Maternal DHA intake in mice increased DHA metabolites in the pup brain and ameliorated MeHg-induced behavioral disorder.

Although pregnant women's fish consumption is beneficial for the brain development of the fetus due to the DHA in fish, seafood also contains methylmercury (MeHg), which adversely affects fetal brain development. Epidemiological studies suggest that high DHA levels in pregnant women's sera may protect the fetal brain from MeHg-induced neurotoxicity, but the underlying mechanism is unknown. Our earlier study revealed that DHA and its metabolite 19,20-dihydroxydocosapentaenoic acid (19,20-DHDP) produced by cytochrome P450s (P450s) and soluble epoxide hydrolase (sEH) can suppress MeHg-induced cytotoxicity in mouse primary neuronal cells. In the present study, DHA supplementation to pregnant mice suppressed MeHg-induced impairments of pups' body weight, grip strength, motor function, and short-term memory. DHA supplementation also suppressed MeHg-induced oxidative stress and the decrease in the number of subplate neurons in the cerebral cortex of the pups. DHA supplementation to dams significantly increased the DHA metabolites 19,20-epoxydocosapentaenoic acid (19,20-EDP) and 19,20-DHDP as well as DHA itself in the fetal and infant brains, although the expression levels of P450s and sEH were low in the fetal brain and liver. DHA metabolites were detected in the mouse breast milk and in human umbilical cord blood, indicating the active transfer of DHA metabolites from dams to pups. These results demonstrate that DHA supplementation increased DHA and its metabolites in the mouse pup brain and alleviated the effects of MeHg on fetal brain development. Pregnant women's intake of fish containing high levels of DHA (or DHA supplementation) may help prevent MeHg-induced neurotoxicity in the fetus.

The effect of hand therapy on alleviating chemotherapy-induced peripheral neuropathy in a model mouse.

The use of neurotoxic chemotherapeutic agents induces numbness in the limbs through chemotherapy-induced peripheral neuropathy (CIPN). Recently, we found that hand therapy involving finger massage improved mild to moderate numbness in CIPN patients. In this study, we behaviorally, physiologically, pathologically, and histologically investigated the mechanisms underlying hand therapy-induced numbness improvement in a CIPN model mouse. Hand therapy was performed for 21 days after the disease induction. Its effects were evaluated using mechanical and thermal thresholds and blood flow in the bilateral hind paw. Moreover, 14 days after the hand therapy was administered, we assessed the blood flow and conduction velocity in the sciatic nerve, the level of serum galectin-3, and the histological myelin and epidermis-related changes in the hindfoot tissue. Hand therapy significantly improved allodynia, hyperalgesia, blood flow, conduction velocity, serum galectin-3, and epidermal thickness in the CIPN model mouse. Furthermore, we observed the images of repairs of the myelin degeneration. Thus, we found that hand therapy could improve numbness in the CIPN model mouse and that it could help to repair peripheral nerves by promoting blood circulation in the limbs.

Combined Treatment with Curcumin and Ferulic Acid Suppressed the Aß-Induced Neurotoxicity More than Curcumin and Ferulic Acid Alone.

Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive cognitive decline. Several effective natural components have been identified for the treatment of AD. However, it is difficult to obtain conclusive evidence on the safety and effectiveness of natural components, because a variety of factors are associated with the progression of AD pathology. We hypothesized that a therapeutic effect could be achieved by combining multiple ingredients with different efficacies. The purpose of this study was thus to evaluate a combination treatment of curcumin (Cur) and ferulic acid (FA) for amyloid-ß (Aß)-induced neuronal cytotoxicity. The effect of Cur or FA on Aß aggregation using thioflavin T assay was confirmed to be inhibited in a concentration-dependent manner by Cur single or Cur + FA combination treatment. The effects of Cur + FA on the cytotoxicity of human neuroblastoma (SH-SY5Y) cells induced by Aß exposure were an increase in cell viability, a decrease in ROS and mitochondrial ROS, and repair of membrane damage. Combination treatment showed an overall higher protective effect than treatment with Cur or FA alone. These results suggest that the combined action mechanisms of Cur and FA may be effective in preventing and suppressing the progression of AD.

Associations between metal concentrations in whole blood and placenta previa and placenta accreta: the Japan Environment and Children's Study (JECS).

