Epidermolysis Bullosa: A Review of the Tissue-Engineered Skin Substitutes Used to Treat Wounds.

Skin wound healing is a crucial process for regenerating healthy skin and avoiding the undesired consequences associated with open skin wounds. For epidermolysis bullosa (EB), a debilitating group of fragile skin disorders currently without a cure, skin blistering can often be severe and heal poorly, increasing susceptibility to life-threatening complications. To prevent these, investigational therapies have been exploring the use of tissue-engineered skin substitutes (TESSs) aimed at replacing damaged skin and promoting long-term wound closure. These products have either been developed in house or commercially sourced and are composed of allogeneic or autologous human skin cells, often with some form of bioscaffolding. They can be broadly classified based on their cellular composition: keratinocytes (epidermal substitutes), fibroblasts (dermal substitutes) or a combination of both (composite substitutes). Encouraging long-term wound healing has been achieved with epidermal substitutes. However, these substitutes have not demonstrated the same efficacy for all patients, which may be due to the molecular heterogeneity observed between EB subtypes. Autologous composite TESSs, which more closely resemble native human skin, are therefore being investigated and may hold promise for treating an extended range of patients. Additionally, future TESSs for EB are focused on using gene-corrected patient skin cells, which have already demonstrated remarkable long-term wound healing capabilities. In this review, we provide an overview of the different TESSs that have been investigated in clinical studies to treat patients with EB, as well as their long-term wound healing results. Where available, we describe the methods used to develop these products to inform future efforts in this field.

RECOMMENDATIONS FOR USE AND SCORING OF ORAL HEALTH IMPACT PROFILE VERSIONS.

BACKGROUND: OHIP's original seven-domain structure does not fit empirical data, but a psychometrically sound and clinically more plausible structure with the four OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact has emerged. Consequently, use and scoring of available OHIP versions need to be revisited. AIM: We assessed how well the overall construct OHRQoL and its four dimensions were measured with several OHIP versions (20, 19, 14, and 5 items) to derive recommendations which instruments should be used and how to score them. METHODS: Data came from the "Dimensions of OHRQoL Project" and used the project's learning sample (5,173 prosthodontic patients and general population subjects with 49-item OHIP data). We computed correlations among OHIP versions' summary scores. Correlations between OHRQoL dimensions, on one hand, and OHIP versions' domain scores or OHIP-5's items, on the other hand, were also computed. OHIP use and scoring recommendations were derived for psychometrically solid but also practical OHRQoL assessment. RESULTS: Summary scores of 5-, 14-, 19- and 49-item versions correlated highly (r = 0.91-0.98), suggesting similar OHRQoL construct measurement across versions. The OHRQoL dimensions Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact were best measured by the OHIP domain scores for Physical Disability, Physical Pain, Psychological Discomfort, and Handicap, respectively. CONCLUSION: Recommendations were derived which OHIP should be preferably used and how OHIP versions should be scored to capture the overall construct and the dimensions of OHRQoL. Psychometrically solid and practical OHRQoL assessment in all settings across all oral health conditions can be achieved with the 5-item OHIP.

STANDARDIZATION OF DENTAL PATIENT-REPORTED OUTCOMES MEASUREMENT USING OHIP-5 - VALIDATION OF "RECOMMENDATIONS FOR USE AND SCORING OF ORAL HEALTH IMPACT PROFILE VERSIONS".

