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.

Immunohistochemical Expression of Choline Acetyltransferase and Catecholamine-Synthesizing Enzymes in Head-and-Neck and Thoracoabdominal Paragangliomas and Pheochromocytomas.

Paragangliomas (PGLs) are neural-crest-derived, non-epithelial neuroendocrine tumors distributed along the parasympathetic and sympathetic nerves. Head-and-neck PGLs (HNPGLs) have been recognized as nonchromaffin, nonfunctional, parasympathetic tumors. By contrast, thoracoabdominal paragangliomas and pheochromocytomas (PPGLs) are chromaffin, functional, sympathetic tumors.

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.

PET imaging of C-labeled coenzyme Q: Comparison of biodistribution between [C]ubiquinol-10 and [C]ubiquinone-10.

Coenzyme Q (CoQ) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form).

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.

Multi-institutional survey of carotid body tumors in Japan.

There has been no attempt to clarify the status of patients with carotid body tumor (CBT) in Japan. This multi-institutional survey analyzed patients with CBT throughout Japan by gathering information on these patients from institutions that performed head and neck surgeries. Information from a total of 150 patients from 25 institutions from the past 20 years was employed in the present survey.

Sensory defects and developmental delay among children with congenital rubella syndrome.

This study investigated the features of developmental difficulties combined with sensory defects in children with congenital rubella syndrome (CRS). Following a large rubella outbreak in Khanh Hoa Province, Vietnam, in 2011, we enrolled 41 children with CRS from September 2011 through May 2013. Fourteen participants died and six became untraceable by October 2013; the remaining 21 children were followed up from 2013 to 2015.

Efficacy of aprepitant for nausea in patients with head and neck cancer receiving daily cisplatin therapy.

Background: Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin has been demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonist during daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant in patients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy).

Materials And Methods: Twenty patients with HNC were prospectively studied who received a triple antiemetic regimen comprising granisetron (40 μg/kg on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125 mg on day 1 and 80 mg on days 2-5) with FP therapy (cisplatin 20 mg/m2 on days 1-4; 5-FU 400 mg/m2 on days 1-5) (aprepitant group).

Human organic anion transporters function as a high-capacity transporter for p-cresyl sulfate, a uremic toxin.

Background: Recent clinical studies have shown that increased serum levels of p-cresyl sulfate (PCS), a uremic toxin, are associated with the progression of chronic kidney disease (CKD) and cardiovascular outcomes. Using rat renal cortical slices, we previously reported that the rat organic anion transporter (OAT) could play a key role in the renal tubular secretion of PCS. However, no information is currently available regarding the transport of PCS via human OAT (hOAT) isoforms, hOAT1 and hOAT3.

Multiparametric MR imaging for differentiating between benign and malignant thyroid nodules: initial experience in 23 patients.

Purpose: To evaluate multiparametric MR imaging with combined use of apparent diffusion coefficients (ADCs) and time-signal intensity curves (TICs) for discriminating malignant thyroid nodules from benign ones.

Materials And Methods: ADCs and TICs of 7 benign and 16 malignant nodules were retrospectively analyzed on lesion-by-lesion (overall ADCs and TICs) and pixel-by-pixel (ADC and TIC mapping) bases. ADCs were determined using b-values of 500 and 1000 s/mm(2) .

Negative middle ear pressure and otitis media with effusion after surgery under general anesthesia.

Conclusion: Negative middle ear pressure was observed in many patients and otitis media with effusion (OME) developed in 3.3% of ears after surgery under general anesthesia. Gas dynamics in the middle ear cavity induced by nitrous oxide inhalation anesthesia and transient blockage of the eustachian tube induced by surgery are considered to be involved in development of OME after surgery under general anesthesia.

Subdomain IIIA of dog albumin contains a binding site similar to site II of human albumin.

Dog albumin contains a specific drug-binding site that binds most of the site II ligands of human albumin. This study was undertaken to elucidate the structural configuration of this binding site using a photoaffinity labeling technique. Dog albumin and albumins of other animal species were photolabeled with [(14)C]ketoprofen.

A case report of myasthenia gravis localized to the larynx.

