bDenture stomatitis (DS) is a fungal infection characterized by inflammation of the oral mucosa in direct contact with the denture and affects up to 50% of denture wearers. Despite the prevalence, very little is known about the role of fungal or host factors that contribute to pathogenesis. Recently, we developed a novel intraoral denture system for rodent research. This denture system consists of custom-fitted fixed and removable parts to allow repeated sampling and longitudinal studies. The purpose of this study was to use this denture system to develop a clinically relevant animal model of DS. To establish DS, rats were inoculated with pelleted Candida albicans, which resulted in sustained colonization of the denture and palate for 8 weeks postinoculation. Biofilm formation on the denture was observed by week 4 and on the palate by week 6 postinoculation. Rats were monitored for clinical signs of disease by assigning a clinical score after macroscopic examination of the palate tissue according to Newton's method. By week 4 postinoculation, the majority of inoculated rats with dentures exhibited a clinical score of 1 (pinpoint erythema). By week 6 and week 8 postinoculation, increasing percentages of rats exhibited a clinical score of 2 (diffuse erythema/ edema). Histological analysis of palate tissue demonstrated progressively increasing inflammatory cell recruitment throughout the time course of the infection. Palatal biofilm formation was commensurate with development of palatal erythema, which suggests a role for biofilm in the inflammatory response.
SUMMARYThe objective was to engineer an inexpensive intraoral removable denture system for rodents that can be utilized in numerous oral health research applications. At the forefront is biofilm research related to Candida-associated denture stomatitis. Previously described intraoral devices are primitive and inadequate. The denture system was engineered consisting of a fixed part that is anchored to the posterior palate by orthodontic wires and acrylic resin, and a removable part fitted to the anterior palate that is retained by magnets embedded in the fixed part. Both parts are custom-fitted to the rodent palate by impression making and cast fabrication.Rats fitted with the intraoral denture system maintained body weight and normal activity with the device maintaining integrity and durability for upwards of 8 weeks. The denture system was used successfully to establish a working model of denture stomatitis. This newly engineered inexpensive intraoral removable denture system for rodents can be utilized in numerous oral health research applications, including denture-associated infections, biofilms, and a variety of biomaterial applications. The removable portion is advantageous for longitudinal analyses and charging/discharging of biomaterials.
Ricin toxin, derived from the castor bean, is a potent toxin that inhibits protein synthesis. It has been considered a possible agent of bioterrorism for many years. In experimental studies antibodies have been shown to be an effective treatment against ricin poisoning. Maddaloni et al, described a murine monoclonal anti‐ricin A chain antibody, mRAC 18, that was shown to neutralize in vitro and protect in vivo. This antibody has been found effective, even when administered 12 hours post exposure. The use of monoclonal antibodies in therapy has steadily increased since their development. A limitation to the utility of mAb therapy is their immunogenicity. In an effort to create an antibody for use in post‐exposure human therapy of ricin intoxication, we have created a chimeric ricin A chain antibody. We combined the antigen‐specific variable region genes of the mouse antibody RAC 18 to human gamma‐1 and kappa constant region genes. The resultant chimeric antibody retained the same specificity for ricin as the parental antibody, offered passive protection in vivo, and had enhanced in vitro neutralizing ability. A lectin binding assay showed the chimeric antibody had significantly less sialic acid than the parental antibody. We conclude that differences in sialic acid content may be responsible for the increased in vitro neutralizing ability, and that this effect is independent of Fc receptor binding.
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