BACKGROUND: Recently, "Recommendations for use and scoring of Oral Health Impact Profile versions" (here abbreviated as Recommendations Project) were proposed by an international group of oral health researchers to standardize assessment of perceived oral health. They recommended a four-dimensional measurement approach consisting of Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact as the set of dental patient-reported outcomes to be measured with the 5-item Oral Health Impact Profile (OHIP-5). AIM: This study aimed to validate the "Recommendations for use and scoring of Oral Health Impact Profile versions" by replicating the findings they are based on. METHODS: OHIP data came from the "Dimensions of OHRQoL Project." Its Validation Sample (5,022 prosthodontic patients and general population subjects) as well as its Additional Sample (N = 583 prosthodontic patients and general population subjects) were used. Validation of the Recommendations Project's findings was performed in two steps. First, correlations among OHIP versions presented in the Recommendations Project were replicated in the Validation Sample. Second, participants of the Additional Sample were subjected to a hypothetical treatment program that assigned two treatments to them according to their level of perceived oral health impact using OHIP versions. The performance of abbreviated OHIP versions was evaluated. RESULTS: The high correlations among summary scores of 5-, 14-, 19-, and 49-item OHIP versions (r = 0.91-0.98), found in the Recommendations Project, were replicated. All short OHIP versions performed similarly when classifying participants for a hypothetical tailored treatment program. CONCLUSIONS: Findings reported in "Recommendations for use and scoring of Oral Health Impact Profile versions" were validated, thus supporting the feasibility of a standardized assessment of perceived oral health in all settings across all oral diseases. Psychometrically solid and practical assessment can be performed with OHIP-5.

Brij-functionalized chitosan nanocarrier system enhances the intestinal permeability of P-glycoprotein substrate-like drugs.

The highly expressed P-glycoprotein (Pgp) in the intestine plays a key role in preventing drugs across the intestinal epithelium, which linked by tight junctions (TJs). Thus increasing the oral bioavailability of Pgp substrate-like drugs (PSLDs) remains a great challenge. Herein, we construct a nanocarrier system derived from Brij-grafted-chitosan (BC) to enhance the oral bioavailability and therapeutic effect of berberine (BBR, a typical PLSD) against diabetic kidney disease. The developed BC nanoparticles (BC-NPs) are demonstrated to improve the intestinal permeability of BBR via transiently and reversibly modulating the intercellular TJs (paracellular pathway) and Pgp-mediated drug efflux (transcellular pathway). As compared to free BBR and chitosan nanoparticles, the BC-NPs enhanced the relative oral bioavailability of BBR in rats (4.4- and 2.7-fold, respectively), and the therapeutic potency of BBR in renal function and histopathology. In summary, such strategy may provide an effective nanocarrier system for oral delivery of BBR and PSLDs.

Brij-grafted-chitosan copolymers with function of P-glycoprotein modulation: Synthesis, characterization and in vitro investigations.

Chitosan (CS), a nature-derived polysaccharide, is a promising nano-carrier material with good biocompatibility and biodegradability. However, the biomedical applications of CS are hindered because of its poor aqueous solubility. To circumvent this drawback, a series of Brij-grafted-chitosan copolymers (BCs) with various grafting degree of Brij-S20 were first developed and reported. The results indicated that the water solubility of BCs (from 9.13 to 9.54 mg/mL) were much higher than that of CS (0.32 mg/mL), due to the broken intra- and/or inter-molecular hydrogen bonds and the decreased initial crystallinity in BCs. The amphiphilic structure of BCs presented lower critical micelle concentration (0.116-0.376 mg/mL) thus facilitating its self-aggregation into micelles for drug encapsulation. Moreover, BCs markedly enhanced the intracellular uptake of rhodamine-123 in MDCK-MDR1 cells. This inhibition on Pgp-mediated efflux was also confirmed by confocal microscopy. In conclusion, BCs could be further developed as polymeric nano-carriers for those drugs with Pgp-mediated efflux.

Response of phase I and II detoxification enzymes, glutathione, metallothionein and acetylcholine esterase to mercury and dimethoate in signal crayfish (Pacifastacus leniusculus).

