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We aimed to determine the association between disease activity during pregnancy and pregnancy outcomes of women with polymyositis and dermatomyositis (PM/DM). Patients with PM/DM who were managed from pregnancy to delivery at Kagawa University Hospital from March 2006 to May 2021 were enrolled. Clinical data were retrospectively analyzed to evaluate the association between disease activity during pregnancy and pregnancy outcomes. Eight pregnancies in 5 women with PM/DM were analyzed. The mean age at conception was 28.3 ± 3.8 years, and mean disease duration was 6.3 ± 3.2 years. Four patients required an increased glucocorticoid dosage because of worsening disease activity (sustained elevation of creatine phosphokinase [CPK] concentration). Two patients who continuously received immunosuppressive drugs from conception to delivery showed no increase in disease activity and did not need increased glucocorticoid dosages. The pregnancy outcomes were 1 spontaneous abortion and 7 live births. The mean gestation length was 35.3 ± 5.2 weeks, and mean birthweight was 2297.7 ± 1041.4 g. Five adverse pregnancy outcomes (APOs) occurred (2 preterm births and 4 low birthweights); most of these cases had sustained elevation of CPK concentration and increased glucocorticoid dosages. No APOs occurred in the 2 patients who received continuous immunosuppressive medication. Continued use of pregnancy-compatible medications and control of disease activity with lower glucocorticoid dosages in pregnancies with PM/DM may be important to achieve good pregnancy outcomes.

Background: This study aimed to investigate the effect of glucocorticoid doses on adverse pregnancy outcomes (APOs) in women complicated by systemic lupus erythematosus (SLE). Methods: We investigated 74 pregnancies complicated by SLE or SLE-dominant mixed connective tissue disease. The pregnancies were managed from conception to delivery in our institution. We retrospectively evaluated whether the mean glucocorticoid dose during pregnancy is associated with APOs, including preterm birth (PB), low birth weight (LBW), and light-for-date (LFD). We also calculated the cut-off dose of glucocorticoid that affected APOs. Results: All APOs occurred in 35 (50.7%) patients, with 14 cases of PB, 23 cases of LBW, and 10 cases of LFD. Patients with all APOs or PB had a higher dose of glucocorticoid during pregnancy than patients without all APOs or with full-term birth (P= 0.03, P<  0.01, respectively). Logistic regression analysis for all APOs and PB showed that the cut-off values of the mean glucocorticoid dose were 6.5 and 10.0 mg/day, respectively. Patients who delivered LBW or LFD newborns showed no significant difference in the glucocorticoid dose used during pregnancy than patients without LBW or LFD newborns. Patients who delivered LBW newborns were more likely to have used glucocorticoids during pregnancy (P<  0.01). Conclusions: In pregnancies complicated by SLE, a relatively lower dose of glucocorticoid than previously reported is significantly related to APOs, especially PB. Therefore, the disease activity of patients with SLE should be managed with the appropriate lower dose of glucocorticoid during pregnancy.

We investigated serum total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain after BNT162b2 mRNA vaccination against coronavirus disease 2019 (COVID-19) in Japanese patients taking various immunosuppressive medications for rheumatic disease. In 212 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers (controls), all of whom had received 2 doses of BNT162b2 vaccine, serum antibody titers of SARS-CoV-2 spike protein were analyzed at least 14 days after the second dose. Many of the patients were taking immunosuppressive agents to manage their rheumatic disease. The antibody titers against SARS-CoV-2 spike protein in these patients were significantly lower than those in controls. The analysis of therapeutic agents revealed that the antibody titers in patients treated with rituximab were much lower than those in controls. In patients treated with tacrolimus, baricitinib, azathioprine, mycophenolate mofetil, abatacept, tumor necrosis factor inhibitors, cyclosporine, interleukin-6 inhibitors, methotrexate, or glucocorticoids, antibody titers were moderately lower than those of controls. Interleukin-17 and interleukin-23 inhibitors did not impair the humoral response. In addition, the combination of methotrexate with various immunosuppressive agents reduced titers, although not significantly. In Japanese patients with rheumatic disease, many immunosuppressants impaired the immune response to the BNT162b2 vaccine. The degree of decline in antibody titers differed according to immunosuppressant. When used concomitantly with other immunosuppressants, methotrexate may impair the immune response to the BNT162b2 vaccine. However, immunomodulatory treatments such as interleukin-17 and -23 inhibitors may not attenuate this response in patients with rheumatic disease.

A most potent natural α-glucosidase inhibitor named salacinol has been isolated from an antidiabetic Ayurvedic traditional medicine, Salacia reticulatawight, through bioassay-guided separation. The stereostructure of salacinol was determined on the basis of chemical and physicochemical evidence, which included the X-ray crystallographic analysis, and the molecular conformation showed the unique spiro-like configuration of the inner salt comprised of 1-deoxy-4-thioarabinofuranosyl cation and 1′-deoxyerythrosyl-3′-sulfate anion.

It is known that N‐nitrosopyrrolidine (NPYR), a carcinogen in rodents, is metabolically activated by microsomal cytochrome P450 to form an α‐hydroxylated derivative, which induces mutations. The mutations have been demonstrated by use of Salmonella typhimuriumand Escherichia coli. We discovered directly acting mutagenicity of NPYR plus ultraviolet light‐A (UVA) in bacteria and phage. With an O6‐alkyltransferase‐deficient strain of S.typhimurium, the NPYR plus UVA treatment gave greater mutation frequencies compared to those found with the parent strain. We identified the structure of the direct‐acting mutagen as N‐nitroso‐1‐phosphonooxypyrrolidine, and analyzed the spectrum of mutations induced in the DNA of M13mp2 phage. The basepair substitutions GC to TA and GC to AT appear to occur predominantly. Several hotspots were observed. In the conditions where SOS response was induced in the host E.coli, greater varieties of mutations were observed in phage DNA compared to those without the SOS response induction. These results suggest that alkylations of DNA occur by the photoactivated NPYR. The roles of the produced damage to the mutations are discussed. Environ. Mol. Mutagen. 34:24–29, 1999 © 1999 Wiley‐Liss, Inc.

It is known that N-nitrosopyrrolidine (NPYR), a carcinogen in rodents, is metabolically activated by microsomal cytochrome P450 to form an α-hydroxylated derivative, which induces mutations. The mutations have been demonstrated by use of Salmonella typhimurium and Escherichia coli. We discovered directly acting mutagenicity of NPYR plus ultraviolet light-A (UVA) in bacteria and phage. With an O⁶-alkyltransferase-deficient strain of S.typhimurium, the NPYR plus UVA treatment gave greater mutation frequencies compared to those found with the parent strain. We identified the structure of the direct-acting mutagen as N-nitroso-1-phosphonooxypyrrolidine, and analyzed the spectrum of mutations induced in the DNA of M13mp2 phage. The basepair substitutions GC to TA and GC to AT appear to occur predominantly. Several hotspots were observed. In the conditions where SOS response was induced in the host E.coli, greater varieties of mutations were observed in phage DNA compared to those without the SOS response induction. These results suggest that alkylations of DNA occur by the photoactivated NPYR. The roles of the produced damage to the mutations are discussed. Environ. Mol. Mutagen. 34:24–29, 1999 © 1999 Wiley-Liss, Inc.