Clinical evaluation of [F]pitavastatin for quantitative analysis of hepatobiliary transporter activity.

It is widely accepted that uptake and efflux transporters on clearance organs play crucial roles in drug disposition. Although in vitro transporter assay system can identify the intrinsic properties of the target transporters, it is not so easy to precisely predict in vivo pharmacokinetic parameters from in vitro data. Positron emission tomography (PET) imaging is a useful tool to directly assess the activity of drug transporters in humans.

[F]DPA-714 PET imaging for the quantitative evaluation of early spatiotemporal changes of neuroinflammation in rat brain following status epilepticus.

Background: Most antiepileptic drug therapies are symptomatic and adversely suppress normal brain function by nonspecific inhibition of neuronal activity. In recent times, growing evidence has suggested that neuroinflammation triggered by epileptic seizures might be involved in the pathogenesis of epilepsy. Although the potential effectiveness of anti-inflammatory treatment for curing epilepsy has been extensively discussed, the limited quantitative data regarding spatiotemporal characteristics of neuroinflammation after epileptic seizures makes it difficult to be realized.

PET imaging of C-labeled thiamine tetrahydrofurfuryl disulfide, vitamin B derivative: First-in-human study.

Unlabelled: Vitamine B thiamine is an essential component for glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is more absorbent compared to readily-available water-soluble thiamine salts since it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions were not clarified yet.

Effectiveness of a Teacher Training Program for Students with Symptoms of Developmental Disorders: Data from a Correspondence High School in Japan.

In the present study, a teacher training program based on behavioral therapy was conducted for high school correspondence course teachers of adolescents aged between 15 and 18 years who showed developmental difficulties. Participating teachers were assigned to either an immediate treatment (IT; = 13) or delayed treatment control (DTC; = 17) group to evaluate the effectiveness of the program, which comprised five 90-min sessions with small groups of three to six participants and was conducted over three months. The results showed significant improvement in students' behaviors and social responsiveness and in teachers' confidence among those in the IT group; however, those in the DTC group did not show any such improvement.

Practical Synthesis of [F]Pitavastatin and Evaluation of Hepatobiliary Transport Activity in Rats by Positron Emission Tomography.

We developed a practical synthetic method for fluorine-18 (F)-labeled pitavastatin ([F]PTV) as a positron emission tomography (PET) tracer to assess hepatobiliary transporter activity and conducted a PET scan as a preclinical study for proof-of-concept in rats. This method is a one-pot synthesis involving aromatic F-fluorination of an arylboronic acid ester followed by deprotection under acidic conditions, which can be reproduced in general clinical sites equipped with a standard radiolabeling system due to the simplified procedure. PET imaging confirmed that intravenously administered [F]PTV was rapidly accumulated in the liver and gradually transferred into the intestinal lumen through the bile duct.

A Clinical Quantitative Evaluation of Hepatobiliary Transport of [C]Dehydropravastatin in Humans Using Positron Emission Tomography.

Various positron emission tomography (PET) probes have been developed to assess in vivo activities in humans of drug transporters, which aid in the prediction of pharmacokinetic properties of drugs and the impact of drug-drug interactions. We developed a new PET probe, sodium (3, 5)-3, 5-dihydroxy-7-((1 2, 6, 8)-6-hydroxy-2-methyl-8- ((1-[C]-()-2-methyl-but-2-enoyl) oxy) -1, 2, 6, 7, 8, 8-hexahydronaphthalen-1-yl) heptanoate ([C]DPV), and demonstrated its usefulness for the quantitative investigation of Oatps (gene symbol ) and Mrp2 (gene symbol ) in rats. To further analyze the species differences and verify the pharmacokinetic parameters in humans, serial PET scanning of the abdominal region with [C]DPV was performed in six healthy volunteers with and without an OATP1Bs and MRP2 inhibitor, rifampicin (600 mg, oral), in a crossover fashion.

Deep sequencing of the prothoracic gland transcriptome reveals new players in insect ecdysteroidogenesis.

Ecdysteroids are steroid hormones that induce molting and determine developmental timing in arthropods. In insect larva, the prothoracic gland (PG) is a major organ for ecdysone synthesis and release. Released ecdysone is converted into the active form, 20-hydroxyecdysone (20E) in the peripheral tissues.

Exploration of Antiemetics for Osteoporosis Therapy-Induced Nausea and Vomiting Using PET Molecular Imaging Analysis to Gastrointestinal Pharmacokinetics.

Purpose: To select appropriate antiemetics relieving teriparatide-induced nausea and vomiting during osteoporosis treatment using PET molecular imaging and pharmacokinetic analysis.

Methods: Rats were pretreated with subcutaneous teriparatide, followed by oral administration of antiemetics with different pharmacological effects. The pharmacokinetics of antiemetics were assessed by oral administration of 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) under free moving conditions in vivo.