BACKGROUND: Placenta previa and placenta accreta associate with high morbidity and mortality for both mothers and fetus. Metal exposure may have relationships with placenta previa and placenta accreta. This study analyzed the associations between maternal metal (cadmium [Cd], lead [Pb], mercury [Hg], selenium [Se], and manganese [Mn]) concentrations and placenta previa and placenta accreta. METHODS: We recruited 17,414 women with singleton pregnancies. Data from a self-administered questionnaire regarding the first trimester and medical records after delivery were analyzed. Maternal blood samples were collected to measure metal concentrations. The subjects were classified into four quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. RESULTS: The odds ratio for placenta previa was significantly higher among subjects with Q4 Cd than those with Q1 Cd. The odds ratio for placenta previa was significantly higher for subjects with Q2 Pb than those with Q1 Pb. CONCLUSION: Participants with placenta previa had higher Cd concentrations. However, this study was cross-sectional and lacked important information related to Cd concentration, such as detailed smoking habits and sources of Cd intake. In addition, the subjects in this study comprised ordinary pregnant Japanese women, and it was impossible to observe the relationship between a wide range of Cd exposure and placenta previa. Therefore, epidemiological and experimental studies are warranted to verify the relationship between Cd exposure and pregnancy abnormalities.

Protection of Differentiating Neuronal Cells from Amyloid ß Peptide-induced Injury by Alkaline Extract of Leaves of Sasa senanensis Rehder.

BACKGROUND/AIM: We have previously reported the protection of doxorubicin-induced keratinocyte toxicity by alkaline extract of the leaves of Sasa senanensis Rehder (SE). In order to extend the generality of the cell protective effect of SE, we investigated whether it also protects rat PC12 and human SH-SY5Y neuron model cells from amyloid ß-peptide (Aß)-induced injury. MATERIALS AND METHODS: Viability of cells was determined by the MTT method. Cytotoxicity was evaluated by the concentration that reduces the cell viability by 50% (CC50). Protection from Aß-induced cytotoxicity was evaluated by the concentration that reversed the Aß-induced reduction of viability by 50% (EC50). The selectivity index (SI) of neuroprotective activity was defined as the ratio of EC50 to CC50 Aß1-42 aggregation was assayed using Aß1-42 ammonium hydroxide. RESULTS: SE showed hormetic growth stimulation at lower concentrations in both neuron precursors and differentiated cells. SE reproducibly inhibited Aß-induced cytotoxicity against both undifferentiated and differentiated neuron cells. Both the extent of differentiation induction and viability depended on the cell density, suggesting the release of growth and differentiation stimulation substances into culture supernatant. Higher concentrations of SE partially reduced the Aß1-42 aggregation. CONCLUSION: Hormetic growth stimulation and inhibition of aggregation may be involved in the neuroprotective activity of SE.

Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms.

BACKGROUND: Dietary fibers are metabolized by gastrointestinal (GI) bacteria into short-chain fatty acids (SCFAs). We investigated the potential role of these SCFAs in ß-amyloid (Aß) mediated pathological processes that play key roles in Alzheimer's disease (AD) pathogenesis. RESEARCH DESIGN AND METHODS: Multiple complementary assays were used to investigate individual SCFAs for their dose-responsive effects in interfering with the assembly of Aßß1-40 and Aß1-42 peptides into soluble neurotoxic Aß aggregates. RESULTS: We found that several select SCFAs are capable of potently inhibiting Aß aggregations, in vitro. CONCLUSION: Our studies support the hypothesis that intestinal microbiota may help protect against AD, in part, by supporting the generation of select SCFAs, which interfere with the formation of toxic soluble Aß aggregates.

Soy isoflavones inducing overt hypothyroidism in a patient with chronic lymphocytic thyroiditis: a case report.

