Insulin Sensitivity Initially Worsens but Later Improves With Aging in Male C57BL/6N Mice.

Aging is believed to induce insulin resistance in humans. However, when and how insulin sensitivity changes with aging remains unclear in both humans and mice. In this study, groups of male C57BL/6N mice at 9-19 weeks (young), 34-67 weeks (mature adult), 84-85 weeks (presenile), and 107-121 weeks of age underwent hyperinsulinemic-euglycemic clamp studies with somatostatin infusion under awake and nonrestrained conditions. The glucose infusion rates for maintaining euglycemia were 18.4 ± 2.9, 5.9 ± 1.3, 20.3 ± 7.2, and 25.3 ± 4.4 mg/kg/min in young, mature adult, presenile, and aged mice, respectively. Thus, compared with young mice, mature adult mice exhibited the expected insulin resistance. In contrast, presenile and aged mice showed significantly higher insulin sensitivity than mature adult mice. These age-related changes were mainly observed in glucose uptake into adipose tissue and skeletal muscle (rates of glucose disappearance were 24.3 ± 2.0, 17.1 ± 1.0, 25.5 ± 5.2, and 31.8 ± 2.9 mg/kg/min in young, mature adult, presenile, and aged mice, respectively). Epididymal fat weight and hepatic triglyceride levels were higher in mature adult mice than those in young and aged mice. Our observations indicate that, in male C57BL/6N mice, insulin resistance appears at the mature adult stage of life but subsequently improves markedly. These alterations in insulin sensitivity are attributable to changes in visceral fat accumulations and age-related factors.

Rituximab Monotherapy for Grade 2-3 Lymphomatoid Granulomatosis with Central Nervous System Involvement in a Patient Receiving Methotrexate for Rheumatoid Arthritis.

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder (LPD). The optimal management strategy of methotrexate (MTX) related-LPD with central nervous system (CNS) involvement and histological features of LYG remains unclear. We herein report a case of grade 2-3 LYG in a rheumatoid arthritis patient, in which an intracranial mass accompanied by hemorrhaging and pulmonary and skin lesions developed. The patient received successful rituximab monotherapy. The tumor cells in the skin and brain showed monoclonal and oligoclonal proliferation, respectively. Our case suggests that rituximab monotherapy may be effective against MTX-LPD with CNS involvement, especially in cases with LYG histology.

Adalimumab administration after infliximab therapy is a successful treatment strategy for generalized pustular psoriasis.

We report a case of a 70-year-old woman with generalized pustular psoriasis (GPP) who responded well to infliximab therapy and adalimumab therapy after secondary failure of infliximab therapy, but did not respond to ustekinumab therapy. We speculate that the pathogenic factor in this case favored anti-tumor necrosis factor (TNF)-α therapy to anti-interleukin-12/23 therapy. Herein, we also briefly present three additional cases of treatment with adalimumab after secondary failure of infliximab. GPP is often difficult to treat, and no placebo-controlled trials have been conducted to guide the use of biologics against it because of a paucity of cases. Infliximab and adalimumab are anti-TNF-α antibodies that specifically block the interaction of TNF-α with its receptors. Infliximab has been reported to be effective, with a rapid clearance of symptoms, even in cases of severe GPP. Adalimumab could be a good biologic candidate that can be administrated after secondary failure of infliximab therapy.

Effects of maxacalcitol ointment on skin lesions in patients with psoriasis receiving treatment with adalimumab.

Adalimumab is a biologic that is very effective for treatment of psoriasis. However, recalcitrant or recurrent lesions sometimes occur during treatment. Maxacalcitol is an active vitamin D3 ointment that is effective in treatment of psoriasis. Topical therapy may be beneficial in treatment of recalcitrant or recurrent lesions during treatment with systemic therapy, but there is little evidence on this topic. We investigated the effect of maxacalcitol on skin lesions during treatment with adalimumab in patients with psoriasis. Twelve patients with psoriasis were randomly assigned to two groups after informed consent - treatment with adalimumab only (n = 6), and treatment with adalimumab and maxacalcitol (n = 6) - and they were evaluated every 4 weeks for 44 weeks. Exacerbation was defined as an increase of the Psoriasis Area and Severity Index (PASI) score. The interval between adalimumab treatments was elongated to 3-4 weeks from 2 weeks according to the individual patient's condition. The PASI score was evaluated every 4 weeks, and the frequency of exacerbations was counted. The overall improvement in PASI score was not statistically different between the two groups, but the frequency of exacerbations was significantly less in the maxacalcitol combination group compared with the adalimumab monotherapy group (Mann-Whitney U-test, P < 0.05). The better control of skin lesions in patients who elongated the interval of adalimumab administration was achieved in the maxacalcitol combination group compared with the adalimumab monotherapy group. Topical maxacalcitol treatment is effective and useful in controlling skin lesions in patients with psoriasis when used in combination with adalimumab.