BackgroundNeonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults.Methodology/Principal FindingsDeuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53–3.66 μg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 μg/day for dinotefuran, and this was <1% of the acceptable daily intake.

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Although dissociation of the transthyretin (TTR) tetramer is suspected of being the first step in amyloid fibril formation in hereditary TTR amyloidosis, including familial amyloid polyneuropathy (FAP), the TTR monomer has never been examined in vivo. Therefore, we analyzed the TTR monomer in the serum of FAP patients and normal individuals. Free TTR monomer was detected in both groups using gel filtration chromatography and immunoblotting. Both the mean concentration of free TTR monomer and the total serum TTR were significantly lower in FAP patients than in normal individuals. Moreover, in FAP patients, mass spectrometry showed that the variant TTR monomer was markedly decreased compared with the wild-type TTR monomer. These findings suggest that the free variant TTR monomer is unstable in serum, and that it aggregates in deposits in various organs or is adsorbed by preexisting amyloid fibrils before it is degraded

Seven flavonoid profiles, some of which were reported to show antiallergic activity in vitro, were surveyed in 28 kinds of tea. Flavonoids were extracted with hot water, hydrolyzed to aglycons, and determined by HPLC. The hydrolysis time needed to obtain the maximum for each aglycon was examined. Flavonols quercetin and kaempferol were found in 17 kinds of tea infusions, as well as Japanese green tea infusions. Myricetin was found in jasmine and pu-erh tea infusions. A flavon, luteolin, was found in 5 kinds of tea infusions including great plantain tea. Apigenin was found in 4 kinds of tea infusions including perilla leaf tea, and scutellarein was found in 3 kinds of tea infusions. Scutellarein, which is a potent antiallergic and low cytotoxic flavonoid, is found in great plantain tea and was detected in perilla leaf and safflower tea infusions at concentrations of approximately 2 mg/g and 0.3 mg/g in dried whole tea leaves, respectively. The presence of scutellarein in both samples was confirmed by LC/MS. Keywords: Tea; green tea; flavonoids; quercetin; kaempferol; scutellarein

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