The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.

No abstract

The volatile fractions of three famous Chinese green tea cultivar infusions (Longjing, Maofeng, and Biluochun) were prepared by a combination of the adsorptive column method and the SAFE techniques. The aroma extract dilution analysis (AEDA) applied to the volatile fractions revealed 58 odor-active peaks with flavor dilution (FD) factors between 4(1) and 4(7). Forty-six of the odorants, which included six odorants that have not been reported in the literature in Chinese green tea (2-isopropyl-3-methoxypyrazine, 2-ethenyl-3,5-dimethylpyrazine, cis-4,5-epoxy-(E)-2-decenal, 4-ethylguaiacol, (E)-isoeugenol, and 3-phenylpropionic acid), were identified or tentatively identified by GC-MS and GC-O. Among the perceived odorants, 4-hydroxy-2,5-dimethyl-3(2H)-furanone, 3-hydroxy-4,5-dimethyl-2(5H)-furanone, coumarin, vanillin, geraniol, (E)-isoeugenol, and 2-methoxyphenol showed high FD factors in all of the cultivars, irrespective of the cultivar or harvesting season, suggesting that these seven odorants are essential for the aroma of Chinese green tea. On the other hand, the contents of the odorants, FD factors of which were uneven between the cultivars, were suggested to influence the characteristic aroma of each cultivar. In addition, the formation mechanism of (E)-isoeugenol, one of the odorants which have not been reported in the literature with a high FD factor common to all the cultivars, was investigated, and it was suggested that the (E)-isoeugenol content of the tea products has a close correlation with the manufacturing process of the tea leaves.

Blockage of hepatic autophagic degradation system occurs in obesity and is associated with the development of nonalcoholic fatty liver disease. However, the mechanism of this blockage remains unclear. We found a high-fat diet induced accumulation of autophagosomes in the mice livers. However, autophagy substrates such as p62 and ubiquitinated proteins also accumulated in the livers in this model. These findings indicate the possibility that a high-fat diet impairs autophagic flux in the liver. Then, to assess the autophagic flux in more detail, we performed analyses of autophagic flux in cultured hepatocytes exposed to monounsaturated fatty acids (FAs) or saturated FAs (SFAs). SFAs but not monounsaturated FAs suppressed degradation of contents in the autophagosomes. We analyzed each stage of the autophagy pathway (ie, autophagosome formation, autophagosome-lysosome fusion, lysosomal degradation) in cultured hepatocytes treated with monounsaturated FAs or SFAs and found that SFAs impaired autophagosome-lysosome fusion. This impairment occurred in an endoplasmic reticulum stress-dependent manner. Moreover, ubiquitin and p62-positive inclusions observed in high-fat diet-fed mice livers and SFA-treated cells were sequestered within autophagosomes. We also found that SFA-induced accumulation of Ser351-phosphorylated p62, which is indispensable for selective autophagy, further increased on administration of a lysosomal proteinase inhibitor. Although lipid-induced endoplasmic reticulum stress interferes with the autophagosome-lysosome fusion, selective autophagic sequestration of aggregated proteins is not inhibited.

Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury.

Food allergies represent an important medical problem throughout the developed world. The epithelium of the digestive tract is an important area of contact between the organism and its external environment. Accordingly, we must reconsider the transport of intestinal transepithelial macromolecules, including food allergens, in vivo. The intestinal epithelium of the neonatal-suckling rat is a useful model system for studies into endocytosis and transcytosis. Macromolecules and food allergens can be transferred intact with maternal immunoglobulins across the absorptive cells of duodenum and jejunum during the neonatal-suckling period. This review summarizes these observations as well as our recent molecular morphological studies.

These results indicate that acid leakage through the cholesteatoma epithelium probably participates in the resorption of the underlying bone structure. The increased permeability of the cholesteatoma epithelium may be explained by a decrease in filaggrin expression.

The odorants contributing to the characteristic aroma of matcha were investigated by analysis of the headspace samples and the volatile fractions prepared by a combination of solvent extraction and the SAFE techniques using three matcha powders of different grades (high, medium, and low). Gas chromatography-olfactometry of the headspace samples (GCO-H) and aroma extract dilution analysis (AEDA) applied to the volatile fractions revealed 16 (FD factor ≥1) and 39 (FD factor ≥4) odor-active peaks, respectively. Among them, 14 and 37 of the odorants, most of which were newly detected in matcha, were identified or tentatively identified by GC-MS and GC-O, respectively. By comparing the perceived odorants of three matcha powders, it was revealed that eight compounds with sweet, green, metallic, and floral notes showed high flavor dilution (FD) factors irrespective of the grades. In addition, some odorants were suggested to influence the characteristic aroma of each grade. Furthermore, trans-4,5-epoxy-(E)-2-decenal, one of the potent odorants of matcha, was revealed to exist as a racemic mixture in matcha. This result suggested that trans-4,5-epoxy-(E)-2-decenal is formed by a nonenzymatic reaction in matcha, different from that in black tea, and that the unique manufacturing process of matcha has a close connection with its formation.