Metals and pesticides are common pollutants and the modulation of biomarkers can indicate sub-lethal influences on the physiology of organisms inhabiting impacted aquatic systems. We examined the effects of mercury and the organophosphate pesticide dimethoate on EROD, MROD, glutathione S-transferase (GST), acetylcholine esterase (AChE), metallothionein (MT) and glutathione (GSH) in the signal crayfish (Pacifastacus leniusculus). Crayfish were injected with mercury chloride or dimethoate (0.3, 0.6, 0.9 µg kg-1) and dissected after 72 h. EROD activity in the hepatopancreas did not change in response to mercury chloride treatment but exhibited a dose dependent decrease at all concentrations of dimethoate tested. MROD (hepatopancreas) exhibited a significant decrease at the 0.9 µg kg-1 treatment for both chemicals. GST (hepatopancreas) demonstrated a significant dose dependent decrease at all concentrations of both mercury chloride and dimethoate. AChE (tail muscle) decreased at the 0.6 and 0.9 µg kg-1 concentrations of dimethoate and 0.9 µg kg-1 mercury chloride. In gill tissue, MT increased in response to 0.3 and 0.6 µg kg-1 of mercury chloride but no effect was observed at the 0.9 µg kg-1 concentration of mercury chloride or any concentrations of dimethoate tested. MT did not change in response to mercury or dimethoate in tail tissue. Furthermore, neither chemical modulated GSH concentrations. Our results indicate that, apart from GSH, these markers are sensitive to the pollutants tested and that animals exposed in the wild are potentially compromised in their ability to detoxify environmental contaminants and carry out normal cellular processes.

Quantitative Determination of Vinpocetine in Dietary Supplements.

Current United States regulatory policies allow for the addition of pharmacologically active substances in dietary supplements if derived from a botanical source. The inclusion of certain nootropic drugs, such as vinpocetine, in dietary supplements has recently come under scrutiny due to the lack of defined dosage parameters and yet unproven short- and long-term benefits and risks to human health. This study quantified the concentration of vinpocetine in several commercially available dietary supplements and found that a highly variable range of 0.6-5.1 mg/serving was present across the tested products, with most products providing no specification of vinpocetine concentrations.

Methylglyoxal-induced neuroinflammatory response in in vitro astrocytic cultures and hippocampus of experimental animals.

Diabetes mellitus is characterized by chronic hyperglycemia and its diverse complications. Hyperglycemia is associated with inflammatory responses in different organs and diabetic patients have a higher risk of developing neurodegenerative disorders. Methylglyoxal is a reactive advanced glycation end product precursor that accumulates in diabetic patients. It induces various stress responses in the central nervous system and causes neuronal dysfunction. Astrocytes are actively involved in maintaining neuronal homeostasis and possibly play a role in protecting the brain against neurodegeneration. However it is not clear whether methylglyoxal exerts any adverse effects towards these astrocytes. In the present study we investigated the effects of methylglyoxal in astrocytic cultures and hippocampi of experimental animals. The cells from the astrocytic line DITNC1 were treated with methylglyoxal for 1 to 24 h. For the in vivo model, 3 months old C57BL/6 mice were treated with methylglyoxal solution for 6 weeks by intraperitoneal injection. Following the treatment, both astrocytes and hippocampi were harvested for MTT assay, Western blot and real time PCR analyses. We found that methylglyoxal induced astrogliosis in DITNC1 astrocytic cultures and C57BL/6 mice. Further, activation of the pro-inflammatory JNK signaling pathway and its downstream effectors c-Jun were observed. Furthermore, increased gene expression of pro-inflammatory cytokines and astrocytic markers were observed from real time PCR analyses. In addition, inhibition of JNK activities resulted in down-regulation of TNF-α gene expression in methylglyoxal treated astrocytes. Our results suggest that methylglyoxal may contribute to the progression of diabetes related neurodegeneration through JNK pathway activation in astrocytes and the subsequent neuroinflammatory responses in the central nervous system.

Patterns of impaired oral health-related quality of life dimensions.

