Vasorelaxant activity of caffeic acid derivatives from Cichorium intybus and Equisetum arvense

The vasorelaxant activities of chicoric acid (Compound 1) from Cichorium intybus and dicaffeoyl-meso-tartaric acid (Compound 2) from Equisetum arvense L. in isolated rat aorta strips were studied. Compound 1 is a diester composed of (S,S)-tartaric acid and caffeic acid, and 2 is composed of its meso type. Both 1 and 2 showed slow relaxation activity against norepinephrine (NE)-induced contraction of rat aorta with/without endothelium. These compounds did not affect contraction induced by a high concentration of potassium (60 mM K+), while they inhibited NE-induced vasocontraction in the presence of nicardipine. These results show that the inhibition by 1 and 2 of NE-induced vasocontraction is due to a decrease in calcium influx from the extracellular space caused by NE. In addition, dicaffeoyl tartaric acids showed vasorelaxant activity, regardless of their stereochemistry.     

Involvement of H2O2 and O2- in the cytotoxicity of N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), a novel insect-derived anti-tumor compound

We investigated the mechanism underlying the cytotoxicity of N-β-alanyl-5-S-glutathionyl-3, 4-dihydroxyphenylalanine (5-S-GAD) toward MDA-MB-435S, a human breast cancer cell line sensitive to 5-S-GAD. We found that the addition of either catalase or superoxide dismutase (SOD) to a culture medium of MDA-MB-435S cells almost completely abolished the cytotoxic effect of 5-S-GAD, indicating that both hydrogen peroxide (H₂O₂) and the superoxide anion (O₂^-) are involved in the cytotoxic action of 5-S-GAD. We compared the catalase and SOD levels in MDA-MB-435S and T47D, a cell line resistant to 5-S-GAD, and found that the levels in resistant cells are higher than those in sensitive cells. We concluded that the levels of these enzymes are crucial determinants of the sensitivity or insensitivity of cells to 5-S-GAD. (Cancer Sci 2003; 94: 400–404)     

Ethnic difference in serology of Helicobacter pylori CagA between Japanese and non-Japanese Brazilians for non-cardia gastric cancer

The usefulness of serology against CagA of Helicobacter pylori as a biomarker to identify high-risk individuals for non-cardia gastric cancer (ncGC) remains unclear among several ethnic populations with a high prevalence of cagA-positive strains. We investigated ethnic differences of CagA serology in two sets of case-control subjects, Japanese-Brazilians (JB) and non-Japanese Brazilians (NJB). We performed a cross-sectional comparison of IgG antibody titers to CagA (CagA-Ab) and the combination of CagA-Ab with conventional surface antigen (Hp-Ab) in 80 JB and 178 NJB ncGC patients and their controls (160 JB and 178 NJB). The level of CagA-Ab titer in cancer cases was significantly higher in NJB than in JB. The strength of the association between CagA-Ab seropositivity (+) (>10 U/ml) and ncGC was almost 2-fold higher in NJB than in JB [odds ratio (OR) (95% confidence interval), 4.5 (2.6–7.8) and 2.1 (1.2–3.6), respectively]. However, in both JB and NJB, the OR was highest in CagA-Ab(+) subjects with low titer (10–29 U/ml), and decreased inversely with elevating CagA-Ab titer. In addition, the serological status of CagA-Ab(+) and Hp-Ab(-) showed a similar close association with ncGC between JB and NJB [5.4 (1.9–15.3) and 5.4 (2.0–15.0), respectively]. These results suggest that although the roles of CagA in the carcinogenic process of ncGC might be different between JB and NJB, the CagA-Ab could be a useful marker for ncGC, independently of ethnicity, particularly in high-risk individuals with the serological status of CagA-Ab(+) with low IgG titer or combined with Hp-Ab(-). (Cancer Sci 2003; 94: 64–69)     

Effects of ketamine on voltage-dependent calcium currents and membrane potentials in single bullfrog atrial cells

Purpose. This study was undertaken to assess the effect of ketamine on L-type calcium channel current (I_Ca) and membrane action potential in the bullfrog single atrial myocyte. Methods. Bullfrog single atrial myocytes were prepared by enzymatic dispersion. Whole-cell voltage-clamp technique and current clamp technique were used to monitor I_Ca, membrane resting potential, and action potential. Results. Ketamine (10⁻⁵–10⁻³ M) showed dose-dependent inhibition of I_Ca in a reversible manner. The 50% inhibitory concentration (IC₅₀) of ketamine on I_Ca was estimated to be 0.92 × 10⁻⁵ M. Use-dependent block of I_Ca was not observed. The resting membrane potential was depolarized at a high concentration (10⁻⁴ M) of ketamine. Reduction of the plateau phase and prolonged duration of the action potential were observed in the presence of a high concentration of ketamine (10⁻⁴ M). Conclusion. Ketamine has an inhibitory effect on I_Ca in the bullfrog single atrial myocyte, and a high dose (10⁻⁴ M) of ketamine prolonges the duration of the action potential. The mechanism of inhibition of I_Ca seems to be a direct effect on the L-type calcium channel, not like an open channel blocker. Received: October 2, 2000 / Accepted: February 19, 2001     

