Medicines and Vegetable Oils as Hidden Causes of Cardiovascular Disease and Diabetes.

BACKGROUND: Positive associations have been observed between cardiovascular disease (CVD) and type 2 diabetes mellitus (DM), but their causal relationship has not been clarified. Nevertheless, guidelines from relevant medical societies recommend using cholesterol lowering medication (statin) for both types of patients. Medicines with several different action mechanisms have been developed, and the effectiveness of different lifestyle modifications has been studied extensively for the prevention of DM, which was successful in improving clinical marker status in relatively short-term treatments, but none have been shown to be effective in improving long-term outcomes (mortality from CVD and all causes). SUMMARY: Statin-induced suppression of prenyl intermediates in the cholesterol biosynthetic pathway has been linked to stimulated atherosclerosis and heart failure. On the other hand, certain types of vegetable oil and hydrogenated oil shortened the survival of stroke-prone spontaneously hypertensive rats by decreasing platelet number, increasing hemorrhagic tendency and damaging kidney functions, which could not be accounted for by their fatty acid and phytosterol compositions. These vegetable oils and medicines such as statin and warfarin share, in part, a common mechanism to inhibit vitamin K2-dependent processes, which was interpreted to lead to increased onset of CVD, DM, chronic kidney disease, bone fracture and even mental disorder. Impaired vitamin K2-dependent processes by some types of vegetable oils and medicines, but not plasma high low density lipoprotein cholesterol, were proposed as the cause of CVD, DM and other lifestyle-related diseases. High n-6/n-3 fatty acid ratio of ingested foods, but not animal fats, was emphasized to be another risk factor for many of the diseases described above. KEY MESSAGES: To date, no randomized controlled trials (RCTs) have been performed to prove the above interpretation. However, the opposite types of RCT trials have been performed by increasing the intake of high-linoleic vegetable oils and reducing that of animal fats, which resulted in increased CVD and all-cause mortality. The amounts of these vegetable oils to exhibit adverse effects in animal studies are not huge (<6 energy %), which should not be overlooked nor disregarded.

Combustion of volatile organic compounds over composite catalyst of Pt/γ-Al2O3 and beta zeolite.

Catalytic oxidation of volatile organic compounds (VOCs) was carried out over a composite catalyst comprising Pt/γ-Al2O3 and protonated beta zeolite. The conversion of several VOCs such as ethyl acetate, butyl acetate, 2-propanol, 1,2-dichloroethane, and chloroethane over the composite catalyst was higher than the conversion over the conventional Pt/γ-Al2O3 catalyst, indicating a remarkable improvement in the oxidation activity of the composite. On the other hand, no difference in the conversion of methyl ethyl ketone, methyl isobutyl ketone, toluene, benzene, and chloroethylene was observed for the composite catalyst versus the Pt/γ-Al2O3 catalyst. To clarify the role of the zeolite component, the reaction products obtained using the composite catalyst were compared with those obtained using the Pt/γ-Al2O3 catalyst. For the cases in which considerable improvement in the oxidation activity was observed with the composite, it was revealed that the conversion of VOCs to intermediate compounds took place over the acidic sites of the zeolite; the intermediates tended to be easily oxidized to CO2 on the Pt/γ-Al2O3 catalyst. In addition, the composite catalyst also exhibited high durability. High catalytic activity was maintained even after aging at 600°C for more than 1000 h.

Clinical efficacy of macrophage-activating Chinese mixed herbs (MACH) in improvement of embryo qualities in women with long-term infertility of unknown etiology.

