Developmental fluoxetine exposure in zebrafish reduces offspring basal cortisol concentration via life stage-dependent maternal transmission.

Fluoxetine (FLX) is a pharmaceutical used to treat affective disorders in humans, but as environmental contaminant also affects inadvertently exposed fish in urban watersheds. In humans and fish, acute FLX treatment and exposure are linked to endocrine disruption, including effects on the reproductive and stress axes. Using the zebrafish model, we build on the recent finding that developmental FLX exposure reduced cortisol production across generations, to determine possible parental and/or life-stage-dependent (age and/or breeding experience) contributions to this phenotype. Specifically, we combined control and developmentally FLX-exposed animals of both sexes (F0) into four distinct breeding groups mated at 5 and 9 months, and measured offspring (F1) basal cortisol at 12 dpf. Basal cortisol was lower in F1 descended from developmentally FLX-exposed F0 females bred at 5, but not 9 months, revealing a maternal, life-stage dependent effect. To investigate potential molecular contributions to this phenotype, we profiled maternally deposited transcripts involved in endocrine stress axis development and regulation, epigenetic (de novo DNA methyltransferases) and post-transcriptional (miRNA pathway components and specific miRNAs) regulation of gene expression in unfertilized eggs. Maternal FLX exposure resulted in decreased transcript abundance of glucocorticoid receptor, dnmt3 paralogues and miRNA pathway components in eggs collected at 5 months, and increased transcript abundance of miRNA pathway components at 9 months. Specific miRNAs predicted to target stress axis transcripts decreased (miR-740) or increased (miR-26, miR-30d, miR-92a, miR-103) in eggs collected from FLX females at 5 months. Increased abundance of miRNA-30d and miRNA-92a persisted in eggs collected from FLX females at 9 months. Clustering and principal component analyses of egg transcript profiles separated eggs collected from FLX-females at 5 months from other groups, suggesting that oocyte molecular signatures, and miRNAs in particular, may serve as predictive tools for the offspring phenotype of reduced basal cortisol in response to maternal FLX exposure.

Synovial tissue in internal derangement of temporomandibular joint.

The aim of this study was to examine the changes of the synovial tissue in rabbit temporomandibular joint (TMJ) internal derangement (ID) models using light and electron microscope. Thirteen rabbits were included in our study. The right TMJ of all animals were used as the experimental group while the left ones as the control group. ID model was established by using elastic rubber rope to stretch anteriorly. Synovial tissues were collected and examined by light and electron microscope to observe microstructure and ultrastructure changes after establishing the model. CD34 was used to count small blood vessels. A paired t test was performed with SPSS 16.0 software package to compare the data of the experimental and the control side. The average number of small blood vessels in the experimental side was significantly greater than the control side both in the first and second week. Numerous synovial cells of type A and type B were detected under electron microscope, and type A cells shrunk after a period of time. This study is helpful to understand the development of the TMJ intra-articular adhesion.

Expression of VEGF-receptors in TMJ synovium of rabbits with experimentally induced internal derangement.

Our aim was to evaluate the expression of vascular endothelial growth factor receptors (VEGFRs) in the synovium of the temporomandibular joints (TMJ) of rabbits with experimentally induced internal derangement. Internal derangement was experimentally induced in 52 rabbit TMJ, and established on the right side of TMJ while the left side was used as the control. Each joint and its control was evaluated by magnetic resonance imaging (MRI) and endoscopy. The synovial tissues on both sides were harvested after one, two, three, and four weeks. The expression of VEGFRs mRNA was investigated in the experimental joint and its control using real-time polymerase chain reaction (PCR). Internal derangement was successfully confirmed in 45 of the 52 of the experimental joints (87%) on the right side by MRI and endoscopy. In the first and fourth week, the VEGFR-2 mRNA expression was higher in the experimental joints than in the controls (P=0.008 and P=0.02). Meanwhile, the VEGFR-1 mRNA expression was up-regulated in the experimental group compared with the controls during the fourth week (P=0.02). However, we found no significant differences in VEGFR-3 mRNA expression in the two groups during the first and fourth weeks. During the second and third weeks, the mRNA expression of the three receptors did not differ significantly among the groups. Our data have shown increased expression of VEGFR-1 and VEGFR-2 mRNA in the synovium of rabbit TMJ with internal derangement, which indicates that VEGFR-1 and VEGFR-2 may have important roles in the processes of internal derangement and formation of adhesions.

