The lectin‐like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice

Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin-like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion-induced liver damage in a dose-dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage

Differential Reactivity of Attention Biases in Patients with Social Anxiety Disorder

nformation-processing biases based on cognitive and cognitive behavioral models have been reported in social anxiety disorder (SAD). One such bias is the attention bias, or selectively attending to threat stimuli. This bias has been associated in anxiety with maintenance and worsening of SAD symptoms. The objective of the present study was to examine, compare, and clarify differences in attention biases to language stimuli between SAD patients and healthy people. Results indicated, no differences between the two groups, but differences were seen in the attention bias score among SAD patients. This suggests that there is an increased threat effect among SAD patients triggered by their attention bias toward social threat stimul

Time series changes in pseudo-R2 values regarding maximum glomerular diameter and the Oxford MEST-C score in patients with IgA nephropathy: A long-term follow-up study.

There is no effectual pathological factor to predict the long-term renal prognosis of IgA nephropathy. Glomerular hypertrophy plays a crucial role in kidney disease outcomes in both experimental models and humans. This study aimed to 1) confirm the long-term prognostic significance of a maximal glomerular diameter (Max GD) ≥ 242.3 μm, 2) test a renal prognosis prediction model adding Max GD ≥ 242.3 μm to the Oxford classification (MEST-C), and 3) examine the time series changes in the long-term renal prognosis of patients with IgA nephropathy. The study included 43 patients diagnosed with IgA nephropathy from 1993 to 1998 at Kameda General Hospital. Renal prognosis with the endpoint of a 50% reduction in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease requiring dialysis was examined using logistic regression analysis, Cox regression analysis, and the Kaplan-Meier method. Pathological evaluation was performed using MEST-C and Max GD, and the validity of the prediction model was evaluated. Patients with Max GD ≥ 242.3 μm had significantly poor renal prognosis with multivariate Cox analysis (P = 0.0293). The results of the Kaplan-Meier analysis showed that kidney survival rates in the high-Max GD group were significantly lower than those in the low-Max GD group (log rank, P = 0.0043), which was confirmed in propensity score-matched models (log rank, P = 0.0426). Adding Max GD ≥ 242.3 μm to MEST-C improved diagnostic power of the renal prognosis prediction model by renal pathology tissue examination (R2: 3.3 to 14.5%, AICc: 71.8 to 68.0, C statistic: 0.657 to 0.772). We confirm that glomerular hypertrophy is useful as a long-term renal prognostic factor