Competitive displacement of serum protein binding of radiopharmaceuticals with amino acid infusion investigated with N-isopropyl-p-123I-iodoamphetamine.

Unlabelled: When a therapeutic drug is competitively displaced at the binding sites of serum proteins, the free fraction of the drug will be increased, with an increase in the manifestation of pharmacologic properties. In the case of molecular imaging probes, total clearance and tissue distribution are increased in such circumstances. The aim of this study was to observe the increase in cerebral accumulation of N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) using the protein-binding displacement method with amino acid infusion.

Relationship between periodontal status and HbA1c in nondiabetics.

Objectives: Many studies have reported an association between diabetes and periodontitis. We analyzed the periodontal status and glycosylated hemoglobin (HbA1c) level in nondiabetic subjects to investigate the relationship between periodontitis and glucose control in nondiabetics.

Methods: Periodontal status, HbA1c, serum cholesterol, triglyceride, body mass index (BMI), and demographic variables were assessed in 141 Japanese adults.

A validated HPLC-fluorescence method with a semi-micro column for routine determination of homocysteine, cysteine and cysteamine, and the relation between the thiol derivatives in normal human plasma.

A semi-micro column HPLC-fluorescence method for routine determination of thiol derivatives such as homocysteine (Hcy), cysteine (Cys) and cysteamine (CA) is described. The thiol derivatives labeled with ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulfonate (SBD-F) were isocratically separated within 12 min on a semi-micro ODS column (Daisopak-SP-120-5-ODS-BP) with a mixture of 25 mm acetate buffer (pH 2.00) and CH(3)CN as a mobile phase.

Prevalence of chronic obstructive pulmonary diseases in general clinics in terms of FEV1/FVC.

Background: The prevalence of chronic obstructive pulmonary disease (COPD) continues to increase all over the world. Nonetheless, COPD is often misdiagnosed in general clinics because of insufficient use of spirometry.

Objectives: To estimate the prevalence of COPD in general clinics in Japan, we performed spirometry to screen patients who consulted general clinics.

Serum protein binding displacement: theoretical analysis using a hypothetical radiopharmaceutical and experimental analysis with 123I-N-isopropyl-p-iodoamphetamine.

Introduction: The binding of radiopharmaceutical to serum proteins is thought to be an important factor that restricts its excretion and accumulation in tissue. We calculated the effect of inhibitors of serum protein binding using a hypothetical radiopharmaceutical. In vitro experiments and protein binding inhibitor-loaded monkey scintigraphy were then conducted using (123)I-N-isopropyl-p-iodoamphetamine (IMP) as the radiopharmaceutical.

Urinary iodine concentrations in urban and rural areas around Chernobyl Nuclear Power Plant.

In 2007, we screened urinary iodine (UI) concentrations in urban (Gomel city) and in rural areas (Hoiniki city) of the Gomel Region, Republic of Belarus, which was heavily contaminated by the accident at the Chernobyl Nuclear Power Plant, in order to evaluate the current state of iodine supplementation in these areas. Median levels of UI were 220.5 microg/L (151.

Thyroid function is associated with carotid intima-media thickness in euthyroid subjects.

To investigate the relationship between thyroid function and carotid intima-media thickness (CIMT) in a relatively large general population with euthyroid status we initially enrolled 1772 Japanese adults (421 men and 1351 women) who participated in a medical screening program for the general population over 40 years old. To evaluate only euthyroid subjects without vascular diseases and/or its major risk factors, 1129 were excluded and 643 participants (175 men and 468 women) were included for further analysis. Simple and multivariate linear regression analyses were performed to evaluate free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels and other existing parameters, including carotid intima-media thickness.

Contrasting impacts of invasive engineers on freshwater ecosystems: an experiment and meta-analysis.

Invasion by common carp (Cyprinus carpio) and red swamp crayfish (Procambarus clarkii) in shallow lakes have been followed by stable-state changes from a macrophyte-dominated clear water state to a phytoplankton-dominated turbid water state. Both invasive carp and crayfish are, therefore, possible drivers for catastrophic regime shifts. Despite these two species having been introduced into ecosystems world-wide, their relative significance on regime shifts remains largely unexplored.

