Influence of Endogenous Substances on Site-II to Site-I Displacement of Diclofenac Bound to Albumin in the Aqueous Humor of Patients with Cataract.

Diclofenac instillation is useful in preventing intraoperative miosis and macular edema caused by postoperative inflammation in cataract surgery; however, optimum efficacy is not attained when the instilled diclofenac strongly binds to albumin in patients' aqueous humor. Therefore, a method that inhibits diclofenac binding and increases the concentration of its free fraction is needed. We conducted a basic study regarding the effects of inhibitors on the binding of instilled diclofenac to albumin and endogenous substances in aqueous humor.

Establishment of a new initial dose plan for vancomycin using the generalized linear mixed model.

Background: When administering vancomycin hydrochloride (VCM), the initial dose is adjusted to ensure that the steady-state trough value (Css-trough) remains within the effective concentration range. However, the Css-trough (population mean method predicted value [PMMPV]) calculated using the population mean method (PMM) often deviate from the effective concentration range. In this study, we used the generalized linear mixed model (GLMM) for initial dose planning to create a model that accurately predicts Css-trough, and subsequently assessed its prediction accuracy.

Development of the Virtual Physical Assessment Learning Material That Allows the Learners to Check Drug Efficacy and Early Detection of Adverse Effects through Virtual Experience.

 We utilized the information and communication technology to develop the physical assessment (PA) learning materials in the virtual experience type. This learning material consists of two parts which include case learning and basic learning. We created example scenarios about various conditions that a pharmacist may experience in medical scenes such as in a hospital ward, community pharmacy, home, and drugstore.

[Physical Assessment Education Using Various Simulators].

Pharmacists are in demand not only because of their knowledge of medical therapy but also due to their skills in basic physical assessment and emergency care as medical personnel. Pharmaceutical education has developed using patient simulators in bedside training, seminars in hospital pharmacies, and physical assessment practice at the Kyushu University of Health and Welfare School of Pharmaceutical Sciences. We first explain the outline of the method to confirm basic vital signs with simulators and then demonstrate some simulations to enable the reproduction of drug misadministration/changes in condition.

[Necessity of research of pharmaceutical departments in the creation of new pharmaceutical skills through technical education of physical assessment].

Physical assessment skills are now being more widely accepted by pharmacists and pharmaceutical departments than in the past. This is explained by the realization that pharmacists can prevent serious adverse effects and evaluate drug efficacy for their patients through assessment, thus providing effective medical care. However, is that all physical assessment can provide to pharmacists and pharmaceutical students? These students, in turn, should recognize the "need for skill" and the "pleasure to be gained in acquiring that skill" through the physical assessment performed by doctors.

An advanced objective structured clinical examination using patient simulators to evaluate pharmacy students' skills in physical assessment.

Objective: To implement an advanced objective structured clinical examination (OSCE) in the curriculum and to evaluate Japanese pharmacy students' skills in physical assessment such as measuring pulse and blood pressure, and assessing heart, lung, and intestinal sounds.

Design: An advanced OSCE was implemented in a hospital pharmacy seminar as a compulsory subject. We programmed patient simulators with 21 different patient cases in which normal and abnormal physiological conditions were produced.

A novel injection strategy of flurbiprofen axetil by inhibiting protein binding with 6-methoxy-2-naphthylacetic acid.

Flurbiprofen axetil (FPA) is an injection product and a prodrug of a non-steroidal anti-inflammatory drug (NSAID). After injection, it is rapidly hydrolyzed to the active form, flurbiprofen (FP). Since frequent injections of FPA can lead to abnormal physiology, an administration strategy is necessary to ensure there is enhancement of the analgesic efficiency of FP after a single dose and to reduce the total number of doses.

Influences of artificial heart-lung machine operation on the binding sites of albumin: possibility of an effective administration plan.

Purpose: The purpose of this study is to investigate the influence of changes in the human serum albumin (HSA) and free fatty acid (FFA) on alteration of the binding abilities of sites I and II after the operation of an artificial heart-lung machine.

Methods: The binding abilities of phenytoin (site I) and diazepam (site II) to patients' sera collected before and after the operation of an artificial heart-lung machine and pseudopatient serum samples were examined by ultra-filtration.

Results: The binding ability of site I markedly decreased after the operation of an artificial heart-lung machine in all patients, and the binding ability of site II unexpectedly increased in some patients.

Albumin-binding of diclofenac and the effect of a site II inhibitor in the aqueous humor of cataract patients with the instillation of diclofenac.

Diclofenac instillation has been used widely in cataract surgery to prevent postoperative inflammation. Since diclofenac binds strongly to albumin in the circulation, it does not have a sufficient effect on patients in whom diclofenac binds strongly to albumin in the aqueous humor. A decrease in diclofenac binding and an increase in free diclofenac levels are necessary in these patients.

