Lactoferrin from bovine colostrum regulates prolyl hydroxylase 2 activity and prevents prion protein-mediated neuronal cell damage via cellular prion protein.

Prion disorders are associated with the conversion of normal cellular prion protein (PrPc) to the abnormal scrapie isoform of prion protein (PrPsc). Recent studies have shown that expression of normal PrPc is regulated by hypoxia-inducible factor-1 alpha (HIF-1α), and that lactoferrin increases full-length PrPc on the cell surface. Lactoferrin is an 80-kDa iron-binding glycoprotein with various biological activities, including iron-chelating ability. HIF-1α and the associated ubiquitin-proteasome pathway are regulated by HIF prolyl-hydroxylases 2 (PHD2). We hypothesized that lactoferrin regulates PHD2 expression and enzymatic activity, and the PHD2 regulation promotes HIF-1α stability and prevention of neuronal cell death mediated by prion protein (PrP) residues (106-126). Lactoferrin prevented PrP (106-126)-induced neurotoxicity by the induction of PrPc expression via promoting HIF-1α stability in neuronal cells. Our results demonstrated that lactoferrin prevented PrP (106-126)-induced neurotoxicity via the up-regulation of HIF-1α stability determined by PHD2 expression and enzymatic activity. These findings suggest that possible therapies such as PHD2 inhibition, or promotion of lactoferrin secretion, may have clinical benefits in neurodegenerative diseases, including prion disease.

Relationship between inspiratory muscle strength and cough capacity in cervical spinal cord injured patients.

STUDY DESIGN: Prospective single centre study. OBJECTIVES: Pulmonary rehabilitation focuses on improving the expiratory muscle function in order to increase the reduced cough capacity in patients with cervical spinal cord injuries (SCI). However, an improvement in the inspiratory function is also important for coughing effectively. Therefore, this study was to examine the significance of the inspiratory muscle strength on the cough capacity in the patients with a cervical SCI. SETTING: SCI unit, Yonsei Rehabilitation Hospital, Seoul, Korea. METHODS: The vital capacity (VC), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP) were measured. Moreover, the unassisted peak cough flow (PCF) and assisted PCF under three conditions were evaluated. RESULTS: All three assisted cough methods showed a significantly higher value than the unassisted method (P < 0.001). The VC correlated with the voluntary cough capacity and the MIP (R = 0.749) correlated more significantly with the VC than the MEP (R = 0.438) (P < 0.01). The MIP showed a higher correlation with both the unassisted PCF and all three assisted PCFs than the MEP (P < 0.001). CONCLUSIONS: The management of the inspiratory muscle strength should be considered in the pulmonary rehabilitation at cervical SCI patients.

Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women.

Quercetin is a typical flavonoid present mostly as glycosides in plant foods; it has attracted much attention for its potential beneficial effects in disease prevention. In this study, we examined human volunteers after the short-term ingestion of onion, a vegetable rich in quercetin glucosides. The subjects were served diets containing onion slices (quercetin equivalent: 67.6-93.6 mg/day) with meals for 1 wk. Quercetin was only found in glucuronidase-sulfatase-treated plasma, and its concentration after 10 h of fasting increased from 0.04 +/- 0.04 microM before the trial to 0.63 +/- 0.72 microM after the 1-wk trial. The quercetin content in low-density lipoprotein (LDL) after glucuronidase-sulfatase treatment corresponded to <1% of the alpha-tocopherol content. Human LDL isolated from the plasma after the trial showed little improvement of its resistance to copper ion-induced oxidation. It is therefore concluded that conjugated metabolites of quercetin accumulate exclusively in human blood plasma in the concentration range of 10(-7) approximately 10(-6) M after the short-term ingestion of vegetables rich in quercetin glucosides, although these metabolites are hardly incorporated into plasma LDL.

NMR analytical approach to clarify the molecular mechanisms of the antioxidative and radical-scavenging activities of antioxidants in tea using 1,1-diphenyl-2-picrylhydrazyl.

