Design, synthesis, and in vitro cancer cell growth inhibition evaluation and antimalarial testing of trioxanes installed in cyclic 2-enoate substructures.

A novel series of 1,2,4-trioxanes were synthesized from 2H-pyrans via photooxidation, and their antiproliferative and growth factor inhibitory activity has been investigated across a variety of human cancer cell lines. Compounds 5k, 5l, 5s, 7a and 7c exhibited the highest activity and selectivity against a human leukemia (MV4-11) cell line (IC50 = 0.5 µM). Compound 5o showed the highest growth factor inhibitory activity against a melanoma (LOX-IMVI) cancer cell line (GI50 = 1.0 µM). A SAR study has confirmed the importance of the 1,2,4-trioxane unit as a pharmacophore for anticancer activity. The computer-assisted database analysis, COMPARE, has suggested that the compounds have unique mechanisms of actions that were different from those of known anticancer drugs. Some of the selected trioxanes were tested against the NF54 strain, albeit showing weak antiplasmodial activity. The molecular docking of trioxanes and hemin reveals that a short distance (1.30 Å) leads to their physical contact. The UV-vis spectroscopic analysis ensured the definite complexation between 1,2,4-trioxanes and hemin. The role of hemin-trioxane interaction in the hemin-induced oxidative damage has been studied using methylene blue as a substrate by UV-vis spectroscopy.

Improvement of vision after a combined midfacial and maxillary distraction with a rigid external distraction device.

We report a rare case of visual improvement in a 19-year-old patient with Apert syndrome after segmental distraction with a rigid external distraction device. We used the Rigid External Distraction Device II System (R.E.D. II, KLS Martin) after Le Fort I and III osteotomies.

Dual segmental distraction osteogenesis of the midface in a patient with Apert syndrome.

OBJECTIVE: To present orthodontic treatment combined with dual segmental distraction osteogenesis in a patient with Apert syndrome. PATIENT: A 15-year-old boy exhibited severe midfacial hypoplasia with retruded and hypoplastic maxilla and anterior open bite. The patient was treated with a rigid external distraction II system for distraction osteogenesis, a preadjusted edgewise appliance, and a modified maxillary protraction headgear. The concave profile with midfacial hypoplasia was improved. A tight occlusal relationship between maxillary and mandibular teeth was achieved. Postoperative treatment results have been stable for 1 year.

Craniofacial morphology in an unusual case with nasal aplasia studied by roentgencephalometry and three-dimensional CT scanning.

OBJECTIVE: To examine the three-dimensional morphology of internal structures of the craniofacial region and present the orthodontic problems in an unusual case with nasal aplasia. PATIENT: The patient was an 11.5-year-old boy with aplasia of the nose and nasal cavity with extremely constricted nasopharyngeal airway. He did not have mental or somatic retardation. The patient had dacryostenosis. The morphology of the craniofacial structures was characterized by absence of septal structures, including cribriform plate, perpendicular plate of ethmoid bone, vomer, and septal cartilage; bony hypotelorism; midface hypoplasia; short and retrognathic maxilla with Class III jaw relationship; average mandibular plane angle; high arched palate; severe anterior open bite with bilateral posterior crossbites; and dental anomalies (agenesis of four maxillary permanent teeth, microdontia, taurodontism, and short roots). Thus, the patient had characteristic dentofacial phenotype, which might be caused by a combination of the primary anomaly and the functional disturbances secondary to the nasal obstruction.

Evaluation of temporomandibular joint in patients with hemifacial microsomia.

