Longitudinal Study of Scar Hyperplasia Formation Following Cleft Lip Wound Healing.

The purpose of this study was to observe the hyperplasia trend of scar after the cleft lip surgery in a rabbit animal model, and determine the time-point of the highest hypertrophic degree of scar after cleft lip repair. Forty New Zealand white rabbits from the same offspring were used to establish a cleft lip wound healing model using Millard surgery procedure. The scar volumes were measured and granulation tissues were observed visually in the 2, 3, 4, and 5 weeks after operation. The scar tissues were harvested at the indicated time-points. Immunohistochemical (IHC) and Western Blot analyses were performed to detect the expression level of α-smooth muscle actin (α-SMA) in the scar tissue. The scars shrunk and the volumes reduced at 3 to 4 weeks after surgery; however, at 5 weeks postsurgery, the volumes increased. IHC and Western blot analyses indicated the expression of α-SMA was significantly enhanced 3 to 4 weeks, but reduced in the 5 weeks after surgery. Overall, the degree of scar hyperplasia after cleft lip surgery in rabbits was normally distributed and the scarring was most severe in the 3 to 4 weeks after cleft lip surgery. The study confirms a novel animal model for the assessment of therapies for the treatment of scar hyperplasia of human cleft lip in future.

The relationship between maternal corticosteroid use and orofacial clefts-a meta-analysis.

The aim was to evaluate the relationship between maternal corticosteroid use during first trimester of pregnancy and risk of orofacial clefts (OC). The overall findings showed a certain association between maternal corticosteroid use and occurrence of OC, compared with non-users (OR=1.16 [95% CI: 1.01-1.33]). When study type was considered this association was significant only for case-control studies (OR=1.22 [95% CI: 1.02-1.47]), and not for cohort studies (OR=1.09 [95% CI: 0.88-1.34]) when there are many confounders (dose, route of application, disease etc.) and biases (re-call, loss-to follow-up etc.) that still need to be considered. A subgroup analysis based on the type of OC gave an overall OR of 1.41 (95% CI: 1.14-1.74) in the case-control studies for cleft lip with or without palate (CL/P) and 1.09 (95% CI: 0.80-1.48) for cleft palate only (CPO), when comparing maternal corticosteroid users with non-users. However, for cohort studies, the overall OR for CL/P is 1.06 (95% CI: 0.82-1.37) and 1.20 (95% CI: 0.83-1.75) for CPO. The absolute risk of facial cleft after prenatal exposure to corticosteroids, if any, is small.

Dhcr7 Regulates Palatal Shelf Fusion through Regulation of Shh and Bmp2 Expression.

The aim of this study was to investigate the effect of the 7-dehydrocholesterol reductase (Dhcr7) gene and identify signaling pathways involved in regulation of embryonic palatogenesis. The expression of Dhcr7 and its protein product were examined during murine normal embryonic palatogenesis via a reverse transcription polymerase chain reaction (RT-PCR) and Western blot (WB). RNA interference (RNAi) technology was used to inhibit Dhcr7 expression in a palatal shelf culture in vitro. The effects of Dhcr7 on palatogenesis and palatal fusion were examined by scanning electron microscopy (SEM). The expression changes of Dhcr7, Sonic Hedgehog (Shh), and bone morphogenetic protein-2 (Bmp2) were measured by RT-PCR and WB after Dhcr7 gene silencing and the addition of exogenous cholesterol. The results showed that the palatal shelf failed to complete normal development and fusion when Dhcr7 expression was inhibited. The inhibitory effect study of RNAi on the development of the palatal shelf supported that cholesterol supplementation did not alter the silencing of Dhcr7. Shh and Bmp2 expressions were reduced after Dhcr7 gene silencing, and administration of exogenous cholesterol did not affect Dhcr7 expression; however Shh and Bmp2 expressions increased. We conclude that Dhcr7 plays a role in growth of the palatal shelf and can regulate palatogenesis through alterations in the levels of Shh and Bmp2.

