Lipoteichoic acid may affect the pathogenesis of PBC-like bile duct damage and might be involved in systemic multifocal epithelial inflammations in chronic colitis-harboring TCRα−/−×AIM−/− mice

Background: Chronic colitis-harboring TCRα^{? / ?} × AIM^{? / ?} mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα^{? / ?} × AIM^{? / ?} mice.

Methods: Thirteen female TCRα^{? / ?} × AIM^{? / ?} mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out.

Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation.

Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα^{? / ?} × AIM^{? / ?} mice.     

Imaging of muscle activity-induced morphometric changes in fibril network of myofascia by two-photon microscopy

Myofascia, deep fascia enveloping skeletal muscles, consists of abundant collagen and elastin fibres that play a key role in the transmission of muscular forces. However, understanding of biomechanical dynamics in myofascia remains very limited due to less quantitative and relevant approaches for in vivo examination. The purpose of this study was to evaluate the myofascial fibril structure by means of a quantitative approach using two-photon microscopy (TPM) imaging in combination with intravital staining of Evans blue dye (EBD), a far-red fluorescence dye, which potentially labels elastin. With focus on myofascia of the tibial anterior (TA) muscle, the fibril structure intravitally stained with EBD was observed at the depth level of collagen fibrous membrane above the muscle belly. The EBD-labelled fibril structure and orientation in myofascia indicated biomechanical responses to muscle activity and ageing. The orientation histograms of EBD-labelled fibrils were significantly modified depending upon the intensity of muscle activity and ageing. Moreover, the density of EBD-labelled fibrils in myofascia decreased with habitual exercise but increased with muscle immobilization or ageing. In particular, the diameter of EBD-labelled fibrils in aged mice was significantly higher. The orientation histograms of EBD-labelled fibrils after habitual exercise, muscle immobilization and ageing showed significant differences compared to control. Indeed, the histograms in bilateral TA myofascia of exercise mice made simple waveforms without multiple sharp peaks, whilst muscular immobilization or ageing significantly shifted a histogram with sustaining multiple sharp peaks. Therefore, the dynamics of fibre network with EBD fluorescence in response to the biomechanical environment possibly indicate functional tissue adaptation in myofascia. Furthermore, on the basis of the knowledge that neutrophil recruitment occurs locally in working muscles, we suggested the unique reconstruction mechanism involving neutrophilic elastase in the myofascial fibril structure. In addition to the elastolytic susceptibility of EBD-labelled fibrils, distinct immunoreactivities and activities of neutrophil elastase in the myofascia were observed after electric pulse stimulation-induced muscle contraction for 15 min. Our findings of EBD-labelled fibril dynamics in myofascia through quantitative approach using TPM imaging and intravital fluorescence labelling potentially brings new insights to examine muscle physiology and pathology.     

Evaluation of bioartificial renal tubule device prepared with human renal proximal tubular epithelial cells cultured in serum-free medium

Bioartificial renal tubule devices (BTD) use cell therapy to improve conditions commonly observed in recipients of artificial kidneys for treatment of kidney diseases. We previously reported significant improvement of the condition of acute kidney injury (AKI) animals after treatment with BTD prepared with lifespan-extended human renal proximal tubular cells (hRPTEC). However, a major obstacle to use of BTD for patients is their biological safety, because hRPTEC are cultured in medium containing fetal calf serum. To establish the biological safety of BTD, we prepared BTD with lifespan-extended hRPTEC cultured in a newly developed serum-free medium and compared these with BTD prepared with hRPTEC cultured in serum-containing conventional medium. Lifespan-extended hRPTEC cultured in serum-free medium (hRPTEC-SFM) can proliferate similar to hRPTEC cultured in serum-containing conventional medium (hRPTEC-CM). Comparison of leakage and of reabsorption of small molecules for BTD prepared with hRPTEC-SFM (BTD-SFM) with those for our previous BTD prepared with hRPTEC-CM (BTD-CM) showed transportation in these two types of BTD was almost identical. When AKI goats were treated with BTD-SFM for 26 h, increase of survival time and reduction of cytokine expression in blood cells were almost same as for AKI goats treated with BTD-CM. Quantification of the expression of some genes of hRPTEC in BTD revealed significant changes during BTD treatment for AKI goats. In conclusion, lifespan-extended hRPTEC-SFM work as well as hRPTEC-CM, and the biological safety of BTD for patients could be elevated without loss of function by preparation from hRPTEC-SFM.     

Does oral dryness influence pressure pain sensitivity in the oral mucosa of removable denture wearers?

Clinical Oral Investigations - This study aimed to determine if oral dryness is associated with oral pain sensitivity in removable denture wearers. The pressure pain threshold (PPT) in the mucosa...     

Development of 18 novel polymorphic microsatellite markers for the mysid crustacean Mesopodopsis orientalis

Conservation Genetics Resources - We have developed microsatellite DNA markers for Mesopodopsis orientalis (Tattersall 1908), a widely distributed mysid crustacean in shallow waters of the coastal...     

Clustered features of the metabolic syndrome and the risk for increased aortic pulse wave velocity in middle-aged Japanese men

The association between different features of the metabolic syndrome (MS) (obesity, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol level, hypertriglyceridemia, high fasting plasma glucose level, and hyperuricemia) and the risk for increased aortic pulse wave velocity (PWV) of > or = 8.0 m/sec was examined in 2431 Japanese men aged 35 to 54 years who were not taking antihypertensive medication. After controlling for age, cigarette smoking, and alcohol intake, the odds ratios for increased aortic PWV in subjects with 1, 2, 3, and > or = 4 features of the MS, compared with those without features of the MS, were 1.35 (95% CI, 0.86 to 2.11), 1.90 (95% CI, 1.18 to 3.06), 1.57 (95% CI, 0.89 to 2.76), and 2.38 (95% CI, 1.26 to 4.49), respectively (p for trend = 0.003). A 9-year longitudinal study was also performed to prospectively examine the association between clustered features of the MS and the development of increased aortic PWV in 2073 men without aortic stiffness with a PWV < 8.0 m/sec and without antihypertensive medication during the follow-up period. The multivariate-adjusted hazard ratios for the incidence of increased aortic PWV in subjects with 1, 2, 3, and > or = 4 features of the MS, compared with those without features of the MS, were 1.39 (95% CI, 1.10 to 1.77), 1.46 (95% CI, 1.1 1 to 1.92), 1.75 (95% CI, 1.27 to 2.40), and 2.22 (95% CI, 1.52 to 3.25), respectively (p for trend < 0.001). These results suggest that clustered features of the MS are closely associated with the risk for increased aortic PWV in middle-aged Japanese men.