Brachial-ankle pulse wave velocity and symptomatic cerebral infarction in patients with type 2 diabetes: a cross-sectional study

BACKGROUND: Recently a new automatic device that measures brachial-ankle pulse wave velocity using an oscillometric method has been developed. However, the practical significance of brachial-ankle pulse wave velocity measurement remains uncertain. The purpose of this study was to examine the association between brachial-ankle pulse wave velocity and symptomatic cerebral infarction in patients with type 2 diabetes. METHODS: One thousand sixty six patients with type 2 diabetes were studied cross-sectionally. Measurements of brachial-ankle pulse wave velocity were made using the automatic device. Logistic regression analysis was used to calculate the odds ratio for cerebral infarction. RESULTS: The presence of symptomatic cerebral infarction was confirmed in 86 patients. In these patients brachial-ankle pulse wave velocity was found to be significantly higher than in patients without cerebral infarction (18.94 ± 4.95 versus 16.46 ± 3.62 m/s, p < 0.01). The association between brachial-ankle pulse wave velocity and cerebral infarction remained significant after adjustment for traditional risk factors. There was an increasing odds ratio for each tertile of brachial-ankle pulse wave velocity, from the second tertile (odds ratio, 2.28; 95% confidence interval, 1.05 to 4.94), to the third (odds ratio, 2.53; 95% confidence interval, 1.09 to 5.86). CONCLUSION: Overall, we conclude that an increase in brachial-ankle pulse wave velocity is associated with symptomatic cerebral infarction in patients with type 2 diabetes

Effect of TU-100 on Peyer's patches in a bacterial translocation rat model

Background: Daikenchuto (TU-100), a Japanese herbal medicine, is widely used for various gastrointestinal diseases. We have previously reported that TU-100 suppresses CPT-11-induced bacterial translocation (BT) by maintaining the diversity of the microbiome. In this study we show that TU-100 modulates the immune response during BT by inducing PD-1 expression in Peyer's patches. Methods: Eighteen male Wistar rats were divided into four groups: a control group; a control + TU-100 group, given TU-100 1000 mg/kg orally for 5 d; a BT group, given CPT-11 250 mg/kg intra-peritoneal for 2 d; and a TU-100 group, given TU-100 1000 mg/kg orally for 5 d with CPT-11 250 mg/kg intra-peritoneal on days 4 and 5. Results: The size of Peyer's patch was significantly bigger in the BT group compared to the control group (9.0 × 104 µm2 vs 29.4 × 104 µm2, P < .05), but improved in the TU-100 group (15.4 × 104 µm2, P < .005). TU-100 significantly induced PD-1 expression in Peyer's patch compared to the control group and the BT group (control vs BT vs TU-100 = 4.3 ± 4.9 vs 5.1 ± 10.3 vs 17.9 ± 17.8). The CD4+ cells were increased in the BT group (P < .05) compared to the control group but decreased in the TU-100 group. The Foxp3+ cells were increased in the BT group compared to the control group (P < .05), and further increased in the TU-100 group compared to the BT group. CPT-11 significantly increased TLR4, NF-κβ, TNF-α mRNA expressions in the BT group. TU-100 cotreatment significantly reversed these mRNA expressions. Conclusion: TU-100 may have a protective effect against BT through PD-1 expression in Peyer's patch

Novel treatment of chronic graft-versus-host disease in mice using the ER stress reducer 4-phenylbutyric acid

Chronic graft-versus-host disease (cGVHD) is a notorious complication of allogeneic hematopoietic stem cell transplantation and causes disabling systemic inflammation and fibrosis. In this novel study, we focused on a relationship between endoplasmic reticulum (ER) stress and cGVHD, and aimed to create effective treatment of cGVHD. A series of experiments were conducted using a mouse model of cGVHD. Our data suggested (1) that ER stress was elevated in organs affected by cGVHD and (2) that 4-phenylbutyric acid (PBA) could reduce cGVHD-induced ER stress and thereby alleviate systemic inflammation and fibrosis. Because fibroblasts are thought to be implicated in cGVHD-elicited fibrosis and because macrophages are reported to play a role in the development of cGVHD, we investigated cGVHD-triggered ER stress in fibroblasts and macrophages. Our investigation demonstrated (1) that indicators for ER stress and activation markers for fibroblasts were elevated in cGVHD-affected lacrimal gland fibroblasts and (2) that they could be reduced by PBA. Our work also indicated that splenic macrophages from PBA-dosed mice exhibited the lower levels of ER stress and M2 macrophage markers than those from cGVHD-affected mice. Collectively, this study suggests that the reduction of ER stress utilizing PBA can be a clinically translatable method to treat systemic cGVHD