Effects of IgY against Candida albicans and Candida spp. Adherence and Biofilm Formation.

The fungal pathogen Candida albicans is an opportunistic fungal pathogen that causes oral and vaginal mucosal infections as well as systemic disease. The ability of C. albicans to adhere to host surfaces is positively correlated with its pathogenicity. We prepared a polyclonal anti-Candida albicans antibody in chicken egg yolk (anti-C. albicans IgY) and investigated its in vitro effectiveness in preventing C. albicans adherence and biofilm formation. Anti-C. albicans IgY significantly reduced the adherence of C. albicans SC5314 to human oral epithelial cells in a dose-dependent manner. The same effect was also observed in other Candida spp. including C. albicans serotype A and B. Further, the IgY inhibited biofilm formation of C. albicans in medium without serum, but the inhibition was slightly restored in medium conditioned with 10% serum. The data indicate that anti-C. albicans IgY cross-reacted with various Candida spp. and may have a protective effect against oral candidiasis and reduce the dissemination of Candida spp. This effect may be due to the blocking of the binding of Candida spp. to the host cells. However, the blocking did not play a role when Candida formed a germ tube in the presence of serum. Therefore, anti-C. albicans IgY may be considered as a prophylactic immunotherapy or possibly an adjunctive antifungal therapy under limited conditions.

Safety assessment of biopharmaceuticals: Japanese perspective on ICH S6 guideline maintenance.

Safety assessment of biopharmaceuticals in preclinical studies is guided by the ICH S6 guideline issued in 1997. Along with enormous experiences and knowledge on safety assessment of some classes of biopharmaceuticals over the last decade, the necessity and feasibility of updating the guideline has been discussed. According to a recommendation by safety experts at the ICH meeting in Chicago in 2006, regional discussions of ICH S6 were held in the USA, EU and Japan. The meeting to clarify the values, challenges and recommendations for ICH S6 from Japanese perspective was held as a part of the first Drug Evaluation Forum in Tokyo on August 10, 2007. Of utmost importance, the "case-by-case" approach must be preserved as the basic principle of the ICH S6 guideline. It is our opinion that oligonucleotides, siRNA, aptamers and related molecules should be excluded from ICH S6 and may be more appropriate for separate guidance. However, based on experiences and accumulated knowledge, there are a number of issues that can be updated including new types of biopharmaceuticals such as bioconjugates, use of homologous proteins and transgenic animals, reproductive/developmental toxicity studies in non-human primates, in vitro cardiac ion channel assay and alternative approaches for carcinogenicity assessment. Preliminary recommendations for some of these topics were outlined at the meeting. The overall Japanese recommendation is that the ICH S6 guideline should be updated to address these topics.

Current opinion: safety evaluation of drug metabolites in development of pharmaceuticals.

Safety assessment of drug metabolites in the development of pharmaceuticals was discussed in January 2007 at the kick-off meeting of a "Drug Evaluation Forum", with reference to the views of clinicians and other academic representatives. Safety evaluation of metabolites cannot readily be based on a single theoretical framework, and basically a case-by-case approach is called for. These evaluations should be performed precisely and an accurate profile secured taking into account adverse reactions that are unpredictable from the parent compound administered in clinical studies and any signs or symptoms that may be associated with the metabolites. In addition, elimination of scientifically meaningless metabolite safety assessment studies is essential for prompt supply of high-quality drugs to the medical frontline. Preparation of an outline concept paper would be useful for achievement of shared understanding of issues of this type. Collective viewpoints obtained in this fashion are also relevant to the discussion on the need for guidance, and given a degree of flexibility may also be helpful for drug development and, in turn, society at large.

Study of the oral microbial flora in patients with renal disease.

AIM: The aim of this study is to bacteriologically investigate the oral environment in patients with renal disease and thereby reveal their influence on both caries and periodontal diseases. METHODS: The authors compared oral microbial flora between patients with renal disease (non-haemodialysis: n = 40, haemodialysis: n = 41) and healthy people (n = 62), and also between haemodialysis patients and non-haemodialysis patients in the disease group. Cariogenic bacteria were identified according to Dentocult System, whereas periodontal bacteria were identified using the polymerase chain reaction method. RESULTS: When comparing between patients with renal disease and healthy people, the detected number of cariogenic bacteria and the detection rates of the periodontal bacteria in the patients with renal disease were significantly higher than in healthy people (P < 0.05). When comparing the patients on haemodialysis with those not receiving it, no significant differences in the detected number of cariogenic bacteria were observed. However, the detection rates of periodontal bacteria were lower in patients on haemodialysis (P < 0.05). CONCLUSION: The findings suggest that patients with renal disease tend to have a high risk of dental caries and periodontal disease than the control.