Prevention and treatment for the rare complications of arthroscopic surgery in the temporomandibular joint.

PURPOSE: To analyze the rare complications of arthroscopic surgeries in the temporomandibular joint (TMJ) and to investigate the preventive and treating methods. PATIENTS AND METHODS: In this study, 2,034 consecutive patients (2,431 joints), diagnosed as TMJ internal derangement, were treated by arthroscopic surgeries when visiting the TMJ clinic at the Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, between May 2001 and September 2009. The clinical complications were analyzed to investigate cause, prevention, and control measures. RESULTS: Of all 2,034 cases, the complications were shown as follows: 5 joint hemorrhages of the lateral pterygoid muscle vascular, injuries of the lateral pterygoid muscle nerve in 5 joints, 3 joints with broken instruments, rejection reaction in 2 joints, and perforation of tympanic membrane in 2 joints. CONCLUSIONS: Arthroscopic surgery was a safe and effective method to treat TMJ internal derangement; its complications were limited and acceptable, but an experienced operator was required for this surgical technique.

Application of rapid prototyping for temporomandibular joint reconstruction.

PURPOSE: To introduce the preliminary application of rapid prototyping (RP) for temporomandibular joint (TMJ) surgery. MATERIALS AND METHODS: This study included 11 consecutive patients (13 joints) seeking TMJ replacement. All patients had previously undergone 3-dimensional computed tomography (CT) scanning (0.625-mm slice thickness) of the craniofacial skeleton. The data from CT scanning in DICOM (Digital Imaging and Communications in Medicine) format were input into the interactive Simplant CMF software program (Materialise Medical, Leuven, Belgium). Preoperative planning included segmentation and osteotomies. The movements of the jaw bones were simulated by use of Simplant CMF. The affected mandible was reconstructed based on the contralateral side. Then, the titanium plate was shaped on the reconstructed model before surgery. The bone graft was transplanted by the shaped titanium plate during the operation to reconstruct the TMJ. Twenty-four patients who underwent traditional surgery were used as the control group. The operative time of the 2 groups was analyzed with the SPSS software package, version 13.0 (SPSS, Chicago, IL), with the Student t test. The data from CT scanning in the experimental group before and after surgery were compared by paired t test. RESULTS: All the incisions healed primarily without any complications. All patients were satisfied with the operation, because of their symmetric faces and good occlusion. Postoperative magnetic resonance imaging confirmed the position of the transplanted costochondral cartilage in the glenoid fossa. A group t test showed that the operative time was longer in the control group (mean, 7.09 hours) than that in the RP group (mean, 5.67 hours). Three parameters (condyle-incisor, condyle-mental foramen, and condyle-angle) from the postoperative CT scan were analyzed by paired t test, and there was no significant difference between the 2 sides. CONCLUSION: RP technology provides an advanced method for TMJ reconstruction that can make the TMJ reconstruction more accurate and symmetric, improve the mandible's function, and consequently, enhance the reconstructive effect.

Temporomandibular joint disc repositioning using bone anchors: an immediate post surgical evaluation by magnetic resonance imaging.

BACKGROUND: Open joint procedures using bone anchors have shown clinical and radiograph good success, but post surgical disc position has not been documented with MRI imaging. We have designed a modified technique of using two bone anchors and 2 sutures to reposition the articular discs. This MRI study evaluates the post surgical success of this technique to reposition and stabilize the TMJ articular discs. METHODS: Consecutive 81 patients with unilateral TMJ internal derangement (ID) (81 TMJs) were treated between December 1, 2003, and December 1, 2006, at the Department of Oral and Maxillofacial Surgery, Ninth Peoples Hospital, Shanghai, Jiao Tong University School of Medicine. All patients were subjected to magnetic resonance imaging before and one to seven days post surgery to determine disc position using the modified bone anchor technique. RESULTS: Postoperative MRIs (one to seven days) confirm that 77 of 81 joints were identified as excellent results and one joint was considered good for an overall effective rate of 96.3% (78 of 81 joints). Only 3.7% (3 of 81) of the joints were designated as poor results requiring a second open surgery. CONCLUSIONS: This procedure has provided successful repositioning of the articular discs in unilateral TMJ ID at one to seven days post surgery.