Despite the recent technological advances in in vitro fertilization and embryo transfer (IVF-ET), a significant proportion of women still do not become pregnant after long-term infertility, whether it is originally due to older age or other undetermined factors. In the present study, macrophage activating Chinese herbs (MACH) were evaluated for their effects on embryo qualities in women who were undergoing repeated IVF-ET because of long-term infertility. Thirty women, who had significantly low rates of developing good quality cleaved embryos and did not become pregnant after three or more cycles of Assisted Reproductive Technology (ART) procedure, were included in the study. Oral administration of MACH significantly increased the percentage of good quality early stage blastocysts (the number of grade 1 or grade 2 cleaved embryos/the number of retrieved oocytes) from 18.7 ± 16.2% to 36.1 ± 27.1% (1.9-fold increase, p < 0.01). The rate of good quality early stage blastocysts increased in all patients. In 19 patients who desired embryo transfer using late stage blastocysts, MACH significantly increased the percentage of late stage blastocysts from the initial value of 14.8 ± 11.2% to 21.1 ± 23.1% (1.4-fold increase, p < 0.05). The rate of embryonic progress into late stage blastocyst increased in 52.6% (10/19) of the patients. Furthermore, treatment with MACH significantly decreased the plasma follicle stimulating hormone (FSH) concentration on the day of oocyte retrieval from 14.4 ± 3.2 to 10.5 ± 2.4 mIU/ml (p < 0.05). No adverse events were observed with MACH supplementation, and there was no patient dropout. Administration of MACH resulted in improved embryo quality in the difficult cases. The present study demonstrates a new benefit of this herbal blend in women with refractory infertility of unknown etiology.

Distribution of radiocesium and stable elements within a pine tree.

Distributions of (137)Cs and stable elements in different parts of a pine tree collected in Chernobyl-contaminated area in Belarus were determined. Samples include annual tree rings of wood, branches and needles with different ages. The concentrations of (137)Cs and stable Cs in annual tree rings were the highest in cambium and decreased sharply towards inside. The youngest needles and branches contained higher (137)Cs and stable Cs than older ones. The concentration of (137)Cs being highest in growing parts suggests the highest radiation dose to the radiation-sensitive parts of tree. Distribution patterns of stable elements in pine tree differ among the elements. Distributions similar to those of Cs were observed for K and Rb, suggesting that alkaline metals tend to be translocated to young growing parts of pine tree. A similar distribution was also observed for phosphorus. Distributions of alkaline earth metals and several heavy metals were different from those of alkaline metals.

A novel mechanism regulates H(2) S and SO(2) production in Saccharomyces cerevisiae.

Sulfite (SO(2) ) plays an important role in flavour stability in alcoholic beverages, whereas hydrogen sulfide (H(2) S) has an undesirable aroma. To discover the cellular processes that control SO(2) and H(2) S production, we screened a library of Saccharomyces cerevisiae deletion mutants. Deletion of 12 genes led to increased H(2) S productivity. Ten of these genes are known to be involved in sulfur-containing amino acid metabolism, whereas UBI4 functions in the ubiquitin-proteasome system and SKP2 encodes an F-box-containing protein whose function is unknown. We found that the skp2 mutant accumulated H(2) S and SO(2) , because the adenosylphophosulfate kinase Met14p is a substrate of SCF(Skp2) and more stable in the skp2 mutant than in the wild-type strain. Furthermore, the skp2 mutant grew more slowly than the wild-type strain under nutrient-limited conditions. Metabolome analysis showed that the concentration of intracellular cysteine is lower in the skp2 mutant than in the wild-type strain. The slow growth of the skp2 mutant was due to a lower concentration of intracellular cysteine, because the addition of cysteine suppressed the slow growth. In the skp2 mutant, the cysteine biosynthesis proteins Str2p, Str3p and Str4p are more stable than in the wild-type strain. Moreover, supplementation with methionine, S-adenosylmethionine, S-adenosylhomocysteine and homocysteine also suppressed the slow growth. Overexpression of STR1 or STR4 caused a more severe defect in the skp2 mutant. These results suggest that the balance of methionine and cysteine biosynthesis is important for yeast cell growth. Thus, Skp2p is one of the key components regulating this balance and H(2) S/SO(2) production.

Metabolism of fatty acids and lipid hydroperoxides in human body monitoring with Fourier transform Infrared Spectroscopy.

