Recently, we demonstrated the natural occurrence of geranylgeranoic acid in various medicinal SBE-β-CD order herbs (Shidoji and Ogawa, 2004). In this present study, we present several lines of evidence to demonstrate that geranylgeranyl diphosphate taken in foods could be
metabolized to GGA through geranylgeraniol and geranylgeranyl aldehyde via the following steps: 1) The conversion from geranylgeranyl diphosphate to geranylgeraniol was demonstrated to occur by the action of bovine intestinal alkaline phosphatase, with a K-m of 46.1 mu M. 2) Geranylgeraniol oxidase-mediated conversion of geranylgeraniol to geranylgeranyl aldehyde was revealed in rat liver homogenates, which activity was mainly localized in the mitochondrial fraction. The mitochondrial enzyme showed a K-m of 92.9 mu M. 3) The conversion of geranylgeranyl aldehyde to geranylgeranoic acid by geranylgeranyl aldehyde dehydrogenase in rat liver homogenates was absolutely dependent on exogenously added NAD(+) or NADP(+). The K-m of the mitochondrial
geranylgeranyl aldehyde dehydrogenase was 27.5 mu M for geranylgeranyl aldehyde. Taken together, our data suggest that cancer preventive geranylgeranoic acid could be a physiological metabolite from commonly consumed foods.”
“Vitamin D displays many extraosseous immuno-modulatory effects. The aim of the study was to evaluate the level of vitamin D in patients with systemic selleckchem sclerosis (SSc) and to analyze the associations between the concentration of the PXD101 cost vitamin and clinical manifestations. In March-April 2009, 65 consecutive SSc patients underwent evaluation of vitamin D concentrations by the LIAISON immunoassay (normal 30-100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency, while concentrations
<10 ng/ml as vitamin D deficiency. None of the patients were receiving vitamin D supplementation at the time of or during the year prior to study entry. The mean level of vitamin D was 15.8 +/- 9.1 ng/ml. Only three cases showed normal values; vitamin D insufficiency and deficiency were found in 43 and 19 cases, respectively. Patients with vitamin D deficiency showed longer disease duration (13.1 +/- 6.8 versus 9.4 +/- 5.5 years, P=0.026), lower diffusing lung capacity for carbon monoxide (63.7 +/- 12.4 versus 76.4 +/- 20.2, P=0.014), higher estimated pulmonary artery pressure (28.9 +/- 9.9 versus 22.8 +/- 10.4, P=0.037) and higher values of ESR (40 +/- 25 versus 23 +/- 13 mm/h, P=0.001) and of CRP (7 +/- 7 and 4 +/- 2 mg/l, P=0.004) in comparison with patients with vitamin D insufficiency; moreover, late nailfold videocapillaroscopic pattern was more frequently found (52.6% versus 18.6%, P=0.013). None of the patients showed evidence of overt malabsorption. Low levels of vitamin D are very frequent in patients with SSc.