A practical validation approach for virus titer testing of avian infectious bursal disease live vaccine according to current regulatory guidelines

The method for virus titer determination of avian infectious bursal disease (IBD) live vaccine, developed long before regulatory validation guidelines is a cell culture based biological assay intended for use in vaccine release testing.The aim of our study was to perform a validation, based on fit-for-purpose principle, of an old 50% tissue culture infectious dose (TCID₅₀) method according to Guidelines of the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH).This paper addresses challenges and discusses some key aspects that should be considered when validating biological methods. A different statistical approach and non-parametric statistics was introduced in validation protocol in order to derive useful information from experimental data. This approach is applicable for a wide range of methods.In conclusion, the previous virus titration method had showed to be precise, accurate, linear, robust and in accordance with current regulatory standards, which indicates that there is no need for additional re-development or upgrades of the method for its suitability for intended use.     

Prediction of lymph node metastasis in oral squamous cell carcinoma based on protein profile

Objective: Lymph node metastasis leads to high mortality rates of oral squamous cell carcinoma (OSCC). However, it is still controversial to define clinically negative neck (cN0) and positive neck (cN1-3).

Methods: We retrieved candidate biomarkers identified by proteomic analysis in OSCC from published works of literature. In training stage, immunohistochemistry (IHC) analysis was used to determine the expression of proteins and logistic regression models with stepwise variable selection were used to identify potential factors that might affect lymph node metastasis and life status. Furthermore, the prediction model was validated in validating stage.

Results: We screened eight highly expressed proteins related to lymph node metastasis in OSCC and found that the expression levels of SOD2, BST2, CAD, ITGB6, and PRDX4 were significantly elevated in patients with lymph node metastasis compared to the patients without lymph node metastasis. Furthermore, in training and validating stages, the prediction model base on the combination of CAD, SOD2 expression levels, and histopathologic grade was developed and validated in patients with OSCC.

Conclusions: Our findings showed that the developed model well predicts the lymph node metastasis and life status in patients with OSCC, independent of TNM stage.     

Atypical lipomatous tumour/well-differentiated liposarcoma found in the buccal mucosa: A rare case report

Oral liposarcomas are uncommon diseases, the most predominant histopathological subtype being atypical lipomatous tumour/well-differentiated liposarcoma. In regard to its clinical aspects in the oral cavity, it is challenging to confirm a diagnosis and develop a treatment plan. In this case report, we present a rare case of atypical lipomatous tumour/well-differentiated liposarcoma in the right cheek of a 77-year-old male patient. Conservative surgery was performed considering the histopathological subtype of the neoplasm. Knowledge of the clinical and histopathological characteristics of this rare disease is essential to maintaining function and aesthetics through conservative treatment in older patients.     

A 3-year longitudinal study of quality-of-life outcomes of elderly patients with implant- and tooth-supported fixed partial dentures in posterior dental regions

doi: 10.1111/j.1741‐2358.2011.00592.x
A 3‐year longitudinal study of quality‐of‐life outcomes of elderly patients with implant‐ and tooth‐supported fixed partial dentures in posterior dental regions Background: Clinical studies have mainly been focused on oral health‐related quality‐of‐life (OHRQoL) outcomes of removable dentures. Objective: To evaluate therapy of elderly patients with implant‐supported fixed partial dentures (IFPD) and tooth‐supported fixed partial dentures (FPD) in the posterior dental regions. Patients and methods: The OHIP49 was used to measure OHRQoL in 64 patients with IFPD and 38 patients with FPD, before, 3 weeks and 3 years after rehabilitation. A control group (CG) consisted of 62 individuals. Results: The Oral Health Impact Profile questionnaire (OHIP) follow‐up scores of the patients with FPD and the patients with IFPD were significantly smaller in comparison with the baseline scores (p < 0.01). The OHIP scores were further reduced at the 3‐year follow‐up. The patients with IFPD had significantly higher scores than the patients with FPD and the CG at the baseline and at the follow‐ups. In the patients with FPD, both age groups (≤60 and >60) showed equal improvement of the OHRQoL. In the IFPD group, patients older than 60 years showed better improvement (p < 0.05). There were no significant differences dependent on gender and antagonistic teeth (p > 0.05). Conclusion: The FPD and the IFPD treatment showed significant improvement of OHRQoL. The FPD treatment improved OHRQoL equally in both age groups, while the IFPD treatment improved OHRQoL better in older patients.     

A review of advanced oral drug delivery technologies facilitating the protection and absorption of protein and peptide molecules

The oral delivery of proteins and peptides is a dynamic research field despite the numerous challenges limiting their effective delivery. Successful oral delivery of proteins and peptides requires the accomplishment of three key tasks: protection of the macromolecules from degradation in the gastrointestinal tract (GIT), permeation through the intestinal barrier and absorption of molecules into the systemic circulation. Currently, no clinically useful oral formulations have been developed but several attempts have been made to overcome the challenges of low oral bioavailability resulting from poor absorption, poor permeation and enzymatic degradation of the proteins and peptides in the GIT. Present strategies attempt to provide structural protection of the proteins and peptides and improved absorption through the use of enzyme inhibitors, absorption enhancers, novel polymeric delivery systems and chemical modification. However, each of these technologies has their limitations despite showing positive results. This review attempts to discuss the physical and chemical barriers of the GIT with particular emphasis on the current approaches employed to overcome these barriers, including the evaluation of other non-parenteral routes of protein and peptide delivery. In addition, this review assimilates oral formulation strategies under development and within the clinical trial stage in relation to their benefits and drawbacks with regard to facilitating optimal protection and absorption of proteins and peptides, as well as pertinent future challenges and opportunities governing oral drug delivery.     