BACKGROUND: The metabolism of dietary fatty acids in human has been measured so far using human blood cells and stable-isotope labeled fatty acids, however, no direct data was available for human peripheral tissues and other major organs. To realize the role of dietary fatty acids in human health and diseases, it would be eager to develop convenient and suitable method to monitor fatty acid metabolism in human. RESULTS: We have developed the measurement system in situ for human lip surface lipids using the Fourier transform infrared spectroscopy (FTIR) - attenuated total reflection (ATR) detection system with special adaptor to monitor metabolic changes of lipids in human body. As human lip surface lipids may not be much affected by skin sebum constituents and may be affected directly by the lipid constituents of diet, we could detect changes of FTIR-ATR spectra, especially at 3005 to approximately 3015 cm(-1), of lip surface polyunsaturated fatty acids in a duration time-dependent manner after intake of the docosahexaenoic acid (DHA)-containing triglyceride diet. The ingested DHA appeared on the lip surface and was detected by FTIR-ATR directly and non-invasively. It was found that the metabolic rates of DHA for male volunteer subjects with age 60s were much lower than those with age 20s. Lipid hydroperoxides were found in lip lipids which were extracted from the lip surface using a mixture of ethanol/ethylpropionate/iso-octane solvents, and were the highest in the content just before noon. The changes of lipid hydroperoxides were detected also in situ with FTIR-ATR at 968 cm(-1). CONCLUSION: The measurements of lip surface lipids with FTIR-ATR technique may advance the investigation of human lipid metabolism in situ non-invasively.

Uranium accumulation of crop plants enhanced by citric acid.

Citric acid was applied to soil to enhance U accumulation in four crop plants. While the highest enhanced U accumulation of aboveground tissues (a.c. 2000 mg kg(-1) dry weight) occurred in the leaves of Indian mustard (Brassica juncea), the highest enhanced U accumulation of roots (a.c. 3500 mg kg(-1) dry weight) occurred in canola (Brassica napus var. napus). Uranium translocation among tissues of test plants is in the relation of roots>shoots congruent with leaves. The flowers of sunflower (Helianthus annuus) contained similar or higher U concentrations than those found in shoots, but concentrations in seeds are close to zero. In conclusion, Indian mustard is recommended as a potential species for phytoextraction for U-contaminated soil due to its high U accumulation of aboveground biomass (a.c. 2200 microg per plant). There is no evidence that two types of soils cause a significant difference of the enhanced U accumulation (p<0.05). Results, however, indicate that additional citric acid may result in downward U migration that may contaminate groundwater. Speciation of U that is taken up by plants is also discussed in the end.

An open-label study of administration of EH0202, a health-food additive, to patients with chronic hepatitis C.

BACKGROUND: In this study, we examined the effect of EH0202, a mixture of four herbal extracts that are known to induce interferons, on hepatitis C virus (HCV)-RNA levels in patients with chronic hepatitis C. METHODS: This was an open-label uncontrolled study. The study subjects ingested food containing EH0202 daily for 3 months, which was equivalent to 1 g of desiccated herbs daily. Clinical symptoms, hematology and biochemical examinations, urine, and HCV-RNA levels were examined before, during (1 month), and after the EH0202 treatment (3 months). RESULTS: Among the 35 patients who successfully completed the study, there were improvements in malaise (seen in 6 patients before and in 2 after EH0202 treatment), bloating sensation in the abdomen (seen in 2 before and in none after treatment), and nausea and vomiting (seen in 2 before and in 1 after treatment). There were no changes in hematology or biochemical examination parameters. There was a statistically significant decrease in HCV-RNA levels in patients with high viral titers after 3 months of EH0202 administration. No serious adverse events were observed with the EH0202 treatment. CONCLUSIONS: These findings suggest that EH0202 may be safe and useful in the treatment of patients with chronic hepatitis C. Further studies are, however, needed to obtain a definitive conclusion.