Effects of oral care on development of oral mucositis and microorganisms in patients with esophageal cancer.

We evaluated the effects of special oral care using a toothbrush with combined irrigation and suctioning functions, along with povidone-iodine to treat oral bacteria and mucositis, in esophageal cancer patients undergoing chemoradiotherapy. In the special care group, oral hygiene was performed 3 days a week after dinner. Bacteria in saliva and plague samples were measured at various sampling points after chemoradiotherapy. The incidence of mucositis was significantly reduced in the special care group in comparison with the control group. Total streptococci were significantly decreased in the opportunistic pathogens-positive and lower-level mutans streptococci control group during chemoradiotherapy, but they were not reduced in the opportunistic pathogens-negative and higher-level mutans streptococci control groups or in the special care group. Our results showed that a special oral care regimen enabled the total population of streptococci microflora to remain stable, was negatively correlated with opportunistic pathogens and positively correlated with mutans streptococci infection, and prevented the development of mucositis.

Establishment of rat model of drug-induced gingival overgrowth induced by continuous administration of phenytoin.

It is well-known that the anticonvulsant drug, phenytoin (PHT), induces gingival overgrowth as a side effect. The mechanism of PHT-induced gingival overgrowth, however, is not well understood. One reason for this is the lack of an adequate animal model for the PHT-induced gingival overgrowth. The purpose of this study was to establish a rat model of the drug-induced gingival overgrowth. Fourteen-day-old rats were randomly divided into 3 groups (5 rats/group). The control rats received only the vehicle. The rats in the experimental group were injected with 50 mg/kg per day (group L) and 100 mg/kg per day (group H) of PHT. They received a subcutaneous injection of vehicle or PHT twice a day for 42 days. A charge-coupled device (CCD) laser displacement sensor was used for measurement of the severity of gingival overgrowth of the mandibles. There was no significant difference in the growth of rats between the PHT-injected and the control groups. The CCD laser displacement sensor can measure minute changes in the gingival overgrowth in rats, and a significant extension of the buccal gingiva was observed in groups L and H. Using the CCD sensor, it is possible to quantify the change in the gingiva under precise control of the PHT dose.

Changes in salivary components by drug administration in patients with heart diseases.

In this study, patients with heart diseases were classified into 2 groups: Warfarin user and Warfarin non-user, and six salivary components were determined to assess intraoral pathologic conditions. Groups of healthy subjects and patients with periodontal disease without receiving any medication were set as control groups, and they were compared with those of the 2 groups with heart diseases. In patients with heart diseases in both the groups, albumin (ALB) level was found to be significantly higher compared to that in the control groups, and it was significantly higher in the patient group receiving Warfarin user and Warfarin non-user compared to that in the patient group with periodontal disease. C-reactive protein (CRP) levels were found to be higher in both the groups with heart diseases than those in the healthy group. Correlations between various salivary components and the clinical parameters were examined, showing significant correlations between ALB and gingival index (GI) and clinical attachment level (CAL), and between alanine aminotransferase (ALT) and GI, probing depth (PlI), bleeding on probing (BOP) and CAL. Significant correlations were also found between creatine kinase (CK) and PlI, GI and BOP. Thus, it was suggested that ALB and CRP might serve as the markers of intraoral pathologic conditions, and CK and ALT might serve as those alternative to GI.

Complete denture treatments for a cerebral palsy patient by using a treatment denture. A case report.

This article describes the prosthodontic treatment for a patient with cerebral palsy, in which complete dentures were successfully stabilized using treatment dentures. A 69-year-old edentulous male with no medical complications or mental retardation presented to our clinic. Opening movement of the jaw was possible, but a conspicuous mandibular shift towards the right was observed. He had never received any prosthodontic treatment. Initially, treatment dentures with flat tables were fabricated to rectify his erratic mandibular movements. During the first 3 weeks, the treatment dentures functioned poorly. Eventually, the patient could make tapping movement to some degree and have a meal with less effort. Indentation marks from the cusps of the opposing maxillary denture could be clearly seen on the flat tables. After six weeks, as he did not complain of any pain, definitive dentures were fabricated. When flat table treatment dentures are used, it is considered that the mucosa provides information regarding the vertical stop and bite force. In addition, it is speculated that there is an increase in the response from masseter muscle. In the present case, flat tables were effective for rehabilitation of the mandibular movement.