Momoko Chiba

Long-term oral lithium treatment attenuates motor disturbance in tauopathy model mice: implications of autophagy promotion.

Lithium, a drug used to treat bipolar disorders, has a variety of neuroprotective mechanisms including inhibition of glycogen synthase kinase-3 (GSK-3), a major tau kinase. Recently, it has been shown that, in various neurodegenerative proteinopathies, lithium could induce autophagy. To analyze how lithium is therapeutically beneficial in tauopathies, transgenic mice overexpressing human mutant tau (P301L) were treated with oral lithium chloride (LiCl) for 4 months starting at the age of 5 months. At first, we examined the effects of treatment on behavior (using a battery of behavioral tests), tau phosphorylation (by biochemical assays), and number of neurofibrillary tangles (NFTs) (by immunohistopathology). In comparison with control mice, LiCl-treated mice showed a significantly better score in the sensory motor tasks, as well as decreases in tau phosphorylation, soluble tau level, and number of NFTs. Next, we examined lithium effects on autophagy using an antibody against microtubule-associated protein 1 light chain 3 (LC3) as an autophagosome marker. The number of LC3-positive autophagosome-like puncta was increased in neurons of LiCl-treated mice. Neurons containing NFTs were completely LC3-negative, whereas LC3-positive autophagosome-like puncta contained phosphorylated-tau (p-tau). The protein level of p62 was decreased in LiCl-treated mice. These data suggested that oral long-term lithium treatment could attenuate p-tau-induced motor disturbance not only by inhibiting GSK-3 but also by enhancing autophagy in tauopathy model mice.

Blood lead at currently acceptable levels may cause preterm labour

Objectives Although occupational and environmental exposures to lead have been dramatically reduced in recent decades, adverse pregnancy outcomes have been observed at ‘acceptable’ levels of blood lead concentrations (≤10 μg/dl). Methodology Blood samples were collected from 348 singleton pregnant women, aged 16–35 years, during the first trimester of pregnancy (8–12 weeks) for lead measurement by inductively coupled plasma–mass spectrometry. Subjects were followed up and divided into two groups (preterm and full-term deliveries) according to duration of gestation. Results The average (range) and geometric means of blood lead levels were 3.8 (1.0–20.5) and 3.5 μg/dl, respectively. Blood lead level was significantly (p<0.05) higher in mothers who delivered preterm babies than in those who delivered full-term babies (mean±SD: 4.46±1.86 and 3.43±1.22 μg/dl, respectively). Logistic regression analysis demonstrated that a 1 unit increase in blood lead levels led to an increased risk of preterm birth (OR 1.41, 95% CI 1.08 to 1.84). Conclusion Adverse pregnancy outcomes may occur at blood lead concentrations below the current acceptable level.

Anemia and Iron Deficiency among Schoolchildren in the Aral Sea Region, Kazakhstan

The objectives of this study were to estimate the prevalence of anemia and iron deficiency among schoolchildren in the Aral Sea region of Kazakhstan and to determine the various factors associated with anemia in this population. We conducted a cross-sectional study of randomly selected schoolchildren. Blood samples were collected for measuring hemoglobin (Hb), serum ferritin (SF), total iron binding capacity (TIBC), and other hematological indices, and subjects were screened for anemia and iron deficiency. Associations between Hb concentration and SF, TIBC, anthropometric, and socioeconomic data were evaluated using regression analysis. The prevalence of anemia was 49.8 per cent although levels were mostly mild. Twenty-two per cent of the children were iron depleted (SF < 12 microg/l). Of the anemic children, 32.4 per cent were found to have iron deficiency anemia (anemia with SF < 12 microg/l). There were significant positive correlations between the levels of Hb and SF, but a negative correlation with serum TIBC. Age, mean corpuscular volume (MCV) and SF were found to be significantly related to Hb by stepwise multiple regression analysis. Multiple logistic regression analysis revealed that anemia was independently related to living district, education of father, and childs age. The results suggest that iron deficiency is an important determinant of anemia in this population; however, whole anemia cannot be solely explained by iron deficiency. Further studies are needed for consideration of micronutrients status, parasite infestation, hereditary disorders, and exposure to environmental pollutants.

Anaemia in relation to low bioavailability of dietary iron among school-aged children in the Aral Sea region, Kazakhstan

This study investigates anaemia related to the sufficiency of dietary iron intake of school-aged children in the Kzyl-Orda region of Kazakhstan. We conducted a cross-sectional study of 97 school-aged children living in Kzyl-Orda. Blood samples were collected for measuring haemoglobin. Dietary intake data were obtained from 24-h dietary recalls. Iron bioavailability was estimated with algorithms adjusting for absorption enhancers (meat, fish and poultry, and vitamin C) and inhibitors (tea and phytates) consumed in the same meal. The median total iron intakes were adequate compared with the median basal iron requirement; however, the median bioavailable iron intakes were well below the median absorbed iron requirement. Available iron was 6.9–7.2% of the total iron intake after adjusting for the absorption enhancers, and was reduced by 3.1–4.4% after adjusting for both enhancers and inhibitors. After adjustment for energy intake, higher iron intake was significantly associated with a decreased prevalence of anaemia (odds ratio, 0.39; 95% confidence interval, 0.16–0.93; P=0.034). Some evidence suggested an association between bioavailable iron intake after adjustment of absorption enhancers and inhibitors (odds ratio, 0.43; 95% confidence interval, 0.18–1.01; P=0.053). In conclusion, low bioavailability of dietary iron seems related to anaemia in the region. Although iron fortification or supplementation programmes can be useful for promoting the anaemia prevention control programme, further efforts for nutritional education suited for family level dietary practice are necessary.