A pilot study of a Kampo formula, EH0202, with intriguing results for menopausal symptoms.

OBJECTIVES: To investigate the effects of EH0202, a Japanese herbal supplement, on the immune and endocrine systems in women with menopausal symptoms. DESIGN AND SUBJECTS: Thirty-two (32) postmenopausal women (53.0 +/- 5.1 years old) presenting with menopausal complaints were enrolled in a clinical study. Patients were given an herbal supplement, EH0202 (6 g per day for 6 months) and were assessed for reduction of their overall symptoms using Greene's Climacteric Scale and Visual Analog Scale. Plasma interleukin-6 (IL-6), soluble IL-6 receptor, tumor necrosis factor-alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), granulocyte-colony stimulating factor, follicle-stimulating hormone (FSH), and luteinizing hormone concentrations were measured before and 6 months after EH0202 administration. RESULTS: There was a significant decrease in the climacteric scale score (p = 0.0007) and visual analogue scale (p < 0.0001) after 6 months of EH0202 treatment. There was significant increase (p = 0.0097) in plasma GM-CSF levels and a significant decrease (p = 0.018) in plasma FSH levels after 6 months of EH0202 administration. CONCLUSIONS: EH0202 (MACH) decreased the plasma FSH level and stimulated myelopoiesis through the cytokine system, thereby clinically reduced menopausal symptoms in postmenopausal women. Therefore, in postmenopausal women, this product probably acts as an immunomodulator and endocrine modulator.

Aldoxime dehydratase co-existing with nitrile hydratase and amidase in the iron-type nitrile hydratase-producer Rhodococcus sp. N-771.

We identified an aldoxime dehydratase (Oxd) gene in the 5'-flanking region of the nitrile hydratase-amidase gene cluster in the photoreactive iron-type nitrile hydratase-producer, Rhodococcus sp. N-771. The enzyme showed 96.3%, 77.6%, and 30.4% identities with the Oxds of Rhodococcus globerulus A-4, Pseudomonas chlororaphis B23, and Bacillus sp. OxB-1, respectively. The enzyme was expressed in Escherichia coli under the control of the lac- or T7 promoters in its intact and His6-tagged forms, purified, and characterized. The enzyme had heme b as a prosthetic group, catalyzed a stoichiometric dehydration of aldoxime into nitrile, and exhibited the highest activity at neutral pH and at around 30 degrees C similar to the known Oxd from Bacillus sp. OxB-1. The activity was enhanced by reducing agents, such as Na2S, Na2S2(O4), 2-mercaptoethanol, and L-cysteine and supplementary additions of electron acceptors such as flavins, sulfite ion, and vitamin K3. The effect of various chemicals on the enzyme activity was different in the presence and absence of the reducing reagent, Na2S. The enzyme preferentially acts on aliphatic-type substrates and the substrate specificity of the enzyme coincides with that reported for nitrile hydratase produced by the strain.

Clinical efficacy of EH0202, a Kampo formula, on the health of middle-aged women.

To investigate the clinical effects of EH0202, a Japanese herbal supplement, on the menopausal symptoms and physical status of peri- and post-menopausal women. Thirty-two post-menopausal women (53.0+/-5.1 years) presented with menopausal complaints were enrolled in the clinical study. Patients were administered an herbal supplement, EH0202 (6 g/day for 6 months), and were assessed for improvement of their overall symptoms using the Greene Climacteric Scale and the Visual Analog Scale (VAS). Blood pressure, skin surface blood flow and plasma lipid profiles were measured before and 1,3 and 6 months after EH0202 administration. There was a significant decrease in the climacteric scale score (P < 0.001) and VAS (P < 0.0001) after 6 months of EH0202 treatment. There was a significant decrease in systolic (P < 0.001) and diastolic (P < 0.05) blood pressure, and a significant decrease in facial skin surface blood flow (P < 0.05) after 3 months of EH0202 administration. We observed a significant decrease in plasma TG and LDL-cholesterol concentrations after 3 months of EH0202 administration (P < 0.05). EH0202 (MACH) reduced blood pressure, excess facial skin blood flow (flushing) and abnormal lipid levels, as well as clinically improved menopausal symptoms in post-menopausal women. In post-menopausal women, this product appears to help maintain normal biological function and improves quality of life.