[Implementation of bedside training and advanced objective structured clinical examination (OSCE) trial to learn and confirm about pharmacy clinical skills].

Bedside training for fourth-year students, as well as seminars in hospital pharmacy (vital sign seminars) for fifth-year students at the Department of Pharmacy of Kyushu University of Health and Welfare have been implemented using patient training models and various patient simulators. The introduction of simulation-based pharmaceutical education, where no patients are present, promotes visually, aurally, and tactilely simulated learning regarding the evaluation of vital signs and implementation of physical assessment when disease symptoms are present or adverse effects occur. A patient simulator also promotes the creation of training programs for emergency and critical care, with which basic as well as advanced life support can be practiced.

Pharmacokinetic alteration of (99m)Tc-MAG3 using serum protein binding displacement method.

Introduction: When a radiopharmaceutical is simultaneously administered with a medicine that has high affinity for the same plasma protein, the radiopharmaceutical is released at higher concentrations in blood, leading to enhanced transfer into target tissues. This is known as the serum protein binding displacement method. In this study, we investigated the pharmacokinetic alteration of technetium-99m-labeled mercaptoacetylglycylglycylglycine ((99m)Tc-MAG3) using the serum protein binding displacement method.

A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis.

Diclofenac suppository, a non-steroidal anti-inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated.

Preparation of simulation programs regarding excess-dose drug administration and acute-phase condition changes and its evaluation by students.

Vital-sign checks and physical assessment have been performed by physicians and nurses among medical staff in particular. However, pharmacists must also have basic skills of vital-sign checking and physical assessment to evaluate the patient condition/drug efficacy or prevent adverse reactions to drugs. To promote the acquisition of these skills, we prepared simulation programs with an emergency-care simulator, which facilitate the reproduction of excess-dose drug administration/condition changes.

Vital sign monitoring using human patient simulators at pharmacy schools in Japan.

Objective: To develop, implement, and assess an experience-based education program using human patient simulators to instruct pharmacy students in monitoring vital signs to identify drug treatment effects and adverse events.

Design: Medical emergency care programs using human patient simulators were prepared and facilitated practical clinical training in resuscitation, which required selecting drugs while monitoring changes in blood pressure, pulse, and arterial blood oxygen saturation. Training encompassed the monitoring of routes of drug administration, drawing of simulated blood, vital-sign monitoring based on a pharmaceutical universal training model, vital-sign monitoring devices and simulators, and medical emergency education using biological simulators.

Survey of student pharmacists' attitudes toward new procedures expected for future pharmacists.

Bedsides conventional bedside training the Department of Pharmacy of Kyushu University of Health and Welfare covers advanced practices focused on new procedures expected for future pharmacists. A questionnaire survey was conducted among the 4th year students of the 6-year curriculum of the department in order to retrospectively evaluate their attitudes toward basic life support, and the necessity and feasibility of items related to the training. Sixty-nine percent of the students responded that they would provide appropriate treatment under a situation where basic life support was needed.

[Life-support training to improve the clinical competence of pharmacy students].

Life-support (particularly, advanced life-support) training is not included in pharmacist education; however, the life-support should be mastered since a pharmacist is a medical professional. We consider it to be important to master other skills before the life-support practicing, because a pharmacist does not check a patient to assess their clinical condition and administer drugs (suppository, intravenous injection etc.) The pharmacist prepares medicines, but does not administer medicines to treat the patient.

Anti-human very late antigen-alpha4 (CD49d) monoclonal antibody (BU49) cross-reacts with the canine B-cell leukemia cell line GL-1, resulting in the induction of homotypic cell aggregation.

We have found that the anti-human very late antigen-alpha4 (VLA-alpha4) (CD49d) monoclonal antibody (mAb) BU49 cross-reacts with the canine B-cell leukemia cell line GL-1. Interestingly, the BU49 mAb specifically induced the homotypic cell aggregation of GL-1 cells accompanied by morphological changes. Homotypic cell aggregates induced by BU49 mAb were blocked by the presence of a protein kinase C inhibitor, a protein kinase A inhibitor, an actin filament formation inhibitor, and an EDTA.

The citrus flavonoids hesperetin and naringenin block the lipolytic actions of TNF-alpha in mouse adipocytes.

Obese adipose tissue is characterized by an excessive production of inflammatory adipokines including tumor necrosis factor-alpha (TNF-alpha). TNF-alpha stimulates free fatty acid (FFA) secretion through adipocyte lipolysis, and increased plasma levels of FFA promote insulin resistance. In this report, we show that hesperetin and naringenin, two citrus flavonoids, inhibit TNF-alpha-stimulated FFA secretion from mouse adipocytes.

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.

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.

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.

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.