Extract of Torreya nucifera Pericarps Exhibits a Parasiticidal Effect on the Nematode Parasite, Trichinella spiralis.

Benzimidazole derivatives can effectively treat nematode parasitic infections; however, some derivatives demand distinct administrative strategies depending on plasma concentration and patient conditions. Numerous studies have examined the potential of natural extracts to exert parasiticidal activity with minimal side effects. Herein, we examined the potential parasiticidal effects of Torreya nucifera extract. The pericarps of T. nucifera were extracted with methanol, dried, and the pellet was dissolved in hot water (Tn-Phw). We designed four individual mouse experiments to clarify the prophylactic and therapeutic effects of Tn-Phw on Trichinella spiralis infection. Also, 100 L1 larvae were isolated and treated with Tn-Phw (10 mg/mL) in vitro to confirm the killing effect. Furthermore, we microscopically examined the morphology of L1 larvae to confirm the parasite-killing effect and analyzed the morphology using a scanning electron microscope (SEM). The expression of three molting-related genes was confirmed to determine whether Tn-Phw induced morphological changes in L1 larvae. Following treatment with Tn-Phw, L1 larvae death was observed after 16 h. Following SEM examination, the healthy muscle larvae showed striated ridges and wrinkles; this was not observed in extract-treated muscle larvae. Expression levels of the three molting-related genes did not differ between the Tn-Phw-treated and control groups. T. spiralis-infected mice pretreated with Tn-Phw showed significantly reduced muscle larva infection when compared with control mice. In all experiments, treatment with Tn-Phw afforded preventive and therapeutic effects against T. spiralis infection and parasitism. Natural substances against nematode parasites could be developed as therapeutic agents with few side effects and enhanced parasiticidal efficacy.

Maternal and Fetal Effects of Gestational Vitamin D Concentration.

Most (90%) vitamin D synthesis occurs in the skin using sunlight (ultraviolet rays), and 10% is obtained through food. Vitamin D is an essential nutrient for skeletal growth and maintenance, cell proliferation and differentiation, and immune function. This study investigated whether maternal serum vitamin D concentrations induce maternofetal effects. Hematological analysis, serological changes, and precision fetal ultrasound findings were analyzed by maternal vitamin D concentration in gestational weeks 22-25 to ascertain direct effects on fetal growth. Bone density-vitamin D concentration correlation was analyzed. No hematologic or serological effect of maternal vitamin D concentration was detected; however, the sexually transmitted infection and cross-infection rates were inversely proportional to maternal vitamin D concentration. No significant correlation between vitamin D concentration and vertebral and femoral BMD was detected. For fetal growth, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length were analyzed. Humerus (p < 0.05) and femur (p < 0.001) lengths were higher in the vitamin D-sufficient group than in the vitamin D-deficient group. Vitamin D concentration did not positively affect hematologic changes and bone density; maternal vitamin D concentration essentially affected fetal bone growth. Vitamin D inhibits sexually transmitted infections in mothers and promotes fetal bone growth. Prevention of vitamin D deficiency, supplementation, or outdoor activities is recommended.

Association between use of vitamin and mineral supplement and non-alcoholic fatty liver disease in hypertensive adults.

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic metabolic disorder in hypertensive adults. Impaired metabolism of micronutrients may increase NAFLD risk by exacerbating oxidative stress, insulin resistance, and inflammation among hypertensive adults. In this first cross-sectional analysis of 7,376 hypertensive adults with 2,015 NAFLD cases in the Korea National Health and Nutrition Examination Survey, vitamin and mineral supplements (VMS) use was identified via questionnaire. NAFLD was defined by a hepatic steatosis index > 36. Multivariable-adjusted odds ratios (MVOR) and 95% confidence intervals (CIs) were calculated using logistic regression models. In our study, 18.6% were current users of VMS; of these, 76.7% used multi-vitamin/mineral supplements. Current VMS users had significantly lower odds of NAFLD, compared with non-users (MVOR [95% CI]: 0.73 [0.58-0.92]). The inverse association became attenuated and non-significant among those consuming VMS at higher frequency (≥ 2 times/day), for longer duration (> 16 months), and taking ≥ 2 VMS products. The inverse association with current use of VMS was only evident in those aged < 56 years (MVOR [95% CI]: 0.54 [0.40-0.72]) and men (MVOR [95% CI]: 0.56 [0.40-0.80])(Pinteraction ≤ 0.04). Our results suggest that VMS use may lower NAFLD risk, particularly among younger or male hypertensive adults, if taken in moderation.

