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Oral function in patients with myasthenia gravis.

ABSTRACT: Myasthenia Gravis (MG) is characterised by muscle weakness and increased fatigability. The aim of this pilot study was to investigate if patients with MG demonstrate different functional chewing patterns and report more complaints related to mastication as compared with healthy controls. Twelve patients (median 60 years Q1-Q3: 46-70) with generalised MG and nine healthy controls (median 57 years Q1-Q3: 55-63) participated. All participants underwent dental and oral examination and were asked to fill in a questionnaire concerning oral health. Static maximum bite force was measured with a bite force transducer, electromyography in the masseter, temporalis, and suprahyoid muscles were recorded, and jaw movement was tracked, during a 5-minute gum chewing test. The patients had more oral complaints (oral health impact profile total score 22.6 vs 7.5 P < 0.01) and had lower peak bite force than controls (18.8kgf (11.1;26.4) (95% CI) vs 29.5 kgf (21.6; 37.4) (P = 0.04)). In contrast, fatigability of the masticatory muscles, as defined by number of chewing cycles during the gum-chewing test, did not differ between patients and controls (P = 0.10). In conclusion, patients had more oral complaints and lower bite force than controls, but did not show significantly different functional chewing patterns. Future studies should aim at integrating measurement of peak force into functional tests. Attention should be given to oral complaints of patients with MG.

SUBMITTER: Donskov AO

PROVIDER: S-EPMC8253106 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

Project description:Objective: This study was conducted to determine whether regulatory T cells (CD4+CD25+T, Tregs) show abnormal mitophagy as well as the function of Tregs in patients with myasthenia gravis (MG). Methods: CD4+T cells and CD4+CD25+Treg cells were obtained from 15 patients with MG (MG group) and 15 controls (N group). Tregs from the MG group were subjected to rapamycin-induced culture for 48 h (Rapa group) and 3-methyladenine-induced culture for 48 h (3-MA group). The levels of mitophagy in Tregs were then observed through electron and confocal microscopy. Expression of the autophagy-related protein LC3-II was detected by western blotting, and mitochondrial function in each group was evaluated by flow cytometry. Inhibition of Treg cell proliferation was detected by flow cytometry. Results: Mitophagy in the MG group was lower than that in the N group; it was higher in the Rapa group compared to that in the MG group and lowered in the 3-MA group than in the MG group. Expression of the autophagy-related protein LC3-II was lower in the MG group than in the N group, higher in the Rapa group than in the MG group, and lower in the 3-MA group than in the MG group. The mitochondrial membrane potential was lower in the MG group compared to that in the N group; it was higher in the Rapa group than in the MG group and lowered in the 3-MA group than in the MG group. Inhibition of Treg proliferation was lower in the MG group than in the N group; it was higher in the Rapa group than in the MG group and lowered in the 3-MA group than in the MG group. Conclusion: The decreased mitochondrial membrane potential and mitophagy in Tregs in the MG group may be related to a decreased inhibition of Treg proliferation. The mitochondrial membrane potential was increased after adding the autophagy agent Rapa to enhance mitophagy, and the proliferation inhibition function of Tregs was also enhanced. The autophagy agent 3-MA down-regulated mitophagy, which decreased the mitochondrial membrane potential and inhibitory effect of Tregs. These results reveal the possible cellular immune mechanism of Treg dysfunction in MG.

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Oral function in patients with myasthenia gravis.

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