Pharmacological effectiveness of the active phytochemicals contained in foods and herbs.

Food ingestions generally regulate many physiological functions to maintain a healthy life. Furthermore, herbal medicine is prescribed for the prevention and the treatment of various diseases. There are not a few herbal medicine-derived drugs (phytochemicals) clinically using now. The phytochemicals such as digitalis, curare, morphine, quinidine, atropine, and so on are so much important drugs for clinical treatments. Herbal medicine and foods are composed of many constituents. The pharmacological actions that contain phytochemicals are exerted each by each mediated through different receptors, ionic channels, and cellular signal transductions. Thus, they produce multiple pharmacological and pathophysiological functions mediated by the complex interactions with lots of the ingredients.

Pharmacological characteristics of Kampo medicine as a mixture of constituents and ingredients.

Herbal medicine in Japan is termed as Kampo medicine, which is derived from traditional Chinese medicine. Shakuyakukanzoto (Shao-Yao-Gan-Cao-Tang) as a kind of Kampo formulations is composed of just two components; Paeoniae Radix and Glycyrrhizae Radix, which produced marked relaxation of intestinal tract. Mokuboito (Mu-Fang-Ji-Tang) inhibited cardiac ionic channel currents, and as a mixture also produced great vasodilatation. Sinomenine (a main ingredient of Mokuboito) as a single compound also caused the vasodilatation, but decreased it along with ageing. Gypsum containing in Mokuboito and Chotosan (Diao-Teng-San) caused more marked effects, as compared with those without Gypsum. On the other hand, Rokumigan (Liu-Wei-Wan), Hachimijiogan (Ba-Wei-Di-Huang-Wan) and Goshajinkigan (Niu-Che-Shen-Qi-Wan) increase in order the number of contained ingredients. The formulations with more herbs (ingredients) produced much more effective actions on rat aorta, presumably due to compensation of the decline of pharmacological sensitivity with ageing. Thus, there are some important differences between single chemical drugs and mixture drugs with many ingredients. The effects of Kampo medicine (mixture) are never just a sum of each effect induced by a lot of ingredients. For elder persons, furthermore, Kampo medicine exerts more effective actions.

Gender differences in the phosphorus content of the sino-atrial nodes and other cardiac regions of monkeys.

To examine whether there were gender differences in the sino-atrial node (SAN), the authors investigated the gender difference in the SAN using monkey hearts by direct chemical analysis from a viewpoint of element contents. The used rhesus and Japanese monkeys consisted of 30 males (average age=6.5±7.5 years) and 30 females (average age=12.2±10.3 years), ranging in age from newborn to 30 years. The SAN tissues were removed from the anatomical position of monkey hearts and were confirmed by means of histological observation. After ashing with nitric acid and with perchloric acid, element contents of the SANs, such as Ca, P, S, Mg, Zn, Fe, and Na, were determined by inductively coupled plasma-atomic emission spectrometry. In addition, gender differences in the right atrial walls, left ventricular walls, mitral valves, and left coronary arteries of monkeys were also investigated as controls. It was found that the P content was significantly higher in females than in males in the SANs of monkeys, but the other six element contents, Ca, S, Mg, Zn, Fe, and Na, were not significantly different between males and females in the SANs of monkeys. Regarding the P content, a similar finding was also obtained in both the right atrial walls and the left ventricular walls of monkeys, but it was not obtained in the mitral valves and the left coronary arteries of monkeys. The P content of tissue is mostly determined by the nucleic acid (DNA and RNA) content and the phospholipid content of tissue. Nucleic acids in the cell nucleus and the cytosol, and phospholipids in the cell membrane are all indicators of metabolically active cells. It is reasonable to presume that the P content in the SAN indicates the active cell density, namely, the number of active cells per volume. Therefore, there is a possibility that the active cell density of the SAN is significantly higher in females than in males.

Effect of aspartate and glutamate on the fate of enhanced biological phosphorus removal process and microbial community structure.

This study investigated the fate of enhanced biological phosphorus removal (EBPR) and changes in microbial speciation in a sequencing batch reactor (SBR) fed with aspartate and glutamate. It involved SBR operation for 288 days, batch tests for observation of metabolic functions together with microscopic and phylogenetic analyses. Polyphosphate accumulating organisms (PAOs) were observed in abundance with complete removal of phosphorus. Fluorescence in situ hybridization (FISH) combined with 4',6-dia-midino-2-phenylindole (DAPI) staining confirmed the accumulation of polyphosphate by Rhodocyclus-related and Actinobacterial PAOs. Aspartate seemed to favor the competitive growth of Rhodocyclus-related PAOs since EBPR population used the common biochemical pathways followed by Rhodocyclus-related PAOs in the aspartate fed batch tests. In the glutamate fed batch reactors, however, Actinobacterial PAOs appeared to be competitively selected which explains the lower levels of PHA generation. Even though operational conditions did not change, effective EBPR could not be maintained during the latter part of the study.

Effect of pH reduction on polyphosphate- and glycogen-accumulating organisms in enhanced biological phosphorus removal processes.

