Bilateral treatment of the masseter with botulinum toxin: Consequences for mastication, muscle force and the mandibular condyle.

BACKGROUND: Clinical use of botulinum neurotoxins (BoNTs) in masticatory muscles is usually bilateral, but most studies on the functional consequences of BoNT treatment have used unilaterally treated animals. OBJECTIVES: To test the hypothesis that bilateral BoNT treatment of the rabbit masseter hampers mastication and to assess its effects on bone density of the mandibular condyles. METHODS: Ten 5-month-old female rabbits received injections of BoNT into both masseter muscles and nine sham animals received saline. Body weight, incisor bite force during masseter tetany, and surface and fine-wire electromyography (EMG) of the masseter and medial pterygoid muscles were assessed at regular intervals. Half the sample was terminated after 4 weeks and the remainder after 12 weeks. Muscles were weighed and mandibular condyles were scanned with microCT to analyse bone density. RESULTS: BoNT rabbits lost weight and required a soft-food diet. Incisor occlusal force plummeted after BoNT injection and remained lower than the shams. The duration of masticatory cycles was increased in the BoNT rabbits for 5 weeks, with most of the increase due to the adductor burst. Masseteric EMG amplitude began to improve at Week 5, but remained low on the working side throughout the experiment. At the 12-week endpoint, masseter muscles were smaller in the BoNT rabbits. Medial pterygoid muscles did not compensate. Condylar bone density was reduced. CONCLUSION: Bilateral treatment of the rabbit masseter by BoNT severely affected chewing performance. Even after a 3-month recovery period, deficits remained in bite force, muscle size and condylar bone density.

Effect of Ageing on the Common Bile Duct Diameter.

INTRODUCTION: The aim of the study was to determine if the common bile duct (CBD) diameter increases physiologically with age and investigate whether gallstones lead to changes in CBD diameter. METHOD: Our study is composed of 721 patients in 2 groups: 517 asymptomatic patients and 204 gallstones patients who underwent MRCP. Their CBD diameter was measured at its widest visible portion on MRCP. Simple linear regression of the average of these measurements was used to investigate the relationship between age and CBD diameter in both populations. Subjects were further divided into 8 subgroups age-wise, respectively, and their means compared decade-wise using ANOVA. Furthermore, each subgroup mean from both populations was compared with each other using a t test. RESULTS: Among the 517 subjects, the mean CBD diameter was 5.3663 mm ± 1.43546 and correlated with age (p < 0.01), dilating at 0.07 mm/year. The mean diameter of our oldest group was 7.9 mm, resulting in a plausible upper limit of 8 mm for the asymptomatic population. The mean CBD diameter of the cholelithiasis population was 5.6738 mm ± 1.40986 and also correlated with age (p < 0.01). The mean CBD diameter of the age groups from the cholelithiasis population was larger than that from the asymptomatic population, but none were statistically significant. CONCLUSION: Although the CBD increases physiologically with age, there is no significant difference in CBD size between the general population and the cholelithiasis patients at any particular age. Gallstones do not independently dilate the CBD.

Dual-acting antibacterial porous chitosan film embedded with a photosensitizer.

This study proposes to develop a dual-acting antibacterial film of porous chitosan (Cs) embedded with small molecular compound, which possesses photosensitive characteristics with bactericidal efficacy, to promote the accelerated recovery of infectious wounds. The Cs/small molecular compound (Cs-cpd.2) dressing was prepared using the freeze-drying method. Characterization of the synthesized Cs-cpd.2 indicated that it has high porosity and moisture absorption effect, hence enhancing the absorption of wound exudate. Experimental results showed that Cs-cpd.2 dressing has good bactericidal and bacteriostatic effects on Staphylococcus aureus under visible-light irradiation and has antibacterial effect in the dark. It was also found that the small molecular compound does not have cytotoxicity at a dose of 0-5 µM. Furthermore, Cs-cpd.2 that contained small molecular compound with a concentration of 0.3-1 µM has positive effect on both the cell viability rate and cell proliferation rate of human fibroblast CG1639. Cs-cpd.2 can significantly promote cell proliferation when the small molecular compound and the basic fibroblast growth factor bFGF were added together. Therefore, the proposed Cs-cpd.2 dressing is feasible for photodynamic therapy (PDT) and clinical wound dressing applications.

Osseous Loading by a Volume-Reduced Tongue During Muscle Contractions.

