Palladium-catalyzed C-C bond cleavage of N-cyclopropyl acylhydrazones.

Despite their utility as directing groups, the C-C bond cleavage of cyclopropanes utilizing hydrazones has not been explored. Herein, Pd-catalyzed C-C bond cleavage reaction of N-cyclopropyl acylhydrazones, followed by cycloisomerization to yield pyrazoles, has been developed. The protocol enables the synthesis of various α-pyrazole carbonyl compounds, which have a potential of biological activity. Control experiments and DFT calculations suggest that ß-carbon elimination of a stable 6-membered chelate palladium complex occurs, generating a conjugated azine as a reaction intermediate for the following cycloisomerization.

Anhydrous Hydrogen Iodide-Mediated Reductive Indolization of In Situ-Generated Cyclopropyl Hydrazones.

Fischer-type indolization of N-aryl-C-cyclopropyl hydrazones generated in situ followed by chemoselective reduction using tert-butyl iodide as an anhydrous HI generator was developed. This protocol provides indoles bearing carboxylic acid derivative units. A series of control experiments indicated the HI-mediated formation and reduction of spirocyclopropyl indolenines. Anhydrous HI functions as a Brønsted acid as well as a reducing agent, facilitating the successful conversion of unstable reaction intermediates and iodinated mixtures in equilibrium.

[Breast-feeding and the mother's sentiment towards child rearing. Analysis of database on health checkups].

OBJECTIVES: This study aimed to identify the breast-feeding rate and associated factors and to get better understanding on the mother's sentiment towards child rearing due to differences in feeding methods. This information can be used as primary sources providing effective support through community-based health care for mothers and infants. METHODS: The study was carried out in Osaka city from April 2005 to December 2009. Data from the health-checkup records on infants aged 3-5 months were used after excluding any personal information. The data used included feeding methods (exclusive breast-feeding, mixed-feeding, and bottlefeeding), gestational age, multiple pregnancy status, gender, birth weight, use of an incubator, and birth year. Moreover, the data included the following maternal factors: planned or unplanned nature of pregnancy, smoking and drinking status during pregnancy, presence or absence of pregnancy-induced hypertension, maternal age at delivery, working status, presence or absence of financial anxiety, presence or absence of child-rearing support, presence or absence of individuals who can provide advice concerning child rearing, and sentiments of mothers during child rearing. RESULTS: From April 2005 to December 2009, 2552 infants underwent health checkups designed for infants. Of these, data on 2476 children, excluding 61 infants with unknown feeding methods and 15 infants aged 6 months, were used for analyses. The results showed that 56.6%, 28.7%, and 14.7% of children received exclusive breast-feeding, mixed-feeding, and bottle-feeding, respectively. Infant feeding methods were significantly associated with the birth year: in recent years, a decrease in the number of mothers who chose to bottle-feed their infants was observed. Furthermore, the feeding methods were associated with multiple births, birth weight, maternal smoking status during pregnancy, and maternal age at delivery. The results revealed that mothers who chose to breast-feed exclusively enjoyed child rearing at a significantly higher rate of 93.4%00, compared to 88.4%0 of mothers who chose to bottle-feed or mixed-feed. CONCLUSION: The study revealed that among infants aged from 3 to 5 months, 57% and 15% were exclusively breast-fed and bottle-fed, respectively; additionally, the proportion of bottle-fed infants declined every year. A significantly larger number of exclusively breast-feeding mothers enjoyed child rearing than the bottle-feeding or mixed-feeding mothers. These feeding methods were associated with multiple births, birth weight, maternal smoking status during pregnancy, and maternal age at delivery.

Biopterin in the acute phase of hypoxia-ischemia in a neonatal pig model.