Usefulness of competitive inhibitors of protein binding for improving the pharmacokinetics of 186Re-MAG3-conjugated bisphosphonate (186Re-MAG3-HBP), an agent for treatment of painful bone metastases.

Purpose: We have developed a (186)Re-mercaptoacetylglycylglycylglycine complex-conjugated bisphosphonate ((186)Re-MAG3-HBP) for the treatment of painful bone metastases. We assumed competitive inhibitors of protein binding to be useful for procuring a favorable biodistribution of (186)Re-MAG3-HBP for the palliation of bone pain because it has been reported that the concurrent administration of (99m)Tc-MAG3 and drugs with high affinity for serum protein produced competitive displacement at specific binding sites and enhanced total clearance and tissue distribution.

Methods: The displacement effects of several protein-binding inhibitors on the protein binding of (186)Re-MAG3-HBP were investigated.

[Medical emergency education using emergency care simulators in the School of Pharmaceutical Sciences].

Clinical pharmacy training III (bedside training) in the School of Pharmaceutical Sciences, Kyushu University of Health and Welfare is intended to train pharmacists who can also cope with medical emergencies. Therefore we produced original scenarios that provide experience of various medical emergencies using emergency care simulators. As a result, these simulators enabled students to experience dealing with various medical emergencies such as cardiopulmonary resuscitation, automated external defibrillation (AED), adrenalin administration, and oxygen inhalation.

Association between C677T/MTHFR genotype and homocysteine concentration in a Kazakh population.

We recently suggested that due to insufficient intake of vegetables, low folate status and mild homocysteinemia might exist in the Kazakh population. To clarify the determinants of homocysteine concentrations among this population, we determined concentrations of serum folate, albumin, creatinine, vitamin B12, and the C677T/ MTHFR genotype in 110 Kazakh individuals and compared these with plasma total homocysteine. In Kazakh, after adjustment for age and sex, folate was correlated with plasma total homocysteine, whereas concentrations in those with the TT genotype was almost twice as high as in those with the CC and CT genotypes (19.

Influences of haemodialysis on the binding sites of human serum albumin: possibility of an efficacious administration plan using binding inhibition.

Background: We have studied the possibility that low-dose treatment utilizing the inhibition that may occur between two drugs at the same site of human serum albumin (HSA) improves the pharmacological effects. The purpose is to elucidate the differences in the binding capacities of sites I and II of HSA between pre-haemodialysis (HD) and post-HD in patients with end-stage renal disease.

Methods: We evaluated free fractions of site probes, (14)C-warfarin (site I) and (14)C-diazepam (site II), by ultrafiltration in serum between pre-HD and post-HD.

Effect of acute hepatic failure on epirubicin pharmacokinetics after intrahepatic arterial injection in rats.

In the case of cancer chemotherapy for hepatocellular carcinoma, anthracycline anticancer agents such as epirubicin are widely used, and have typically been given by intrahepatic arterial (i.a.) infusion to increase treatment efficacy and to reduce systemic toxicity.

Microcystin production by Microcystis aeruginosa exposed to different stages of herbivorous zooplankton.

Microcystin (MC) production by four monoclonal Microcystis aeruginosa strains was evaluated in response to infochemicals (indirect exposure) released from different stages of herbivorous zooplankton (neonate/juvenile and adult Daphnia magna and Moina macrocopa). The intracellular MC and extracellular MC concentrations were significantly different among the control and treatments with zooplankton culture media filtrates (p<0.05), and in most cases MC production was significantly higher (p<0.

Availability of cardio-ankle vascular index (CAVI) as a screening tool for atherosclerosis.

Background: A novel index, the cardio-ankle vascular index (CAVI), which reflects the stiffness of the aorta, femoral artery, and tibial artery, was recently developed by measuring brachial - ankle pulse wave velocity and blood pressure.

Methods And Results: In the present study 1,014 Japanese adults from the general population were screened to clarify the correlation between CAVI and other existing markers related to atherosclerosis, including carotid intima - media thickness (CIMT) and homocysteine (HCY). CAVI was strongly associated with age in both men and women.

Dosage plan of a flurbiprofen injection product using inhibition of protein binding by lipid emulsion in rats.