Functionality of a next generation biosynthetic bacterial 6-phytase in enhancing phosphorus availability to weaned piglets fed a corn-soybean meal-based diet without added inorganic phosphate.

The utility of a next generation biosynthetic bacterial 6-phytase (PhyG) in restoring bone ash, bone phosphorus (P) content and performance in piglets depleted in P was evaluated. A total of 9 treatments were tested as follows. Treatment 1, a negative control (NC) diet; treatments 2, 3, 4, NC supplemented with 250, 500 or 1,000 FTU/kg of PhyG; treatments 5, 6, NC supplemented with 500 or 1,000 FTU/kg of a commercial Buttiauxella sp phytase (PhyB); treatments 7, 8, 9, NC supplemented with monocalcium phosphate (MCP) to provide 0.7, 1.4 and 1.8 g/kg digestible P, equating to a digestible P content of 1.8, 2.5 and 2.9 g/kg. The latter constituting the positive control (PC) diet with adequate P and calcium (Ca). The NC was formulated without inorganic P (1.1 g digestible P/kg) and reduced in Ca (5.0 g/kg). Additional limestone was added to treatments 7 to 9 to maintain Ca-to-P ratio between 1.2 and 1.3. A total of 162 crossed Pietrain × (Large White × Landrace) 21-d-old piglets (50% males and 50% females) were fed adaptation diets until 42 d old and then assigned to pens with 2 pigs/pen and 9 pens/treatment in a completely randomized block design. Piglets were fed mash diets based on corn and soybean meal ad libitum for 28 d. At the end of the study, one piglet perpen was euthanized and the right feet collected for determination of bone strength, bone ash and mineral content. Compared with the PC, the NC group had reduced average daily gain (ADG) and increased feed conversion ratio (FCR) during all growth phases and overall, and at d 28 (70 d old) NC pigs had bones with reduced ash, Ca and P content (P < 0.05). The PhyG at 250 FTU/kg improved bone ash vs. NC. Increasing PhyG dose linearly or quadratically improved bone ash, ADG and FCR (P < 0.05). At ≥ 500 FTU/kg, both PhyG and PhyB maintained ADG and FCR equivalent to PC. Linear regression analysis was done to compare the measured response parameters to increasing digestible P from MCP. Based on this analysis it was shown that PhyG and PhyB at 1,000 FTU/kg could replace 1.83 and 1.66 g/kg digestible P from MCP in the diet, respectively, on average across metacarpi bone ash, ADG or FCR. These findings suggest that the biosynthetic phytase is highly effective in the tested dietary setting.

The Effects of Curcuma longa L., Purple Sweet Potato, and Mixtures of the Two on Immunomodulation in C57BL/6J Mice Infected with LP-BM5 Murine Leukemia Retrovirus.