To clarify the participation of inducible NOS (iNOS) in the hypoxia-ischemia, we examined iNOS and its tetrahydrobiopterin co-factor in the cerebral cortex and plasma in a newborn-piglet model. We also investigated the role of hypothermia in iNOS expression and biopterin production. Male newborn piglets were ventilated 6% oxygen for 45 min. Their common carotid arteries were clamped during hypoxia. Then they were resuscitated with 30% oxygen (HI group). Piglets of the hypothermia group were treated as the HI group and their body was cooled to 35.5 degrees C after hypoxic-ischemic insults. Sham-treated piglets were also reserved. In the HI group, iNOS was present in neurons and macrophages of the cerebral cortex 12h after the insult. The concentrations of nitrite and nitrate were elevated in the cerebral cortex 12h after hypoxic-ischemic insults but the biopterin level was unchanged. The plasma biopterin concentration after the insult (377.9+/-78.7 nM) was five times higher than before the insult (80.1+/-4.3 nM); this level peaked 4h after the insult (604.8+/-200.9 nM) and only slightly decreased after 12h (445.9+/-57.8 nM). In the hypothermia group, no iNOS expression was observed 12h after the insult. The plasma biopterin concentration after the insult (464.2+/-92.3 nM) was similar to that in the HI group, but was suppressed by 4h of hypothermia (229.3+/-106.8 nM). In this study, neuronal iNOS expression and increase of NO production were found in the acute phase of hypoxia-ischemia. Brain biopterin did not increase in hypoxia-ischemia although plasma biopterin was five-fold elevated. The discrepancy may also affect hypoxic-ischemic organ damage.

Plasma biopterin levels and tetrahydrobiopterin responsiveness.

Tetrahydrobiopterin (BH4) responsive hyperphenylalaninemia (HPA) with a mutant phenylalanine hydroxylase (PAH) gene was found during neonatal screening for PKU. This study determined blood BH4 and phenylalanine in two patients with hyperphenylalaninemia following oral load with BH4 10 mg/kg. Our patients underwent neonatal screening for PKU, had normal biopterin metabolism and their PAH mutations were determined. Peak plasma biopterin levels in Case 1, which were reached at between 2 and 4h after loading, were 612, 297, and 178 nmol/L at age 30 days, 55 days, and 19 months, respectively, and the maximum phenylalanine decreasing rates, which were found at 24h, were 54, 16, and 4%, respectively. In Case 2, peak plasma biopterin levels were 747 and 327 nmol/L at age 20 and 55 days, respectively, and the maximum phenylalanine decreasing rates were 39 and 32%, respectively. In the BH4 loading test, the peaks of BH4 in both patients lowered ( approximately 50%), on the same dose schedule of BH4, as patients got older.

Spatial distribution and temporal variation of Microcystis species composition and microcystin concentration in Lake Biwa.

Spatial and temporal variation in Microcystis species composition and microcystin concentration, quantified by enzyme-linked immunosorbent assay and high-performance liquid chromatography, were investigated during a 3-year period (1998-2000) in the Northern Basin of Lake Biwa. The Northern Basin generally had a concentration of 5 microg L(-1) or less, except at station 1 (Nagahama Bay) from July to October during the study period. The maximum concentration at station 1 was 22.7, 35.9, and 22.0 microg L(-1) in October of 1998, 1999, and 2000, respectively. Eleven species of cyanobacteria were observed: Microcystis aeruginosa, M. ichthyoblabe, M. novacekii, M. wesenbergii, Oscillatoria raciborskii, Anabaena oumiana, A. affinis, A. flos-aquae, A. ucrainica, A. smithii, and A. crassa. Of these, M. aeruginosa and M. wesenbergii were the main components observed. A high concentration of microcystin in the lake water was mostly a result of variation in the relative amount of toxic M. aeruginosa rather than of the total Microcystis cell number. This was supported by the analytical results for isolated strains. Microcystis spp. cell density in the Northern Basin appeared to increase gradually over the course of the study. This is the first study to have surveyed the Northern Basin of Lake Biwa, which supplies drinking water to 14 million people and is the largest lake in Japan.