We investigated the effect of pH reduction on polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs) in the enhanced biological phosphorus removal (EBPR) process. Three laboratory-scale EBPR reactors were used. Initially, the reactors were operated at pH 7.9±0.1 and 6.5±0.1, and after 27 days, the pH was lowered to 6.5±0.1 and 6.0±0.1, respectively. PAOs and GAOs were monitored using real-time quantitative polymerase chain reaction and/or fluorescent in situ hybridization. Phosphorus removal performance was also monitored. During the start-up period, high EBPR activity and increases in Candidatus 'Accumulibacter phosphatis' (Accumulibacter) and Candidatus 'Competibacter phosphatis' (Competibacter) were observed. In all runs, Accumulibacter and Competibacter were the dominant PAO and GAO, respectively. Accumulibacter began to decline 10-18 days after lowering the pH to 6.5±0.1. After lowering the pH to 6.0±0.1, the Accumulibacter population decreased immediately. Contrastingly, an obvious adverse effect of pH reduction on Competibacter was not observed. In all runs, EBPR activity began to deteriorate 6-12 days after Accumulibacter decline began. Thus, our results show that pH reduction had an immediate or delayed effect on Accumulibacter decline. Moreover, the time lag between the start of Accumulibacter decline and that of EBPR deterioration implies that EBPR deterioration by pH reduction went through unknown process.

Population dynamics in a sequencing batch reactor fed with glucose and operated for enhanced biological phosphorus removal.

The study investigated the effect of glucose feeding as the sole carbon source on population dynamics in a sequencing batch reactor (SBR) operated for enhanced biological phosphorus removal (EBPR). The lab-scale SBR operation was started with a biomass taken from a WWTP plant performing EBPR and continued around two months. It exhibited a sequence of periods with different performance and biomass characteristics. The first period indicated predominant EBPR activity, involving phosphorus release in the anaerobic phase with PHA production as expected. Lactate generated from glucose fermentation was presumably converted to PHA by PAOs as an essential part of the EBPR activity. In the second period a major shift occurred in the population dynamics favoring the preferential growth and the predominance of GAOs which have the advantage of utilizing glucose directly and eventually the EBPR activity was deteriorated. The significant feature of the third period was the proliferation of filamentous microorganisms.

Acute effects of acupuncture treatment with Baihui (GV20) on human arterial stiffness and wave reflection.

OBJECTIVES: Treatment by manual acupuncture needling affects the vascular wall tone, and hemodynamic parameters for arterial stiffness may be characterized by treatment at the traditional acupuncture point (acupoint) of Baihui (GV20). METHODS: The acute effects of acupuncture treatment on arterial stiffness and wave reflection were investigated and, simultaneously, an augmentation index (AI), as an index of wave reflection, was estimated. These parameters were measured in male volunteers using applanation tonometry during 20 minutes of acupuncture treatment and 40 minutes post-acupuncture. RESULTS: During treatment, diastolic blood pressure (BP), but not systolic BP, increased significantly. Heart rates (HR) initially tended to increase and then decrease. The AI from radial arteries increased significantly, while central aortic blood pressure (CBP) was unaffected. Post-acupuncture, the effects lasted for 30-40 minutes. The average BP and HR were +10.1+/-0.3% and -7.2+/-0.2%, respectively, and the CBPs were not altered, but the AI decreased markedly; this latter effect presumably resulted from the involvement of neurovascular modulators. CONCLUSIONS: These results indicated that acute treatment at Baihui enhanced arteriosclerotic parameters. In post-acupuncture, the AI profoundly decreased, presumably resulting from the involvement with neurovascular modulators.

Vascular pharmacology of mokuboito (mu-fang-yi-tang) and its constituents on the smooth muscle and the endothelium in rat aorta.

Pharmacological actions of Mokuboito and its constituents (Sinomenium acutum and sinomenine) on rat aorta were examined. Mokuboito and S. acutum at lower concentrations (0.03-1 mg ml(-1)) contracted the non-loaded aorta, but at higher concentrations (1-3 mg ml(-1)), reversed to dilate it. The vasoconstriction was blocked by phentolamine (10 muM). Sinomenine failed to exhibit the vasoconstriction. On the other hand, Mokuboito and S. acutum dilated the NE (5 muM)-induced vasoconstriction: at 3 mg ml(-1), by 98.9 +/- 2.5% (n = 6, P < 0.01) and 97.0 +/- 4.8% (n = 6, P < 0.01). Vasorelaxation induced by Mokuboito and S. acutum was attenuated by indomethacin, L-NMMA and nicardipine. Propranolol decreased the vasorelaxation induced by Mokuboito, but not by S. acutum. Sinomenine also relaxed the constriction and at 100 muM, by 68.8 +/- 5.1% (n = 7, P < 0.01). This vasorelaxation was attenuated by indomethacin, L-NMMA and nicardipine, and also by propranolol. Therefore, these results indicate that Mokuboito and its constituents exert both vasodilating actions mediated by endothelium-dependent mechanisms (PGI(2) and NO from endothelium) and by endothelium-independent mechanisms (Ca(2+) influx control on smooth muscle cells). Simultaneously, Mokuboito and S. acutum cause the vasoconstrictions mediated through alpha-adrenoceptor stimulation, but not sinomenine. Also, Mokuboito and sinomenine possess beta-adrenoreceptor stimulating action, but not S. acutum.