New arthroscopic disc repositioning and suturing technique for treating internal derangement of the temporomandibular joint: part II--magnetic resonance imaging evaluation.

PURPOSE: To evaluate the efficiency of an arthroscopic suturing technique for stabilizing anteriorly displaced discs in patients with internal derangement of the temporomandibular joint (TMJ) by magnetic resonance (MR) imaging. PATIENTS AND METHODS: Six hundred thirty-nine patients (764 joints) diagnosed as having stages II to V of internal derangement were treated with arthroscopic disc repositioning and suturing from August 2004 to March 2007. Consecutive MR images were used to evaluate internal derangement before and approximately 1 to 7 days after the operation for all 639 patients. The disc position of the TMJ was judged according to the success criteria, which included 3 different sagittal planes (lateral, central, and medial). Operative efficiency in those patients, whose discs of the TMJ were affirmed to be in a normal position in all 3 planes, was evaluated to be excellent. Those patients whose discs were in a normal position in 2 planes were evaluated to be good. The others were evaluated to be poor. Cases evaluated as excellent and good were considered success cases (if the disc is displaced only in 1 or 2 planes before operation, the efficiency of the operation would be evaluated as a success only if the whole disc was in normal position). RESULTS: Postoperative consecutive MR images for all 764 joints confirmed that 95.42% (729/764) of the joints were excellent, 3.14% (24/764) were good, and only 1.44% (11/764) were poor. Repeated arthroscopic surgery or open surgery was carried out for the joints that were evaluated as poor. CONCLUSION: This study indicates that the TMJ arthroscopic suturing technique is effective in repositioning the TMJ disc as confirmed by an MR imaging examination, but long-term follow-up is necessary.

Intra-articular adhesions of the temporomandibular joint: Relation between arthroscopic findings and clinical symptoms.

BACKGROUND: Intra-articular adhesion (IA) is one of the important pathologic signs of intracapsular temporomandibular joint (TMJ) diseases, but this factor has been rarely described with respect to its arthroscopic characteristics and histology. The purpose of this study was to describe the incidence and distribution of IA in patients with internal derangement (ID) and to investigate the correlation between adhesions and the clinical symptoms of patients with ID of TMJ with closed-lock. METHODS: A retrospective analysis was conducted of 1822 TMJs with ID that were refractory to nonsurgical treatments and underwent arthroscopic surgery between May 2001 and June 2008 in our department. Clinical findings were assessed on the basis of mandibular range of motion, patients' age and locking duration at the initial visit. ID stages were judged according to the Wilkes and Bronstein classification based on clinical symptoms and pre-operative magnetic resonance imaging. 1506 patients (1822 joints) with ID were divided into an adhesion group (486 patients) and a non-adhesion group (1020 patients). The associations between the two groups with respect to interincisal opening, clicking duration, locking duration and patients' age were statistically analyzed using a t-test. RESULTS: Arthroscopy confirmed occurrences of adhesion in 28.76% of the joints (524 joints out of a total of 1822). Grade 1 adhesion was found in 68.89% of those cases; grade 2 in 20.61%; grade 3 in 4.58%; and grade 4 in 5.92%. The percentages of instances of adhesion in different stages were as follows: 13.89% of the joints in Stage II had adhesion, 25.47% in Stage III, 37.99% in Stage IV, and 40.37% in Stage V. There were statistically significant differences for patients' age (t = 10.41, P < 0.001), interincisal opening (t = 9.54, P < 0.001), paining duration (t = 3.66, P < 0.001) and locking duration (t = 3.89, P < 0.001) between the two groups, while no statistically significant difference was found for clicking duration (t = 1.08, P > 0.05). CONCLUSION: The arthroscopic findings confirmed that the incidence ratio of adhesion was high and occurred predominantly with older patients with longer locking duration and less interincisal opening. As the stage of ID increased, the adhesion grade rose.

Hydride transfer versus hydrogen radical transfer in thymidylate synthase.

The nature of a H-transfer in the thymidylate synthase catalyzed reaction was investigated by comparison of the wild-type enzyme with the W80M mutant. The nature of the H-transfer was not affected, as indicated by intrinsic isotope effects and their temperature dependence. These findings support a single-step hydride transfer instead of a two-step radical transfer.