Dermal Nanoemulsion Treatment Reduces Burn Wound Conversion and Improves Skin Healing in a Porcine Model of Thermal Burn Injury.

Burn wound progression is an inflammation-driven process where an initial partial-thickness thermal burn wound can evolve over time to a full-thickness injury. We have developed an oil-in-water nanoemulsion formulation (NB-201) containing benzalkonium chloride for use in burn wounds that is antimicrobial and potentially inhibits burn wound progression. We used a porcine burn injury model to evaluate the effect of topical nanoemulsion treatment on burn wound conversion and healing. Anesthetized swine received thermal burn wounds using a 25-cm2 surface area copper bar heated to 80°C. Three different concentrations of NB-201 (10, 20, or 40% nanoemulsion), silver sulfadiazine cream, or saline were applied to burned skin immediately after injury and on days 1, 2, 4, 7, 10, 14, and 18 postinjury. Digital images and skin biopsies were taken at each dressing change. Skin biopsy samples were stained for histological evaluation and graded. Skin tissue samples were also assayed for mediators of inflammation. Dermal treatment with NB-201 diminished thermal burn wound conversion to a full-thickness injury as determined by both histological and visual evaluation. Comparison of epithelial restoration on day 21 showed that 77.8% of the nanoemulsion-treated wounds had an epidermal injury score of 0 compared to 16.7% of the silver sulfadiazine-treated burns (P = .01). Silver sulfadiazine cream- and saline-treated wounds (controls) converted to full-thickness burns by day 4. Histological evaluation revealed reduced inflammation and evidence of skin injury in NB-201-treated sites compared to control wounds. The nanoemulsion-treated wounds often healed with complete regrowth of epithelium and no loss of hair follicles (NB-201: 4.8 ± 2.1, saline: 0 ± 0, silver sulfadiazine: 0 ± 0 hair follicles per 4-mm biopsy section, P < .05). Production of inflammatory mediators and sequestration of neutrophils were also inhibited by NB-201. Topically applied NB-201 prevented the progression of a partial-thickness burn wound to full-thickness injury and was associated with a concurrent decrease in dermal inflammation.

Impact of the Levonorgestrel-Releasing Intrauterine System on the Progression of Chlamydia trachomatis Infection to Pelvic Inflammatory Disease in a Baboon Model.

Background: Understanding the relationship between the levonorgestrel (LNG)-releasing intrauterine system (IUS) and sexually transmitted infections (STIs) is increasingly important as use of the LNG-IUS grows to include women at higher risk for STIs. This study assessed the impact of the LNG-IUS on development of Chlamydia trachomatis pelvic inflammatory disease, using a baboon model. Methods: Baboons with and those without the LNG-IUS were cervically inoculated with C. trachomatis and monitored daily, and cervical and fallopian tube swab specimens were collected weekly for C. trachomatis quantitation by nucleic acid amplification testing and culture. Vaginal swab specimens were collected for cytokine analysis, and serum samples were obtained for detection of C. trachomatis antibodies. Results: The LNG-IUS resulted in an increased C. trachomatis burden in the cervix, with the bacterial burden in the LNG-IUS group diverging from that in the non-LNG-IUS group by 6 weeks after infection. One of 7 baboons in the non-LNG-IUS group and 2 of 6 in the LNG-IUS group developed pelvic inflammatory disease, while 3 animals in each group met criteria suggestive of pelvic inflammatory disease. LNG-IUS increased baseline interleukin 8 levels but failed to further upregulate interleukin 8 during infection. In LNG-IUS recipients, early perturbations in the interleukin 1ß axis corresponded to decreased C. trachomatis clearance and increased T-helper type 2 immune responses. Conclusion: LNG-IUS use results in delayed clearance of C. trachomatis and might alter the reproductive tract immune environment.

The levonorgestrel-releasing intrauterine system is associated with delayed endocervical clearance of Chlamydia trachomatis without alterations in vaginal microbiota.

Progestin-based contraception may impact women's susceptibility to sexually transmitted infection. We evaluated the effect of the levonorgestrel intrauterine system (LNG-IUS) on cervical persistence of Chlamydia trachomatis (CT) in a baboon model. Female olive baboons (Papio anubis) with or without an LNG-IUS received CT or sham inoculations. CT was detected in cervical epithelium with weekly nucleic acid amplification testing (NAAT) and culture. Presence of the LNG-IUS was associated with prolonged persistence of CT. Median time to post-inoculation clearance of CT as detected by NAAT was 10 weeks (range 7-12) for animals with an LNG-IUS and 3 weeks (range 0-12) for non-LNG-IUS animals (P = 0.06). Similarly, median time to post-inoculation clearance of CT by culture was 9 weeks (range 3-12) for LNG-IUS animals and 1.5 weeks (range 0-10) for non-LNG-IUS animals (P = 0.04). We characterized the community structure of the vaginal microbiota with the presence of the LNG-IUS to determine if alterations in CT colonization dynamics were associated with changes in vaginal commensal bacteria. Vaginal swabs were collected weekly for microbiome analysis. Endocervical CT infection was not correlated with alterations in the vaginal microbiota. Together, these results suggest that LNG-IUS may facilitate CT endocervical persistence through a mechanism distinct from vaginal microbial alterations.

The influence of quarantine on reproductive cycling in wild-caught Baboons (Papio anubis).

Stress impacts nonhuman primate menstrual cycle length but the impact of quarantine is unknown. A retrospective analysis was performed on cycle data from 31 wild-caught baboons during and following quarantine. Cycling initiated in 94 days (19-181) and length normalized within 4-6 cycles. Quarantine significantly impacts menstrual cycle length.

Animal models of contraception: utility and limitations.

Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development.