PURPOSE: To investigate how tongue volume reduction affects loads on surrounding bone surfaces produced by neuromuscular stimulation of the tongue. MATERIALS AND METHODS: Of each pair of same-gender minipig siblings, 1 received tongue reduction and 1 underwent sham surgery. Either immediately (acute, 6 pairs) or 1 month (chronic, 5 pairs) after surgery, bone surface and/or suture strains and pressures were recorded from the following locations when the hypoglossal nerve trunk, hypoglossal nerve medial branch, hypoglossal nerve lateral branch, genioglossus, and styloglossus (SG) were electrically stimulated: 1) three rosette strain gauges on the premaxillary palatal surface (premaxilla [PM]) and lingual surfaces of the mandibular alveolus at anterior (mandibular incisor [MI]) and posterior (mandibular molar [MM]) locations; 2) two single-element strain gauges over the palatal surface of the premaxillary-maxillary suture and the lingual surface of the mandibular symphysis; and 3) two pressure transducers on the palatal surface of the maxilla (palatal process) and the lingual surface of the mandibular alveolus (mandibular corpus). RESULTS: Compared with the sham animals in the acute study, reduction animals showed significantly decreased PM and MI strains, as well as palatal process pressure. With muscle contractions, mandibular symphysis and MM strains were enhanced significantly with a more dorsal orientation. In the chronic study, reduction animals showed decreased PM and increased MM strains. On comparison of chronic versus acute studies, PM, MI, and MM strains under SG stimulation were significantly smaller whereas MM strain was significantly larger under hypoglossal nerve trunk, hypoglossal nerve lateral branch, and SG stimulations. CONCLUSIONS: Muscle contractions from a volume-reduced tongue produce lower and higher loads in the anterior and posterior mouth, respectively. However, although the effects on reducing loads in the anterior mouth are persisting over time, compensatory load enhancement in the posterior mouth diminishes owing to surgical healing.

Differential response of pig masseter to botulinum neurotoxin serotypes a and b.

INTRODUCTION: Pigs respond to direct administration of botulinum neurotoxins (BoNTs), although they are resistant to botulism. The human masseter is frequently targeted for BoNT therapy. We aimed to understand how BoNT affects chewing by injecting porcine masseters. METHODS: One masseter of minipigs was injected with BoNT serotype A or B at doses comparable to those used in humans. Masticatory function was evaluated electromyographically. Muscle force was measured during tetany. Four weeks after injection, strain gauges affixed to the mandible assessed bone strain during chewing. Masseter mass and fiber diameter were measured after euthanasia. RESULTS: BoNT-A had no measurable effect. In contrast, BoNT-B reduced electrical activity and muscle force, producing substantial asymmetry between injected and uninjected muscles. CONCLUSIONS: The pig masseter is highly resistant to direct injection of BoNT-A, but it is affected by BoNT-B.

Surgical treatment of giant aneurysm of hepatic artery: report of three cases.

BACKGROUND/AIMS: To explore the surgical way of treating giant hepatic artery aneurysm(HAA). METHODOLOGY: Three hepatic artery aneurysm patients who were performed aneurysm resection without revascularization of the hepatic artery were reviewed. After surgery, the values of liver function and enhanced CT scan of the patients were followed. RESULTS: All the three patients were recovered well postoperatively and only several values of biochemistry marks of liver function as ALT, AST, TBIL and DB in one case with liver cirrhosis were elevated and decreased to normal ranges in a few days postoperatively. The values of biochemistry marks of liver function in other two cases were within normal limits. The enhanced CT scan also showed arteries in the liver after hepatic artery aneurysm resection. CONCLUSIONS: Giant HAA may be safely removed without revascularization of the hepatic artery.

Tongue, palatal, hyoid and pharyngeal muscle activity during chewing, swallowing, and respiration.