How dental patients are affected by oral conditions can be described with the concept of oral health-related quality of life (OHRQoL). This concept intends to make the patient experience measurable. OHRQoL is multidimensional, and Oral Function, Oro-facial Pain, Oro-facial Appearance and Psychosocial Impact were suggested as its four dimensions and consequently four scores are needed for comprehensive OHRQoL assessment. When only the presence of dimensional impact is measured, a pattern of affected OHRQoL dimensions would describe in a simple way how oral conditions influence the individual. By determining which patterns of impact on OHRQoL dimensions exist in prosthodontic patients and general population subjects, we aimed to identify in which combinations oral conditions' functional, painful, aesthetical and psychosocial impact occurs. Data came from the Dimensions of OHRQoL Project with Oral Health Impact Profile (OHIP)-49 data from 6349 general population subjects and 2999 prosthodontic patients in the Learning Sample (N = 5173) and the Validation Sample (N = 5022). We hypothesised that all 16 patterns of OHRQoL dimensions should occur in these individuals who suffered mainly from tooth loss, its causes and consequences. A dimension was considered impaired when at least one item in the dimension was affected frequently. The 16 possible patterns of impaired OHRQoL dimensions were found in patients and general population subjects in both Learning and Validation Samples. In a four-dimensional OHRQoL model consisting Oral Function, Oro-facial Pain, Oro-facial Appearance and Psychosocial Impact, oral conditions' impact can occur in any combination of the OHRQoL dimensions.

Psychometric properties of the English version of the Oral Health Literacy Adults Questionnaire - OHL-AQ.

OBJECTIVE: To test the psychometric properties of the Oral Health Literacy Adult Questionnaire (OHL-AQ) in English. The OHL-AQ was designed to test functional oral health literacy in general populations and was initially validated in Iran. METHODS: The instrument was administered to 405 adult subjects (mean age 45 (SD 16) years and 67% female) attending the 2014 Minnesota State Fair. The OHL-AQ is composed of 17 items measuring four conceptual dimensions: reading comprehension, numeracy, listening, and decision-making. Participants selected the best answer for written or verbally administered items and entered answers on an electronic tablet. Item responses for each individual were combined into a summary score (range 0-17) with higher scores indicating better oral health literacy. Score dimensionality, reliability, and validity were investigated. RESULTS: For dimensionality, both exploratory factor analysis and a parallel analysis yielded evidence for scale unidimensionality. Reliability was sufficient indicated by a Cronbach's alpha ⟩0.74. Validity of scores was supported by "small" and "medium" effect sizes for construct validity. "Small" effect sizes were observed for global oral health self-report, OHIP-5 scores, treatment urgency, and having a regular dentist. "Medium" effect sizes were seen for presence of dentures, number of natural teeth present, and educational level. CONCLUSIONS: Dimensionality, reliability and validity of the English version of the OHL-AQ in a general adult English-speaking population is supported, providing sufficient psychometric properties in an important target population of the instrument.

What is the impact of acute and chronic orofacial pain on quality of life?

OBJECTIVES: Orofacial pain (OFP) is thought to substantially reduce oral health-related quality of life (OHRQoL). Little has been reported about the impact of acute dental pain and persistent (chronic) orofacial pain conditions, other than temporomandibular disorders (TMD), on OHRQoL. The aim of this study was to examine and compare OHRQoL impairment among four OFP conditions: TMD, acute dental pain (ADP), trigeminal neuralgia (TN) and persistent dentoalveolar pain disorder (PDAP). METHODS: OHRQoL was measured using the OHIP-49 in a convenience sample of subjects with four OFP conditions (TMD (n=41), ADP (n=41), TN (n=21), PDAP (n=22) and a pain-free control group (n=21)). The mean OHIP-49 summary score described the level of impact and inferential and descriptive statistics were used to examine any differences inter-condition. The mean of the OHIP-14 and 5 were also measured by extracting the corresponding items from the OHIP-49. RESULTS: All pain conditions presented with statistically significant (P<0.001) and clinically relevant (measured by effect sizes and the OHIP's minimal important difference) impairment when compared to the control group (P<0.001). The OHRQoL for the four OFP conditions had similar levels of impairment (TMD=62.3, ADP=55.5, TN=58.1 and PDAP=69.8). CONCLUSION: TMD, ADP, TN and PDAP have substantial impact on OHRQoL as measured by the OHIP-49 and the extracted items for the OHIP-14 and 5. Differences among the four groups of orofacial pain conditions are likely not to be substantial.