OBJECTIVE: The purpose of this study was to elucidate positional relationships between temporomandibular joint (TMJ) components, including the articular discs, using magnetic resonance imaging (MRI) in patients with hemifacial microsomia (HFM). SUBJECTS AND METHODS: Twenty TMJs in 10 patients with HFM were examined at closed- and open-mouth positions using an MRI scanner. The condyle-fossa and disc-condyle relationships, disc configuration at the closed-mouth position, and the reduction of the disc at the open-mouth position were evaluated. RESULTS: On the unaffected side, the condyle-fossa and disc-condyle relationships appeared fairly normal at the closed mouth position. The disc-condyle relationship at the open-mouth position was also normal. The TMJ disc showed normal biconcave configurations at both closed- and open-mouth positions. On the affected side, there was considerable variation in the state of the TMJ. At the closed-mouth position, 5 of the 10 patients revealed fairly normal disc-condyle relationships, one patient showed anterior displacement of the disc, and four patients had no disc. Two patients appeared biconcave, three patients appeared biplanar, and one patient was hemiconvex. At the open-mouth position, the condyle and disc moved in harmony in five patients with normal disc-condyle relationships, but the disc was reduced in a patients with anterior disc displacement. The degree of the TMJ disc dysplasia did not necessarily correspond with the degree of mandibular dysplasia. CONCLUSIONS: The present study contributes to an improved understanding of TMJ pathology in patients with HFM. The results suggest that, in HFM patients, the examination of the TMJ using MRI is helpful for determining treatment procedures in mandibular distraction osteogenesis.

Mandibular distraction osteogenesis using an intraoral device and bite plate for a case of hemifacial microsomia.

OBJECTIVE: To present orthodontic treatment combined with mandibular distraction osteogenesis using an intraoral device and a bite plate in a patient with hemifacial microsomia, severe facial asymmetry, and unilateral mandibular hypoplasia. PATIENT: An 8-year-old girl exhibited mandibular deviation resulting from hypoplasia of the mandibular condyle and ramus on the left side. The patient was treated with an intraoral device for mandibular distraction osteogenesis, bite plate, and hybrid-type functional appliance. Facial asymmetry was improved, and the mandibular ramus was elongated in an anterior and primarily posterior direction with slightly posterior and superior displacement of the proximal segment. Postdistraction treatment results have been stable for 1 year. At the 1-year follow-up, the volume of the lateral and medial pterygoid muscles on the left side had increased. The condyle and disc on the right temporomandibular joint moved well and in harmony at open mouth position, and a rotational movement of the left temporomandibular joint was observed.

Volume and shape of masticatory muscles in patients with hemifacial microsomia.

OBJECTIVE: To test the following hypotheses in hemifacial microsomia (HFM): (1) the volumes of the masseter, lateral and medial pterygoid, and temporal muscles are reduced on the affected versus unaffected side; (2) significant differences exist between the degrees of right-left disproportion in these four masticatory muscles; (3) circumferential shapes of the masticatory muscles are more irregular on the affected versus unaffected side; and (4) the degree of masticatory muscle right-left disproportion can be judged by the degree of ear, mandibular, or dental anomalies. SUBJECTS AND METHODS: Ten preadolescent patients with HFM were studied using facial photographs, dental casts, cephalometric and panoramic radiographs, and helical computed tomography scanning and three-dimensional reconstruction technique. Volumes of masseter, lateral and medial pterygoid, and temporal muscles on both sides were measured. Muscle volume disproportion was expressed as the affected/unaffected ratio. Muscle circumferential irregularity was expressed as the ratio between the total circumferential length and corresponding cross-sectional area. RESULTS: Masticatory muscle volumes were significantly smaller on the affected versus unaffected side. No significant differences were observed between the degrees of disproportion of the four masticatory muscles examined. Circumferential shapes of masticatory muscles were significantly more irregular on the affected versus unaffected side. There were no significant relationships of the degree of ear, mandibular, or dental anomalies in relation to masticatory muscle disproportion. CONCLUSIONS: In HFM the masseter, lateral and medial pterygoid, and temporal muscles all have a significantly smaller volume on the affected versus unaffected side, and specific muscles were not severely affected in the present subjects. Furthermore, all four muscles showed a significantly more irregular shape on the affected versus unaffected side. Finally, the severity of masticatory muscle disproportion can probably not be judged by the degree of ear, mandibular, and dental anomalies in preadolescent patients with HFM.