Impact of Green Tea Catechin Ingestion on the Pharmacokinetics of Lisinopril in Healthy Volunteers.

Lisinopril, a highly hydrophilic long-acting angiotensin-converting enzyme inhibitor, is frequently prescribed for the treatment of hypertension and congestive heart failure. Green tea consumption may reduce the risk of cardiovascular outcomes and total mortality, whereas green tea or its catechin components has been reported to decrease plasma concentrations of a hydrophilic ß blocker, nadolol, in humans. The aim of this study was to evaluate possible effects of green tea extract (GTE) on the lisinopril pharmacokinetics. In an open-label, randomized, single-center, 2-phase crossover study, 10 healthy subjects ingested 200 mL of an aqueous solution of GTE containing ~ 300 mg of (-)-epigallocatechin gallate, a major catechin component in green tea, or water (control) when receiving 10 mg of lisinopril after overnight fasting. The geometric mean ratio (GTE/control) for maximum plasma concentration and the area under the plasma concentration-time curve of lisinopril were 0.289 (90% confidence interval (CI) 0.226-0.352) and 0.337 (90% CI 0.269-0.405), respectively. In contrast, there were no significant differences in time to reach maximum lisinopril concentration (6 hours in both phases) and renal clearance of lisinopril (57.7 mL/minute in control vs. 56.9 mL/minute in GTE). These results suggest that the extent of intestinal absorption of lisinopril was significantly impaired in the presence of GTE, whereas it had no major effect on the absorption rate and renal excretion of lisinopril. Concomitant use of lisinopril and green tea may decrease oral exposure to lisinopril, and therefore result in reduced therapeutic efficacy.

Phytotoxic activity of crop residues from Burdock and an active substance.

Problems related to weed management such as outbreaks of herbicide-resistant weeds have recently increased. An interesting approach to such problems is to use plant materials with phytotoxic activity. Burdock (Arctium lappa L.) is a biennial herb belonging to Asteraceae and is cultivated in several countries. The present study investigated the phytotoxic activity of burdock and its active substances. Extracts of both burdock leaves and roots inhibited the shoot and root growth of cress and barnyard grass, where the level of inhibition increased with increasing extract concentration. The leaf extracts had 2.0-2.5 times higher activity than the root extracts. Bioassay-guided separations of the leaf extracts led to isolation of a phytotoxic substance, onopordopicrin. Onopordopicrin significantly inhibited the shoot and root growth of cress and barnyard grass. The concentrations of the substance required for 50% growth inhibition were 0.27 and 0.26 mM for cress shoots and roots, respectively, and 1.86 and 0.35 mM for barnyard grass shoots and roots, respectively. The present results suggest that burdock leaves have high phytotoxic activity and onopordopicrin may play a major role in the activity. Burdock leaves may be a good resource for weed management.

Phytotoxic property of the invasive plant Tithonia diversifolia and a phytotoxic substance.

Tithonia diversifolia (Hermsl.) A. Gray is a perennial invasive plant and spreads quickly in the invasive areas. The extracts of T. diversifolia were found to be toxic to several crop plant species such as rice, maize, sorghum, lettuce and cowpea, and several putative allelopathic substances were identified. However, there is limited information available for the effects of T. diversifolia on wild plants including weed plant species. We investigated the allelopathic potential of T. diversifolia extracts on weed plants, and searched for phytotoxic substances with allelopathic activity. An aqueous methanol extract of T. diversifolia leaves inhibited the growth of weed plants, Lolium multiflorum Lam., Phleum pretense L., Echinochloa crus-galli (L.) Beauv. The extract was then purified by several chromatographic runs and a phytotoxic substance with allelopathic activity was isolated and identified by spectral analysis as tagitinin C. The substance inhibited the growth of Lolium multiflorum, Phleum pratense and Echinochloa crus-galli at concentrations greater than 0.1 - 0.3 mM. The present results suggest that T. diversifolia may possess allelopathic potential on weed plants and tagitinin C may be responsible for the allelopathic effects of T. diversifolia. The allelopathic potential of T. diversifolia may contribute to its invasive characteristics.

A Potent Phytotoxic Substance in Aglaia odorata Lour.