Flurbiprofen-axetil (FP-ax), a bolus injection product of a non-steroidal anti-inflammatory drug (NSAID), is a prodrug of flurbiprofen, an NSAID. As flurbiprofen strongly binds to site II of human serum albumin (HSA), the free (unbound) concentration of flurbiprofen after injection of FP-ax is low. We have examined the inhibitory effect of free fatty acid (FFA), a binding inhibitor for site II of HSA, on the binding of flurbiprofen in-vitro and in-vivo by ultrafiltration, to establish an effective dosage of FP-ax.

Determinants of plasma homocysteine levels and carotid intima-media thickness in Japanese.

Although hyperhomocysteinemia is considered to be a key risk factor for atherosclerosis, especially in Western countries, its role in the Asian population is still controversial. In this study, we evaluated the determinants of homocysteine and carotid intima-media thickness, a clinical marker for the detection of atherosclerosis, in Japanese. In 289 Japanese adults (age 37-86 yrs), we screened plasma total homocysteine by high performance liquid chromatography and evaluated maximum carotid intima-media thickness by ultrasound.

[Need for pharmaceutical skill in using displacement of protein binding].

In pharmacotherapy, to alleviate pains of patients and to provide comforts to patients, pharmacists should improve their pharmaceutical skills of their clinical sense involving pharmaceutical investigational outcomes. Without pharmaceutical skills, pharmacists cannot apply the essence of drug therapies for patients in the most urgent 24 hours treatment. To cope with these drug therapies, we have developed search methods which easily identify the diachronic change of protein binding and the factors in serum (=a new pharmaceutical distribution diagnostic method).

New entry for synthesis of N-acylhydrazones, pyridazinones, and 1,3,4-oxadiazin-6-ones from alpha-amino acid esters.

Versatile electrophiles N-acylhydrazones are synthesized via diazotization, reduction, and acylation of alpha-amino acid esters. Reduction of diazo esters with L-selectride or tributylphosphine affords the corresponding hydrazones in good yields. Both reducing agents give anti-hydrazones as the major product although the reactivity of each reductant is slightly different.

Multimers and adiponectin gene 276G>T polymorphism in the Japanese population residing in rural areas.

Background: Although it has been shown that high-molecular weight adiponectin is an active form, few studies have attempted to clarify the relationship between high molecular weight adiponectin and markers linked with cardiovascular diseases in the general population.

Methods: We screened 236 Japanese study participants recruited from the general population, residing in one large and four small islands. In addition to serum lipids and lipoproteins, serum total adiponectin and each multimer were measured.

Proteomics of Caenorhabditis elegans over-expressing human alpha-synuclein analyzed by fluorogenic derivatization-liquid chromatography/tandem mass spectrometry: identification of actin and several ribosomal proteins as negative markers at early Parkinson's disease stages.

It has been known that the over-expression of alpha-synuclein, the main protein of Lewy bodies in Parkinson's disease (PD), leads to neurodegeneration in PD models. In this study, the changes in protein expression between the transgenic over-expressing human alpha-synuclein wild type (alpha-synWT) and the control Caenorhabditis elegans were elucidated by fluorogenic derivatization-liquid chromatography/tandem mass spectrometry (FD-LC-MS/MS) proteome analysis, which is a highly selective, sensitive, repeatable and quantitative method for protein identification. Because the alpha-synuclein wild-type worms showed moderate levels of dopamine loss without overt behavioral abnormalities, it was suggested that the changes in proteins in the alpha-synWT are related in the sequence of the formation of Lewy bodies.

Effect of pre-treatment with St John's Wort on nephrotoxicity of cisplatin in rats.

An herbal health care supplement, St John's Wort (SJW, Hypericum perforatum) has become widely used in the treatment of depression, and is known to interact with therapeutic drugs. Here we report a preventive effect of SJW on cisplatin nephrotoxicity in rats. Rats were given SJW (400 mg/kg/day, p.

Influence of work duration or physical symptoms on mental health among Japanese visual display terminal users.

The present study examined the relationship of work duration or physical symptoms to the mental health of visual display terminal (VDT) workers in Japan. The mental health status of 2,327 VDT users at an administrative office was investigated using the 12-item General Health Questionnaire (GHQ-12). Subjects were asked about their age, sex, hours of daily VDT use, rest and breaks during VDT work, eyestrain, and musculoskeletal pain.