Lactobacillus gasseri PA-3 reduces serum uric acid levels in patients with marginal hyperuricemia.

Several studies have reported that Lactobacillus gasseri PA-3 reduces the level of serum uric acid (SUA) in patients with hyperuricemia. However, it remains unknown how PA-3 affects uric acid metabolism. In the present study, we examined effects of PA-3-containing yoghurt on uric acid metabolism in patients with marginal hyperuricemia. Sixteen patients with SUA > 357 µmol/L (marginal hyperuricemia) were enrolled. PA-3-containing yoghurt was administered for 8 weeks. Uric acid metabolism was evaluated just before and 8 weeks after the administration and at 4 weeks after the administration ended (post-administration). SUA levels after the administration were significantly lower than that before the administration and remained low at post-administration. Urinary uric acid concentration (Uur) after the administration were significantly lower than that before the administration. However, post-administration Uur levels were comparable to those before the administration. Therefore, PA-3-containing yoghurt significantly reduced the levels of SUA and Uur in patients with marginal hyperuricemia.

Effects of Nelumbo nucifera Leaf Extract on Obesity.

The two main components from a Nelumbo nucifera leaf extract (NnEx) were investigated for their ability to prevent triglyceride accumulation and promoting lipolysis. Sun-dried Nelumbo nucifera leaves were immersed in hot water to extract the soluble components, and the resulting solution was analyzed by LC-MS and nuclear magnetic resonance. The results showed that quercetin-3-O-ß-glucuronide (Q3GA) and quercetin were the key components of the NnEx. In vitro experiments confirmed that quercetin and Q3GA functioned in lipid metabolism by promoting triglyceride degradation through inhibition of the cAMP pathway. In vivo experiments showed that NnEx ingestion inhibited the accumulation of neutral fats in ICR mice and transitioned the hepatocytes of type II diabetic KK-Ay mice out of glycogenosis. These results highlight the ability of NnEx to control metabolism by modulating fat and sugar absorption and may provide an interesting novel treatment for obesity and related lifestyle diseases such as type II diabetes.

Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout: A randomised, double-blind, placebo-controlled study.

PURPOSE: Lactobacillus gasseri PA-3 (PA-3) has been previously shown to decrease serum uric acid (SUA) levels in subjects with increased SUA. In this study, we investigated whether PA-3 is also capable of decreasing SUA levels in patients with hyperuricaemia and/or gout. METHODS: Twenty-five patients with hyperuricaemia and/or gout completed this study. Urate-lowering drugs were discontinued for 12 weeks (week -4 to week 8). After flushing of urate-lowering drugs for 4 weeks (week 0), patients were randomised equally to receive diets containing yoghurt beverages with PA-3 or without PA-3 for a duration of 8 weeks (week 8). The intention to treat (ITT) population included all subjects who were randomised, and the per-protocol (PP) population included subjects who completed the experiment with compliance. We evaluated SUA levels at the end of the study as well as changes in SUA levels in comparison to week 0. RESULTS: In both ITT and PP analyses, there were no significant differences in SUA levels or in the changes in SUA levels compared to week 0 between the two groups. However, in a sub-population whose SUA levels at week 0 were within one SD of the mean of the whole PP population, changes in SUA levels in the group consuming PA-3-containing yoghurt were significantly lower than those of the control group (p = .0378). CONCLUSION: PA-3-containing yoghurt improves SUA levels, even in patients with hyperuricaemia and/or gout.

Detection of gas components as a novel diagnostic method for colorectal cancer.

BACKGROUND: The fecal occult blood test (FOBT) is widely accepted as the most economic and non-invasive screening method for colorectal cancer (CRC). However, the FOBT is inconvenient because it requires a fecal sample and shows limited accuracy. Alternatively, we hypothesized that fecal gas compounds from bowel movements may be a non-invasive biomarker for CRC. METHODS: Gas compounds were collected from the bowel movements of 30 patients with CRC and from 26 healthy controls. The patient group comprised 17 males and 13 females, and the average age was 68 years. Additionally, 22 patients had colon cancer, and eight patients had rectal cancer. Gas compounds were analyzed using gas chromatography and compared with those from healthy controls. RESULTS: In the gas analysis, methyl mercaptan was significantly higher in the CRC group than in the control group. Hydrogen was significantly lower in the CRC group than in the control group and was correlated with tumor depth and advanced disease stage. Sensitivity, specificity, and accuracy of detection by a discriminant formula were 90%, 57.7%, and 75%, respectively. CONCLUSION: Gas compounds from defecation constitute a promising, novel non-invasive approach for CRC screening. (UMIN000028256).

