Role of Thrombin in Soluble Thrombomodulin-Induced Suppression of Peripheral HMGB1-Mediated Allodynia in Mice

High mobility group box 1 (HMGB1), a nuclear protein, once released into the extracellular space under pathological conditions, plays a pronociceptive role in redox-dependent distinct active forms, all-thiol HMGB1 (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), that accelerate nociception through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor 4 (TLR4), respectively. Thrombomodulin (TM), an endothelial membrane protein, and soluble TM, known as TMα, promote thrombin-mediated activation of protein C and also sequester HMGB1, which might facilitate thrombin degradation of HMGB1. The present study aimed at clarifying the role of thrombin in TMα-induced suppression of peripheral HMGB1-dependent allodynia in mice. Thrombin-induced degradation of at-HMGB1 and ds-HMGB1 was accelerated by TMα in vitro. Intraplantar (i.pl.) injection of bovine thymus-derived HMGB1 in an unknown redox state, at-HMGB1, ds-HMGB1 or lipopolysaccharide (LPS), known to cause HMGB1 secretion, produced long-lasting mechanical allodynia in mice, as assessed by von Frey test. TMα, when preadministered i.pl., prevented the allodynia caused by bovine thymus-derived HMGB1, at-HMGB1, ds-HMGB1 or LPS, in a dose-dependent manner. The TMα-induced suppression of the allodynia following i.pl. at-HMGB1, ds-HMGB1 or LPS was abolished by systemic preadministration of argatroban, a thrombin-inhibiting agent, and accelerated by i.pl. co-administered thrombin. Our data clearly indicate that TMα is capable of promoting the thrombin-induced degradation of both at-HMGB1 and ds-HMGB1, and suppresses the allodynia caused by either HMGB1 in a thrombin-dependent manner. Considering the emerging role of HMGB1 in distinct pathological pain models, the present study suggests the therapeutic usefulness of TMα for treatment of intractable and/or persistent pain.     

Antimicrobial action of natural substances on oral bacteria

The antimicrobial action of natural substances was investigated in vitro against oral bacteria including Streptococcus sp., Actinomyces sp., Actinobacillus sp., Bacteroides sp., Capnocytophaga sp., Eikenella sp., Fusobacterium sp. and Propionibacterium sp. Among the natural substances tested, hinokitiol was the most inhibitory to oral bacteria. Cinnamon bark oil, papua-mace extracts, and clove bud oil in spice extracts were also inhibitory against many oral bacteria. Egg white lysozyme exhibited antimicrobial action against the periodontitis associated bacteria.     

Effect of xylitol gum on the level of oral mutans streptococci of preschoolers: block-randomised trial

Objectives: To assess the influence of xylitol chewing gum consumption on mutans streptococci level of 3–4 years old Japanese preschoolers. Methods: 248 participants were examined regarding caries‐related factors at baseline and were followed up at 6, 9, and 12 months after the baseline: assessors were blinded, subjects were open labelled and blocked parallel randomised; 142 were selected to use xylitol gum for 3 months (from months 6 to 9) and 106 were controls. Results: 161 participants were analysed (xylitol n = 76, control n = 85). Nineteen caries‐related variables, including xylitol gum consumption, were analysed for any association with the main outcome, plaque mutans streptococci scores development within the intervention period, by logistic regression. Six showed statistically significant associations by univariate analysis (P < 0.05). However, only xylitol gum consumption remained a significant negative association (P < 0.05) by multiple analyses. Interestingly, over 10% xylitol group children experienced diarrhoea, which was larger than previous investigations. Conclusion: Xylitol gum is effective in avoiding increased plaque mutans streptococci in young children.     

Gender differences in prognosis after esophagectomy for esophageal cancer

Purpose

The purpose of this study was to clarify the gender differences in the prognosis, as well as mortality and morbidity, of patients who have undergone esophagectomy for esophageal cancer.

Methods

The clinical results of esophagectomy were compared between 975 male and 156 female patients with esophageal cancer.

Results

The male to female ratios of cervical and thoracic esophageal cancer were 1.87 and 7.38, respectively (P < 0.01). The incidence of preoperative comorbidities was 32.4 and 17.4 %, respectively, and the rates of both tobacco and alcohol abuse were significantly lower in the females than in the males. The mortality rate was lower in the females (3.8 %) than in the males (5.7 %), although the differences were not significant. The overall survival was significantly better in the female than in the male patients (P = 0.039). The 5- and 10-year overall survival rates were 32.6 and 20.5 % in the males and 39.5 and 32.5 % in the females, respectively. A multivariate analysis revealed gender to be an independent prognostic factor. However, no significant differences were recognized in disease-specific survival.

Conclusions

These results suggest that the prognosis of females with esophageal cancer is better than that of males after esophagectomy, most likely due to multiple clinical factors, such as a more favorable lifestyle and general status.     

A case of thoracic esophageal cancer with an unusual type of duplicated inferior vena cava

We describe here a thoracic esophageal cancer with an unusual type of duplicated inferior vena cava. A 58-year-old man was referred to our hospital because a tumor in his lower esophagus had been identified by endoscopy and radiology. Computed tomography scans showed an unusual type of duplicated inferior vena cava characterized by both common iliac veins flowing back into the left-sided inferior vena cava, which drained into the azygos vein, whereas the right-sided one had no drainage. Esophagectomy was performed 3 weeks later after preoperative chemotherapy. Because the patient could have developed thrombosis of the left-sided inferior vena cava and severe hypotension caused by decreased venous return to the heart if the azygos vein had been severed, the azygos vein was preserved. Thus, when performing surgery for thoracic esophageal cancer, the surgeon should check for a duplicated inferior vena cava and preserve the azygos vein if necessary.