Optical Studies of the coexistence curve of the n-heptane+nitrobenzene mixture near its consolute point measured by an optical method

We have measured the coexistence curve of the binary liquid mixture n-heptane+nitrobenzene near its consolute point using an optical method. In particular, the critical exponent beta describing the coexistence curve was measured for this system. Previous experimental values of beta for n-heptane+nitrobenzene were higher than the typical theoretically calculated value, an unusual, although not unique, occurrence. In an effort to study this discrepancy, we have used an improved experimental apparatus for our measurements. We have taken special care to minimize temperature gradients and maximize the temperature stability of our thermal control system. We have also exploited features of a known optical method to analyze, thoroughly, sources of systematic errors. We measured an apparent value of beta as 0.367+/- 0.006 and by a careful study of the known sources of error we find that they are not able to remove the discrepancy between the measured and the theoretical values of beta. We also measured the critical temperature of the system at Tc=291.80+/- 0.02 K (18.65 C).Comment: 21 pages, 8 figures, submitted to Physical Review B. Shrunk Experimental section, expanded Equilibration and Conclusion sections, eliminated a figure, added reference; 19 pages, 7 figures, resubmitted to PRB. Replaced Fig. 3, added separate simple text file with coexistence curve data (OPvsT.txt); resubmitted to PR

Lorentz-Lorenz Coefficient, Critical Point Constants, and Coexistence Curve of 1,1-Difluoroethylene

We report measurements of the Lorentz-Lorenz coefficient density dependence, the critical temperature, and the critical density, of the fluid 1,1-difluoroethylene. Lorentz-Lorenz coefficient data were obtained by measuring refractive index and density of the same fluid sample independently of one another. Accurate determination of the Lorentz-Lorenz coefficient is necessary for transformation of refractive index data into density data from optics-based experiments on critical phenomena of fluid systems done with different apparatus, with which independent measurement of the refractive indes and density is not possible. Measurements were made along the coexistence curve of the fluid and span the density range 0.01 to 0.80 g/cc. The Lorentz-Lorenz coefficient results show a stronger density dependence along the coexistence curve than previously observed in other fluids, with a monotonic decrease from a density of about 0.2 g/cc onwards, and an overall variation of about 2.5% in the density range studied. No anomaly in the Lorentz-Lorenz coefficient was observed near the critical density. The critical temperature is measured at Tc=(302.964+-0.002) K (29.814 C) and the measured critical density is (0.4195+-0.0018)g/cc.Comment: 14 pages, 6 figures, MikTeX 2.4, submitted to Physical Review

HIV-1 Neutralization Profile and Plant-Based Recombinant Expression of Actinohivin, an Env Glycan-Specific Lectin Devoid of T-Cell Mitogenic Activity

The development of a topical microbicide blocking the sexual transmission of HIV-1 is urgently needed to control the global HIV/AIDS pandemic. The actinomycete-derived lectin actinohivin (AH) is highly specific to a cluster of high-mannose-type glycans uniquely found on the viral envelope (Env). Here, we evaluated AH's candidacy toward a microbicide in terms of in vitro anti-HIV-1 activity, potential side effects, and recombinant producibility. Two validated assay systems based on human peripheral blood mononuclear cell (hPBMC) infection with primary isolates and TZM-bl cell infection with Env-pseudotyped viruses were employed to characterize AH's anti-HIV-1 activity. In hPMBCs, AH exhibited nanomolar neutralizing activity against primary viruses with diverse cellular tropisms, but did not cause mitogenicity or cytotoxicity that are often associated with other anti-HIV lectins. In the TZM-bl-based assay, AH showed broad anti-HIV-1 activity against clinically-relevant, mucosally transmitting strains of clades B and C. By contrast, clade A viruses showed strong resistance to AH. Correlation analysis suggested that HIV-1′s AH susceptibility is significantly linked to the N-glycans at the Env C2 and V4 regions. For recombinant (r)AH expression, we evaluated a tobacco mosaic virus-based system in Nicotiana benthamiana plants as a means to facilitate molecular engineering and cost-effective mass production. Biochemical analysis and an Env-mediated syncytium formation assay demonstrated high-level expression of functional rAH within six days. Taken together, our study revealed AH's cross-clade anti-HIV-1 activity, apparent lack of side effects common to lectins, and robust producibility using plant biotechnology. These findings justify further efforts to develop rAH toward a candidate HIV-1 microbicide

SPL7013 Gel (VivaGel®) Retains Potent HIV-1 and HSV-2 Inhibitory Activity following Vaginal Administration in Humans

SPL7013 Gel (VivaGel®) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with ≥5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup™ pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p≤0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p = 0.9]; HSV-2 [94% (91,97), p = 0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus

Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published.Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina.Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as VivaGel(R) and is currently in clinical development to provide protection against HIV and HSV. SPL7013 could also be combined with other microbicides

Condom use beliefs differ according to regulatory focus: a mixed-methods study in Portugal and Spain

Reports worldwide have been showing increasing rates of sexually transmitted infections (STIs) and condomless sex in recent years. Research has identified several individual and situational variables that can determine the decision to use condoms or forgo their use. We argue that such a decision can also be shaped by motives related to pleasure and safety (i.e., regulatory focus in sexuality). Using open ended questions, we asked 742 Portuguese and Spanish adults to indicate situations and reasons that could inform the decision making process with casual partners and the functions/attributes related to condoms. Using thematic analyses, we coded the drivers of condomless sex and condom use into themes and subthemes, and computed their frequencies. Using quantitative measures, we also asked participants to indicate their condom use expectancies and perceived barriers. Comparing participants according to regulatory focus revealed some differences. Pleasure promotion participants were more likely to consider that condom use decision making is driven by unexpectedness, pleasure, and intimacy pursuit, attached more pleasure reduction functions to condoms, expected more negative outcomes in condom use, and endorsed more sensation and partner barriers in condom use. In contrast, disease prevention participants were more likely to consider that condom use decision making is driven by adequate sexual education, responsibility, and behavioral control, and attached more health protective functions to condoms. These differences can inform the development of tailored intervention and awareness campaigns aimed at helping people to use condoms more consistently with casual partners and to avoid behaviors that put them at risk of STI transmission

Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicits specific immune responses

Rheologically structured vehicle (RSV) gels were developed as delivery systems for vaginal mucosal vaccination with an HIV-1 envelope glycoprotein (CN54gp140). RSVs comprised a mucoadhesive matrix-forming and vaginal fluid absorbing polymer. The mucoadhesive and rheological properties of the RSVs were evaluated in vitro, and the distribution, antigenicity and release of CN54gp140 were analysed by ELISA. CN54gp140 was uniformly distributed within the RSVs and continuously released in vitro in an antigenically intact form over 24 h. Vaginal administration to rabbits induced specific serum IgG, and IgG and IgA in genital tract secretions. The RSVs are a viable delivery modality for vaginal immunization