Interactions among BP, season and gestational age should be considered when evaluating BP in pregnant women. Risks associated with high BP might be underestimated in pregnant woman in summer who will deliver in winter.
Background: β2-glycoprotein I (β2GPI)-dependent antiphospholipid antibodies (aPLs) are considered to play a pivotal pathogenic role in antiphospholipid syndrome (APS) by inducing the expression of tissue factor, inflammatory cytokines, and chemokines, most of which are dependent upon the NF-κB pathway. Therefore, the NF-κB is regarded as a promising target for the development of a novel therapeutic strategy. However, progress has been limited owing to the fact that there are no widely-used in vivo models, or highly specific inhibitors.Objective: This study aimed to test the effects of an NF-κB-specific inhibitor, DH-MEQ, in preventing thrombus formation using an original mouse model of APS. Materials and Methods: Specificity of a monoclonal aPL WB-6 was examined by ELISA. WB-6 was injected into normal BALB/c mice with or without DHMEQ treatment. A pulse laser was radiated to a cutaneous vein in the window of a dorsal skinfold chamber attached to the mouse and thrombus formation was observed and recorded under a microscope. Results: WB-6 bound preferentially to the caldiolipin (CL)-β2GPI complex rather than to CL alone, or β2GPI alone. WB-6, but not isotype-matched control antibody, induced a prothrombotic state in the mice by inducing tissue factor expression upon circulating monocytes, resulting in thrombus formation at the site of laser-induced endothelial injury. This diathesis was almost completely ameliorated by DHMEQ treatment. Conclusions: Inhibition of the NF-κB pathway is a promising strategy for the development of a novel treatment for APS. Implication for health policy/practice/research/medical education:APS causes thrombosis in any organs including the kidney, presenting acute or chronic renal failure, hypertension, and proteinuria. Besides antiplatelet and anticoagulant agents which do not completely prevent the recurrence of the thrombotic events in spite of the risk of bleeding tendency, the development of a novel therapeutic strategy using NF-κB inhibitors appears to be promising.Please cite this paper as: Nishimura M, Nii T, Trimova G, Miura S, Umezawa K, Ushiyama A, Kubota T.The NF-κB specific inhibitor DHMEQ prevents thrombus formation in a mouse model of antiphospholipid syndrome
We have shown that genistein inhibits the growth of adult T-cell leukemia (ATL) cells in vitro and in vivo, and this leads to pronounced G2/M arrest. This report shows that genistein induces apoptotic death in ATL cells. Although the pan-caspase inhibitor, Z-VAD-fmk, did not inhibit genistein-induced apoptosis, release of apoptosis-inducing factor (AIF) into the cytosol occurred. Poly-ADP ribose polymerase inhibition also abrogated genistein-induced apoptosis. Genistein decreased nuclear p65 translocation and IκBα phosphorylation, and downregulated the anti-apoptotic proteins, XIAP, cIAP and survivin, NF-κB-responsive gene products. Thus, genistein is a promising agent for ATL that induces caspase-independent apoptosis through inhibition of the NF-κB pathway.
Here, we examined the effect of tocotrienols (T3) on the growth of adult T-cell leukemia (ATL) cells. All three forms (β-, γ-, and δ-T3) inhibited cell proliferation in a dose-dependent manner; δ-T3 showed the strongest growth-inhibitory effect. δ-T3 increased the G1, G2/M, and subG1 populations and induced internucleosomal DNA fragmentation. δ-T3 treatment also increased the levels of cleaved caspase-3, -6, -7, -9, and poly-ADP ribose polymerase (PARP), and this was accompanied by downregulation of Bcl-2, Bcl-xL, and XIAP. Moreover, δ-T3 decreased nuclear p65 NF-κB levels, indicating downregulation of NF-κB activity. This cytotoxic effect of δ-T3 was abrogated by squalene (SQL) but not mevalonate (MVL), farnesyl diphosphate (FPP), geranylgeranyl diphosphate (GGPP), or cholesterol (CL). δ-T3 decreased intracellular SQL levels, and inhibition of de novo cholesterol synthesis did not affect the action of SQL. Furthermore, δ-T3 significantly decreased farnesyl-diphosphate farnesyltransferase 1 (FDFT1) expression. Taken together, it is evident that δ-T3, due to its ability to potently induce apoptosis via the depletion of intracellular SQL, shows the potential to be considered a therapeutic agent in patients with ATL.
Silva et al 1 have demonstrated the absence of a midpregnancy fall in diastolic blood pressure (BP) in women with a low educational level. Their previous articles also showed that maternal socioeconomic status is associated with a risk of gestational hypertension and preeclampsia. 2 However, they did not demonstrate a midpregnancy fall in systolic BP in all of the educational subgroups. This might be attributable to few measurement points being obtained during pregnancy or to some other confounding factors.Ambulatory BP measurement is one way to resolve inferior results from isolated BP measurements. Hermida et al 3 measured ambulatory BP in 403 pregnant women for 48 consecutive hours every 4 weeks from the first obstetric visit until delivery. They found that BP steadily decreased up to 20 weeks of pregnancy and increased up to the day of delivery. Conversely, in women with gestational hypertension and preeclampsia, BP remained stable until the 22nd week of gestation and then linearly increased for the remainder of the pregnancy.The American Heart Association, American Society of Hypertension, and Preventive Cardiovascular Nurses Association scientific statements indicate that home BP monitoring might overcome many of the limitations of traditional office BP measurements, and it is less expensive and easier to perform than ambulatory BP monitoring. 4 Home BP measurements are theoretically ideal for monitoring changes in BP during pregnancy, because home measurement is the optimal way to record multiple readings taken at the same time of day over prolonged periods. 4 We recently conducted a prospective observational study (Babies and Their Parents' Longitudinal Observation in Suzuki Memorial Hospital on Intrauterine Period Study), in which we averaged 100 BP measurement points during pregnancy in 101 normotensive pregnant women. 5 We found that BP during pregnancy is associated with both seasonal effects and gestational age. We found that the gestational week when BP reached the nadir differed according to the season in which delivery was predicted.As Silva et al 1 commented in their Discussion, the absence of a midpregnancy fall in BP is reportedly associated with preeclampsia, according to a population study, and may be a sign of latent endothelial dysfunction. However, the amplitude of the fall in midpregnancy BP seems smaller than that of circadian, daily, and seasonal BP variations. Home BP measurement would be a good tool with which to detect such small changes in BP during early pregnancy.
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