BACKGROUND: Many people have thyroid conditions that make them susceptible to hypothyroidism. If the foods they eat may interfere with the production of thyroid hormone, which can lead to development of serious hypothyroidism. The danger of health drinks should always be noted. CASE PRESENTATION: A 72-year-old Japanese woman was previously diagnosed with chronic lymphocytic thyroiditis caused by a goiter and had an elevated thyroid-stimulating hormone level (6.56 µIU/ml), a high anti-thyroid peroxidase antibody level (>600 IU/ml), and a high antithyroglobulin level (> 4000 IU/ml) but normal levels of free triiodothyronine (3.08 pg/ml) and thyroxine (1.18 ng/ml). She presented to our hospital with sudden-onset general malaise, edema, and hoarseness with an elevated thyroid-stimulating hormone (373.3 µIU/ml) level and very low triiodothyronine (< 0.26 pg/ml) and thyroxine (0.10 ng/ml) levels. It was determined that for 6 months she had been consuming a processed, solved health drink ("barley young leaf") in amounts of 9 g/day, which included soybean and kale powder extract. Hypothyroidism might be affected by ingredients of health drinks. She discontinued consumption of the health drink immediately and began taking 12.5 µg of levothyroxine. The amount of levothyroxine was gradually increased every 3 days up to 100 µg. At day 61, her thyroid-stimulating hormone level had decreased (6.12 µIU/ml), her free triiodothyronine (2.69 pg/ml) and thyroxine (1.56 ng/ml) levels had increased, and her general condition was improved. Among risky foods lowering thyroid function, some experimental studies have revealed that isoflavones reduce thyroid function. Therefore, we measured the presence of isoflavones in the patient's frozen serum with thin-layer chromatography. After she discontinued consumption of the health drink, two components quickly disappeared, and the other three components gradually decreased. On the basis of developing solvent composition and a positive ferric chloride reaction in thin-layer chromatography experiment, the five ingredients that disappeared or decreased were highly suspected to be soy isoflavones. CONCLUSIONS: This case emphasizes that consuming health drinks that include soy isoflavone powder extracts can lead to severe hypothyroidism.

Potentiation of 17ß-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid.

Several studies have shown that docosahexaenoic acid (DHA) attenuates epileptic seizures; however, the molecular mechanism by which it achieves this effect is still largely unknown. DHA stimulates the retinoid X receptor, which reportedly regulates the expression of cytochrome P450 aromatase (P450arom). This study aimed to clarify how DHA suppresses seizures, focusing on the regulation of 17ß-estradiol synthesis in the brain. Dietary supplementation with DHA increased not only the expression of P450arom, but also 17ß-estradiol in the cerebral cortex. While DHA did not affect the duration or scores of the seizures induced by pentylenetetrazole, DHA significantly prolonged the seizure latency. A P450arom inhibitor, letrozole, reduced 17ß-estradiol levels and completely suppressed the elongation of seizure latency elicited by DHA. These results suggest that DHA delays the onset of seizures by promoting the synthesis of 17ß-estradiol in the brain. DHA upregulated the expression of anti-oxidative enzymes in the cerebral cortex. The oxidation in the cerebral cortex induced by pentylenetetrazole was significantly attenuated by DHA, and letrozole completely inhibited this suppressive action. Thus, the anti-oxidative effects of 17ß-estradiol may be involved in the prevention of seizures mediated by DHA. This study revealed that 17ß-estradiol in the brain mediated the physiological actions of DHA.

Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AßPP/PS1 Mice.

Alzheimer's disease (AD) is the most common cause of dementia. The cardinal neuropathological characteristic of AD is the accumulation of amyloid-ß (Aß) into extracellular plaques that ultimately disrupt neuronal function and lead to neurodegeneration. One possible therapeutic strategy therefore is to prevent Aß aggregation. Previous studies have suggested that vitamin E analogs slow AD progression in humans. In the present study, we investigated the effects of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm oil, on amyloid pathology in vitro and in vivo. TRF treatment dose-dependently inhibited the formation of Aß fibrils and Aß oligomers in vitro. Moreover, daily TRF supplementation to AßPPswe/PS1dE9 double transgenic mice for 10 months attenuated Aß immunoreactive depositions and thioflavin-S-positive fibrillar type plaques in the brain, and eventually improved cognitive function in the novel object recognition test compared with control AßPPswe/PS1dE9 mice. The present result indicates that TRF reduced amyloid pathology and improved cognitive functions, and suggests that TRF is a potential therapeutic agent for AD.

Oral vitamin C supplementation in hemodialysis patients and its effect on the plasma level of oxidized ascorbic acid and Cu/Zn superoxide dismutase, an oxidative stress marker.

