Platelet function in patients with a history of unexplained recurrent miscarriage who subsequently miscarry again.

OBJECTIVE: This study was designed to evaluate platelet aggregation in pregnant women with a history of unexplained recurrent miscarriage (RM) and to compare platelet function in such patients who go on to have either another subsequent miscarriage or a successful pregnancy. STUDY DESIGN: A prospective longitudinal study was performed to evaluate platelet function in a cohort of patients with a history of unexplained RM. Platelet reactivity testing was performed at 4-7 weeks gestation, to compare platelet aggregation between those with a subsequent miscarriage and those who had successful live birth outcomes. Platelet aggregation was calculated using a modified assay of light transmission aggregometry with multiple agonists at different concentrations. RESULTS: In a cohort of 39 patients with a history of RM, 30 had a successful pregnancy outcome while nine had a subsequent miscarriage again. Women with subsequent miscarriage had reduced platelet aggregation in response to adenosine diphosphate (P value 0.0012) and thrombin receptor activating peptide (P value 0.0334) when compared to those with successful pregnancies. Women with subsequent miscarriages also had a trend towards reduced platelet aggregation in response to epinephrine (P value 0.0568). CONCLUSION: Patients with a background history of unexplained RM demonstrate reduced platelet function if they have a subsequent miscarriage compared to those who go on to have a successful pregnancy.

Perinatal outcomes of women with a prior history of unexplained recurrent miscarriage.

OBJECTIVE: We sought to determine subsequent pregnancy outcomes in a cohort of women with a history of unexplained recurrent miscarriage (RM) who were not receiving medical treatment. STUDY DESIGN: This was a prospective cohort study, of women with a history of three unexplained consecutive first trimester losses, who were recruited and followed in their subsequent pregnancy. Control patients were healthy pregnant patients with no previous adverse perinatal outcome. RESULTS: A total of 42 patients with a history of unexplained RM were recruited to the study. About nine (21.4%) experienced a further first trimester miscarriage, one case of ectopic and one case of partial molar pregnancy. About 74% (23/31) of the RM cohort had a vaginal delivery. There was one case of severe pre-eclampsia. The RM group delivered at a mean gestational age of 38 + 2 weeks and with a mean birthweight of 3.23 kg. None of the neonates were under the 10th centile for gestational age. Overall, there was no significant difference in pregnancy outcomes between the two cohorts. CONCLUSION: Our study confirms the reassuring prognosis for achieving a live birth in the unexplained RM population with a very low incidence of adverse events with the majority delivering appropriately grown fetuses at term.

Antiviral breadth and combination potential of peptide triazole HIV-1 entry inhibitors.

The first stage of human immunodeficiency virus type 1 (HIV-1) infection involves the fusion of viral and host cellular membranes mediated by viral envelope glycoprotein gp120. Inhibitors that specifically target gp120 are gaining increased attention as therapeutics or preventatives to prevent the spread of HIV-1. One promising new group of inhibitors is the peptide triazoles, which bind to gp120 and simultaneously block its interaction with both CD4 and the coreceptor. In this study, we assessed the most potent peptide triazole, HNG-156, for inhibitory breadth, cytotoxicity, and efficacy, both alone and in combination with other antiviral compounds, against HIV-1. HNG-156 inhibited a panel of 16 subtype B and C isolates of HIV-1 in a single-round infection assay. Inhibition of cell infection by replication-competent clinical isolates of HIV-1 was also observed with HNG-156. We found that HNG-156 had a greater than predicted effect when combined with several other entry inhibitors or the reverse transcriptase inhibitor tenofovir. Overall, we find that HNG-156 is noncytotoxic, has a broad inhibition profile, and provides a positive combination with several inhibitors of the HIV-1 life cycle. These results support the pursuit of efficacy and toxicity analyses in more advanced cell and animal models to develop peptide triazole family inhibitors of HIV-1 into antagonists of HIV-1 infection.

Preclinical evaluation of lime juice as a topical microbicide candidate.

BACKGROUND: The continued growth of the global HIV epidemic highlights the urgent need to develop novel prevention strategies to reduce HIV transmission. The development of topical microbicides is likely to take a number of years before such a product would be widely available. This has resulted in a call for the rapid introduction of simpler vaginal intervention strategies in the interim period. One suggested practice would be vaginal douching with natural products including lime or lemon juice. Here we present a comprehensive preclinical evaluation of lime juice (LiJ) as a potential intervention strategy against HIV. RESULTS: Pre-treatment of HIV with LiJ demonstrated direct virucidal activity, with 10% juice inactivating the virus within 5 minutes. However, this activity was significantly reduced in the presence of seminal plasma, where inactivation required maintaining a 1:1 mixture of neat LiJ and seminal plasma for more than 5 minutes. Additionally, LiJ demonstrated both time and dose-dependent toxicity towards cervicovaginal epithelium, where exposure to 50% juice caused 75-90% toxicity within 5 minutes increasing to 95% by 30 minutes. Cervicovaginal epithelial cell monolayers were more susceptible to the effects of LiJ with 8.8% juice causing 50% toxicity after 5 minutes. Reconstructed stratified cervicovaginal epithelium appeared more resilient to LiJ toxicity with 30 minutes exposure to 50% LiJ having little effect on viability. However viability was reduced by 75% and 90% following 60 and 120 minutes exposure. Furthermore, repeat application (several times daily) of 25% LiJ caused 80-90% reduction in viability. CONCLUSION: These data demonstrate that the virucidal activity of LiJ is severely compromised in the presence of seminal plasma. Potentially, to be effective against HIV in vivo, women would need to apply a volume of neat LiJ equal to that of an ejaculate, and maintain this ratio vaginally for 5-30 minutes after ejaculation. Data presented here suggest that this would have significant adverse effects on the genital mucosa. These data raise serious questions about the plausibility and safety of such a prevention approach.