Beneficial Effects of a Formulated Supplement of Ascidiacea (Halocynthia-roretzi)-derived Plasmalogen and Tuna-derived Elastin on Memory Function in Elderly Japanese Subjects; A Randomized, Double-blind, Placebo-controlled Study.

The beneficial effects of a formulated supplement of plasmalogen and elastin on the memory function in healthy elderly subjects were investigated by a randomized, double-blind, placebo-controlled, parallel-group analysis. Plasmalogen has been shown to exert beneficial effects on cognitive function in animal models and human clinical trials, while elastin improves vascular elasticity and increases blood flow. The levels of plasmalogen and elastin decreases with aging.

Doping control analysis of trimetazidine in dried blood spot.

Dried blood spot (DBS) analysis has been an inherent part of sports drug testing through the technological advancements of the past decade. Trimetazidine, a non-threshold banned substance, is excreted into urine after a dose of the permitted drug lomerizine. Therefore, a lomerizine-specific metabolite (M6) is analyzed to confirm the origin of trimetazidine in traditional urine analysis.

Doping control analyses during the Tokyo 2020 Olympic and Paralympic Games.

The doping control analyses at the XXXII Olympic Games (July 23 to August 8, 2021) and the XVI Paralympic Games (August 24 to September 5, 2021) held in Tokyo, Japan, after a year of delay due to the COVID-19 pandemic are summarized in this paper. A new satellite facility at the existing World Anti-Doping Agency (WADA)-accredited Tokyo laboratory was established and fully operated by 278 staff, including 33 Tokyo laboratory staff, 49 international experts, and 196 Japanese temporary staff. The numbers of urine samples were 5081 (Olympics) and 1519 (Paralympics), and the numbers of blood samples were 1103 (Olympics) and 500 (Paralympics).

Beneficial Effects of Saw Palmetto Fruit Extract on Urinary Symptoms in Japanese Female Subjects by a Multicenter, Randomized, Double-Blind, Placebo-Controlled Study.

Saw palmetto berry extract (SPE) is the most commonly consumed supplement by men with benign prostatic hyperplasia (BPH). The oral administration of SPE was previously shown to significantly attenuate urodynamic symptoms in the hyperactive bladders of female rats by increasing bladder capacity and prolonging the micturition interval. The amelioration of urodynamic symptoms by SPE may be partly attributed to its binding to muscarinic receptors in the urinary bladder and its inhibition of vanilloid receptors on afferent nerves.

Detection of bazedoxifene, a selective estrogen receptor modulator, in human urine by liquid chromatography-tandem mass spectrometry.

Bazedoxifene, a selective estrogen receptor modulator, has been explicitly included in the prohibited list issued by the World Anti-Doping Agency (WADA) since January 2020. A high-resolution liquid chromatography-tandem mass spectrometric detection method was developed to identify bazedoxifene and its metabolites in human urine and to quantify bazedoxifene (free plus glucuronide) for doping control purposes. Bazedoxifene acetate (20 mg) was orally administered to seven male volunteers, and the urine samples collected were analyzed using the developed method.

Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

Objective: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients.

Methods: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47).

Impact of community pharmacist-led intensive education on the control of serum phosphate levels in haemodialysis patients.

Background Administration of phosphate binders can decrease serum phosphate levels and improve the prognosis of patients on dialysis. However, patients are often non-adherent to phosphate binder medication. Although community pharmacist-led education could be effective in the maintenance of adherence to phosphate binder medication, its impact has not been evaluated.

A randomized controlled study of the efficacy of tadalafil monotherapy versus combination of tadalafil and mirabegron for the treatment of persistent overactive bladder symptoms in men presenting with lower urinary tract symptoms (CONTACT Study).

Aim: To evaluate efficacy and safety of combination of tadalafil + mirabegron for overactive bladder/benign prostatic hyperplasia (OAB/BPH).

Methods: Male patients with lower urinary tract symptoms (50 to 89 years), with remaining OAB symptoms even after administering tadalafil for more than 8 weeks were randomly assigned to either tadalafil monotherapy group (5 mg/day) or tadalafil/mirabegron combination therapy group (5 mg/50 mg/day). The primary endpoint was change from baseline in total OAB symptom score (OABSS) at week 12.

Analysis of tretoquinol and its metabolites in human urine by liquid chromatography-tandem mass spectrometry.

Tretoquinol (trimetoquinol), a β2-agonist, has been explicitly listed on the World Anti-Doping Agency Prohibited List 2019 since January 2019; however, it has been distributed as an antiasthmatic on the medical market. This study aimed to develop a liquid chromatography-tandem mass spectrometric method for the quantification of tretoquinol (free form plus glucuronide) in human urine for doping control purposes. An excretion study (n = 6) of tretoquinol hydrochloride hydrate (6 mg) was performed, and urine samples were collected prior to oral administration and during the first 48 h, along with spot urine samples at 7 and 14 days after administration.

Changes in QTc interval in long-term hemodialysis patients.

Background: Cardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of death in hemodialysis (HD) patients. A prolonged QT interval on the electrocardiogram (ECG) is a risk factor for SCD in HD patients. This study investigated whether the heart rate-corrected QT (QTc) interval becomes prolonged along with dialysis vintage.

Lomerizine, trimetazidine and bis-(4-fluorophenyl)-methylpiperazine in human urine after oral administration of lomerizine dihydrochloride: analysis by liquid chromatography-high resolution-tandem mass spectrometry.