Botulinum Toxin Type A and the Prevention of Hypertrophic Scars on the Maxillofacial Area and Neck: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The purpose of the meta-analysis was to evaluate the efficiency of therapeutic botulinum toxin type A (BTX-A) in the prevention of maxillofacial and neck scars. METHODS AND FINDINGS: Information came from the following electronic databases: Medline, PubMed, Cochrane Library, and EMBASE (time was ended by August 31, 2015) to retrieve RCTs evaluating the effect of the BTX-A for hypertrophic scar on the maxillofacial or neck. All languages were included as long as they met the inclusion criteria. Here the effects of BTX-A were evaluated by comparing the width of the scar, patient satisfaction, and the visual analysis scores (VAS), respectively. Pooled weighted mean differences (WMDs), pooled odds ratios (ORs), and 95% confidence intervals (CI) were calculated. Nine RCTs covering a total of 539 patients were included. A statistically significant difference in scar width was identified between the BTX-A group and control group (non-BTX-A used) (WMD = -0.41, 95% CI = -0.68 to -0.14, P = 0.003). A statistically significant difference in patient satisfaction was observed between the BTX-A group and control group (OR = 25.76, 95% CI = 2.58 to 256.67, P = 0.006). And in patients regarding visual analysis scores (VAS), a statistically significant difference was also observed between the BTX-A group and control group (WMD = 1.30, 95% CI = 1.00 to 1.60, P < 0.00001). CONCLUSIONS: This meta-analysis evaluates the efficacy of the BTX-A and confirms that BTX-A is a suitable potential therapy for the prevention of hypertrophic scars in patients in the maxillofacial and neck areas.

The caries prevalence of oral clefts in eastern China.

Little information is available concerning the prevalence of caries among patients with oral clefts in Eastern China. Consecutive patients aged 6-18 with oral clefts were recruited. Patients were stratified into 2 groups according to their ages, namely Group I with aged 6-12 and Group II with aged 13-18. For each age group, the children were further divided into three subgroups according to the types of oral clefts they had: cleft lip/cleft lip and alveolus (CL), cleft palate only (CP), and cleft lip and palate (CLP). Dental caries were examined by using the decayed, missing, and filled index for primary teeth (dmft) and Decay, Missing and Filled index for Permanent teeth (DMFT) according to criteria of the World Health Organization. 268 eligible patients with oral clefts were included in the study. The mean DMFT for Group I was 1.77 (SD2.58) while that for Group II was 6.96 (SD4.35). The mean DMFT was statistically significant different between the age group I and age group II (t=12.21, P<0.05). In Group I, the dmft scores was 4.68 (SD3.67) for CL group, while that for the CP group was 7.36 (SD3.93), and that for the CLP group was 5.72 (SD 3.87). The mean dmft was no statistically significant different among cleft types (F=3.13, P>0.05). Also in Group I, the mean DMFT was 1.56 (SD2.18) for CL group, while that for the CP group was 1.24 (SD 1.81) and that for the CLP group was 2.08 (SD2.96). There were no statistically significant different in mean DMFT among different cleft types (F=1.09, P>0.05). In Group II, the mean DMFT was 6.06 (SD3.97) for CL group while that for the CP group was 7.71 (SD 4.94) and that for the CLP group was 7.05 (SD4.32). No significant difference was shown in the mean DMFT among different cleft groups (CL, CP, and CLP) (F=0.55, P>0.05). During assess the prevalence of dental caries among Eastern Chinese with oral clefts; the study confirmed that the prevalence of caries was increased with increasing age for oral clefts patients. It was also demonstrated that there was no significant difference in the mean dmft/DMFT scores among different cleft types.

Evaluation of Bone Height and Bone Mineral Density Using Cone Beam Computed Tomography After Secondary Bone Graft in Alveolar Cleft.

The purpose of this study was to assess the optimal timing of subsequent dental implant placement and orthodontics after alveolar bone grafting (ABG) in patients with unilateral complete clefts of the alveolar process. Iliac bone graft surgery was performed on 60 patients. Bone mineral density (BMD) and height of the ABG areas were assessed using cone beam computed tomography at 3 and 6 months postoperatively. The heights of the labial and palatal bone graft areas were classified using the modified Bergland classification. The study found that there was no change in BMD between 3 months (mean ±â€ŠSD: 406.51 ±â€Š71.28 Hounsfield units [HU]) and 6 months (409.53 ±â€Š46.37 HU; P = 0.381). Significant changes in the distribution of bone height classifications were observed in the labial and palatal sides of the ABG between 3 and 6 months (P = 0.025 for labial bone height, P = 0.008 for palatal bone height). These results indicate that the alveolar density remained stable between 3 and 6 months, whereas bone height level declined during that period after ABG, the latter indicating bone graft absorption over time. It is, therefore, suggested that subsequent orthodontic or dental implants be placed 3 months after ABG rather than at 6 months or later.