OBJECTIVE: Chewing, swallowing, and respiration are synchronized oropharyngeal functions. This study aimed to analyze the dynamics and coordination during natural chewing and swallowing in relation to respiratory phases. DESIGN: Eight oropharyngeal muscles in minipigs were recorded using electromyography, X-ray fluoroscopy, and nasopharyngeal dynamics. Chewing cycles and swallowing episodes were analyzed for timing and activity amplitude along respiratory cycles. Digastric and middle pharyngeal constrictor were used as zero-points for timing analysis in chewing cycles and swallowing episodes, respectively. The beginning of these cycles and episodes were used as the zero-point for timing analysis in respiration during feeding. RESULTS: The timing of jaw closing (57.8%) was longer than opening (42.2%) during chewing. Muscle activity occurred 20% later than digastric onsets and 15% earlier than jaw closing phase. Duration of muscle activity was shorter in ipsilateral than contralateral sides except for palatal muscles. Pharyngeal, palatal, and hyoid muscles showed longer durations than tongue muscles in jaw opening (p < 0.05). Palatal and hyoid muscles showed 2-phased activity in chewing while hyoid muscles showed higher amplitude in chewing and swallowing than other muscles. About 80% of the chewing cycles and swallowing episodes occurred in expiration. Nasopharyngeal airflow velocity increased from jaw opening to swallowing while airflow pressure decreased. CONCLUSION: These findings indicate key activity of palatal and pharyngeal muscles mostly in chewing. The respiratory cycle changes in chewing and swallowing simultaneously with the activation of the tongue, palatal, and pharyngeal muscles. These findings will be useful for further understanding the mechanisms in swallowing and breathing disorders.

Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of five Yucatan and two Panepinto minipigs to verify obstructive sleep apnea (OSA), eight and four ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D deformational changes of the circumscribed regions were measured simultaneously with electromyographic activity of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in three nonobese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions, respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of deformational changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The distance changes between the dorsal surface of tongue base and soft palate during inspiration increased in normal but decreased in obese OSA minipigs.

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation.

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Botulinum neurotoxin type A in the masseter muscle: effects on incisor eruption in rabbits.

INTRODUCTION: Botulinum neurotoxins are responsible for the paralytic food poisoning, botulism. Commercial formulations such as botulinum neurotoxin type A are increasingly used for various conditions, including cosmetic recontouring of the lower face by injection of the large masseter muscles. The paralysis of a major muscle of mastication lowers occlusal force and thus might affect tooth eruption. The purpose of this study was to investigate the effects of unilateral masseter muscle injection of botulinum neurotoxin type A on the rate of eruption of incisors in a rabbit model. We hypothesized that the teeth would overerupt in an underloaded environment. METHODS: Forty rabbits were injected with either botulinum neurotoxin type A or saline solution in 1 masseter muscle. Mastication and muscle force production were monitored, and incisor eruption rate was assessed by caliper measurement of grooved teeth. RESULTS: The injection of saline solution had no effect. The masseter muscle injected with botulinum neurotoxin type A showed a dramatic loss of force 3 weeks after injection despite apparently normal mastication. Incisor eruption rate was significantly decreased for the botulinum neurotoxin type A group, an effect attributed to decreased attrition. CONCLUSIONS: This study has implications for orthodontics. Although findings from ever-growing rabbit incisors cannot be extrapolated to human teeth, it is clear that botulinum neurotoxin type A caused a decrease in bite force that could influence dental eruption.

The nasal septum and midfacial growth.

The nasal septum is the only element of the chondrocranium which never completely ossifies. The persistence of this nonarticular cartilage has given rise to a variety of theories concerning cranial mechanics and growth of the midface. Previously, using pigs, we demonstrated that the septum is not a strut supporting the snout and that septal growth seems capable of stretching the overlying nasofrontal suture, a major contributor to snout elongation. Here we investigate whether abnormalities of the septum are implicated in cases of midfacial hypoplasia, in which growth of the midface is inadequate. Mild midfacial hypoplasia is common in domestic pig breeds and often severe in the Yucatan minipig, a popular laboratory breed. Normal-snouted and midfacial hypoplastic heads of standard (farm mixed breed) and minipigs ranging in age from perinatal to 12 months were dissected, imaged by CT, and/or prepared for histology. Even at birth, Yucatan minipigs with midfacial hypoplasia exhibited greater caudal ossification than normal; the ventral cartilaginous sphenoidal "tail" was diminished or missing. In addition, cells that morphologically appeared to have divided recently were less numerous than in newborn standard pigs. Juvenile Yucatan minipigs lacked caudal cartilaginous growth zones almost completely. In standard newborns, the ventral caudal septum was more replicative than the dorsal, but this trend was not seen in Yucatan newborns. In conclusion, accelerated maturation of the caudal septum was associated with midfacial hypoplasia, a further indication that the septum, particularly its ventral portion, is important for midfacial elongation.

Tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig.

