Intradermal Delivery of a Near-Infrared Photosensitizer Using Dissolving Microneedle Arrays

Nodular basal cell carcinoma is a deep skin lesion and one of the most common cancers. Conventional photodynamic therapy is limited to treatment of superficial skin lesions. The parenteral administration of near-IR preformed photosensitizers suffers from poor selectivity and may result in prolonged skin photosensitivity. Microneedles (MNs) can provide localized drug delivery to skin lesions. Intradermal delivery of the preformed near-IR photosensitizer; 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl bacteriochlorin (Redaporfin?) using dissolving MN was successful in vitro and in vivo. MN demonstrated complete dissolution 30 min after skin application and showed sufficient mechanical strength to penetrate the skin to a depth of 450 μm. In vitro deposition studies illustrated that the drug was delivered and detected down to 5 mm in skin. In vivo biodistribution studies in athymic nude mice Crl:NU(NCr)-Foxn1^nu showed both fast initial release and localized drug delivery. The MN-treated mice showed a progressive decrease in the fluorescence intensity at the application site over the 7-day experiment period, with the highest and lowest fluorescence intensities measured being 9.2 × 10¹⁰ ± 2.5 × 10¹⁰ and 3.8 × 10⁹ ± 1.6 × 10⁹ p/s, respectively. By day 7, there was some migration of fluorescence away from the site of initial MN application. However, the majority of the body surfaces showed fluorescence levels that were comparable to those seen in the negative control group. This work suggests utility for polymeric MN arrays in minimally invasive intradermal delivery to enhance photodynamic therapy of deep skin lesions.     

Urinary metal concentrations among mothers and children in a Mexico City birth cohort study

Personal care product use is a potential source of metals exposure among children, but studies have been limited. We measured urinary concentrations of 10 metals (aluminum, arsenic [As], barium [Ba], cadmium, cobalt [Co], lead [Pb], manganese [Mn], molybdenum [Mo], nickel, and zinc [Zn]) in third trimester pregnant women (n?=?212) and their children at 8–14 years of age (n?=?250). Demographic factors (child sex, age, socioeconomic status, and maternal education), body mass index (BMI) z-score, and child personal care product use in the 24?h prior to urine collection were examined as predictors of urinary metal concentrations. Metals were detected in 80–100% of urine samples, with significant differences in maternal versus childhood levels. However, metal concentrations were not strongly correlated within or between time points. In linear regression models including all demographic characteristics, BMI z-score, and specific gravity, age was associated with higher Co (6% [95% CI: 2, 10]), while BMI z-score was associated with lower Mo (-6% [95% CI: -11, -1). In addition, significantly higher metal concentrations were observed among users of colored cosmetics (Mo: 42% [95% CI: 1, 99]), deodorant (Ba: 28% [3, 58]), hair spray/hair gel (Mn: 22% [3, 45]), and other toiletries (As: 50% [9, 108]), as well as with an increasing number of personal care products used (As: 7% [3, 11]) after adjustment for child sex, age, total number of products used, and specific gravity. However, significantly lower metal concentrations were noted for users of hair cream (As and Zn: -20% [-36, -2] and -21% [-35, -2], respectively), shampoo (Pb: -40% [-62, -7]), and other hair products (Pb: -44% [-65, -9]). We found that personal care product use may be a predictor of exposure to multiple metals among children. Further research is recommended to inform product-specific exposure source identification and related child health risk assessment efforts.     