Content of delusional thoughts in Alzheimer's disease and assessment of content-specific brain dysfunctions with BEHAVE-AD-FW and SPECT.

BACKGROUND: A consensus on the brain dysfunction(s) underlying the delusions of Alzheimer's Dementia (AD) remains to be achieved. The aim of the present study was to test the hypothesis that content-based categorization of delusional ideas manifests as dysfunction of category-specific brain regions. METHODS: Fifty-nine consecutive first-visit AD outpatients underwent Single Photon Emission Computed Tomography (SPECT), Mini-Mental State Examination, and Behavioral Pathology in Alzheimer's Disease Frequency-Weighted Severity scale (BEHAVE-AD-FW) to assess cerebral blood flow (CBF), cognitive function, and delusion, respectively. SPECT images were analyzed by SPM5. RESULTS: CBF decreased at the temporal poles and right inferior temporal gyrus in "delusion of theft," at the temporal poles in "suspiciousness/paranoia," at the right parahippocampal gyrus and insula in "abandonment," and at the right amygdala in "Residence is not home." CONCLUSIONS: Our findings offer a perspective on the discrete categories of the pathological thoughts of AD patients that have previously been lumped together as "delusions." Dysfunction of the temporal poles may be associated with a socioemotional deterioration that may include pathological suspiciousness. Delusion of theft may be a manifestation of socioemotional deterioration and poor insight. Emotional factors may be essential for delusions of abandonment and "not home."

Effect of quercetin and its glucuronide metabolite upon 6-hydroxydopamine-induced oxidative damage in Neuro-2a cells.

Quercetin is ubiquitously distributed in plant foods. This antioxidative polyphenol is mostly converted to conjugated metabolites in the body. Parkinson disease (PD) has been suggested to be related to oxidative stress derived from abnormal dopaminergic activity. We evaluated if dietary quercetin contributes to the antioxidant network in the central nervous system from the viewpoint of PD prevention. A neurotoxin, 6-hydroxydopamine (6-OHDA), was used as a model of PD. 6-OHDA-induced H2O2 production and cell death in mouse neuroblastoma, Neuro-2a. Quercetin aglycone suppressed 6-OHDA-induced H2O2 production and cell death, although aglycone itself reduced cell viability at higher concentration. Quercetin 3-O-ß-D-glucuronide (Q3GA), which is an antioxidative metabolite of dietary quercetin, was little incorporated into the cell resulting in neither suppression of 6-OHDA-induced cell death nor reduction of cell viability. Q3GA was found to be deconjugated to quercetin by microglial MG-6 cells. These results indicate that quercetin metabolites should be converted to their aglycone to exert preventive effect on damage to neuronal cells.

Safety of high doses of Propionibacterium freudenreichii ET-3 culture in healthy adult subjects.

Propionibacterium freudenreichii ET-3 (7025) culture, a cell-free product of whey fermentation by P. freudenreichii ET-3, has been shown to promote the growth of Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA). Here we report the results of two clinical studies designed to evaluate the safety of high doses of P. freudenreichii ET-3 culture medium. Study 1 had a randomized, double-blind, crossover design. Ten healthy male and four healthy female subjects received 45 tablets of either P. freudenreichii ET-3 culture medium (total daily intake of 3g solid content and 283.5µg of DHNA; active group) or placebo (unfermented product) during two 1-week supplementation periods separated by a 4-week washout period. In Study 2, 11 healthy men took four tablets of P. freudenreichii ET-3 culture medium per day (total daily intake of 0.267g solid content and 22.5µg of DHNA) for a period of 13weeks. In both studies, hematological, clinical chemistry, and urinary parameters were measured before and after each supplementation period and gastrointestinal symptoms were assessed by questionnaire. In Study 1, there were no statistically significant differences between placebo and active supplementation periods in any measured parameter and the incidence of gastrointestinal symptoms were similar between groups. In Study 2, total protein, white blood cell count, hemoglobin, and mean corpuscular hemoglobin concentration decreased significantly from baseline and mean corpuscular volume and urine pH increased from baseline. The changes in hematological parameters were deemed not to be due to P. freudenreichii ET-3 culture medium supplementation given that all parameters remained within normal ranges and were not consistent with any clinically meaningful effect.