Obesity is a common finding and a major pathogenetic factor in obstructive sleep apnea (OSA) in adults. To understand the mechanisms behind this, the present study investigated the tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig model. In 4 verified obese/OSA and 3 non-obese/non-OSA control minipigs, MRI fat-weighted images, ultrasound elastography (USE), and sleep video-fluoroscopy (SVF) were performed to quantify the fat composition, tissue stiffness, and respiratory kinematics of the tongue base and soft palate during sedated sleep. The results indicated that the fat composition gradually increased from the rostral to caudal tongue base, particularly in the posterior 1/3 of the tongue base, regardless of the presence of obesity and OSA. However, this trend was not seen in the soft palate and pharyngeal wall. The pharyngeal wall presented the highest fat composition as compared with the tongue base and soft palate. Overall, obese OSA minipigs showed stiffer tongue tissue than the controls, particularly in the rostral region of the tongue in obese Yucatan minipigs. The respiratory moving ranges of the soft palate were greater in both dorsal-ventral and rostral-caudal directions and during both respiratory and expiratory phases in OSA obese than control minipigs, and the largest moving ranges were seen in OSA obese Panepinto minipigs. The moving range of the tongue base was significantly smaller. These results suggest more fat infiltration in the caudal region of the tongue base regardless of the presence of obesity and/or OSA. The greater tissue stiffness of the tongue in obese OSA minipigs may result from altered neuromuscular drive.

Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of 5 Yucatan and 2 Panepinto minipigs to verify obstructive sleep apnea (OSA), 8 and 4 ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D dimensional changes of the circumscribed regions were measured simultaneously with electromyographic activity (EMG) of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in 3 non-obese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of dimensional changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The opposite direction of the respiratory spatial relationship between these two structures was seen in obese/OSA as compared to normal minipigs.

Recurrence of common bile duct stones after choledocholithotomy in elderly patients: risk factor analysis and clinical prediction model development.

Background: The reasons for the recurrence of common bile duct stones (CBDS) in elderly patients after choledocholithotomy are still unclear. This study aims to establish a prediction model for CBDS recurrence by identifying risk factors. Methods: We conducted a retrospective analysis of 1804 elderly patients aged 65 years and above who were diagnosed to have CBDS and were admitted to Nanjing First Hospital between January 1, 2010, and January 1, 2021. According to inclusion and exclusion criteria, 706 patients were selected for the final analysis. The patients were assigned to two groups according to the presence or absence of CBDS recurrence, and their clinical data were then statistically analyzed. Subsequently, a prediction model and nomogram were developed, evaluating effectiveness using the concordance index (C-index). Results: Of the 706 elderly patients, 62 patients experienced CBDS recurrence after surgery, resulting in a recurrence rate of 8.8%. The multivariate Cox analysis showed that prior history of cholecystectomy (hazard ratio [HR] = 1.931, 95% confidence interval [CI]: 1.051-3.547, p = 0.034), white blood cell (WBC) count ≥11.0 × 109/L (HR = 2.923, 95% CI: 1.723-4.957, p < 0.001), preoperative total bilirubin (TBIL) level ≥ 36.5 mmol/L (HR = 2.172, 95% CI: 1.296-3.639, p = 0.003), number of stones ≥2 (HR = 2.093, 95% CI: 1.592-5.294, p = 0.001), maximum stone diameter ≥ 0.85 cm (HR = 1.940, 95% CI: 1.090-3.452, p = 0.024), and T-tube drainage (HR = 2.718, 95% CI: 1.230-6.010, p = 0.013) were independent risk factors of CBDS recurrence in elderly patients after choledocholithotomy. A postoperative CBDS recurrence prediction model was constructed with a C-index value of 0.758 (95% CI: 0.698-0.818) and internal validation value of 0.758 (95% CI: 0.641-0.875). Conclusion: A history of cholecystectomy, WBC count ≥11.0 × 109/L, preoperative TBIL level ≥ 36.5 mmol/L, number of stones ≥2, maximum stone diameter ≥ 0.85 cm, and T-tube drainage are the independent risk factors of CBDS recurrence after choledocholithotomy in elderly patients. Our developed prediction model for CBDS recurrence has good predictive ability and can help predict the prognosis of patients with CBDS.

[Inhibitory effect of siRNA targeting ADAM17 on the proliferation of prostate cancer PC-3 cells].