Psychometric properties of the Dutch version of the Orofacial Esthetic Scale (OES-NL) in dental patients with and without self-reported tooth wear.

The aim of this study was to test the psychometric properties of the Dutch version of the Orofacial Esthetic Scale (OES) in dental patients with and without self-reported tooth wear. The English version of the OES was translated into Dutch, following established guidelines for cross-cultural adaptation of health-related quality of life measures. The reliability of the resulting OES-NL was tested in a test-retest study on 343 subjects; its validity was tested with the use of convergent validity on 582 subjects. The test-retest reliability of the OES-NL showed intra-class correlation coefficients (ICC) that ranged from 0·76 to 0·82, which can be qualified as excellent. The Cronbach's alpha revealed that the overall internal consistency of the scale was good (α = 0·89). Convergent validity was confirmed by the association between the OES-NL summary scores and three questions of the Dutch version of the Oral Health Impact Profile (OHIP-NL). The calculated Spearman's rank correlation coefficients ranged from -0·43 to -0·54 and were all significant (P < 0·001). The Dutch version of the Orofacial Esthetic Scale (OES-NL) showed good psychometric properties, making it suitable for the assessment of self-perceived aesthetics in Dutch dental patients with and without self-reported tooth wear.

Temporomandibular joint disorders' impact on pain, function, and disability.

The aim of this study was to determine the association between more advanced stages of temporomandibular joint (TMJ) intra-articular disorders ("TMJ intra-articular status"), representing a transition from normal joint structure to TMJ disc displacement with and without reduction (DDwR and DDwoR) to degenerative joint disease (DJD), and patient-reported outcomes of jaw pain, function, and disability ("TMD impact"). This cross-sectional study included 614 cases from the RDC/TMD Validation Project with at least one temporomandibular disorder (TMD) diagnosis. TMJ intra-articular status was determined by 3 blinded, calibrated radiologists using magnetic resonance imaging and computed tomography as one of normal joint structure, DDwR, DDwoR, or DJD, representing the subject's most advanced TMJ diagnosis. TMD impact was conceptualized as a latent variable consisting of 1) pain intensity (Characteristic Pain Index from the Graded Chronic Pain Scale [GCPS]), 2) jaw function (Jaw Functional Limitation Scale), and 3) disability (Disability Points from GCPS). A structural equation model estimated the association of TMJ intra-articular status with the latent measure TMD impact as a correlation coefficient in all TMD cases (n = 614) and in cases with a TMD pain diagnosis (n = 500). The correlations between TMJ intra-articular status and TMD impact were 0.05 (95% confidence interval [CI], -0.04 to 0.13) for all TMD cases and 0.07 (95% CI, -0.04 to 0.17) for cases with a pain diagnosis, which are neither statistically significant nor clinically relevant. Conceptualizing worsening of TMJ intra-articular disorders as 4 stages and characterizing impact from TMD as a composite of jaw pain, function, and disability, this cross-sectional study found no clinically significant association. Models of TMJ intra-articular status other than ours (normal structure → DDwR → DDwoR → DJD) should be explored.

Confirmatory factor analysis of the Oral Health Impact Profile.

