Clinical significance of suboptimal hormonal levels in men with prostate cancer treated with LHRH agonists.

Purpose: We examined the serum levels of testosterone (T) (total and bioavailable) dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prostate-specific antigen (PSA) in men receiving treatment with luteinizing hormone releasing-hormone (LHRH) agonists for metastatic prostate cancer. In doing this, we want to determine the efficacy of these agents in lowering T levels and whether a possible relationship exists between PSA values, as a surrogate measure of tumour activity, and hormone levels.

Methods: This was a single centre prospective study of patients on LHRH agonists.

Specific recognition of cytosine by hypoxanthine in pyrrolidinyl peptide nucleic acid.

Hypoxanthine is an unnatural base that can potentially pair with all natural nucleobases. While hypoxanthine in DNA exhibits marginal preference for pairing with cytosine (C), little is known about its pairing behavior in other DNA analogues. In this study, we synthesized a hypoxanthine-containing monomer and incorporated it into pyrrolidinyl peptide nucleic acid with α/β-peptide backbone derived from D-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid (acpcPNA).

Interindividual variations in aprepitant plasma pharmacokinetics in cancer patients receiving cisplatin-based chemotherapy for the first time.

The pharmacokinetics of aprepitant, a neurokinin-1 receptor antagonist, have not been fully evaluated in clinical settings. The aim of this study was to characterize the plasma pharmacokinetics of aprepitant and reveal their influence of laboratory tests and cytochrome P450 (CYP) 3A5 gene polymorphisms in cancer patients. Forty-four Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled.

Compliance monitoring system using screen printing technology based on conductive ink.

We developed a compliance monitoring system that electrically detects which drug among the multiple prescribed drugs a patient has taken and the date of drug-taking by a patient to prevent the patient from missing doses and taking drugs incorrectly at home. A conductive pattern is screen printed using conductive ink (silver paste) on the surface of a calendar-type pill organizer containing medications for as long as 1 week (4 times per day × 7 days, 28 doses) to create a sensor for detecting the opening of a pill organizer. Whenever the patient opens the pill organizer and removes a dose of the drug (pill), information about which of the 28 locations is opened and the date of opening are recorded in nonvolatile memory.

Comparison of contamination levels on the exterior surfaces of vials containing platinum anticancer drugs in Japan.

Contamination of the external surface of anticancer drug vials supplied to hospital pharmacies has been recognized as a potential health hazard. The aim of this study was to investigate the levels of contamination on the exterior surface of vials containing platinum anticancer drugs in Japan. Platinum contamination on the exterior surface of vials containing cisplatin or carboplatin was examined using products commercially available in Japan.

Challenging the 10-year rule: The accuracy of patient life expectancy predictions by physicians in relation to prostate cancer management.

Introduction: : We assess physicians' ability to accurately predict life expectancies. In prostate cancer this prediction is especially important as it affects screening decisions. No previous studies have examined accuracy in the context of real cases and concrete end points.

Hydroxy-itraconazole pharmacokinetics is similar to that of itraconazole in immunocompromised patients receiving oral solution of itraconazole.

Background: The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole (ITZ), is not fully known.

Methods: Oral solution of ITZ was administered in 46 immunocompromised patients as a single 200 mg dose for at least 12 days. The plasma concentrations of ITZ, active OH-ITZ, and keto-itraconazole (keto-ITZ), an inactive metabolite, 12 h after administration were determined by LC-UV or LC-MS/MS.

Mitochondrial swelling and incipient outer membrane rupture in preapoptotic and apoptotic cells.

Outer mitochondrial membrane (OMM) rupture was first noted in isolated mitochondria in which the inner mitochondrial membrane (IMM) had lost its selective permeability. This phenomenon referred to as mitochondrial permeability transition (MPT) refers to a permeabilized inner membrane that originates a large swelling in the mitochondrial matrix, which distends the outer membrane until it ruptures. Here, we have expanded previous electron microscopic observations that in apoptotic cells, OMM rupture is not caused by a membrane stretching promoted by a markedly swollen matrix.

Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients.

Background: Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphism.

Methods: The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus.

[Comparison of 1 mg/body and 3 mg/body of intravenous granisetron for the prevention of chemotherapy-induced nausea and vomiting and adverse events in hematological malignancy patients].

Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network.

Detection of fluoroquinolone-induced tendon disorders using a hospital database in Japan.

Purpose: Tendinitis and tendon rupture are well-known side effects of fluoroquinolones (FQs) in Western countries. In Japan, some case reports have been reported; however, the incidence of FQ-induced tendon disorders has not been investigated. The aims of this study were to measure the occurrence of tendon disorders associated with FQs in Japanese patients and to compare the observed risk with that of previous reports.

Impact of cachexia on pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients.

Purpose: Cancer cachexia is characterized by hypoalbuminemia and with the hepatic production of acute-phase proteins in response to malignant growth. The aim of this study was to evaluate the influence of cachexia on the pharmacokinetic disposition of and clinical responses to oxycodone in cancer patients.

Methods: Forty-seven Japanese patients receiving oxycodone extended-release tablets as a starting opioid for cancer pain were enrolled in this study.

Assisting the diagnosis of overt hypothyroidism with pattern recognition methods, making use of a set of routine tests, and their multiple correlation with total T4.

In our previous papers we proposed a novel screening method that assists the diagnosis of patients with overt Graves' hyperthyroidism by making use of routine test data and pattern recognition methods. This method can be applied by non-specialists during physical check-ups at low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists, that is, to improve patients' QOL. In this report, we investigate whether a similar screening method is also applicable for overt hypothyroidism.

