We studied whether hydrogen peroxide (H(2)O(2)) at =10 microM activates the ryanodine receptor and decreases releasable Ca(2+) content in the sarcoplasmic reticulum after fatigue. Exposure of rabbit or frog skeletal muscle ryanodine receptors to 10 microM H(2)O(2) enhanced channel activity in lipid bilayers when the redox potential was defined at cis = -220 mV and trans = -180 mV. Channel activation by 10 microM H(2)O(2) was also observed when cis potential was set at -220 mV without defining trans potential, but the effect was less. Reduction of trans redox potential from -180 to -220 mV did not alter channel activity. H(2)O(2) at 500 microM failed to activate the channel when the redox potential was not controlled. Stimulation of the frog muscle fiber for 2 min (50 Hz, a duty cycle of 200 ms/s) decreased tetanus tension by approximately 50%. After 1 min, tetanus recovered rapidly to approximately 70% of control and thereafter slowly approached the control level. Amplitudes of caffeine- and 4-chloro-m-cresol-induced contractures were decreased after a 60-min rest. The decrease is not enhanced by exposure to 10 microM H(2)O(2). These results suggest that H(2)O(2) markedly activates the ryanodine receptor under the redox control in vitro, but externally applied H(2)O(2) may not play an important role in the postfatigue recovery process.
We present the first case of simultaneous development of Graves' disease and type 1 diabetes during anti-programmed cell death 1 therapy. A 48-year-old man with parotid gland adenocarcinoma and lung metastasis had received five courses of nivolumab. Fourteen days after administration of the sixth course, his casual plasma glucose and hemoglobin A1c levels were 379 mg/dL and 7.2%, respectively. Furthermore, thyrotoxicosis was detected with a blood test. Serum total ketone body and thyroid-stimulating hormone receptor antibody levels increased, and serum C-peptide level decreased to 0.01 ng/mL thereafter. Thus, we concluded that he simultaneously developed anti-programmed cell death 1 therapy-associated type 1 diabetes and Graves' disease. Among Japanese patients with autoimmune polyglandular syndrome type III, the frequency of human leukocyte antigen-DRB1*04:05 is higher in those with both type 1 diabetes and Graves' disease. Our case had human leukocyte antigen-DRB1*04:05, which might be associated with the simultaneous development of the two diseases.
Intrinsic insulin secretion capacity may be preserved by discontinuing anti‐PD‐1 antibody treatment in ‘anti‐PD‐1 antibody‐induced‘fulminant type 1 diabetes.
Background Cases of subacute thyroiditis (SAT) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination have been reported. A human leukocyte antigen (HLA) allele, HLA-B*35, appears to be involved in the pathogenesis of SAT. Case presentation We conducted HLA typing of one patient with SAT and another with both SAT and Graves’ disease (GD), which developed after SARS-CoV-2 vaccination. Patient 1, a 58-year-old Japanese man, was inoculated with a SARS-CoV-2 vaccine (BNT162b2; Pfizer, New York, NY, USA). He developed fever (38 °C), cervical pain, palpitations, and fatigue on day 10 after vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum C-reactive protein (CRP) and slightly increased serum antithyroid-stimulating antibody (TSAb) levels. Thyroid ultrasonography revealed the characteristic findings of SAT. Patient 2, a 36-year-old Japanese woman, was inoculated twice with a SARS-CoV-2 vaccine (mRNA-1273; Moderna, Cambridge, MA, USA). She developed fever (37.8 °C) and thyroid gland pain on day 3 after the second vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum CRP, TSAb, and antithyroid-stimulating hormone receptor antibody levels. Fever and thyroid gland pain persisted. Thyroid ultrasonography revealed the characteristic findings of SAT (i.e., slight swelling and a focal hypoechoic area with decreased blood flow). Prednisolone treatment was effective for SAT. However, thyrotoxicosis causing palpitations relapsed thereafter, for which thyroid scintigraphy with 99mtechnetium pertechnetate was conducted, and the patient was diagnosed with GD. Thiamazole treatment was then initiated, which led to improvement in symptoms. Conclusion HLA typing revealed that both patients had the HLA-B*35:01, -C*04:01, and -DPB1*05:01 alleles. Only patient 2 had the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles. The HLA-B*35:01 and HLA-C*04:01 alleles appeared to be involved in the pathogenesis of SAT after SARS-CoV-2 vaccination, and the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles were speculated to be involved in the postvaccination pathogenesis of GD.
Background It is important to distinguish benign thyroid nodules from malignant thyroid nodules. Hence, this study aimed to determine the characteristics of patients with thyroid cancer using thyroid ultrasonography. Methods We retrospectively examined the ultrasonographic findings of 327 patients with 457 thyroid nodules (age: 59.9 ± 14.3 years; sex, n (%): female 242 (74.0%)) at a single center from 2014 to 2016. Ultrasonography was used to determine the nodule size, shape, border, internal echogenicity, presence of coarse calcifications and microcalcifications within the nodule, internal blood flow and whether the nodule was solid or contained cystic structures. Thyroid fine needle aspiration cytology (FNAC) was performed in all patients. The ultrasonographic findings were compared between patients with benign nodules and those with papillary thyroid carcinoma (PTC). Furthermore, in the analysis of anti-thyroglobulin (Tg) antibody-negative patients with single nodules, values of serum Tg/nodule volume were calculated and compared between patients with benign nodules and those with PTC. Results There were 298 (65.2%) benign nodules, 33 (7.2%) PTCs and 126 (27.6%) others (104 follicular neoplasms, 19 masses of undetermined significance and three other malignant tumors). The nodules diagnosed as PTC had significantly lower internal echogenicity (P < 0.01), more microcalcifications (P < 0.01) and comprised more nodules rich in blood flow (P < 0.05) than benign nodules. Solid nodules were found significantly more in the PTC group (P < 0.01). The serum Tg/nodule volume ratio was significantly higher in the PTC group (P < 0.05). Conclusions Findings suggestive of PTC were found from images obtained using thyroid ultrasonography. In the diagnosis of PTC, the frequency of FNAC examinations should be reduced as this method is costly and invasive.
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