrast, although TFV uptake was energy dependent, no competition between unlabeled and radiolabeled TFV was observed, and the previously identified transporters, organic anion transporters ( T opical preexposure prophylaxis (PrEP) with tenofovir (TFV)-based drugs could provide a female-initiated method for the prevention of HIV and genital herpes simplex virus (HSV) infections in women (1). Pericoital dosing with 1% vaginal TFV gel reduced HIV acquisition by 39% overall and by 54% in highly adherent women (2, 3) and reduced HSV-2 acquisition by 51% in the CAPRISA 004 trial (4). However, the same gel did not provide protection against HIV in the Vaginal and Oral Interventions to Control the Epidemic (VOICE) and Follow-On Consortium for Tenofovir Studies (FACTS) 001 phase 3 trials, presumably reflecting low adherence (5, 6). Women with detectable TFV in their plasma at the first quarterly visit were less likely to acquire HIV than women with no drug detected (adjusted hazard ratio, 0.34; 95% confidence interval [CI], 0.13 to 0.87; P ϭ 0.02) in a secondary analysis of VOICE data, but the interpretation of this is complex, as women at highest risk for HIV acquisition were less likely to be adherent (5). These findings underscore the need for drugs and delivery systems that mitigate the difficulties associated with adherence.Intravaginal rings (IVRs) designed to deliver TFV and tenofovir disoproxil fumarate (TDF) are currently in early clinical development (7,8). A TDF ring completely protected macaques against 16 weekly intravaginal challenges with simian HIV (8) and also was highly protective in more susceptible, medroxyprogesteronetreated animals (9). Nonhuman primate challenge studies with the TFV IVR have not been published. Consistent with in vitro antiviral studies, 0.3% TDF gel provided significantly greater protection than 1% TFV gel in mice challenged intravaginally with HSV-2 (10). Moreover, the 0.3% TDF gel demonstrated significantly greater protection than 1% TFV gel in mice transgenic for human CD4, CCR5, and cyclin T1 against HIV and HSV-2 (11). These findings may reflect differences in drug pharmacokinetics (PK).The mechanisms of TFV and TDF cellular tran...
The surface plasmon polariton-enhanced Raman spectra of size-selected, matrix-isolated C 14 neutral clusters are presented along with the calculated vibrational frequencies for the ring and linear chain isomers. The Raman spectra show resonance enhancement over a range of excitation wavelengths from 457.9 to 514.5 nm. The measured vibrational spectra are most consistent with the linear chain isomer. In addition, fluorescence spectra of neutral, mass-selected C n (n ) 14 and 18) clusters are presented. The isolated C 14 clusters display strong fluorescence with vibrational structure between 520 and 700 nm. The origins of the observed fluorescence for both C 14 and C 18 are investigated using the ZINDO/S, CIS, and TD-B3LYP methods.
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