In Brief Background Because topical microbicides designed to prevent the spread of sexually transmitted diseases may be applied frequently, it is important to ensure product safety as well as efficacy. A murine model was developed to test for induction of inflammatory responses following application of candidate microbicides. Goal A comparison was made of the induction of inflammation following vaginal application of detergent-based and sulfated polymer–based microbicides. Study Design Vaginal leukocytes were collected, identified, and quantified following microbicide application to detect the entry of inflammatory leukocytes into the vaginal lumen. Results Large numbers of neutrophils and macrophages entered the vaginal lumen following a single application of detergent-based microbicides. No significant increase in vaginal leukocytes was detected following a single or repeated application of sulfated polymer–based microbicides. Conclusion Application of sulfated polymer–based microbicides was less likely to result in inflammatory responses than was application of detergent-based compounds. This murine model should prove useful as part of a screening process to prioritize candidate microbicides before clinical trial. A murine model was used to detect and quantify inflammatory responses in the vaginal mucosa following application of candidate microbicides. Significant inflammatory responses were detected following application of detergent-based but not sulfated polymer-based microbicides.
<p>Fig. S1 presents mutant Trp53 protein expression in lung tumors and metastases. Fig. S2 shows PTEN expression in lung tumors and metastases. Fig. S3 presents mTOR pathway inhibition by rapamycin in primary tumor cell cultures. Fig. S4 shows establishment of chemoresistant and chemosensitive primary cell cultures. Fig. S5 presents chemotherapeutic response of primary tumor cells derived from chemoresistant and chemosensitive lung tumors. Fig. S6 presents the effect of cisplatin and etoposide on cell growth of lung tumors in vitro.</p>
<p>Fig. S1 presents mutant Trp53 protein expression in lung tumors and metastases. Fig. S2 shows PTEN expression in lung tumors and metastases. Fig. S3 presents mTOR pathway inhibition by rapamycin in primary tumor cell cultures. Fig. S4 shows establishment of chemoresistant and chemosensitive primary cell cultures. Fig. S5 presents chemotherapeutic response of primary tumor cells derived from chemoresistant and chemosensitive lung tumors. Fig. S6 presents the effect of cisplatin and etoposide on cell growth of lung tumors in vitro.</p>
Congenital cytomegalovirus (CMV) infection is one of the most common infectious causes of congenital sensorineural hearing loss. To date, a safe and effective therapy for CMV-induced hearing loss does not exist. We hypothesize that the antiviral cidofovir (CDV) can be delivered to the inner ear via intratympanic (IT) injections to safely and effectively mitigate CMV-induced hearing loss.To evaluate the safety of CDV IT injections, weanling guinea pigs with normal hearing were injected intratympanically with 3 mg or 5 mg concentrations of CDV and compared to control animals injected with sterile saline. A separate group of weanling guinea pigs were inoculated with CMV and a subset of this group was treated with CDV following inoculation.The 3 mg/ml and 5 mg/ml CDV concentrations resulted in hearing loss following IT injection into uninfected animals. No signs of inflammation or toxicity were noted on histologic analysis and there was no evidence of systemic toxicity in serology. Hearing loss induced as a result of guinea pig CMV infection recovered by day 21 in animals treated with IT injections of 5 mg/ml CDV.We provide promising evidence demonstrating both the efficacy and safety of IT CDV in the guinea pig animal model. This research further establishes a sound framework upon which ongoing investigations into drug delivery mechanisms for CMV-induced hearing loss will be based.