BACKGROUND/AIM: Oxidative stress is known to be enhanced in hemodialysis patients, and one of its useful markers is plasma copper/zinc superoxide dismutase (Cu/Zn-SOD). The increase in plasma Cu/Zn-SOD can be inhibited by orally administered lipid-soluble vitamin E. We examined the antioxidative effects of water-soluble vitamin C administered orally on Cu/Zn-SOD levels in hemodialysis patients. METHODS: Vitamin C was orally administered to 16 maintenance hemodialysis patients before each dialysis session. Doses were increased from 200 to 1,000 mg over 3 months. The levels of plasma vitamin C and Cu/Zn-SOD and its mRNA expression in leukocytes were determined 1, 2, and 3 months after the start of vitamin C administration. Furthermore, the levels of oxidized and reduced forms of plasma vitamin C were determined before the start of vitamin C administration and before and after dialysis at 1,000-mg vitamin C doses. RESULTS: Following oral administration, the plasma levels of vitamin C and its oxidized form were increased. However, significant changes in plasma Cu/Zn-SOD or its mRNA expression in leukocytes were not observed. CONCLUSION: In maintenance hemodialysis patients, vitamin C administration resulted in a significant increase in the postdialysis level of the oxidized form of vitamin C, which suggested an increase in antioxidant effect. However, water-soluble vitamin C did not significantly suppress Cu/Zn-SOD expression enhancement.

Scalp hair mercury concentrations in Pakistan.

The presence of mercury in the environment is widespread and persistent, but the extent of exposure of Pakistanis to mercury is virtually unknown. We collected toenail and scalp hair samples from 158 subjects (83 males and 75 females) residing in Lahore and its suburbs. We also conducted a questionnaire survey and personal interviews to obtain information on demographic factors, lifestyles, and socioeconomic factors, among others. Mercury concentration in hair samples was measured by cold vapor atomic absorption spectrometry (CVAAS). In addition, the concentration of selenium in the toenail and hair samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). The mean hair mercury concentration was 0.45 ppm (95% CI = 0.34-0.60) and did not show correlation with fish consumption, age, area of origin, or present residence. Mercury concentration was higher (p = 0.021) in females than in males, and was also higher in subjects with 11 or more years of education (p for trend = 0.013). There were 13 subjects with mercury concentration higher than 10 ppm. Most of them were young females and a few were middle-aged males. When the analysis was confined to subjects with mercury concentrations lower than 0.6 ppm, the amount of fish consumed showed correlation with hair mercury concentration with a marginal statistical significance (p = 0.065). The geometric means of selenium in hair and toenails were 0.87 and 1.01 ppm, respectively. Mercury and selenium concentrations in hair showed no correlation (correlation coefficient = 0.057, p = 0.478). This study shows that mercury exposure levels among residents in Lahore and its suburban areas are relatively low, except among outliers, wherein mercury exposure might be brought about by the use of mercury-containing soaps.

Comparison of effect of vitamin E-coated dialyzer and oral vitamin E on hemodialysis-induced Cu/Zn-superoxide dismutase.

BACKGROUND: We reported earlier that production of Cu/Zn-superoxide dismutase (SOD) increases markedly in hemodialysis patients but not in non-dialyzed chronic renal failure (CRF) patients. In this study, we compared the antioxidant effects of oral vitamin E supplementation (VE-PO) and vitamin E coating of a dialyzer (VE-BMD) by measuring increased Cu/Zn-SOD in hemodialysis patients. METHODS: 31 hemodialysis patients were divided into two groups: 16 hemodialysis patients underwent usual dialysis with vitamin E supplementation 600 mg/day while 15 others were dialyzed using vitamin E-coated membrane for 6 months. Total plasma SOD activity was determined by NBT method, plasma Cu/Zn-SOD contents by ELISA and Cu/Zn-SOD mRNA in leukocytes by RT-PCR. RESULTS: VE-PO and VE-BMD showed almost comparable effects on Cu/Zn-SOD contents and its mRNA levels in hemodialysis patients. VE-PO resulted in a progressive decrease of Cu/Zn-SOD content (p < 0.001). A comparable progressive decrease was observed also in VE-BMD (p < 0.0001). Both VE-PO and VE-BMD resulted in a progressive decrease of Cu/Zn-SOD mRNA (p < 0.01), which reached the level of non-dialyzed CRF patients.