scholarly journals L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

2012 ◽  
Vol 56 (6) ◽  
pp. 3121-3132 ◽  
Author(s):  
Maohua Zhong ◽  
Benxia He ◽  
Jingyi Yang ◽  
Rong Bao ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Murine Model ◽  
Sodium Dodecyl ◽  
Safety Evaluation ◽  
Mucosal Inflammation ◽  
Antibody Array ◽  
Preclinical Development ◽  
Sexually Transmitted ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Microbicide Candidate

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.

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

2022 ◽  
Author(s):  
Ignacio Rodríguez‐Izquierdo ◽  
Daniel Sepúlveda‐Crespo ◽  
Jose María Lasso ◽  
Salvador Resino ◽  
Ma Ángeles Muñoz‐Fernández
Keyword(s):  
Preclinical Development ◽  
Vaginal Microbicides ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Impact of HIV‐1 viremia or sexually transmitted infection on semen‐derived anti‐HIV‐1 antibodies and the immunosuppressive capacity of seminal plasma

2019 ◽  
Vol 49 (12) ◽  
pp. 2255-2258
Author(s):  
Kevin J. Selva ◽  
Benjamin R. Bavinton ◽  
Andrew E. Grulich ◽  
Marzena Pazgier ◽  
Anthony D. Kelleher ◽  
...  
Keyword(s):  
Seminal Plasma ◽  
Sexually Transmitted Infection ◽  
Transmitted Infection ◽  
Sexually Transmitted ◽  
Anti Hiv ◽  
Hiv 1

scholarly journals Antimicrobial and anti-inflammatory activities of selected medicinal plants against pathogens causing sexually transmitted infections

2020 ◽  
Vol 9 (2) ◽  
pp. 130-137 ◽  
Author(s):  
Ndivhuwo Patience Nthulane ◽  
Salerwe Mosebi ◽  
Thilivhali Emmanuel Tshikalange ◽  
Monde Alfred Nyila ◽  
Ledile Thabitha Mankga
Keyword(s):  
Medicinal Plants ◽  
Ethyl Acetate ◽  
Methanol Extract ◽  
Antimicrobial Activities ◽  
Bidens Pilosa ◽  
Sexually Transmitted ◽  
Methanol Extracts ◽  
Anti Inflammatory ◽  
Anti Hiv ◽  
Hiv 1

Introduction: Worldwide, more than one million sexually transmitted infections (STIs) are acquired daily. The diversity and frequency of sexual infections caused by pathogenic microorganisms have increased thus becoming a major cause of illness and mortality amongst young adults. Medicinal plants have been good remedies for the treatment of STIs since ancient times. In this study, we evaluated antimicrobial, anti- Human immunodeficiency virus (HIV) and anti-inflammatory activities of five selected medicinal plants. Methods: We determined the antimicrobial activities of plant extracts against the bacteria causing common STIs. Then, the anti-inflammatory activities were evaluated by measuring the inhibition of the pro-inflammatory enzyme, 15-lipoxygenase (15-LOX) and we further investigated the plants extracts of anti-HIV activities against the recombinant HIV-1 enzyme, reverse transcriptase. Results: Methanol extract of Terminalia sericea and dichloromethane (DCM) extract of Bidens pilosa exhibited good activities against Neisseria gonorrhoeae and Gardnerella vaginalis. Ethyl acetate, dichloromethane and methanol extracts of Bidens pilosa exhibited good activities against Candida albicans. Ethyl acetate extract of K. africana and methanol extract of B. pilosa showed good anti-inflammatory activities. Ethyl acetate, DCM and methanol extracts of T. sericea exhibited promising anti-HIV-1 activities by inhibiting the reverse transcriptase whilst methanol extracts of T. dregeana showed low anti-HIV-1 activity. Conclusion: These plants showed promising activity against the propagation of inflammation, displayed good antimicrobial activities against the bacteria causing STIs and could be used as potential leads and/or source for new drug candidates.

scholarly journals Preclinical Evaluation of Synthetic −2 RANTES as a Candidate Vaginal Microbicide To Target CCR5