This report describes a very rare case of myasthenia gravis (MG) localized to the larynx, with the onset of dyspnea requiring tracheotomy. The vocal cords of this patient were fixed in the paramedian position. Under fiberscopic observation, improvement of laryngeal function was demonstrated after intravenous injection of edrophonium.

Characterization of benzodiazepine binding site on human alpha1-acid glycoprotein using flunitrazepam as a photolabeling agent.

The binding of flunitrazepam (FNZP) by human alpha1-acid glycoprotein (hAGP) and the relationships between the extent of drug binding and desialylation and the genetic variants of hAGP were examined. The photolabeling specificity of [3H]FNZP was confirmed by findings in which other hAGP-binding ligands inhibited the formation of covalent bonds between [3H]FNZP and hAGP. The photolabeling of asialo-hAGP suggested that sialic acid does not involve in the binding of [3H]FNZP.

Steroid injection to vocal nodules using fiberoptic laryngeal surgery under topical anesthesia.

Since 1990, we have performed steroid injection into the vocal fold by fiberoptic laryngeal surgery (FLS) under local anesthesia. In this study, the usefulness of this method was evaluated in 28 patients with vocal nodules. Under monitoring using a fiberoptic laryngoscope, a curved injection needle was inserted via the oral cavity and steroid was injected.

Suppressed responses to self-triggered sounds in the human auditory cortex.

Humans are assumed to predict the sensory consequences of their own actions by means of forward models that enable discrimination between self-produced and external sensory signals. Here we tested whether responses in the human auditory cortex would differ to self-triggered versus externally triggered tones. The responses were recorded with a whole-scalp neuromagnetometer from 12 healthy subjects who either themselves triggered a tone by pressing a button once every 5 s or passively listened to externally triggered tones, presented in an identical sound sequence.

Binaural interaction in the human auditory cortex revealed by neuromagnetic frequency tagging: no effect of stimulus intensity.

Frequency tagging of magnetoencephalographic signals was recently introduced as a new tool to study binaural interaction in the human auditory cortex [Fujiki et al., J. Neurosci.

Steroid injection for Reinke's edema using fiberoptic laryngeal surgery.

Objective: Since 1990, we have performed steroid injections into the vocal fold under topical anesthesia using fiberoptic laryngeal surgery (FLS) in an outpatient clinic. The aim of this study was to retrospectively assess the usefulness of this treatment method in 44 patients with mild Reinke's edema.

Material And Methods: Using fiberoptic monitoring of the larynx, a curved injection needle was inserted via the oral cavity and triamcinolone acetonide was injected into Reinke's space of the bilateral vocal fold.

Inner ear hearing loss modulates ipsilateral temporal lobe activation by monaural speech stimuli.

We examined cortical activation by speech in patients with moderate inner ear hearing loss using PET to investigate the response of the language network to insufficient speech input. We made two word lists, well-perceived words and poorly-perceived words, and measured rCBF during monaural presentation of these words. Well-perceived words activated bilateral temporal lobes, bilateral inferior frontal gyri (IFG) and left angular gyrus (AG) regardless of the ear stimulated, Poorly-perceived words activated contralateral temporal lobe and bilateral IFG, while little or no activation was observed in the ipsilateral temporal lobe and left AG.

Occurrence of yersiniosis and listeriosis in wild boars in Japan.

From December 1994 to February 1995, 131 wild boars (Sus scrofa leucomysta) living in a mountainous area in Japan were examined for yersiniosis and listeriosis. Of 131 wild boars, 76 (58%) were males and 55 (42%) were females. Four Yersinia spp.

Occurrence of Zoonotic Bacteria in Retail Game Meat in Japan with Special Reference to Erysipelothrix.

From December 1993 to March 1994, a total of 93 wild boar and 30 deer meat samples were purchased from 13 retail shops and examined for the presence of species of Erysipelothrix , Yersinia , Listeria , Salmonella and Campylobacter . Erysipelothrix spp. were isolated from 41 wild boar and 15 deer samples.

Occurrence of Erysipelothrix rhusiopathiae in Retail Raw Pork.

A total of 52 strains of Erysipelothrix rhusiopathiae was isolated from 38 (33.9%) of 112 retail raw pork samples which were purchased in the Tama area of Tokyo, Japan, February to November 1988. These isolates were classified into 14 different serovars: 6 (19.