Visualization of drug translocation in the nasal cavity and pharmacokinetic analysis on nasal drug absorption using positron emission tomography in the rat.

We performed positron emission tomography (PET) using 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) to evaluate the pharmacokinetics of nasal drug absorption in the rat. The dosing solution of [(18)F]FDG was varied in volume (ranging from 5 to 25 μl) and viscosity (using 0% to 3% concentrations of hydroxypropylcellulose). We modeled the pharmacokinetic parameters regarding the nasal cavity and pharynx using mass balance equations, and evaluated the values that were obtained by fitting concentration-time profiles using WinNonlin® software.

Pigment dispersing factor regulates ecdysone biosynthesis via bombyx neuropeptide G protein coupled receptor-B2 in the prothoracic glands of Bombyx mori.

Ecdysone is the key hormone regulating insect growth and development. Ecdysone synthesis occurs in the prothoracic glands (PGs) and is regulated by several neuropeptides. Four prothoracicotropic and three prothoracicostatic factors have been identified to date, suggesting that ecdysone biosynthesis is intricately regulated.

Novel middle-type Kenyon cells in the honeybee brain revealed by area-preferential gene expression analysis.

The mushroom bodies (a higher center) of the honeybee (Apis mellifera L) brain were considered to comprise three types of intrinsic neurons, including large- and small-type Kenyon cells that have distinct gene expression profiles. Although previous neural activity mapping using the immediate early gene kakusei suggested that small-type Kenyon cells are mainly active in forager brains, the precise Kenyon cell types that are active in the forager brain remain to be elucidated. We searched for novel gene(s) that are expressed in an area-preferential manner in the honeybee brain.

A highly specific and sensitive quantification analysis of the sterols in silkworm larvae by high performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

The biochemical quantification of sterols in insects has been difficult because only small amounts of tissues can be obtained from insect bodies and because sterol metabolites are structurally related. We have developed a highly specific and sensitive quantitative method for determining of the concentrations of seven sterols-7-dehydrocholesterol, desmosterol, cholesterol, ergosterol, campesterol, stigmasterol, and β-sitosterol-using a high performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (HPLC/APCI-MS/MS). The sterols were extracted from silkworm larval tissues using the Bligh and Dyer method and were analyzed using HPLC/APCI-MS/MS with selected reaction monitoring, using cholesterol-3,4-(13)C(2) as an internal standard.

In situ hybridization analysis of the expression of futsch, tau, and MESK2 homologues in the brain of the European honeybee (Apis mellifera L.).

Background: The importance of visual sense in Hymenopteran social behavior is suggested by the existence of a Hymenopteran insect-specific neural circuit related to visual processing and the fact that worker honeybee brain changes morphologically according to its foraging experience. To analyze molecular and neural bases that underlie the visual abilities of the honeybees, we used a cDNA microarray to search for gene(s) expressed in a neural cell-type preferential manner in a visual center of the honeybee brain, the optic lobes (OLs).

Methodology/principal Findings: Expression analysis of candidate genes using in situ hybridization revealed two genes expressed in a neural cell-type preferential manner in the OLs.

Distribution of Kakugo virus and its effects on the gene expression profile in the brain of the worker honeybee Apis mellifera L.

We previously identified a novel insect picorna-like virus, termed Kakugo virus (KV), obtained from the brains of aggressive honeybee worker bees that had counterattacked giant hornets. Here we examined the tissue distribution of KV and alterations of gene expression profiles in the brains of KV-infected worker bees to analyze possible effects of KV infection on honeybee neural and physiological states. By use of in situ hybridization, KV was broadly detected in the brains of the naturally KV-infected worker bees.

Differential gene expression in the hypopharyngeal glands of worker honeybees (Apis mellifera L.) associated with an age-dependent role change.

Associated with the age-dependent role change of worker honeybees (Apis mellifera L.) from nurse bees to foragers, some structural and functional changes occur in the hypopharyngeal glands (HPGs): nurse bee HPGs are well developed and synthesize major royal jelly proteins (MRJPs), while forager HPGs shrink and synthesize alpha-glucosidase, which converts nectar into honey. To identify candidate genes involved in the structural and functional HPG changes associated with the age-dependent role change of worker honeybees, we searched for genes whose expression in the HPGs depends on the role of workers, by using differential display and quantitative reverse transcription-polymerase chain reaction.

Laying workers in queenless honeybee (Apis mellifera L.) colonies have physiological states similar to that of nurse bees but opposite that of foragers.

Honeybee workers shift their labors from nursing their brood to foraging according to their age after eclosion. When the queen is lost from the colony, however, some workers become 'laying workers' whose ovaries develop to lay eggs. Here we investigated whether the physiological state of laying workers is more similar to that of nurse bees or foragers by examining the hypopharyngeal gland (HPG) and hemolymph vitellogenin titers.