Previous exploratory analyses suggest that the Oral Health Impact Profile (OHIP) consists of four correlated dimensions and that individual differences in OHIP total scores reflect an underlying higher-order factor. The aim of this report is to corroborate these findings in the Dimensions of Oral Health-Related Quality of Life (DOQ) Project, an international study of general population subjects and prosthodontic patients. Using the project's Validation Sample (n = 5022), we conducted confirmatory factor analyses in a sample of 4993 subjects with sufficiently complete data. In particular, we compared the psychometric performance of three models: a unidimensional model, a four-factor model and a bifactor model that included one general factor and four group factors. Using model-fit criteria and factor interpretability as guides, the four-factor model was deemed best in terms of strong item loadings, model fit (RMSEA = 0·05, CFI = 0·99) and interpretability. These results corroborate our previous findings that four highly correlated factors - which we have named Oral Function, Oro-facial Pain, Oro-facial Appearance and Psychosocial Impact - can be reliably extracted from the OHIP item pool. However, the good fit of the unidimensional model and the high interfactor correlations in the four-factor solution suggest that OHRQoL can also be sufficiently described with one score.

Exploratory factor analysis of the Oral Health Impact Profile.

Although oral health-related quality of life (OHRQoL) as measured by the Oral Health Impact Profile (OHIP) is thought to be multidimensional, the nature of these dimensions is not known. The aim of this report was to explore the dimensionality of the OHIP using the Dimensions of OHRQoL (DOQ) Project, an international study of general population subjects and prosthodontic patients. Using the project's Learning Sample (n = 5173), we conducted an exploratory factor analysis on the 46 OHIP items not specifically referring to dentures for 5146 subjects with sufficiently complete data. The first eigenvalue (27·0) of the polychoric correlation matrix was more than ten times larger than the second eigenvalue (2·6), suggesting the presence of a dominant, higher-order general factor. Follow-up analyses with Horn's parallel analysis revealed a viable second-order, four-factor solution. An oblique rotation of this solution revealed four highly correlated factors that we named Oral Function, Oro-facial Pain, Oro-facial Appearance and Psychosocial Impact. These four dimensions and the strong general factor are two viable hypotheses for the factor structure of the OHIP.

Ginsenosides attenuate methylglyoxal-induced impairment of insulin signaling and subsequent apoptosis in primary astrocytes.

Diabetes mellitus (DM), which is characterized by chronic hyperglycemia, is known to increase the risk of neurodegeneration. In type 2 diabetes, hyperglycemia could cause insulin resistance and neurodegeneration in various cells including neurons and astrocytes. Hyperglycemia is also known to result in the formation of advanced glycation end-products (AGE) Methylglyoxal (MG) is one of the most reactive AGE precursors in which its abnormal accumulation is usually found in diabetic patients and induces neuronal cell death in central nervous system. Ginseng is a herb that has been widely used to treat various diseases in traditional Chinese medicine. Ginsenosides, the pharmacologically active component isolated from ginseng, have been shown to have cryoprotective effects in different neural cells. In the present study we investigated the effects of MG in disturbing insulin signaling and leading to further cellular apoptosis in rat primary astrocytes. Furthermore, the protective effects of different subtypes of ginsenosides were studied. From the results, impairment of insulin signaling was found in astrocytes under MG treatment. Moreover, cleavage of caspase and Poly ADP ribose polymerase (PARP) was observed in line with insulin signaling disruption, showing the neurotoxic effects of MG towards astrocytes. The effects of ginsenosides in MG treated astrocytes were also investigated. After treatment, ginsenosides Rd and R-Rh2 were shown to ameliorate the cell viability of MG-treated astrocytes. In addition, Rd and R-Rh2 could improve insulin signaling and inhibit apoptosis, indicating that Rd, R-Rh2 and related compounds may have therapeutic potential in treating diabetes-induced neurodegeneration.

General population norms of the Swedish short forms of oral health impact profile.