The immune response is stimulated to protect the body from external antigens and is controlled by several types of immune cells. In the present study, the immunomodulatory effects of Curcuma longa L., purple sweet potato, and mixtures of the two (CPM) were investigated in C57BL/6 mice infected with LP-BM5 murine leukemia virus (MuLV). Mice were divided into seven groups as follows: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 300 mg/kg body weight), the original powder of C. longa L. (C; LP-BM5 MuLV infection+dietary supplement of C 189 mg/kg body weight), the original powder of purple sweet potato (P; LP-BM5 MuLV infection+dietary supplement of P 1811 mg/kg body weight), CPM Low (CPL; LP-BM5 MuLV infection+CPM 2 g/kg body weight), and CPM High (CPH; LP-BM5 MuLV infection+CPM 5 g/kg body weight). Dietary supplementation lasted for 12 weeks. Dietary supplementation of CPM inhibited LP-BM5 MuLV-induced lymphadenopathy and splenomegaly and inhibited reduction of messenger RNA (mRNA) expression of major histocompatibility complex (MHC) I and II. Moreover, CPM reduced the decrease in T- and B cell proliferation, reduced the population of CD4(+)/CD8(+) T cells, and remedied the unbalanced production of T helper-1 (Th1)/T helper-2 (Th2) cytokines in LP-BM5 MuLV-infected mice. In addition, CPM inhibited reduction of phagocytosis in peritoneal macrophages and decreased serum levels of immunoglobulin A (IgA), immunoglobulin E (IgE), and immunoglobulin G (IgG). These results suggest that CPM had a positive effect on immunomodulation in C57BL/6 mice induced by LP-BM5 leukemia retrovirus infection.

Association of maternal omega-6 fatty acid intake with infant birth outcomes: Korean Mothers and Children's Environmental Health (MOCEH).

BACKGROUND: Maternal fatty acids (FAs) intake has an effect on birth weight, birth length, and gestational age, as fetal development is entirely dependent on the maternal essential FA supply. This study aimed to identify the association between the maternal intake of FAs and birth outcomes among pregnant women who participated in the Mothers and Children's Environmental Health (MOCEH) prospective cohort study in South Korea. METHODS: A total of 1407 pregnant women, aged 30.2 ± 3.7 years, at 12 to 28 weeks' gestation were recruited between August 2006 and December 2010. Their dietary intake during pregnancy was investigated by the 1-day 24-h dietary recall method. The pregnancy outcome data-namely infant's gestational age, birth weight, and birth length-were analyzed for their associations with their mothers' intake of FAs. RESULTS: When adjusted for confounding factors, multiple regression analysis revealed adverse effects on birth weight (P = 0.031) and birth length (P = 0.025) with high maternal intake of omega-6 FAs. In the multiple logistic regression analysis, the odds ratio (OR) for the risk of being below the 10th percentile for birth weight was higher in the highest quintile (Q5) compared to the lowest quintile (Q1) of omega-6 FA intake levels (OR = 2.444; 95% CI = 1.038-5.751; P for trend = 0.010). Also, the OR for being above the 90th percentile of birth length was lower in the highest quintile (Q5) compared to that in the lowest quintile (Q1) of omega-6 FA intake (OR = 0.432; 95% CI = 0.211-0.884; P for trend = 0.020). However, the maternal intake of omega-3 FAs was not related to gestational age, birth weight, or birth length. CONCLUSIONS: A high maternal omega-6 FA intake was negatively associated with birth weight and birth length.

Effects of folic acid supplementation on serum homocysteine levels, lipid profiles, and vascular parameters in post-menopausal Korean women with type 2 diabetes mellitus.

BACKGROUND/OBJECTIVES: Complications of diabetes, such as cardiovascular disease, are associated with increased mortality among type 2 diabetes mellitus patients. Homocysteine has been recently identified as a predictor of cardiovascular disease-related complications in diabetes. We investigated whether or not supplementation with folic acid tablets can lower homocysteine levels and improve parameters related with vascular complications. SUBJECTS/METHODS: We conducted a non-randomized 8-week trial involving postmenopausal diabetic women (n = 25) supplemented with 800 µg of folic acid (400 µg twice a day) daily. Subjects' serum levels of folate, homocysteine, and vitamin B12 were measured, along with vascular function and brachial-ankle pulse wave velocity. RESULTS: Folic acid supplementation significantly increased serum folate levels (P < 0.0001), reduced homocysteine levels (P < 0.0001), and increased vitamin B12 levels (P = 0.0063). There were significant decreases in low-density lipoprotein cholesterol levels as well as the ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol and total cholesterol to high-density lipoprotein cholesterol. Brachial-ankle pulse wave velocities were not altered by supplementation. Changes in serum vitamin B12 after folic acid supplementation were negatively correlated with changes in brachial-ankle pulse wave velocity. CONCLUSIONS: In this study on postmenopausal Korean women with type 2 diabetes mellitus, folic acid supplementation reduced serum homocysteine levels, increased serum folate and vitamin B12 levels, and lowered lipid parameters.

