RESUMO
BACKGROUND: Difficulties and limitations on masticatory function are among the main reasons why patients with temporomandibular disorder (TMD) seek care. OBJECTIVE: To evaluate the masticatory behaviour and perception of chewing difficulties in adults with mild TMD of recent onset, considering the presence of malocclusion. METHODS: Eighty-one young adults were divided into groups according to the presence of TMD and malocclusion: Non-TMD Normal Occlusion (n = 18), Non-TMD Malocclusion (n = 22), TMD Normal Occlusion (n = 18) and TMD Malocclusion (n = 23). TMD was assessed using the TMD Research Diagnostic Criteria and volunteers also answered questionnaires regarding their perception about jaw functional limitation and difficulty to chew foods of different textures. Masticatory and swallowing behaviours were assessed using the Orofacial Myofunctional Evaluation with Scores (OMES) protocol. Chewing time and chewing frequency taken to ingest the test-food were also obtained. Two-way-ANOVA was used to analyse the TMD, occlusion and TMD × occlusion interaction effects. RESULTS: Temporomandibular disorder effect was observed on vertical jaw mobility and jaw function limitation total scores, meaning that groups differed in the perception of opening limitation and mandibular limitation according to TMD status with a medium effect size. Also, more changes in chewing function (OMES-chewing score) and higher chewing frequency was observed in the presence of TMD (P < 0.05). Occlusion effect was only observed on OMES-swallowing score and no TMD × occlusion interaction effect was observed. CONCLUSION: Changes in chewing behaviour, frequency and perception of mandibular limitation was observed in the presence of TMD, pointing out the importance of functional evaluation when planning and establishing a treatment plan.
Assuntos
Mastigação , Transtornos da Articulação Temporomandibular , Deglutição , Oclusão Dentária , Humanos , Mandíbula , Adulto JovemRESUMO
BACKGROUND: L-type calcium channels (LTCCs) play important roles in regulating cardiomyocyte physiology, which is governed by appropriate LTCC trafficking to and density at the cell surface. Factors influencing the expression, half-life, subcellular trafficking, and gating of LTCCs are therefore critically involved in conditions of cardiac physiology and disease. METHODS: Yeast 2-hybrid screenings, biochemical and molecular evaluations, protein interaction assays, fluorescence microscopy, structural molecular modeling, and functional studies were used to investigate the molecular mechanisms through which the LTCC Cavß2 chaperone regulates channel density at the plasma membrane. RESULTS: On the basis of our previous results, we found a direct linear correlation between the total amount of the LTCC pore-forming Cavα1.2 and the Akt-dependent phosphorylation status of Cavß2 both in a mouse model of diabetic cardiac disease and in 6 diabetic and 7 nondiabetic cardiomyopathy patients with aortic stenosis undergoing aortic valve replacement. Mechanistically, we demonstrate that a conformational change in Cavß2 triggered by Akt phosphorylation increases LTCC density at the cardiac plasma membrane, and thus the inward calcium current, through a complex pathway involving reduction of Cavα1.2 retrograde trafficking and protein degradation through the prevention of dynamin-mediated LTCC endocytosis; promotion of Cavα1.2 anterograde trafficking by blocking Kir/Gem-dependent sequestration of Cavß2, thus facilitating the chaperoning of Cavα1.2; and promotion of Cavα1.2 transcription by the prevention of Kir/Gem-mediated shuttling of Cavß2 to the nucleus, where it limits the transcription of Cavα1.2 through recruitment of the heterochromatin protein 1γ epigenetic repressor to the Cacna1c promoter. On the basis of this mechanism, we developed a novel mimetic peptide that, through targeting of Cavß2, corrects LTCC life-cycle alterations, facilitating the proper function of cardiac cells. Delivery of mimetic peptide into a mouse model of diabetic cardiac disease associated with LTCC abnormalities restored impaired calcium balance and recovered cardiac function. CONCLUSIONS: We have uncovered novel mechanisms modulating LTCC trafficking and life cycle and provide proof of concept for the use of Cavß2 mimetic peptide as a novel therapeutic tool for the improvement of cardiac conditions correlated with alterations in LTCC levels and function.