人用狂犬病疫苗过敏性反应探讨

采用超滤浓缩技术生产人用狂犬病疫苗后,疫苗效力得到明显提高;胆在使用中,包括过敏反应等在内的不良反应等有所增多且严重程度明显增大。以豚鼠为实验动物模型,探讨人用狂犬病疫苗引起过敏反应的原因。结果显示,地鼠民分是引起过敏的重要物质,过敏的严重程度随制品浓缩倍数的增大而增大。     

Getting in shape: adaptation and phylogenetic inertia in morphology of Australian anuran larvae

The external morphology of frog larvae is predicted to vary among habitats, for a variety of functional reasons. I performed a phylogenetic comparative study to test whether correlations between habitat and the shape of the tadpole and its oral disc are adaptive in 82 species from south‐eastern Australia in the families Hylidae and Myobatrachidae. Habitat distributions and phylogenetic relationships were compiled from the literature and shape was quantified using geometric morphometric analysis of published drawings. Results indicate that shape evolved towards different optima in different habitats while also showing appreciable levels of phylogenetic inertia. Within myobatrachids, evolution of terrestrial tadpoles was associated with a short and shallow head/body and a shallow tail. In aquatic species, the use of benthic microhabitats was correlated with a long shallow tail, dorsal eye position, shallow head/body and ventral mouth with robust jaw sheaths. Even traits with evidence for adaptation evolved slowly in response to habitat shifts, usually requiring ≥10 million years to evolve half‐way to a new optimum. Although these findings support adaptive evolution of tadpole body form, they also highlight a strong influence of ancestral character states and indicate that phenotypes in extant species are partly maladaptive.     

Recognition and behaviour of caregiver managers related to oral care in the community

Objectives: The purposes of this study were to investigate the knowledge, practice and educational background of caregiver managers regarding oral health, how they cope with visiting activities, and to explore related factors to develop an appropriate working strategy for them in the community. Methods: The subjects were 102 caregiver managers, who voluntarily participated in a seminar organised by the M city government. The collected data were analysed to assess the relationship between the related factors of oral health, career and age, and the correlation amongst items of action process concerning oral health using Spearman’s correlation coefficient and Fisher’ s exact test with spss 14.0 for Windows. Results: The results were as follows; (i) the mean length of careers of home‐care staff and caregiver managers was 3.6 ± 3.2 and 1.6 ± 1.6 years respectively, (ii) 90.2% recognised the importance of oral care and 92.2% were interested in oral care, although 32.4% hesitated to provide oral care, (iii) the career of caregiver managers was not significantly related to recognition of concrete objectives of oral care, soft debris and symptoms of periodontal disease, but they recognised the effectiveness of oral care in prevention of aspiration pneumonia, (iv) there was a total of 11 significantly correlated items of knowledge, recognition and practice of oral care and (v) there was a total of 10 significantly correlated items amongst factors of action process. Conclusion: Results suggested that knowledge of oral care was related not only to the career but also to age and revealed a basic gap in the range of abilities between the respondent caregiver managers. Some did perform appropriate oral care and carried out the necessary processes.     

Peptides and multiple antigen peptides from Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase: preparation, immunogenicity and immunoprotective capacity in C57BL/6 mice.

Four monoepitopic MAPs (MAP A, B, C and E) and one bis-diepitopic MAP B-E derived fromthe primary sequence of Schistosoma mansoni glyceraldehyde 3-phosphate dehydrogenase, previously tested in BALB/c mice, were examined for their immunogenicity and protective capacity in C57BL/6 mice. Despite multimerization into MAPs, MAP Aand MAP C were poorly immunogenic. In contrast toBALB/c mice, MAP E was non-immunogenic in C57BL/6 mice. Peptide B in the form of MAP B orbis-diepitopic MAPB-E elicited immune responses in C57BL/6 mice that were associated with a significant decrease in worm burden. The MAPs were prepared by the stepwise solid-phase peptide synthesis using Boc/Bzl chemistry, successfully purified on the RP-HPLC column and characterized by RP-HPLC, HPCE and MALDI-TOF MS techniques. A general strategy for MAPs purification is discussed here and the purification of MAP Band MAP E is documented in detail.     

Relationship between the ability of oral streptococci to interact with platelet glycoprotein Ibalpha and with the salivary low-molecular-weight mucin, MG2

The oral streptococci Streptococcus sanguinis, Streptococcus gordonii and Streptococcus oralis are common aetiological agents of infective endocarditis, and their ability to adhere to and induce the aggregation of platelets is thought to be a virulence trait. The platelet glycoprotein GPIbalpha has been implicated as the adhesion receptor for S. sanguinis and S. gordonii, but it is not known if this is the case for S. oralis and other species. The aim of this study was to determine the GPIbalpha-interactive capability of a range of oral streptococci and to determine the relationship between this capability and their ability to interact with the salivary constituents that they would encounter in their normal habitat. All platelet-adhesive S. sanguinis strains and most S. gordonii strains adhered in a GPIbalpha-dependent manner, but strains of S. oralis, Streptococcus cristatus, Streptococcus parasanguinis and Streptococcus mitis had no direct affinity for platelets. Those strains that were able to bind GPIbalpha also bound to the low-molecular-weight submandibular salivary mucin, MG2, and this interaction was sialic acid-dependent. The data suggest that S. sanguinis and S. gordonii may be efficient colonizers of platelet vegetations because of their adaptation to recognize sialylated salivary mucins. In contrast, S. oralis does not interact with platelets and so is likely to colonize vegetations through an as yet unidentified mechanism.