Breast milk fatty acid composition and fatty acid intake of lactating mothers in South Korea.

The aim of this study was to determine the fatty acid (FA) composition of breast milk, and its association with mothers' FA intake. Milk samples were obtained from 238 healthy lactating women who volunteered to participate in the Human Milk Micronutrients Analysis Research. Dietary intake during lactation was assessed using a 3-d food record, and fat content and FA composition of the breast milk samples were analysed by IR spectrometry using MilkoScan FT2 and GC flame ionisation detector, respectively. The fat content was 3·31 (sd 1·41) g/100 ml breast milk. The concentrations of arachidonic acid (20 : 4 n-6), EPA (20 : 5 n-3) and DHA (22 : 6 n-3) in breast milk were 0·48 (sd 0·13), 0·15 (sd 0·12) and 0·67 (sd 0·47) % of total FA, respectively. Fat content and FA composition of breast milk were associated with maternal age, BMI, supplement use and infant age. Dietary intakes of EPA, DHA, n-3 FA, n-6 FA, SFA and PUFA were positively correlated with the corresponding FA in the milk samples. FA levels in breast milk and maternal diet are highly correlated. Further studies are warranted to explore factors that may be associated with changes in FA composition in human milk.

Retinol, α-tocopherol, and selected minerals in breast milk of lactating women with full-term infants in South Korea.

BACKGROUND/OBJECTIVES: This study was performed to measure fat-soluble vitamins and minerals in breast milk of Korean lactating mothers who exclusively breastfed their babies. SUBJECTS/METHODS: Breast milk samples were collected from 334 mothers. Concentrations of retinol and α-tocopherol were analyzed by high performance liquid chromatography ultraviolet spectrometry while concentrations of minerals were measured by inductively coupled plasma optical emission spectrometry. RESULTS: Retinol and α-tocopherol contents of breast milk were 39.58 ± 19.64 µg/dL and 0.23 ± 0.13 mg/dL, respectively. Average sodium, potassium, calcium, phosphorus, and magnesium levels in breast milk were 11.11 ± 5.16, 38.56 ± 9.01, 27.87 ± 6.10, 13.56 ± 3.30, and 3.05 ± 0.65 mg/dL, respectively. Contents of trace elements such as iron, zinc, copper, and manganese were 40.26 ± 46.21, 98.40 ± 62.47, 24.09 ± 9.03, and 0.90 ± 1.63 µg/dL, respectively. Fat-soluble vitamin concentration was positively correlated with total fat in milk samples, but no significant differences were observed in levels of retinol, α-tocopherol, or minerals based on whether or not lactating women were taking dietary supplements. CONCLUSIONS: Micronutrient contents of breast milk samples from Korean lactating women were comparable to those of other nations. Retinol and α-tocopherol levels were correlated and also with total fat in breast milk.

Association between intake of B vitamins and cognitive function in elderly Koreans with cognitive impairment.

BACKGROUND: It is possible that blood B vitamins level and cognitive function may be affected by dietary intake of these vitamins, no study however has yet been conducted on relationships between B vitamins intake and cognitive function among elderly population in Korea. This study examined the relationship between B vitamins intake and cognitive function among elderly in South Korea. METHODS: Participants consisted of 100 adults with mild cognitive impairment (MCI), 100 with Alzheimer's disease (AD), and 121 normal subjects. Dietary intake data that included the use of dietary supplements were obtained using a 24-hour recall method by well-trained interviewers. Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, and homocysteine (Hcy) was assessed by a high performance liquid chromatography-fluorescence method. RESULTS: Plasma levels of folate and vitamin B12 were positively correlated with B vitamins intake; and plasma Hcy was negatively correlated with total intake of vitamin B2, vitamin B6, vitamin B12 and folate. In the AD group, a multiple regression analysis after adjusting for covariates revealed positive relationships between vitamin B2 intake and test scores for the MMSE-KC, Boston Naming, Word Fluency, Word List Memory and Constructional Recall Tests; and between vitamin B6 intake and the MMSE-KC, Boston Naming, Word Fluency, Word List Memory, Word List Recognition, Constructional Recall and Constructional Praxis Tests. Positive associations were observed between vitamin B12 intake and the MMSE-KC, Boston Naming, Constructional Recall and Constructional Praxis Tests, and between folate intake and the Constructional Recall Test. In the MCI group, vitamin B2 intake was positively associated with the MMSE-KC and Boston Naming Test, vitamin B6 intake was positively associated with the Boston Naming Test, and folate intake was positively associated with the MMSE-KC and Word List Memory test. No associations were observed in the normal group. CONCLUSION: These results suggested that total B vitamins intake is associated with cognitive function in cognitively impaired AD and MCI elderly, and the association is stronger in AD patients.