Intermittent Stretching and Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells via the p38MAPK-Osterix Signaling Pathway.

AIMS: The relationship between the p38MAPK signaling pathway and osterix in osteogenic differentiation of BMMSCs subjected to intermittent stretching was investigated. METHODS: BMMSCs derived from C57BL/6J mice were divided into the following groups: 1) control, 2) stretch, and 3) SB203580+stretch (SB203580 is a p38MAPK signal pathway inhibitor). BMMSCs were exposed to an intermittent mechanical strain of 0.8% (8000µ strain) at 0.5 Hz, twice a day for 30 min each application. BMMSCs were harvested on days 1, 3, and 5 post-treatment. The expression of ALP, COL I, OCN, and osterix mRNA was assessed utilizing RT-PCR while the expression of P-p38MAPK and osterix protein was assessed by Western blot analysis. The osterix gene in mouse BMMSCs was knocked down using RNAi technology and its protein expression was also assessed by Western blot. RT-PCR was used to detect ALP, COL I, and OCN mRNA expression. RESULTS: Intermittent stretching was found to promote expression of ALP, COL I, OCN, and osterix mRNA. Silencing the osterix gene was found to reduce levels of ALP, COL I, and OCN mRNA. Western blot analysis demonstrated that the levels of osterix and P-p38MAPK proteins in the stretch group were significantly higher than in the control group (P<0.05). There was less expression of ALP, COL I, OCN, and osterix mRNA in the SB203580+stretch group than in the control and stretch groups. CONCLUSIONS: Data demonstrate that intermittent stretching promotes osteogenic differentiation of BMMSCs, and the p38MAPK-osterix pathway has an important role in the control of osteogenesis-related gene expression.

The effect of p38MAPK on cyclic stretch in human facial hypertrophic scar fibroblast differentiation.

Hypertrophic scars (HTS), the excessive deposition of scar tissue by fibroblasts, is one of the most common skin disorders. Fibroblasts derived from surgical scar tissue produce high levels of α-smooth muscle actin (α-SMA) and transforming growth factor-ß1 (TGF-ß1). However, the molecular mechanisms for this phenomenon is poorly understood. Thus, the purpose of this study was to evaluate the molecular mechanisms of HTS and their potential therapeutic implications. Fibroblasts derived from skin HTS were cultured and characterized in vitro. The fibroblasts were synchronized and randomly assigned to two groups: cyclic stretch and cyclic stretch pre-treated with SB203580 (a p38MAPK inhibitor). Cyclic stretch at 10% strain was applied at a loading frequency of 10 cycles per minute (i.e. 5 seconds of tension and 5 seconds of relaxation) for 0 h, 6 h and 12 h. Cyclic stretch on HTS fibroblasts led to an increase in the expression of α-SMA and TGF-ß1 mRNA and protein and the phosphorylation of p38MAPK. SB203580 reversed these effects and caused a decrease in matrix contraction. Furthermore, HTS fibroblast growth was partially blocked by p38MAPK inhibition. Therefore, the mechanism of cyclic stretch involves p38 MAPK, and its inhibition is suggested as a novel therapeutic strategy for HTS.

[Establishment of palatal organ culture model of C57BL/6J mouse embryos in vitro].

PURPOSE: To establish palatal organ culture model of C57BL/6J mouse embryos in vitro and provide platform for study of embryo palatal development. METHODS: The mouse palatal shelves were harvested under sterilization from a female mouse of gestation day(GD) 13.5 by stereoscopic microscope and cultured in vitro. Totally 36 pairs of palatal shelves were divided into three groups equally and cultured 6 h, 24 h and 48 h, respectively. Finally, all palatal shelves were embedded and stained by Hematoxylin and Eosin (HE) and subjected to scanning electron microscope (SEM) analysis. RESULTS: The results of HE dyeing showed that the palatal shelves did not fuse on 6 h group, and began to fuse on 24 h group, but still had some medial edge epithelial (MEE) cells remained. The palatal shelves completely fused and all the MEE cells disappeared on 48 h group. The results of SEM showed that there was a gap between palatal shelves on 6 h group. The palatal shelves began to contact and form the medial epithelial seam (MES) on 12 h group. Finally, palatal shelves completely fused and MES disappeared on 48 h group. CONCLUSION: This method provides an effective way for investigating the etiology of cleft palate in vitro.

