Adenosine amine congener as a cochlear rescue agent.

UNLABELLED: We have previously shown that adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. METHODS: ADAC (25-300 µg/kg) was administered intraperitoneally to Wistar rats (8-10 weeks old) at intervals (6-72 hours) after exposure to traumatic noise (8-16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration. RESULTS: ADAC was most effective in the first 24 hours after noise exposure at doses >50 µg/kg, providing up to 21 dB protection (averaged across 8-28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after intravenous administration without detection of degradation products. CONCLUSION: Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.

Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-gamma.

The pathogenesis of T cell-mediated diseases like rheumatoid arthritis (RA) has typically been explained in the context of the Th1-Th2 paradigm: the initiation/propagation by pro-inflammatory cytokines, and downregulation by Th2 cytokines. However, in our study based on the adjuvant-induced arthritis (AA) model of RA, we observed that Lewis (LEW) (RT.1(l)) rats at the recovery phase of AA showed the highest level of IFN-gamma in recall response to mycobacterial heat-shock protein 65 (Bhsp65), whereas AA-resistant Wistar-Kyoto (WKY) (RT.1(l)) rats secreted high levels of IFN-gamma much earlier following disease induction. However, no significant secretion of IL-10 or TGF-beta was observed in either strain. Furthermore, pre-treatment of LEW rats with a peptide of self (rat) hsp65 (R465), which induced T cells secreting predominantly IFN-gamma, afforded protection against AA and decreased IL-17 expression by the arthritogenic epitope-restimulated T cells. These results provide a novel perspective on the pathogenesis of autoimmune arthritis.

Use of a thermoplastic resin stayplate as an alternative to an acrylic stayplate: a case report.

The fabrication of a chrome-cobalt metal partial denture is the standard in terms of removable partial dentures; alternative treatment includes an acrylic partial denture (such as a transitional stayplate). While these types of removable devices have been used successfully for many years, they also have disadvantages. Thermoplastic resin materials are a promising alternative for fabricating a transitional stayplate with improved results. A search of the literature indicated a scarcity of research concerning this material. This article presents a case report in which this material was utilized.

Properly fitted custom-made mouthguards.

With an increase in sporting activities comes an increase in orofacial injuries. A properly fitted mouthguard has been shown to provide protection against orofacial injuries and trauma to the teeth and supporting tissues such as the lips, cheeks, and tongue. However, because it is not mandatory that all athletes (amateur and professional) wear a mouthguard, many do not for reasons such as fit, comfort, social stigma, and speaking constraints. Athletes prefer mouthguards to be comfortable, soft, and resilient, which is characteristic of a custom-fitted mouthguard. This article will review reasons athletes prefer not to wear mouthguards and advantages of a custom-made mouthguard, as well as describe a process to fabricate a custom-made mouthguard.

Comments as part of a clinical competency rating system.

The nature of comments faculty members make about students' clinical performance and the relationship between comments and numerical scores given at the same time have not been studied in dental education. We developed a coding system for comments volunteered by faculty members to supplement the numerical ratings given as part of an established clinical competency evaluation system. Twenty-two hundred coded comments and their matched numerical ratings from more than 100 faculty members were compared for two classes of 146 and 157 students for four quarters. Thirty-seven percent of comments focused on dental performance, 43 percent on patient interactions, and 20 percent on relationships with faculty members or the clinic system. Forty-eight percent of comments were positive in tone. Where multiple comments were available for the same student in a quarter, 33 percent of them were confirmed by other faculty members; 9 percent were contradicted. Significant bidirectional associations were observed between comments (positive or negative) and numerical ratings in the area of patient interactions. For technical procedures and for interactions with faculty and the clinic, including professional demeanor, significant unidirectional associations predominated. The findings suggest that faculty members assume that students are skilled in these areas and tend to comment when their expectations are not fulfilled.

The origins of fear of occupational exposure in the clinical dental setting.

Although there is a growing literature on the incidence of occurrence and reporting of occupational exposures in clinics in dental schools, the contributing factors to fear of such injuries and their dynamic evolution over time remain unstudied. It is hypothesized that fear of occupational exposures is a function of estimated likelihood of such events and their perceived importance. Individual personality factors and situational circumstances are also thought to play a role, although it is believed that these factors recede in importance as students gain direct knowledge through clinical experience. Path analysis methods are applied to longitudinal survey data in a single dental school to confirm these hypotheses.

A posterior composite case utilizing the incremental and stratified layering technique.

Composite restorations should bring out the artist in the dentist. Today's composites are made to produce highly aesthetic, functioning restorations. There are several systems from which practitioners can choose, and the techniques for each system can be daunting. Composite restorations are conservative and a viable alternative, if proper protocol is followed. Each manufacturer has its own steps for applying its composites; however, by following the sound basic principles for bonded restorations, the practitioner can apply these procedures to every composite system. Thus, by utilizing proper techniques and understanding the material, one can both achieve a predictable outcome and desired aesthetics. The case study presented here illustrates the necessary steps required to achieve an anatomical, functional and aesthetic restoration.

Mouse lysozyme-M knockout mice reveal how the self-determinant hierarchy shapes the T cell repertoire against this circulating self antigen in wild-type mice.

We have studied T cell tolerance to defined determinants within ML-M using wild-type (WT; ML-M(+/+)) and LysMcre (ML-M(-/-)) C3H (H-2(k)) mice to determine the relative contribution of ML-M-derived epitopes vs those from other self Ags in selection of the ML-M-specific T cell repertoire. ML-M was totally nonimmunogenic in WT mice, but was rendered immunogenic in LysMcre mice. Most of the response to ML-M in LysMcre mice was directed to the immunodominant determinant region 105-119. This determinant is spontaneously displayed (without adding exogenous ML-M) by macrophages of WT, but not LysMcre, mice and is stimulatory for peptide 105-119 (p105-119)-primed T cells. Moreover, neonatal tolerization of LysMcre mice with p105-119 or ML-M abrogated the T cell response to subsequent challenge with ML-M or p105-119. Furthermore, p95-109 and p110-125 of ML-M were immunogenic in LysMcre mice, but not in WT mice, thereby representing subdominant, tolerance-inducing epitopes of ML-M. As expected, the T cell repertoire to cryptic ML determinants in WT mice was also intact in LysMcre mice. Furthermore, the pattern of response to the related homologue of ML-M, hen eggwhite lysozyme, was similar in these two groups of mice. Thus, several codominant T cell determinants within ML-M contribute significantly to tolerance induction, and the anti-cryptic T cell repertoire to ML-M was positively selected on non-ML-M self ligands. These results reveal that the induction of self tolerance to a multideterminant protein follows the quantitative hierarchy of self-determinant expression and are of relevance in understanding the pathogenesis of autoimmunity.