Suppression of laser-induced choroidal neovascularization by subconjunctival injection of 9alpha-fluoromedroxyprogesterone acetate (FMPA), an anti-angiogenic agent, in rats.

9alpha-Fluoromedroxyprogesterone acetate (FMPA) is a synthetic analog of medroxyprogesterone acetate (MPA). FMPA exhibited more potent anti-tumor and anti-angiogenic activities in some assay systems than the parent agent, MPA. Exudative age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). Anecortave acetate, an angiostatic steroid, is clinically efficacious in patients with exudative AMD. Betamethasone is an anti-angiogenic steroid. Therefore, we examined the effects of FMPA, anecortave acetate and betamethasone on laser-induced CNV in rats. Anecortave acetate and betamethasone were included as positive controls. Crypton laser was applied to the fundus in Brown Norway rats. Laser photocoagulations were performed in each eye between the major retinal vessels of the superior retina. Subconjunctival injection of FMPA, anecortave acetate or betamethasone was performed once just after the photocoagulation (on day 0). The incidence of CNV formation was evaluated by fluorescein angiography (FAG) on day 14. On the next day, examination of the retinal function was performed by electro retinogram (ERG). Subconjunctival injection of FMPA at doses of 300, 1000 and 3000 microg/eye dose-dependently inhibited the incidence of CNV formation. Significant differences were observed at doses of 1000 and 3000 microg/eye of FMPA as compared with the control group. Anecortave acetate and betamethasone significantly inhibited the incidence of CNV formation. FMPA at the doses used in this study did not affect the retinal function in rats, as determined by ERG. FMPA appeared to be effective in a rat model of CNV, so it was demonstrated that FMPA might be useful in the treatment of AMD.

Synthesis and anti-tumor activity of a fluorinated analog of medroxyprogesterone acetate (MPA), 9alpha-fluoromedroxyprogesterone acetate (FMPA).

We synthesized 9alpha-fluoromedroxyprogesterone acetate (FMPA) in order to test whether it is a more potent anti-angiogenic agent than medroxyprogesterone acetate (MPA), which has been widely used as a therapeutic agent for breast and endometrium cancers. FMPA was previously synthesized in 10 steps (total yield: 1%). An efficient synthesis of FMPA has been achieved in 6 steps (total yield: 12%). We examined the anti-tumor effect of FMPA, complexed with dimethyl-beta-cyclodextrin (DM-beta-CyD), on rat mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene (DMBA). FMPA showed great anti-tumor effect on DMBA-induced rat mammary carcinomas.

Regulation of bone metabolism in immunosuppressant (FK506)-treated rats.

After organ transplantation, severe osteoporosis is occasionally seen, and the use of immunosuppressants is thought to be one of the causes of such osteoporosis. In the present study, we investigated the effects of FK506 monotherapy on bones and determined the mechanism of onset of osteoporosis, both by assessing chronological changes in bone metabolism and by identifying factors that facilitate bone resorption. In 8-week-old male Sprague-Dawley rats, FK506 (1 mg/kg) was injected intraperitoneally every day for 5 weeks (FK506-treated group), and for comparison, physiological saline was administered in the same manner in a control group of rats. Serum and urine samples were collected at weeks 0, 1, 3, and 5 of administration. The femur and tibia were collected within 24 h of the final administration. When compared to the control group, findings on three-dimensional micro-computed tomography of the femur for the FK506-treated group showed a significant decrease in trabecular bone volume. The level of serum osteocalcin in the FK506-treated group at week 1 of administration was significantly higher than the control. Throughout the administration period, the sum of urinary pyridinoline (PYD) and deoxypyridinoline (Dpd) was significantly higher in the FK506-treated group. Of the various bone resorption factors tested, the level of serum parathyroid hormone (PTH) in the FK506-treated group was significantly higher than the control at week 3 of administration. The results of the present study confirmed that FK506 monotherapy in rats induced high-turnover osteoporosis. Soon after the start of FK506 administration, bone formation and resorption were elevated, and PTH appeared to have been involved in the maintenance of the elevated bone resorption.