Aspiration of two permanent teeth during maxillofacial injuries.

Aspiration of a tooth in maxillofacial injuries is a known complication necessitating prompt recognition and early treatment to minimize potentially serious and, sometimes, even fatal consequences. Here, we report a rare and unusual case in its presentation, the patient having aspirated 2 permanent teeth after maxillofacial, cervical vertebrae, and thoracic region crush injuries due to a motor vehicle accident. The diagnosis of teeth aspiration was delayed until 2 weeks after the event. An aspirated anterior tooth was expectorated by the patient himself, and the other aspirated anterior tooth was removed by flexible bronchoscopy. The paper also emphasizes that clinicians must be aware of dental injury resulting from maxillofacial injuries and account for all teeth as part of their evaluation, keeping an open mind as to where a missing tooth might be located. A rapid diagnosis depends on high clinical suspicion, clinical signs, and radiologic findings.

Multiple orofacial malformations in a boy who was conceived by intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) and other assisted reproductive technologies (ART) are effective treatments for infertility and are widely used at infertility clinics. Although ICSI is generally considered safe, some studies have suggested an excess occurrence of major birth defects resulting from the procedure. Here, we present a rare case of a boy with multiple orofacial malformations who was conceived by ICSI. We suggest therefore that the risk of genetics abnormalities should be discussed in detail with the parents and sufficient informed consent should be obtained before starting ICSI procedures.

[An in vitro experiment on the antimicrobial effects of ethanol extract from salvia miltiorrhiza bunge on several oral pathogenic microbes].

PURPOSE: To study the in vitro antimicrobial activity of ethanol extract of salvia miltiorrhiza bunge on several oral pathogenic microbes. METHODS: Antimicrobial activities of ethanol extract of salvia miltiorrhiza bunge for porphyromonas gingivalis ATCC 33277, A. actinomycetes comitans ATCC 24523, Streptococcus mutans, and Lactobacillus were determined using the cup-plate method. The minimum antibacterial concentrations of ethanol extract of salvia miltiorrhiza bunge were measured. SPSS10.0 software package was used for Student's t test. RESULTS: Ethanol extract of salvia miltiorrhiza bunge had antimicrobial activities on Porphyromonas gingivalis, A. actinomycetemcomitans, Streptococcus mutans, Lactobacillus, and the minimum inhibitory concentrations were 15.62 mg/ml, 15.62 mg/ml, 62.50mg/ml and 15.62 mg/ml; The pH of the solution was influential to its antimicrobial activity. CONCLUSION: Ethanol extract of salvia miltiorrhiza bunge has an antimicrobial activity on oral pathogenic microbes.

[Relationship between periodontal disease and rheumatoid arthritis].

OBJECTIVE: To study a population of rheumatoid arthritis patients and determine the extent of periodontal disease in these patients, in order to investigate the relationship between periodontal disease and rheumatoid arthritis. METHODS: The experimental group was composed of 70 patients with rheumatoid arthritis and the control group consisted of 70 age- and gender-matched individuals without rheumatoid arthritis. The relationship between periodontal status in rheumatoid arthritis and control groups as well as the relationship between periodontal status and rheumatological findings in patients were analyzed. RESULTS: The percentage of periodontal disease was statistically significant between experimental and control group (P < 0.01). The difference of average number of missing teeth and bleeding on probing in the experimental group and control group were not statistically significant (P >0.05). There were more number of periodontal disease index 5 or 6 in experimental group than in control group ( P < 0.05). Rheumatoid arthritis patients with moderate to severe bone loss had deeper degree of morning stiffness, erythrocyte sedimentation rate levels and serum C-reactive protein levels than patients with no or mild bone loss. CONCLUSION: Individuals with rheumatoid arthritis are more likely to experience periodontal disease compares to healthy subjects. They are also very likely to suffer from moderate to severe periodontitis.