Association between kimchi intake and asthma in Korean adults: the fourth and fifth Korea National Health and Nutrition Examination Survey (2007-2011).

This study was performed to investigate the relationship between dietary factors and asthma in a representative population-based sample of 19,659 men and women, aged 19-64 years, using data from the fourth and fifth Korean National Health and Nutrition Examination Survey (KNHANES), 2007-2011. The presence of asthma was based on self-reported physician diagnosis of asthma in the Health Interview Surveys. Food intake was estimated by trained interviewers using a 24-h recall method. The prevalence of asthma in Korean adults was 2.4%. Adults with asthma consumed fewer amounts of kimchi (P=.0444) and fish (P=.0175) but had a higher cereal intake than those without asthma (P=.0056). Multiple logistic regression analysis after controlling for confounding factors showed a significant inverse relationship between kimchi consumption and the prevalence of asthma [odds ratio (95% confidence interval) for subjects consuming 1 to <2 servings (40-79.9 g), 2 to <3 servings (80-119.9 g), and ≥3 servings (≥120 g), relative to those consuming <1 serving (<40 g): 0.726 (0.534-0.987), 0.506 (0.348-0.736), and 0.678 (0.502-0.916), respectively; P for trend=0.0131]. These results warrant future studies to explore the mechanisms responsible for the association between kimchi consumption and asthma.

New preclinical antimalarial drugs potently inhibit hepatitis C virus genotype 1b RNA replication.

BACKGROUND: Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect. CONCLUSIONS/SIGNIFICANCE: We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.

Comparison of dietary food and nutrient intakes by supplement use in pregnant and lactating women in Seoul.

This study was performed to compare the dietary food and nutrient intakes according to supplement use in pregnant and lactating women in Seoul. The subjects were composed of 201 pregnant and 104 lactating women, and their dietary food intake was assessed using the 24-h recall method. General information on demographic and socioeconomic factors, as well as health-related behaviors, including the use of dietary supplements, were collected. About 88% and 60% of the pregnant and lactating women took dietary supplements, respectively. The proportion of dietary supplements used was higher in pregnant women with a higher level of education. After adjusting for potential confounders, among the pregnant women, supplement users were found to consume 45% more vegetables, and those among the lactating women were found to consume 96% more beans and 58% more vegetables. The intakes of dietary fiber and ß-carotene among supplement users were higher than those of non-users, by 23% and 39%, respectively. Among pregnant women, the proportion of women with an intake of vitamin C (from diet alone) below the estimated average requirements (EAR) was lower among supplement users [users (44%) vs. non-users (68%)], and the proportion of lactating women with intakes of iron (from diet alone) below the EAR was lower among supplement users [usesr (17%) vs. non-users (38%)]. These results suggest that among pregnant and lactating women, those who do not use dietary supplements tend to have a lower intake of healthy foods, such as beans and vegetables, as well as a lower intake of dietary fiber and ß-carotene, which are abundant in these foods, and non-users are more likely than users to have inadequate intake of micro-nutrient such as vitamin C and iron.