(+)-catechin, ethyl gallate, ascorbic acid, and alpha-tocopherol were reacted with 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the reaction mixtures were subjected to 13C-nuclear magnetic resonance (NMR) analyses to clarify the molecular mechanisms of the antioxidative and radical-scavenging activities of each antioxidant. When ascorbic acid was reacted with DPPH, it was oxidized to dehydroascorbic acid by DPPH. When a mixture of ascorbic acid and (+)-catechin was reacted with DPPH, ascorbic acid scavenged DPPH radical faster than (+)-catechin. Ascorbic acid also scavenged DPPH radical faster than ethyl gallate and alpha-tocopherol. When (+)-catechin was reacted with DPPH, the B-ring of (+)-catechin changed to an o-quinone structure. However, it was reduced to (+)-catechin by ethyl gallate or alpha-tocopherol. alpha-Tocopherol and ethyl gallate had almost identical antioxidative activities. Therefore, the order of radical-scavenging ability (speed) suggested by our 13C NMR study was as follows: ascorbic acid > alpha-tocopherol = ethyl gallate > (+)-catechin.

Cis- and trans-linalool 3,7-oxides and methyl salicylate glycosides and (Z)-3-hexenyl beta-D-glucopyranoside as aroma precursors from tea leaves for oolong tea.

Two new alcoholic aroma precursors, cis- and trans-linalool, 3,7-oxides 6-O-beta-D-apiofuranosyl-beta-D-glucopyranosides (1 and 2), as well as two already known compounds, (Z)-3-hexenyl beta-D-glucopyranoside (3) and methyl salicylate 6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside (beta-primeveroside: 4), and another new monoterpendiol glycoside, 8-hydroxygeranyl beta-primeveroside (5) have recently been isolated as aroma precursors in tea leaves (Camellia sinensis var. sinensis cv. Maoxie) ready for oolong tea processing.

The changes in muscle strength and relaxation time after a comprehensive rehabilitation program for patients with myotonic dystrophy.

Myotonic dystrophy is a muscular disorder characterized by muscle weakness and myotonia. Myotonia manifests with abnormally slow relaxation after strong voluntary contraction of the muscles. In our previous study we reported that quinine sulfate provided therapeutic benefit to myotonia and a home exercise program based on muscle strengthening exercises improved muscle strength. The purpose of this study was to determine the effect of a multi-therapeutic program in patients with myotonic dystrophy. For six months, seven patients with myotonic dystrophy received heat therapy, were given psychologic intervention using relaxation techniques, were trained at home, and were given quinine sulfate. The changes in muscle strength and relaxation time between the post-six-months home exercise program combined with quinine sulfate therapy, and the post-six months multi-therapeutic program, were assessed from the first dorsal interossei, the elbow flexors, and the knee extensors. The results were as follows: 1) The mean muscle strength of the each of the three muscles after the six months multi-therapeutic program was improved but was not significant compared with the post-six-months home exercise program combined with quinine sulfate therapy. 2) The mean relaxation time of each of the three muscles after the six months multi-therapeutic program was significantly reduced compared with the home exercise program combined with quinine sulfate therapy. In conclusion, the multi-therapeutic program undertaken in this study was the better program for the patients with myotonic dystrophy.

A study on tea aroma formation mechanism: alcoholic aroma precursor amounts and glycosidase activity in parts of the tea plant.

We have shown in molecular basis that alcoholic tea aroma is mainly formed by endogenous enzymatic hydrolysis of glycosidic aroma precursors during manufacturing. Amounts of alcoholic aroma precursor and glycosidase activity in each part of the tea shoot (Camellia sinensis var. sinensis cv Yabukita and a hybrid of var. assamica & var. sinensis cv Izumi) were indirectly measured by means of a crude enzyme assay. The aroma precursors were abundant in young leaves and decreased as the leaf aged. Glycosidase activity also decreased as leaves aged, but was high in stems.

trans- and cis-linalool 3,6-oxide 6-O-beta-D-xylopyranosyl-beta-D-glucopyranosides isolated as aroma precursors from leaves for oolong tea.

New glycosidic aroma precursors (1 and 2) of the main volatile constituents, trans- and cis-linalool 3,6-oxides (linalool oxides I and II), were isolated from oolong tea leaves (Camellia sinensis var. sinensis cv. Maoxie). The isolation was guided by an enzymatic hydrolysis with acetone powder prepared from fresh tea leaves (cv. Yabukita) followed by GC or GC-MS analyses. Chromatographic purification of hot water extracts of the tea leaves on active charcoal, Amberlite XAD-2, and Sephadex LH-20 columns as well as HPLC gave two new glycosides, trans- and cis-linalool 3,6-oxide 6-O-beta-D-xylopyranosyl-beta-D-glucopyranosides (1 and 2).