Diagnostic & therapeutic strategies for the management of the diabetic patient

The bridge between oral and systemic health exists and becomes more concrete as data continue to emerge in support of this relationship. The medical management of diabetes is affected by the presence of chronic infections, such as periodontitis. This article reviews the pathogenesis of periodontal disease as it relates to diabetes. The author discusses patient susceptibility in terms of risk and recommends risk assessment to determine optimal treatment strategies. Patients with poorly controlled diabetes are at greater risk for developing periodontitis. The opportunity for systemic exposure to periodontal pathogens and proinflammatory mediators associated with periodontitis is discussed relative to their specific effects on patients with diabetes. The importance of good metabolic control in terms of risk for developing long-term complications of diabetes is presented and the impact of periodontitis on achieving adequate metabolic control is described. Special considerations for the management of patients with diabetes in the dental office are reviewed, including the signs and symptoms of diabetes, risk assessment for diabetes, and the challenges of "tight control" with insulin and oral agents with regards to hypoglycemia. It is recommended by the author that a thorough medical history of the patient be obtained, that the patient's medications are known, that the dentist consults with the patient's physician to assess the patient's glycemic control, and that the patient's blood glucose levels and dietary intake be monitored before treatment. Finally, the author reviews the long-term complications of diabetes, particularly the oral complications that can affect overall health. The author concludes with the belief that the treatment of periodontal diseases should not be considered optional or elective but, instead, should be a necessary and integral part of a patient's overall healthcare program.     

Cementum and dentin in hypophosphatasia

Hypophosphatasia (HPP) often leads to premature loss of deciduous teeth, due to disturbed cementum formation. We addressed the question to what extent cementum and dentin are similarly affected. To this end, we compared teeth from children with HPP with those from matched controls and analyzed them microscopically and chemically. It was observed that both acellular and cellular cementum formation was affected. For dentin, however, no differences in mineral content were recorded. To explain the dissimilar effects on cementum and dentin in HPP, we assessed pyrophosphate (an inhibitor of mineralization) and the expression/activity of enzymes related to pyrophosphate metabolism in both the periodontal ligament and the pulp of normal teeth. Expression of nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) in pulp proved to be significantly lower than in the periodontal ligament. Also, the activity of NPP1 was less in pulp, as was the concentration of pyrophosphate. Our findings suggest that mineralization of dentin is less likely to be under the influence of the inhibitory action of pyrophosphate than mineralization of cementum.     

A survey of program directors: trends, challenges, and mentoring in prosthodontics. Part 1.

PURPOSE: This study consisted of two parts. Part 1, a survey of program directors, was conducted to examine current trends in advanced education in prosthodontics in the United States. Part 2 will report on the survey results distributed to the deans of US dental schools to evaluate their observations of trends in prosthodontics. MATERIALS AND METHODS: A national e-mail survey of 45 program directors was used to collect enrollment data for years 1 to 3 of prosthodontics training for US and international dental school graduates, the total number of applicants and applications considered, and the trends over time of applicants to prosthodontic programs for US dental school graduates and for international graduates. In addition, the program directors were asked to rank 13 key factors that may have contributed to any changes in the prosthodontic applicant pool. Comments were accepted on why more or less US- or internationally trained applicants have applied. Program directors were also asked for information on student financial incentives, whether their programs were state or federally funded, and whether their sponsoring institution was a dental school. RESULTS: Of the 45 program directors, 39 responded, for an 86.7% response rate. Respondents reported that 64% of their enrollments were graduates of US dental schools. Between 2000 and 2004 the applicant pool in prosthodontics increased by 23%, with 41% of program directors reporting an increase in US-trained applicants, 46.2% reporting no change, and only 12.8% reporting a decrease. Using the Spearman correlation, there was a moderate, positive statistically significant correlation that the following factors contributed to an increase in the number of US dental graduates applying to prosthodontic programs: (1) mentoring by prosthodontists at the predoctoral level, (2) interest in prosthodontics among US dental students, and (3) society's demand for a higher level of training and credentialing, (4) data depicting current and projected income for dental specialists, and (5) number of trained prosthodontists full- or part-time faculty at the predoctoral level. Only five programs offered no financial packages to offset tuition. The remaining 34 respondents reported some financial package. Among the respondents, there were 25 state-sponsored programs, 9 sponsored by private universities, and 5 sponsored by hospitals or federal agencies. CONCLUSION: An increased applicant pool and more US-trained applicants to prosthodontics programs create a more competitive applicant pool for our specialty. Program directors reported that factors such as mentoring, society's demand for a higher level of training and credentialing, data depicting current and projected income for prosthodontists, exposure to prosthodontic faculty at the predoctoral level, the dollar value of prosthodontic training, and advances in implant, aesthetic, and reconstructive dentistry have all had some impact on increasing the applicant pool to prosthodontic training in the United States.