Aglaia odorata Lour. (Meliaceae) was found to have very strong allelopathic activity and a bioherbicide PORGANIC(™) was developed from its leaf extracts. However, the phytotoxic substances causing the strong allelopathic activity of the plants have not yet been determined. Therefore, we investigated allelopathic properties and phytotoxic substances in A. odorata. Aqueous EtOH extracts of A. odorata leaves inhibited root and shoot growth of garden cress (Lepidum sativum), lettuce (Lactuca sativa), alfalfa (Medicago sativa), timothy (Phleum pratense), ryegrass (Lolium multiflorum), and Echinochloa crus-galli with the extract concentration-dependent manner. The extracts were then purified and a major phytotoxic substance with allelopathic activity was isolated and identified by spectral data as rocaglaol. Rocaglaol inhibited the growth of garden cress and E. crus-galli at concentrations > 0.3 and 0.03 µm, respectively. The concentrations required for 50% inhibition ranged from 0.09 to 2.5 µm. The inhibitory activity of rocaglaol on the weed species, E. crus-galli, was much greater than that of abscisic acid. These results suggest that rocaglaol may be a major contributor to the allelopathic effect of A. odorata and bioherbicide PORGANIC(™) .

Randomized, double-blind, placebo-controlled trial of vitamin D supplementation in Parkinson disease.

BACKGROUND: In our previous study, higher serum 25-hydroxyvitamin D [25(OH)D] concentrations and the vitamin D receptor (VDR) FokI CC genotype were associated with milder Parkinson disease (PD). OBJECTIVE: We evaluated whether vitamin D3 supplementation inhibits the progression of PD on the basis of patient VDR subgroups. DESIGN: Patients with PD (n = 114) were randomly assigned to receive vitamin D3 supplements (n = 56; 1200 IU/d) or a placebo (n = 58) for 12 mo in a double-blind setting. Outcomes were clinical changes from baseline and the percentage of patients who showed no worsening of the modified Hoehn and Yahr (HY) stage and Unified Parkinson's Disease Rating Scale (UPDRS). RESULTS: Compared with the placebo, vitamin D3 significantly prevented the deterioration of the HY stage in patients [difference between groups: P = 0.005; mean ± SD change within vitamin D3 group: +0.02 ± 0.62 (P = 0.79); change within placebo group: +0.33 ± 0.70 (P = 0.0006)]. Interaction analyses showed that VDR FokI genotypes modified the effect of vitamin D3 on changes in the HY stage (P-interaction = 0.045), UPDRS total (P-interaction = 0.039), and UPDRS part II (P-interaction = 0.021). Compared with the placebo, vitamin D3 significantly prevented deterioration of the HY stage in patients with FokI TT [difference between groups: P = 0.009; change within vitamin D3 group: -0.38 ± 0.48 (P = 0.91); change within placebo group, +0.63 ± 0.77 (P = 0.009)] and FokI CT [difference between groups: P = 0.020; change within vitamin D3 group: ±0.00 ± 0.60 (P = 0.78); change within placebo group: +0.37 ± 0.74 (P = 0.014)] but not FokI CC. Similar trends were observed in UPDRS total and part II. CONCLUSION: Vitamin D3 supplementation may stabilize PD for a short period in patients with FokI TT or CT genotypes without triggering hypercalcemia, although this effect may be nonspecific for PD. This trial was registered at UMIN Clinical Trials Registry as UMIN000001841.

Variability in the P1 gene helps to refine phylogenetic relationships among leek yellow stripe virus isolates from garlic.

Nucleotide sequences from the P1 gene and the 5' untranslated region of leek yellow stripe virus (LYSV), collected from several locations, were used to refine the phylogenetic relationships among the isolates. Multiple alignments revealed three distinct regions of insertions and deletions to classify LYSVs. In our phylogenetic analyses, the LYSV isolates separated into two major groups (N-type and S-type). S-type viruses had two large deletions compared to N-type viruses. Considering that the outgroup, onion yellow dwarf virus (OYDV) also has the sequences corresponding to the deletions in the S-type viruses, our study shows that the sequences missing in the S-type were present in the common ancestor of the N-type and S-type. In the phylogenetic trees, we found three distinct clades of isolates, from Uruguay (U), Okinawa (O) and Spain (Sp), suggesting that LYSVs have unique evolutionary histories depending on their garlic origins. The P1 gene of LYSV is thus quite suited to reflecting viral evolution, as recently suggested for other potyviruses.

[A patient with advanced breast cancer refractory to chemotherapy accompanied by carcinomatous pleurisy and multiple bone metastasis that responded to combination therapy with high-dose toremifene and docetaxel].