Maternal iron intake at mid-pregnancy is associated with reduced fetal growth: results from Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND: Iron supplementation is a common recommendation for pregnant women to prevent iron deficiency during pregnancy. There is an increasing concern about excessive iron consumption as a general iron prophylaxis by pregnant women without any due consideration about their dietary iron intake or iron status. Our present study investigated the association between total iron intake from diet and supplements and fetal growth in 337 pregnant women at mid-pregnancy in South Korea. METHODS: Iron intake from diet and supplements was examined by a 24-hour recall method. Subjects were divided into three groups based on tertiles of total iron intake levels. Fetal biometry was assessed by ultrasonography at mid-pregnancy. RESULTS: About 99% of the non-supplement users had iron intake below the recommended nutrient intake (RNI) for pregnant women (24 mg), whereas 64.9% of supplement users had iron intake above the upper level (UL) (45 mg). In the babies of mothers in the third tertile of iron intake (>17.04 mg), biparietal diameter, abdominal circumference, and femur length were lower by 0.41 cm (P =0.019), 0.41 cm (P = 0.027), and 0.07 cm (P = 0.051), respectively, than the babies of mothers in the second tertile of iron intake (11.49 ~ 17.04 mg). CONCLUSION: These results suggest that excessive maternal iron intake at mid-pregnancy is associated with reduced fetal growth. Iron supplementation for pregnant women should be individualized according to their iron status. Appropriate diet education is needed for pregnant women so that they can consume adequate amounts of iron from food and supplements.

Relationship between maternal sodium intake and blood lead concentration during pregnancy.

Pb is released from bone stores during pregnancy, which constitutes a period of increased bone resorption. A high Na intake has been found to be negatively associated with Ca and adversely associated with bone metabolism. It is possible that a high Na intake during pregnancy increases the blood Pb concentration; however, no previous study has reported on the relationship between Na intake and blood Pb concentration. We thus have investigated this relationship between Na intake and blood Pb concentrations, and examined whether this relationship differs with Ca intake in pregnant Korean women. Blood Pb concentrations were analysed in 1090 pregnant women at mid-pregnancy. Dietary intakes during mid-pregnancy were estimated by a 24 h recall method covering the use of dietary supplements. Blood Pb concentrations in whole-blood samples were analysed using graphite furnace atomic absorption spectrophotometry. Multiple regression analysis performed after adjustment for covariates revealed that maternal Na intake was positively associated with blood Pb concentration during pregnancy, but only when Ca intake was below the estimated average requirement for pregnant Korean women (P= 0·001). The findings of the present study suggest that blood Pb concentration during pregnancy could be minimised by dietary recommendations that include decreased Na and increased Ca intakes.

Birth weight of Korean infants is affected by the interaction of maternal iron intake and GSTM1 polymorphism.

Excessive iron consumption during pregnancy can lead to increased oxidative stress in the maternal body, which may result in adverse pregnancy outcomes. Glutathione S-transferases (GSTs) originate from a superfamily of detoxifying enzymes that play a role in reducing xenobiotic compounds and oxidative stress. The aim of this study was to determine the relationship among GST gene expression, maternal iron intake during pregnancy, and neonatal birth weight. The study participants were 1087 Korean gravidas and their newborns recruited for the Mothers and Children's Environmental Health study between 2006 and 2010. A 24-h dietary recall interview was conducted to estimate iron intake; additional intake through nutritional supplements was thoroughly investigated. Deletion polymorphisms of GSTM1 and GSTT1 were genotyped using PCR. Dietary iron consumption during pregnancy was positively associated with birth weight in pregnant women who were GSTM1-present after adjustment for the following covariates: maternal age, prepregnancy BMI, mother's education level, log-transformed urinary cotinine level, infant gender, gestational age at term, log-transformed energy intake, parity, and the use of folic acid supplements (P < 0.05). There were interactions between the GSTM1 genotype and iron intakes from animal foods (P < 0.05), diet (P < 0.05), and diet with supplements (P < 0.05). No relationship was found between maternal iron intake and birth weight for the GSTT1 polymorphism. This study demonstrates that increased iron consumption during pregnancy may improve infant birth weight for mothers who are GSTM1-present, but it might not be beneficial for mothers with the GSTM1-null genotype.

