scholarly journals Baseline and time‐updated factors in preclinical development of anionic dendrimers as successful anti‐HIV ‐1 vaginal microbicides

Author(s):  
Ignacio Rodríguez‐Izquierdo ◽  
Daniel Sepúlveda‐Crespo ◽  
Jose María Lasso ◽  
Salvador Resino ◽  
Ma Ángeles Muñoz‐Fernández
2012 ◽  
Vol 56 (6) ◽  
pp. 3121-3132 ◽  
Author(s):  
Maohua Zhong ◽  
Benxia He ◽  
Jingyi Yang ◽  
Rong Bao ◽  
Yan Zhang ◽  
...  

ABSTRACTA major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens.


1989 ◽  
Vol 61 (01) ◽  
pp. 081-085 ◽  
Author(s):  
Simon Panzer ◽  
Christoph Stain ◽  
Hubert Hartl ◽  
Robert Dudczak ◽  
Klaus Lechner

SummaryLevels of anticardiolipin antibodies (ACA) were measured in 55 patients with haemophilia A in serum samples obtained in 1983 and in 1987. Twenty-one patients were negative for anti HIV-1 antibodies in 1983 and remained negative in 1987; 34 patients had anti HIV-1 antibodies in 1983; 17 of these latter patients remained asymptomatic, whereas 17 patients developed ARC or AIDS during the 4 years follow-up. Thirteen anti HIV-1 negative patients had elevated ACA levels in 1983; subsequently, a significant decrease was observed in all these subjects (p <0.001). All anti HIV-1 positive patients had elevated ACA levels in 1983; normal values were found in 9 patients in 1987. Yet, these changes were not significant (p >0.05). ACA levels were significantly higher in HIV-1 infected patients than in those without anti HIV-1 antibodies (p <0.05). There was no difference of ACA levels between the two anti HIV-1 positive patient groups, be it in 1983 or be it in 1987 (p >0.05). There was no correlation of ACA levels with serum IgG concentrations, CD4+ lymphocytes, or the consumption of factor VIII concentrates.


2009 ◽  
Vol 6 (5) ◽  
pp. 372-376
Author(s):  
Jing LONG
Keyword(s):  
Anti Hiv ◽  

2001 ◽  
Vol 8 (5) ◽  
pp. 413-418 ◽  
Author(s):  
Steve Bryson ◽  
Annie Cunningham ◽  
Jason Ho ◽  
Rosemary Hynes ◽  
David Isenman ◽  
...  

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