OBJECTIVE: To study the effect of siRNA targeting ADAM17 (ADAM17-siRNA) on the proliferation of prostate cancer PC-3 cells. METHODS: After transfecting PC-3 cells with ADAM17-siRNA 1 and ADAM17-siRNA 2, we detected the expressions of ADAM17 mRNA and protein by RT- PCR and Western blotting, respectively. We measured the changes in the proliferation and DNA synthesis of PC-3 cells by MTT and bromodeoxyuridine (BrdU) incorporation assay, examined the cell cycle profile by flow cytometry, and determined the expressions of the genes associated with PC-3 cell proliferation by Western blotting. RESULTS: Both ADAM17-siRNA 1 and 2 effectively reduced the expressions of ADAM17 mRNA and protein in the PC-3 cells. Knockdown of ADAM17 with the two siRNAs significantly inhibited cell proliferation as compared with the control group (0.43 +/- 0.57 and 0.44 +/- 0.64 vs 0.80 +/- 0.51, P < 0.05) and down-regulated DNA synthesis (0.48 +/- 0.43 and 0.54 +/- 0.59 vs 0.79 +/- 0.72, P < 0.05). The cell cycle profile showed that the cell population of the G1 phase was markedly higher in both the ADAM17-siRNA groups than in the control ([61.83 +/- 2.41]% and [59.78 +/- 1.92]% vs [41.38 +/- 1.53]%, P < 0.05), but that of the S phase remarkably lower in the former two than in the latter ([23.64 +/- 2.56]% and [25.24 +/- 1.86]% vs [33.51 +/- 1.47]%, P < 0.05), with a concomitant decrease in the expression of the cell cycle protein cyclin D1 and increase in the cyclin-dependent kinase inhibitor p21. CONCLUSION: ADAM17-siRNA can effectively inhibit the proliferation of PC-3 cells by up-regulating cyclin D1 and down-regulating p21 protein, and ADAM17 has a potential value in the gene therapy of prostate cancer.

Structural characteristics of periodontal ligaments in the pig model with experimental periodontitis.

To investigate how the structure of Sharpey's fibers in the periodontal ligaments (PDL) were affected by experimental periodontitis in a young pig model, 7 were periodically inoculated with four types of bacteria and a ligature around the last maxillary molar for 8 weeks to induce periodontitis (PG), and 10 served as controls (CG). The harvested molar blocks were sectioned coronally and stained with either hematoxylin & eosin (H&E) or Sirius Red (SR). The H&E-stained images were first reviewed. Then, images of each adjacent SR-stained sections were captured at the region close to the apex of mesial roots under polarizing light microscopy. Sharpey's fiber numbers in each bundle, total bundle numbers, connection of the bundle to the cementum and alveoli, as well as bundle angulations to the molar long axis were quantified in the defined area 500µm apical to the root apex. Compared to CG, PG showed the following features: 15.13% less total bundle number; 17.8% less bundle size; significantly less connected fiber bundles; 9.2% more interrupted fiber bundles; and 3.85% more oriented toward the cervical in the bundle angulation. These results suggest that experimental periodontitis alters the PDL structure, leading to more interruptions of Sharpey's fiber attachments to the cementum.

Acute obstructive suppurative pancreatic ductitis (AOSPD) with duodenal obstruction treated by pancreaticoduodenectomy (PD): a rare case report.

We report a rare case of acute obstructive suppurative pancreatic ductitis (AOSPD) accompanied by duodenal obstruction in a patient with chronic pancreatitis (CP). A woman in her 40s was admitted to our hospital for intermittent abdominal distension, epigastric pain, and vomiting, which worsened during the previous 6 months. Gastroscopy showed incomplete pyloric obstruction, and computed tomography (CT) revealed calcification in the enlarged head of the pancreas, dilation of the main pancreatic duct (MPD), and thickening of both the gastric antrum and duodenal walls. The patient was preoperatively diagnosed as having an inflamed head of the pancreas, with a stone, and duodenal obstruction. Pancreaticoduodenectomy (PD) was performed to resolve the duodenal obstruction and remove the pancreatic stone. While transecting the neck of the pancreas, frank pus began to flow from the MPD, and the pus was drained and collected. Bacterial culture of the purulent pancreatic juice revealed the presence of Escherichia coli, confirming AOSPD. The patient's symptoms were relieved, and she recovered fully, after the surgery. In conclusion, AOSPD associated with duodenal obstruction can be treated successfully by PD.