Antimalarial activity of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic acid derivatives.

Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Plasmodium falciparum and Plasmodium berghei parasites. To improve water-solubility for synthetic peroxides, a variety of cyclic peroxides having carboxyl functionality was prepared based on the antimalarial candidate, N-251, and their antimalarial activities were determined. The reactions of N-89 and its derivatives with Fe(II) demonstrated a highly efficient formation of the corresponding carbon radical which may be suspected as a key for the antiparasitic activity.

Toxoplasma gondii: a simple high-throughput assay for drug screening in vitro.

Toxoplasma gondii is the etiologic agent of toxoplasmosis. Although the combination of sulfadiazine and pyrimethamine is used as therapy for this disease, these drugs can have serious side effects and its use is limited in pregnancy. Therefore there is a need for new anti-T. gondii drugs in the clinic. Some systems for T. gondii drug screening have been described, but these have limitations and can be difficult. In order to solve these problems, we established a system to screen drugs in vitro that involved using cell viability methods to calculate drug selectivities, which are Trypan blue, [3-(4,5-dimethylthiazol-zyl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazoliuzolium, inner salt] (MTS) method and lactate dehydrogenase (LDH) assay. These assays were simple to establish and perform. The IC(50) values calculated from the morphological assay were not significantly different from the EC(50) values calculated using the other three methods. In particular, the results of the morphological assay showed a distinct association with the MTS assay (R=0.9841). These assays could be used for a wide range of applications in the screening of new drugs and may provide an alternative to the techniques currently used to screen for candidate anti-T. gondii compounds in vitro. In this study, we also tested many compounds and identified some that had a good anti-T. gondii effect in vitro based on the MTS assay. This simple and fast system allowed us to determine which compounds to investigate further using in vivo experiments.

Gastrodia elata blume and an active component, p-hydroxybenzyl alcohol reduce focal ischemic brain injury through antioxidant related gene expressions.

Ischaemic stroke is a leading cause of death and long-lasting disability. Gastrodia elata blume (GEB) is a Chinese herb that is widely used to treat convulsive disorders, such as epilepsy, and p-hydroxybenzyl alcohol (HBA) is the active ingredient in GEB. The present study was conducted to evaluate the effects of GEB and HBA on the brain damage and transcriptional levels of Protein disulfide isomerase (PDI) and 1-Cys peroxiredoxin (1-Cys Prx) genes known to play a role in antioxidant systems after transient focal ischemia in the rat brain. Focal ischemia was induced in rats by middle cerebral artery occlusion (MCAO). All animals underwent ischemia for 1 h, followed by 24 h of reperfusion. Coronal brain slices were stained with 2,3,5-triphenyltetrazolium chloride or total RNA was extracted for the analysis of gene expression. Histopathologic analysis revealed a significant (p<0.05) decrease in infarct size in the ipsilateral brain with GEB extracts or HBA. Moreover, the levels of PDI and 1-Cys Prx transcription were significantly increased in the GEB extract- or HBA-treated group compared with the untreated group (p<0.05). This study therefore indicated that GEB and HBA provide neuroprotection by preventing brain damage through the increased expression of genes encoding antioxidant proteins after transient focal cerebral ischemia and may be effective as neuroprotective agents at the cellular and molecular levels in the brain.

Synthesis and evaluation of beta-carbolinium cations as new antimalarial agents based on pi-delocalized lipophilic cation (DLC) hypothesis.

Several beta-carbolines including naturally occurring substances and their corresponding cationic derivatives were synthesized and evaluated for antimalarial (antiplasmodial) activity in vitro and in vivo. A tetracyclic carbolinium salt was elucidated for antileishmanial and antitrypanosomal activities in vitro as well as antiplasmodial activity. Quarternary carbolinium cations showed much higher potencies in vitro than electronically neutral beta-carbolines and a good correlation was observed between pi-delocalized lipophilic cationic (DLC) structure and antimalarial efficacy. beta-Carbolinium compounds exhibit medium suppressive activity in vivo against rodent malaria.