The patient was a 76-year-old woman, who found a mass in her left breast around summer of 2003 but ignored it. She visited our hospital in April 2004 because of dyspnea and low-back pain. As there was a mass accompanied by partial ulceration all over the left precordium and bilateral pleural effusion, she was admitted for further evaluation and treatment. The patient was judged to be almost in a life-threatening condition, and thus thoracentesis was performed to remove pleural fluid, and chemotherapy with FEC was also performed. In addition, the patient was placed on oral exemestane (EXE). After four courses of therapy with FEC were completed, the drug was changed to paclitaxel (PTX) and chemotherapy was continued for another 3 months. It was confirmed that the tumor size had been reduced markedly and that the volume of pleural effusion had not increased. The patient was in a state of remission for a short time, but subsequently the tumor size increased again and the tumor bled continually in small amounts. The chemotherapeutic drug was changed to capecitabine, while EXE, which had been continued, was withdrawn and oral administration of 120 mg/day of toremifene (TOR) was started. However, the tumor size was not reduced. TOR was continued, while capecitabine was changed to docetaxel (DOC). Then, the tumor size was reduced again, until the breast became almost flat after 3 months and the patient no longer bled from the tumor. The volume of pleural effusion did not increase, nor did the patient have any more dyspnea. At present, she has been in a state of remission and is living at home with a certain QOL.

Biosynthesis of malonylated flavonoid glycosides on the basis of malonyltransferase activity in the petals of Clitoria ternatea.

The crude malonyltransferase from the petals of Clitoria ternatea was characterized enzymatically to investigate its role on the biosynthetic pathways of anthocyanins and flavonol glycosides. In C. ternatea, a blue flower cultivars (DB) and mauve flower variety (WM) accumulate polyacylated anthocyanins (ternatins) and delphinidin 3-O-(6''-O-malonyl)-beta-glucoside which is one of the precursors of ternatins, respectively. Moreover, WM accumulates minor delphinidin glycosides - 3-O-beta-glucoside, 3-O-(2''-O-alpha-rhamnosyl)-beta-glucoside, 3-O-(2''-O-alpha-rhamnosyl-6''-O-malonyl)-beta-glucoside of delphinidin. These glycosidic patterns for minor anthocyanins in WM are also found among the minor flavonol glycosides in all the varieties including a white flower variety (WW) although the major flavonol glycosides are 3-O-(2''-O-alpha-rhamnosyl)-beta-glucoside, 3-O-(6''-O-alpha-rhamnosyl)-beta-glucoside, 3-O-(2'',6''-di-O-alpha-rhamnosyl)-beta-glucoside of kaempferol, quercetin, and myricetin. How do the enzymatic characteristics affect the variety of glycosidic patterns in the flavonoid glycoside biosynthesis among these varieties? While the enzyme from DB highly preferred delphinidin 3-O-beta-glucoside in the presence of malonyl-CoA, it also has a preference for other anthocyanidin 3-O-beta-glucosides. It could use flavonol 3-O-beta-glucosides in much lower specific activities than anthocyanins; however, it could not utilize 3-O-(2''-O-alpha-rhamnosyl)-beta-glucosides of anthocyanins and flavonols, and 3,3'-di- and 3,3',5'-tri-O-beta-glucoside of delphinidin - other possible precursors in ternatins biosynthesis. It highly preferred malonyl-CoA as an acyl donor in the presence of delphinidin 3-O-beta-glucoside. The crude enzymes prepared from WM and WW had the same enzymatic characteristics. These results suggested that 3-O-(2''-O-alpha-rhamnosyl-6''-O-malonyl)-beta-glucosides of flavonoids were synthesized via 3-O-(6''-O-malonyl)-beta-glucosides rather than via 3-O-(2''-O-alpha-rhamnosyl)-beta-glucosides, and that malonylation proceeded prior to glucosylation at the B-ring of delphinidin in the early biosynthetic steps towards ternatins. It seemed that the substrate specificities largely affected the difference in the accumulated amount of malonylated glycosides between anthocyanins and flavonols although they are not simply proportional to the accumulation ratio. This enzyme might join in the production of both malonylanthocyanins and flavonol malonylglycosides as a result of broad substrate specificities towards flavonoid 3-O-beta-glucosides.

Investigation of the release behavior of diethylhexyl phthalate from polyvinyl chloride tubing for intravenous administration based on HCO60.

The release behavior of diethylhexyl phthalate (DEHP) from polyvinyl chloride (PVC) tubing, which composes materials in an intravenous administration set (IAS), was investigated using polyoxyethylated hydrogenated castor oil (HCO60) in physiological saline (PS), distilled water for injection (DWI), and ribose, fructose, and glucose (TZ) solutions. The amount of DEHP released increased with increasing HCO60 concentration, and the cumulative amount of DEHP released after 4h increased in the following order: 50% TZ