Use of porcine vaginal tissue ex-vivo to model environmental effects on vaginal mucosa to toxic shock syndrome toxin-1

Davis, Catherine; Baccam, Mekhine; Mantz, Mary J.; Osborn, T.W.; Hill, Donna R.; Squier, Christopher A.

doi:10.1016/j.taap.2013.11.021

Cited by 12 publications

(5 citation statements)

References 46 publications

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“…mTSS has been primarily associated with improper tampon use. It has been postulated that certain tampons can unintentionally modify the vaginal environment, thereby stimulating the overexpression of TSST-1 from resident S. aureus [ 64 ]. TSST-1 production in the vaginal environment also appears to be heavily influenced by the vaginal microbiota, especially lactobacilli [ 65 ].…”

Section: Staphylococcal Superantigens and Diseasementioning

confidence: 99%

“…The combined factors of conducive environmental conditions and changes in the microbiota, during menstruation, may allow resident S. aureus growth which in turn could lead to TSST-1 production. The TSST-1 SAg is understood to induce mTSS by translocating across the vaginal epithelium and stimulating local T cells [ 64 , 69 , 70 ]. The peak incidence of mTSS occurred in the early 1980s and was associated with a type of highly absorbent tampon.…”

Section: Staphylococcal Superantigens and Diseasementioning

confidence: 99%

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Manipulation of Innate and Adaptive Immunity by Staphylococcal Superantigens

2018

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Staphylococcal superantigens (SAgs) constitute a family of potent exotoxins secreted by Staphylococcus aureus and other select staphylococcal species. SAgs function to cross-link major histocompatibility complex (MHC) class II molecules with T cell receptors (TCRs) to stimulate the uncontrolled activation of T lymphocytes, potentially leading to severe human illnesses such as toxic shock syndrome. The ubiquity of SAgs in clinical S. aureus isolates suggests that they likely make an important contribution to the evolutionary fitness of S. aureus. Although the apparent redundancy of SAgs in S. aureus has not been explained, the high level of sequence diversity within this toxin family may allow for SAgs to recognize an assorted range of TCR and MHC class II molecules, as well as aid in the avoidance of humoral immunity. Herein, we outline the major diseases associated with the staphylococcal SAgs and how a dysregulated immune system may contribute to pathology. We then highlight recent research that considers the importance of SAgs in the pathogenesis of S. aureus infections, demonstrating that SAgs are more than simply an immunological diversion. We suggest that SAgs can act as targeted modulators that drive the immune response away from an effective response, and thus aid in S. aureus persistence.

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Section: Staphylococcal Superantigens and Diseasementioning

confidence: 99%

Section: Staphylococcal Superantigens and Diseasementioning

confidence: 99%

Manipulation of Innate and Adaptive Immunity by Staphylococcal Superantigens

2018

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“…Porcine vaginal tissue is used as a surrogate for human vaginal tissue. It has been shown to demonstrate excellent correlation with human vaginal tissue in histology and structure, composition, as well as permeability characteristics towards water and hydrophilic molecules [ 30 , 31 ]. Fresh porcine female reproductive tracts were harvested from domestic pigs and transferred to our laboratory immediately after sacrifice.…”

Section: Methodsmentioning

confidence: 99%

Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography

et al. 2017

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Vaginally applied microbicide products offer a female-controlled strategy for preventing sexual transmission of HIV. Microbicide transport processes are central to their functioning, and there is a clear need for a better understanding of them. To contribute to that end, we developed an assay to analyze mass transport rates of microbicide molecules within the epithelial and stromal layers of polarized vaginal mucosal tissue during contact with a gel vehicle. The assay utilizes a new diffusion chamber mounted in a custom instrument that combines confocal Raman spectroscopy and optical coherence tomography. This measures depth-resolved microbicide concentration distributions within epithelium and stroma. Data for a tenofovir gel were fitted with a compartmental diffusion model to obtain fundamental transport properties: the molecular diffusion and partition coefficients in different compartments. Diffusion coefficients in epithelium and stroma were computed to be 6.10 ± 2.12 x 10−8 and 4.52 ± 1.86 x 10−7 cm2/sec, respectively. The partition coefficients between epithelium and gel and between stroma and epithelium were found to be 0.53 ± 0.15 and 1.17 ± 0.16, respectively. These drug transport parameters are salient in governing the drug delivery performance of different drug and gel vehicle systems. They can be used to contrast drugs and vehicles during product design, development and screening. They are critical inputs to deterministic transport models that predict the gels’ pharmacokinetic performance, which can guide improved design of products and optimization of their dosing regimens.

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“…The mucus penetration properties and localization profiles of PCN in the intracellular compartment were evaluated using an ex vivo mucus simulated system. The porcine vaginal tissue was selected as a cell line, as it closely resembles human vagina in terms of physiological morphology and functionality [52]. The porcine tissues were collected from the slaughter house, transported to the laboratory in hanks buffer and used within 3 h of death to preserve mucosal barrier function.…”

Section: Assessment Of Mucus Penetration Rates Of Npsmentioning

confidence: 99%

“…PEG is a hydrophilic substance and confers the particles a near neutral surface charge with an enhanced penetration capability through the mucus [11]. PEG coated NPs can reduce their affinity to mucus constituents [42,[47][48][49][50][51][52][53][54][55][56][57][58] and are able to readily penetrate through even chronic rhinosinusitis mucus (CRSM, highly viscoelastic) [59] or slip through the mucus [11]. Thus, PEGylation or covalent coating of high density of low molecular weight (MW) of conventional/polymeric particles has been explored for various biomedical applications, such as penetration to brain parenchyma [56], a biophysical tool, a means for drug and gene delivery [20], topical delivery of microbicides [47,55], and nano-rods for phototherapy [56].…”

Section: Characterization Of Peg Coated Nps Loaded With Dapivirinementioning

confidence: 99%