[Pharmacological actions of anifrolumab (Saphnelo®) and clinical trial results as a treatment for systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) is an autoimmune disease which causes damaging inflammation in multiple organs via the accumulation of immune complexes. SLE pathogenesis is associated with type I interferons (IFNs), which are central and reflective of disease activity in SLE. Even before clinical development of disease, genetic and environmental contributions to IFN production lead to abnormal innate and adaptive immune activation. Through the Janus kinase-signal transducer and activator of transcription signaling pathway, IFN play a central role in the immunopathogenicity of SLE. Thus, IFN-blocking therapy may be used to regulate inflammation in individuals with SLE. Food and Drug Administration (FDA)-approved anifrolumab (Saphnelo®), which is a human IgG1κ monoclonal antibody that binds to subunit 1 of the type I interferon receptor with high specificity and affinity, was also approved for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy by Pharmaceuticals and Medical Device Agency (PMDA), in Japan in September 2021; anifrolumab is administered as an intravenous infusion, 300 mg over a 30-minute period, every 4 weeks. In this article, we reviewed the actions of type I IFN and anifrolumab as a treatment for SLE.

Mycoplasma pneumoniae induces interleukin-8 production via the epidermal growth factor receptor pathway.

In mycoplasmal pneumonia, the bronchi are histopathologically filled with polymorphonuclear leukocytes. The EGFR pathway is involved in IL-8 production. We investigated the contribution of the EGFR pathway to IL-8 production by bronchial epithelial cells (A549) stimulated with Mp-Ag. The IL-8 production by A549 cells stimulated with Mp-Ag was decreased by the addition of an EGFR kinase inhibitor or transfection with small interfering RNA against EGFR. The levels of epiregulin mRNA in A549 cells were increased by stimulation with Mp-Ag. In conclusion, the EFGR pathway participates in IL-8 production by bronchial epithelial cells stimulated with Mp-Ag.

Cimetidine enhances antigen-specific IgE and Th2 cytokine production.

BACKGROUND: Treatment with anti-ulcer drugs has been shown to enhance IgE production against food antigens. However, little is known about the immunological effects of cimetidine, a histamine receptor type 2 (H2R) antagonist that is widely used as an anti-ulcer drug, in allergy. Therefore, the present study investigated the role of cimetidine in Th2 immune responses in mice. METHODS: BALB/c mice were immunized intraperitoneally with ovalbumin (OVA) with and without cimetidine. The levels of cytokines in supernatants of spleen cells cultured in the presence of OVA for 4 days and the levels of total and OVA-specific IgG(1), IgG(2a) and/or IgE in sera from these mice were determined by ELISA. RESULTS: Administration of cimetidine to OVA-sensitized BALB/c mice promoted Th2 cytokine secretion by OVA-stimulated spleen cells in vitro and increased serum levels of OVA-specific IgE, IgG(1) and IgG(2a). CONCLUSIONS: These results indicate that cimetidine can enhance Th2 responses, suggesting that cimetidine may contribute to IgE production in allergies.

Expression of osteocalcin and Jun D in the early period during reactionary dentin formation after tooth preparation in rat molars.

We examined, in rats, the expression of osteocalcin and Jun D in the early stage of reactionary dentin formation after tooth preparation and the accompanying morphological changes. Reverse transcription/polymerase chain reaction analysis revealed strong expression of osteocalcin mRNA in pulp tissue at 2 and 3 days post-preparation compared with that in control teeth. Light microscopy demonstrated that, at the dentin-pulp interface, damaged odontoblasts were detached from the dentin matrix immediately after preparation, with neutrophils lining the dental surface after 1 day. After 2-3 days, differentiated odontoblasts appeared at the interface. Reactionary dentin with tubular structures was formed under the cavity after 10 days. Immunoelectron microscopy showed that trace amounts of osteocalcin were expressed in odontoblasts at 2 days post-preparation, and abundant osteocalcin was found in the highly developed Golgi apparatus and granules at 3 days post-preparation. Osteocalcin was also found on type I collagen fibrils in newly formed predentin. The existing dentinal tubules were filled with osteocalcin-coated type I collagen fibrils. We observed, by immunohistochemistry, that Jun D was temporally expressed in the nuclei of the odontoblasts at 1 and 2 days post-preparation. However, no Jun D was found in the dental pulp cells at any other time or in control teeth. Thus, osteocalcin expression is correlated with reactionary dentin formation, and Jun D is associated with osteocalcin expression in odontoblasts. Osteocalcin may also serve as an obturator of the dentinal tubules to protect dental pulp vitality against external irritants after preparation.

A comparison of five techniques for detecting cardiac activity in infants.

BACKGROUND: The new guidelines for cardiopulmonary resuscitation recommend that laypersons should begin chest compressions without checking for a pulse because the pulse check has serious limitations in accuracy. We determined the efficacy of the most suitable method to search for cardiac activity in infants. METHODS: Twenty-eight nurses tried to detect infants' cardiac activity and determined their heart rates with five different techniques: palpation of brachial pulse, carotid pulse, femoral pulse, apical impulse and auscultation of apical impulse with the naked ear (direct auscultation technique). RESULTS: The mean time interval required to find the pulse within 30 s in the auscultation, the apical, the brachial, the carotid and the femoral were 2.4 +/- 1.2, 3.5 +/- 2.7, 4.0 +/- 2.7, 9.9 +/- 7.0 and 9.1 +/- 5.9 s, respectively. The required time was significantly shorter in the auscultation method than in the palpation of carotid and femoral pulses. The percentage and 95% confidence intervals (95% CI) of pulses identified within 10 s (= the number of the correct identified within 10 s/the number of all cases) in auscultation, apical, brachial, carotid and femoral palpations were 100.0% (95% CI 51.8, 100), 75.0% (95% CI 28.9, 89.3), 73.1% (95% CI 52.2, 88.4), 50.0% (95% CI 30.6, 69.4) and 42.9% (95% CI 24.5, 62.8), respectively. These values were greater in the auscultation method than in all the palpation methods. CONCLUSIONS: The direct auscultation technique was more rapid and accurate than any other techniques to determine cardiac activity without instruments. It is suggested that direct a auscultation technique is also superior to the palpation of brachial artery in cardiopulmonary resuscitation in infants.