Effect of tin on porphyrin biosynthesis

Certain disturbances in porphyrin biosynthesis were examined in rabbits administered with either tin or lead. Stannous chloride treatment increased the concentrations of coproporphyrin in blood and urine, as did lead acetate treatment. No effect of tin on 5-aminolevulinic acid concentration was observed in blood and urine, whereas lead treatment increased it markedly in both. Tin profoundly inhibited the activity of 5-aminolevulinate dehydratase in blood, but did not alter it in liver although tin content in liver was considerably higher than that in blood. In contrast to a prolonged inhibition of erythrocyte 5-aminolevulinate dehydratase by lead, tin inhibition of erythrocyte 5-aminolevulinate dehydratase activity was rapidly reversed after the cessation of the metal treatment.

Extremely high prevalence of hypercalciuria in children living in the Aral Sea region

The Aral Sea region is a natural area seriously polluted by human activities. In addition to the increased prevalence of diverse chronic diseases in children, the risk of developing urolithiasis is reported to be high in this region. This study was undertaken to clarify the prevalence of hypercalciuria in children of the Aral Sea region. A group of 205 children living in Kazalinsk, close to the Aral Sea, and a group of 187 children living in Zhanakorgan, far from the Aral Sea, were screened for hypercalciuria. Urinary sodium excretion (sodium per creatinine, uNa/Cr) in addition to calcium excretion (calcium per creatinine, uCa/Cr) was also calculated for each subject. Mean uCa/Cr (mmol/mmol) and uNa/Cr (mmol/mmol) excretions were significantly higher in Kazalinsk than in Zhanakorgan (uCa/Cr: 0.75 ± 0.74 and 0.33 ± 0.30; uNa/Cr: 3.54 ± 2.27 and 2.89 ± 1.69, respectively, mean ± SD, p < 0.01). Hypercalciuria regarded as an uCa/Cr of more than 0.703 was observed in 79 out of 205 Kazalinsk children (38.6%) while this was seen in only 24 out of 187 Zhanakorgan children (12.8%). Linear regression analysis revealed a direct positive correlation between urinary calcium and sodium excretion (p < 0.01) in Kazalinsk children.

Activity of erythrocyte delta-aminolevulinic acid dehydrase and its change by heat treatment as indices of lead exposure.

The effect of heat treatment on erythrocyte delta-aminolevulinic acid dehydrase (ALAD) activity in the blood of human subjects was examined in relation to their lead exposure.

The in vitro effects of zinc and manganese on δ-aminolevulinic acid dehydratase activity inhibited by lead or tin

The effects of the administration of lead and tin on delta-aminolevulinic acid dehydratase (5-aminolevulinate hydro-lyase, ALAD, EC 4.2.1.24) activity in human, rabbit, and mouse blood were studied in vivo. In addition the ability of zinc, manganese, and dithiothreitol (DTT) to restore ALAD activity in the blood of lead- or tin-treated subjects was examined in vitro. Manganese, zinc, and DTT restored ALAD activity in vitro. The optimal concentration of zinc required in vitro was 10(-4) M in blood of lead-exposed humans and lead- or tin-administered mice, and 10(-3) M in blood of rabbits treated with either lead or tin. Even at the optimal concentration of zinc, the reactivating effect was incomplete, the highest recovery being about one-third of the control activity. However, the simultaneous addition of zinc and DTT increased ALAD activity to levels comparable with those of controls. Manganese was less effective than zinc in restoring ALAD activity in vitro; the effective dose was 10(-2) M in the blood of lead-exposed subjects, while little effect was noted in tin-treated subjects. Manganese was as effective as DTT in protecting against the inhibition of ALAD activity in vitro by excessive zinc. In contrast, DTT restored ALAD activity completely in the blood of tin-treated rabbits and produced about an 80% recovery of enzyme activity in the blood of tin-treated mice, but only a 35% recovery in the blood of lead-treated rabbits. These results suggest that the mechanisms by which lead and tin inhibit ALAD activity are different.

Effect of tin compounds on activity of 5-aminolevulinate dehydratase in blood

Abstract Erythrocyte 5-aminolevulinate dehydratase activity was measured in rabbits administered with tin(II) or tin(IV). A significant decrease in enzymic activity was observed in the case of tin(II), while any significant effect was not detected in the case of tin(IV).

Twenty-eight element concentrations in mane hair samples of adult riding horses determined by particle-induced X-ray emission

The concentrations of 28 elements (Al, Br, Ca, Cl, Co, Cu, Cr, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Nb, Ni, P, Pb, Rb, S, Se, Si, Sr, Ti, V, Y, and Zn) were measured in mane hair by the particle-induced X-ray emission method. Except for Br, Cl, K, S, and P, the trace element concentrations in mane hair of horses are similar to literature values for human hair. The values obtained are not dependent on the horses age, breed, and sex and could be used as reference values in the assessment of diseases and nutritional status in equines.