2006 ◽  
Vol 50 (4) ◽  
pp. 1497-1509 ◽  
Author(s):  
Tina M. Kish-Catalone ◽  
Wuyuan Lu ◽  
Robert C. Gallo ◽  
Anthony L. DeVico
Keyword(s):  
Sexual Transmission ◽  
Zealand White Rabbit ◽  
Host Cells ◽  
Sexually Transmitted ◽  
Vaginal Microbicide ◽  
Aids Epidemic ◽  
Swiss Webster Mouse ◽  
Potential Strategy ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT A potential strategy that can be used to combat the worldwide AIDS epidemic is the development of a vaginal microbicide that prevents the sexual transmission of human immunodeficiency virus type 1 (HIV-1). Certain CC chemokines, including RANTES, MIP-1α, and MIP-1β, might facilitate the development of such microbicides since they potently suppress HIV-1 infection by binding to CCR5, the viral coreceptor used by most sexually transmitted strains of HIV-1 to enter host cells. In this study, we evaluated whether a CCR5-specific fragment of RANTES that lacks two N-terminal residues (−2 RANTES) and possesses especially potent HIV-1 suppressive activity has toxicity profiles conducive to the advancement of testing in candidate microbicide formulations. Analyses were carried out with a synthetic version of the chemokine, which was formulated with either Novasomes 7474, a nonphospholipid liposome, or methylcellulose gel. Dialysis studies demonstrated that the formulated −2 RANTES was released from both vehicles and retained anti-HIV-1 activity. Preclinical toxicity studies carried out with Swiss Webster mouse and New Zealand White rabbit vaginal irritation models demonstrated minimal inflammation and minimal adverse changes in cervicovaginal tissue integrity after short-term (10 min) and long-term (24 h) exposure to formulations containing up to 1 mg/ml of −2 RANTES. Similarly, no toxicity was observed with formulations of bioactive murine RANTES in the Swiss Webster mouse vaginal irritation model. Overall, these preclinical studies suggest that −2 RANTES is suitable for further testing as a candidate anti-HIV-1 microbicide.

Combination of G2-S16 dendrimer/dapivirine antiretroviral as a new HIV-1 microbicide

2019 ◽  
Vol 11 (23) ◽  
pp. 3005-3013
Author(s):  
Carlos Guerrero-Beltrán ◽  
AnabeI Prieto ◽  
Manuel Leal ◽  
José Luis Jiménez ◽  
M Ángeles Muñoz-Fernández
Keyword(s):  
Cell Lines ◽  
Bacterial Growth ◽  
Mtt Assay ◽  
Synergistic Activity ◽  
Proof Of Concept ◽  
Concept Study ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Microbicide Candidate

Aim: To research the synergistic activity of G2-S16 dendrimer and dapivirine (DPV) antiretroviral as microbicide candidate to prevent HIV-1 infection. Materials & methods: We assess the toxicity of DPV on cell lines by MTT assay, the anti-HIV-1 activity of G2-S16 and DPV alone or combined at several fixed ratios. Finally, their ability to inhibit the bacterial growth in vitro was assayed. The analysis of combinatorial effects and the effective concentrations were performed with CalcuSyn software. Conclusion: Our results represent the first proof-of-concept study of G2-S16/DPV combination to develop a safe microbicide.

scholarly journals Lignosulfonic Acid Exhibits Broadly Anti-HIV-1 Activity – Potential as a Microbicide Candidate for the Prevention of HIV-1 Sexual Transmission

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35906 ◽  
Author(s):  
Min Qiu ◽  
Qin Wang ◽  
Ying Chu ◽  
Zhongping Yuan ◽  
Hongyong Song ◽  
...  
Keyword(s):  
Sexual Transmission ◽  
Lignosulfonic Acid ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Prevention Of Hiv ◽  
Microbicide Candidate

Anticardiolipin Antibodies Are Elevated in HIV-1 Infected Haemophiliacs but Do Not Predict for Disease Progression

1989 ◽  
Vol 61 (01) ◽  
pp. 081-085 ◽  
Author(s):  
Simon Panzer ◽  
Christoph Stain ◽  
Hubert Hartl ◽  
Robert Dudczak ◽  
Klaus Lechner
Keyword(s):  
Normal Values ◽  
Anticardiolipin Antibodies ◽  
Haemophilia A ◽  
Serum Samples ◽  
Factor Viii Concentrates ◽  
Patient Groups ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Cd4 Lymphocytes

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.

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