Impact of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing conversion to a transdermal system.

The aim of this study was to evaluate the influence of CYP3A5 and ABCB1 gene polymorphisms on fentanyl pharmacokinetics and clinical responses in cancer patients undergoing conversion to a transdermal system. Sixty Japanese cancer patients being treated with a fentanyl transdermal reservoir system according to the current Japanese guidelines were enrolled. Blood samples were obtained 192 h after conversion to the fentanyl transdermal system.

Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects.

The aim of this open-label, randomized, and 3-period crossover study was to evaluate the influences of concomitant antacid administration on the plasma disposition, intestinal absorption, and urinary excretion of gabapentin in humans. Gabapentin (200 mg) was orally administered alone, with 1 g magnesium oxide (MgO), or with 20 mg omeprazole to 13 healthy adult subjects. Oral bioavailability (BA) of gabapentin was estimated by 24-h urine collection.

Simple and rapid HPLC-UV method using an ultrafine particle octadecylsilane for determination of residual fentanyl in applied Durotep MT transdermal matrix patches and its clinical application.

A few complicated and time-consuming methods are available for the determination of residual fentanyl in Durotep MT transdermal patches, however, their application to clinical settings is limited. The aim of this study was to develop a simple and rapid HPLC-UV method using an ultrafine particle octadecylsilane (ODS) for the determination of residual fentanyl in applied Durotep MT transdermal matrix patches. Patch extraction involved sonicating a shredded Durotep MT patch in acetonitrile for 15 min.

True left-sided gallbladder with a portal anomaly: report of a case.

A 65-year-old female who presented with back pain was diagnosed to have the presence of biliary sludge in the gallbladder. Computed tomography showed that the round ligament connected to the left portal umbilical portion was in the normal anatomical position. However, the gallbladder was located to the left of the middle hepatic vein and the round ligament, attached to the left lateral segment of the liver.

Rapid simultaneous determination of voriconazole and its N-oxide in human plasma using an isocratic high-performance liquid chromatography method and its clinical application.

Objectives: The aim of this study was to develop a simultaneous determination method for voriconazole (VRCZ) and its N-oxide (VNO) in human plasma and to apply it to clinical samples.

Design And Methods: Plasma specimens were deproteinized with acetonitrile and then injected into an HPLC-UV system. VRCZ and VNO were separated on an ODS column filled with 2.

Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry.

Oral prochlorperazine (PCZ), an antiemetic, undergoes extensive first-pass metabolism. The study developed a simultaneous analytical method for PCZ and its major metabolites, prochlorperazine sulfoxide (PCZSO), N-demethylprochlorperazine (NDPCZ) and 7-hydroxyprochlorperazine (PCZOH), in human plasma using an isocratic liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Deproteinized plasma specimens were separated using a 3 µm particle size octadecylsilyl column, and the run time was 10 min.

Triplet Analysis That Identifies Unpaired Regions of Functional RNAs.

We developed a novel method for analyzing RNA sequences, deemed triplet analysis, and applied the method in an in vitro RNA selection experiment in which HIV-1 Tat was the target. Aptamers are nucleic acids that bind a desired target (bait), and to date, many aptamers have been identified by in vitro selection from enough concentrated libraries in which many RNAs had an obvious consensus primary sequence after sufficient cycles of the selection. Therefore, the higher-order structural features of the aptamers that are indispensable for interaction with the bait must be determined by additional investigation of the aptamers.

Combination of reactive oxygen species and tissue-type plasminogen activator enhances the induction of gelatinase B in brain endothelial cells.

Tissue-type plasminogen activator (t-PA) increases the risk of intracranial hemorrhage by gelatinase B (matrix metalloprotease-9; MMP-9) production in brain endothelial cells. It was recently reported that the free-radical scavenger edaravone significantly decreases t-PA-mediated MMP-9 production. Therefore, by using cultured brain endothelial cells (b.

Pyrrolidinyl peptide nucleic acid with α/β-peptide backbone: A conformationally constrained PNA with unusual hybridization properties.

We describe herein a new conformationally constrained analog of PNA carrying an alternating α/β amino acid backbone consisting of (2'R,4'R)-nucleobase-subtituted proline and (1S,2S)-2-aminocyclopentanecarboxylic acid (acpcPNA). The acpcPNA has been synthesized and evaluated for DNA, RNA and self-pairing properties by thermal denaturation experiments. It can form antiparallel hybrids with complementary DNA with high affinity and sequence specificity.

Validated method using liquid chromatography-electrospray ionization tandem mass spectrometry for the determination of contamination of the exterior surface of vials containing platinum anticancer drugs.

Contamination of the exterior surface of vials of cytostatic drugs by the drugs themselves is a potential hazard to human health. This study developed a validated method using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for the determination of contamination of the exteriors of vials of cisplatin and carboplatin. Large Alpha® sampling swabs were employed to wipe the vial exterior.

Pharmacokinetic variability of mycophenolic acid and its glucuronide in systemic lupus erythematosus patients in remission maintenance phase.

The aim of this study was to identify factors affecting the pharmacokinetics of mycophenolic acid (MPA) and its 7-O-glucuronide (MPAG) in systemic lupus erythematosus (SLE) patients. Thirty-one SLE patients in remission maintenance phase treated with mycophenolate mofetil (median 1500 mg/d) and prednisolone and followed-up for up to 56 months (median 13 months) were enrolled. Creatinine clearance and metal medication were significant predictors accounting for interindividual variability in the dose-normalized predose plasma concentration (C₀) of MPA (adjusted R²=0.