Single Ingestion of Trehalose Enhances Prolonged Exercise Performance by Effective Use of Glucose and Lipid in Healthy Men

Trehalose increases blood glucose levels slowly and induces a slight insulin response. The present study aimed to study the effect of trehalose on prolonged exercise performance. The participants were 12 healthy men (age: 21.3 ± 0.9 y). After an overnight fast (12 h), they first exercised with a constant load (intensity: 40% V˙O₂peak) for 60 min using a bicycle ergometer. They continued to exercise with a constant load (40% V˙O₂peak) for 30 min between four sets of the 30-s Wingate test. After the 1st set, each participant ingested 500 mL water (control), 8% glucose, or 8% trehalose in three trials. These three trials were at least one week apart and were conducted in a double-blind and randomized crossover manner. Blood was collected for seven biochemical parameters at 12 time points during the experiment. The area under the curve of adrenaline after ingestion of trehalose was significantly lower than that for water and tended to be lower than that for glucose in the later stage of the exercise. Lower secretion of adrenaline after a single dose of 8% trehalose during prolonged exercise reflected the preservation of carbohydrates in the body in the later stage of the exercise. In conclusion, a single ingestion of trehalose helped to maintain prolonged exercise performance.     

ULTRASTRUCTURAL STUDY OF LYMPHOCYTIC INTERACTION WITH HEPATOCYTES AND ENDOTHELIAL CELLS IN ACUTE NON-A, NON-B HEPATITIS

In the liver biopsy specimens of all six patients with acute non-A, non-B hepatitis, the lymphocytic interaction with hepatocytes and sinusoidal endothelial cells was observed by electron microscopic study. Lymphocytes were in a close contact with damaged hepatocytes and interrupted endothelial cells, and the microvilli on the surface of these damaged hepatocytes were degenerated and lost. These findings pointed out the possibility that the lymphocyte may play one of the important roles in hepatocytic damage and endothelial cell damage in acute non-A, non-B hepatitis.     

A Case of Sacral Parasite

Abstract A case of sacral parasite is presented. A parasitic body with an incomplete lower limb was attached to the sacrococcygeal region of a female newborn at birth. The twins were easily separated by operation two days after birth. The parasite contained well developed small and/or large intestines, a multilocular cyst and a unilocular cyst. Histologically, the wall of the multilocular cyst consisted of tissues of three germ layers, such as central and peripheral nervous tissues, mature and immature intestine, pancreatic tissue, bronchial cysts, connective tissue, etc. The thick wall of the unilocular cyst consisted of central nervous tissue and connective tissue. The degree of differentiation of these tissues varied considerably. The parasite revealed no organ communication with the autosite. Since the operation, her growth and development have been favorable and no other abnormalities have been found.     

Age-specific relationship between blood pressure and the risk of total and cardiovascular mortality in Japanese men and women.

To examine the impact of age on the relationship between blood pressure (BP) levels and each of cardiovascular disease mortality and all-cause mortality, a total of 30,226 men and 58,798 women aged 40-79 years who had no history of stroke or heart disease underwent health checkups in Ibaraki-ken, Japan, in 1993 and were followed through 2002. Risk ratios for mortality by BP category based on the 1999 WHO-ISH guidelines were calculated by age subgroups (40-59 years, 60-79 years) using a Cox proportional hazards model. Compared with optimal BP levels, the multivariate risk ratios of cardiovascular mortality for stage 2 or 3 hypertension were 5.99 (95% confidence interval: 2.13-16.8) in middle-aged men and 4.09 (1.70-9.85) in middle-aged women. These excess cardiovascular mortality risks were larger in the 40-59 years age group than in the 60-79 years age group for both genders (p for interaction = 0.01 for both). In men, the population attributable risk percents of cardiovascular mortality were 60% for younger men and 28% for older men, while for women they were 15% for younger women and 7% for older women. Weaker but significant excess risks of total mortality were observed for stage 2 or 3 hypertension in men of both age groups and in the older age group for women. The impact of BP on the risk of cardiovascular mortality was larger among middle-aged persons than among the elderly in both men and women. Our findings indicate the importance of BP control to prevent cardiovascular disease among middle-aged individuals.