A pharmacologic study on the mechanism of action of Kakkon-to: body temperature elevation and phagocytic activation of macrophages in dogs.

OBJECTIVE: The phagocytic activity of macrophages as a novel approach to scientific elucidation of the effects of Chinese medicines was studied through administration of a kampo preparation, by measuring the rise in body temperature, which is thought to stimulate innate defensive functions of organisms and enhance the immune systems. DESIGN: Using dogs as experimental models, a rise in body temperature following administration of Kakkon-to was observed, and the average number and average rate of phagocytosis of macrophages in blood using latex micro-particles was investigated. RESULTS: The body temperature of the treated animals significantly increased 30 minutes after administration (p<0.01), and remained elevated for more than 5 hours. A comparison of body temperatures before and after administration showed significant increases over controls from 1 to 11 hours, p<0.01; and at 12 hours, p<0.05 after administration. The average number and the average rate of phagocytosis were significantly increased 1 (p<0.05) and 2 (p<0.01) hours after administration. The mean number of phagocytized cells significantly increased (p<0.05) at 1 hour after administration compared with that before administration, and the mean phagocytic rate also increased significantly (p<0.01) 2 hours after administration. Increases (p<0.01) in both the rate of phagocytosis and the number of cells phagocytized were found at every measurement point from 2 to 24 hours after administration. Significant increases (p<0.01) were also observed in both the rate of phagocytosis and the number of cells phagocytized 3 hours after administration, when compared with the control group. CONCLUSION: This paper demonstrates that ingestion of Kakkon-to not only increases the body temperature but also enhances the phagocytic activity of macrophages, an in vivo defense mechanism, suggesting that Kakkon-to contributes to the suppression of multiplication of common cold viruses and influenza viruses, which consequently results in improvement of various symptoms during infection with common cold viruses.

Nondestructive analyses of unsaturated fatty acid species in dietary oils by attenuated total reflectance with Fourier transform IR spectroscopy.

The aim of this study was to develop a nondestructive method to quantitate relative amounts of n-3 and n-6 polyunsaturated fatty acid (PUFA) species in vegetable oils and oil seeds using Fourier transform IR spectroscopy (FTIR). The alkene Cbond;H stretching vibrations of unsaturated fatty acids in oils showed IR absorption bands with various peak positions and intensities at around 3010 cm(-1), depending on the extent of unsaturation and PUFA species. With the aid of partial least-squares regression analysis, the FTIR measurement could practically predict the content of each PUFA species in the oil to be tested. A calculation method was also presented to directly find PUFA species in oils from the FTIR spectra. This technique was applied to dried soybean seeds to demonstrate a nonhomogenous distribution of saturated fatty acids and PUFAs, as well as glycans, in soybean cross sections.

Effect of Choto-san, a Kampo medicine, on impairment of passive avoidance performance in senescence accelerated mouse (SAM).

Effect of Choto-san (TJ-47), a Kampo medicine, on impairment of learning performance was evaluated by means of a step-through passive avoidance task in SAMP8 mice, a senescence-prone substrain. Tokishakuyaku-san (TJ-23), another Kampo medicine, was also employed for comparison. SAMP8 mice at the age of 10-12 months showed a poorer passive avoidance response than SAMR1 mice, a senescence-resistant substrain, in the memory-retention test, but not in the memory-acquisition test. Improved response in the memory-retention test was observed in SAMP8 mice treated with TJ-47, and almost equal degree of improvement was also observed after treatment with TJ-23. These results suggest that a long-term administration of Choto-san could improve to some extent the impairment of memory caused by aging.