Repeated botulinum treatment of rabbit masseter causes cumulative tissue damage.

OBJECTIVE: Botulinum neurotoxins (BoNT) are used in masticatory muscles for pain relief, unloading of the mandible, and cosmetic facial contouring. Treatment is often repeated every few months as function returns. This study assessed masticatory function and musculoskeletal structure after multiple BoNT treatment of the rabbit masseter. DESIGN: Female rabbits received 3 injections of BoNT (n = 13) or saline (n = 5) into one masseter muscle at intervals of 12 weeks. The contralateral side served as control. Periodic measurements of masticatory electromyography (EMG) and stimulated anterior bite force were made. After the final 12-week recovery interval, neuromuscular connection was investigated by stimulating the masseteric nerve to elicit an evoked EMG response. Mandibular specimens were collected for microCT analysis, and masseters were collected for histomorphometry and counts of replicating cells. RESULTS: Control and saline-injected muscles maintained consistent masticatory EMG and anterior bite force throughout the study. BoNT-injected masseters showed strong declines after each injection; during the 12-week recovery period, masticatory EMG and anterior bite force improved, although only electrical activity reached normal levels. Multiple injection resulted in persistently atrophied muscle fibers with fibrosis, and notable loss of bone from the mandibular body and condyle. The uninjected masseters of the BoNT group also showed evidence of mild toxin-related changes. CONCLUSIONS: Although muscle function is mostly regained after each injection, masseters receiving multiple doses of BoNT show extensive damage. In addition, mandibular bone density is decreased on the injected side.

Botulinum toxin in the masseter muscle: Lingering effects of denervation.

Botulinum neurotoxins (BoNTs) are paralytic agents used to treat a variety of conditions in jaw muscles. Although their effect is considered temporary, there are reports of persistent functional changes. Using rabbits that received BoNT injection in one masseter muscle, the recovery of neuromuscular connection was investigated using nerve stimulation to evoke an electromyographic (EMG) response, and the recovery of muscle fibers was investigated using histological morphometry and bromodeoxyuridine (BrdU) immunohistochemistry. One month after treatment, evoked EMG was greatly reduced in both amplitude and duration, indicating that little reinnervation had taken place. Muscle fibers were atrophied and collagenous tissue was increased. Three months after treatment, evoked EMG duration was normal, indicating that at least some neuromuscular junctions were functional. Histologically, some muscle fibers were hypertrophied, some were still atrophied, and some appeared to have died. Fibrosis was still apparent amid slight increases in dividing cells and regenerating fibers. The histological effects of BoNT were evident although attenuated at a distance of about 1 cm from the injection level, but no regional differences could be discerned for the evoked EMGs. In conclusion, there were persistent muscular deficits seen 3 months after BoNT treatment that may have been caused by the failure of some affected muscle fibers to become reinnervated.

Airflow dynamics in obese minipigs with obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with anatomical restrictions of pharyngeal airway, but the mechanism of airflow dynamics in OSA is largely unknown. This study utilized computational flow dynamics (CFD) to build a 3D model of the pharynx and to test the hypothesis that an increased restriction in the pharynx in OSA/obese minipigs leads to higher resistance, which in turn creates turbulence to induce temporary blockage of pharyngeal airway patency. DESIGN: Of five 9-11-months-old Yucatan minipigs, 3 were non-obese (BMI<35) and two obese (BMI>51). After natural sleep monitoring using BioRadio system, pigs were sedated to collect MRI images and airflow parameters. The MRI images were processed to create 3D configurations of pharynx. These 3D configurations were meshed to create finite element models (FEM) of CFD. The obtained airflow parameters were input into the configurations to identify turbulent airflow and its location. RESULTS: Heavy snoring and multiple >5s hypopnea/apnea episodes (AHI = 32-35) were identified in both obese minipigs during sleep. Compared to the non-obese/non-OSA controls, obese/OSA minipigs showed much lower respiratory tidal volumes and inspiratory airflow speed. FEM simulation found that turbulence was not present in the pharynx in either model. However, a 25% increase of airflow velocity was observed at the narrowest part of the nasal pharynx in the obese/OSA minipig model. CONCLUSIONS: Despite the narrower pharyngeal airway and the higher velocity of airflow, FEM simulation indicated that turbulence was not produced in the obese/OSA minipigs.