We reported the development and psychometric evaluation of a Swedish 14-item and a five-item short form of the Oral Health Impact Profile. The 14-item version was derived from the English-language short form developed by Slade in1997. The five-item version was derived from the German-language short form developed by John et al. in 2006. Validity, reliability and normative values for the two short form summary scores were determined in a random sample of the adult Swedish population (response rate: 46%, N = 1366 subjects). Subjects with sufficient OHRQoL information to calculate a summary score (N = 1309) were on average 50·1 ± 17.4 years old, and 54% were women. Short form summary scores correlated highly with the 49-item OHIP-S (r ≥ 0.97 for OHIP-S14, r ≥ 0.92 for OHIP-S5) and with self-report of oral health (r ≥ 0.41). Reliability, measured with Cronbach's alpha (0.91 for OHIP-S14, 0.77 for OHIP-S5), was sufficient. In the general population, 50% of the subjects had ≥2 OHIP-S14 score points and 10% had ≥11 points, respectively. Among subjects with their own teeth only and/or fixed dental prostheses and with partial removable dental prostheses, 50% of the population had ≥2 OHIP-S14 score points, and 10% had ≥11 points. For subjects with complete dentures, the corresponding figures were 3 and 24 points. OHIP-S5 medians for subjects in the three population groups were 1, 1 and 2 points. Swedish 14-item and 5-item short forms of the OHIP have sufficient psychometric properties and provide a detailed overview about impaired OHRQoL in Sweden. The norms will serve as reference values for future studies.

Normative values for the Oro-facial Esthetic Scale in Sweden.

This study reports the findings and challenges of the assessment of oro-facial aesthetics in the Swedish general population and the development of normative values for the self-reporting Orofacial Esthetic Scale (OES). In a Swedish national sample of 1406 adult subjects (response rate: 47%), OES decile norms were established. The influence of sociodemographics (gender, age, and education), oral health status and general health status on OES scores was analysed. Mean ± standard deviation of OES scores was 50.3 ± 15.6 units (0, worst score; 70, best score); <1% of the subjects had the minimum score of 0, and 11% had the maximum score of 70 OES units. Orofacial Esthetic Scale score differences were (i) substantial (>5 OES units) for subjects with excellent/very good versus good to poor oral or general health status; ii) small (2 units), but statistically significant for gender (P = 0.01) and two age groups (P = 0.02), and (iii) absent for subjects with college versus no college education (P = 0.31) or with and without dentures (P = 0.90). To estimate normative values for a self-reporting health status, instrument is considered an important step in standardisation, and the developed norms provide a frame of reference in the general population to interpret the Orofacial Esthetic Scale scores.

Modulation of endoplasmic reticulum chaperone GRP78 by high glucose in hippocampus of streptozotocin-induced diabetic mice and C6 astrocytic cells.

Diabetes mellitus is known to increase the risk of neurodegeneration, and both diseases are reported to be linked to dysfunction of endoplasmic reticulum (ER). Astrocytes are important in the defense mechanism of central nervous system (CNS), with great ability of tolerating accumulation of toxic substances and sensitivity in Ca(2+) homeostasis which are two key functions of ER. Here, we investigated the modulation of the glucose-regulated protein 78 (GRP78) in streptozotocin (STZ)-induced diabetic mice and C6 cells cultured in high glucose condition. Our results showed that more reactive astrocytes were presented in the hippocampus of STZ-induced diabetic mice. Simultaneously, decrease of GRP78 expression was found in the astrocytes of diabetic mice hippocampus. In in vitro study, C6 cells were treated with high glucose to investigate the role of high glucose in GRP78 modulation in astrocytic cells. GRP78 as well as other chaperones like GRP94, calreticulin and calnexin, transcription levels were down-regulated after high glucose treatment. Also C6 cells challenged with 48h high glucose were activated, as indicated by increased level of glial fibrillary acidic protein (GFAP). Activated C6 cells simultaneously exhibited significant decrease of GRP78 level and was followed by reduced phosphorylation of Akt. Moreover, unfolded protein response was induced as an early event, which was marked by the induction of CHOP with high glucose treatment, followed by the reduction of GRP78 after 48h. Finally, the upsurge of ROS production was found in high glucose treated C6 cells and chelation of ROS could partially restore the GRP78 expression. Taken together, these data provide evidences that high glucose induced astrocytic activation in both in vivo and in vitro diabetic models, in which modulation of GRP78 would be an important event in this activation.