In sports drugs testing, the differentiation between the abuse of the prohibited substance trimetazidine and that of the permitted drug lomerizine is required because trimetazidine is one of the metabolites of lomerizine. Therefore, it is important to identify a lomerizine-specific metabolite in urine that allows making the distinction. In this study, a simple dilute-and-shoot method employing liquid chromatography-high resolution-tandem mass spectrometry for the quantification of trimetazidine, lomerizine and the specific metabolite bis-(4-fluorophenyl)-methylpiperazine (M6) in urine was developed.

Oral L-citrulline and Transresveratrol Supplementation Improves Erectile Function in Men With Phosphodiesterase 5 Inhibitors: A Randomized, Double-Blind, Placebo-Controlled Crossover Pilot Study.

Introduction: Phosphodiesterase type 5 inhibitors (PDE5i) are first-line therapy for most men with erectile dysfunction (ED). If ineffective, vacuum erection devices, intracavernous injections, and penile prosthesis implantation are suitable as second- or third-line therapies. However, very few patients select these therapies.

Determination of higenamine and coclaurine levels in human urine after the administration of a throat lozenge containing Nandina domestica fruit.

Higenamine is a key component of traditional Chinese herbal medicine. The fruit of Nandina domestica (which contains this component) is available as an ingredient in the so-called Nanten-nodo-ame throat lozenge found on the Japanese market, which is an over-the-counter pharmaceutical and is easy to purchase for Japanese athletes. However, higenamine is a non-selective β2-agonist, which is exemplified in the prohibited list of the World Anti-Doping Agency (WADA).

Mass spectrometric characterisation of darbepoetin alfa biosimilars with C-terminal arginine residues.

Human erythropoietin (EPO) and recombinant human EPO (rEPO) are approximately 30-kDa glycosylated proteins comprising 165 amino acids. Darbepoetin alfa (NESP) is a glycosylated protein encompassing five changes in the amino acid sequence of human EPO, which contains two extra sugar chains. NESP is under patent protection in the USA until May 2024 and in Europe until July 2016, which suggests that the number of NESP biosimilars might substantially increase.

Comparison of mirabegron and imidafenacin for efficacy and safety in Japanese female patients with overactive bladder: A randomized controlled trial (COMFORT study).

Objectives: To evaluate the efficacy and safety of mirabegron compared with imidafenacin for the treatment of female patients with overactive bladder.

Methods: Patients (n = 89) were randomized to receive 0.1 mg imidafenacin twice daily (n = 47) or 50 mg mirabegron once daily (n = 42) for 12 weeks.

Effects of intravenous infusion of glycerol on blood parameters and urinary glycerol concentrations.

In sports, the oral intake and intravenous administration of glycerol as a potential masking agent have been prohibited. The effect of glycerol on blood parameters was investigated by comparing the intravenous administration of glycerol (20g/200mL) with that of an electrolyte (8g glucose/200mL) as a comparator (n=7, fixed-dose-rate i.v.

Analytical detection of trimetazidine produced by metabolic conversion of lomerizine in doping control analysis.

The identification of trimetazidine in urine samples might result from administration of the permitted drug lomerizine. Laboratories are therefore urged to carefully investigate suspicious cases where trimetazidine is detected. Differentiation of abuse of the banned substance trimetazidine from use of the permitted drug lomerizine would be supported by analysis of the intact drug lomerizine and/or specific metabolites.

Determination of mepitiostane metabolites in human urine by liquid chromatography/tandem mass spectrometry for sports drug testing.

Mepitiostane (2α,3α-epithio-17β-(1-methoxycyclopentyloxy)-5α-androstane), which is a prodrug of epitiostanol (2α,3α-epitio-5α-androstane-17β-ol), is an epitiosteroid having anti-estrogenic and weak androgenic anabolic activities. The World Anti-Doping Agency prohibits the misuse of mepitiostane by athletes. Detection of the urinary metabolites epitiostanol sulfoxide and epitiostanol was studied using liquid chromatography/mass spectrometry (LC-MS) for doping control purposes.

Comparison of urine analysis and dried blood spot analysis for the detection of ephedrine and methylephedrine in doping control.

When the misuse of stimulants is determined in doping control tests conducted during the in-competition period, athletes are asked to account for the violation of the rules. This study was designed to evaluate whether the urinary threshold values (10 µg/mL) for ephedrine and methylephedrine set by the World Anti-Doping Agency (WADA) can be exceeded after the oral administration of each substance (25 mg). In addition, the study describes the validity of a liquid chromatography-tandem mass spectrometric method using dried blood spot testing to detect ephedrine and methylephedrine by comparing it to a quantitative laboratory urine assay.

Possibility of analytical finding of glycerol caused by self-catheterization in doping control.

Glycerol is listed on the World Anti-Doping Agency (WADA) prohibited list as a masking agent principally because the administration of glycerol increases plasma volume and decreases the concentration of haemoglobin and the value of haematocrit in blood. Glycerol is a naturally occurring substance; therefore, the threshold is set as 1.0 mg/mL in the WADA technical document (WADA TD2013DL).

Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients.

Objectives: This study sought to assess whether spironolactone treatment reduces the high incidence of cardiovascular and cerebrovascular (CCV) morbidity and mortality in hemodialysis (HD) patients.

Background: Aldosterone receptor blockers reduce cardiac-related events, but the efficacy of the agents in HD patients is unclear.

Methods: A 3-year randomized trial involving 5 clinics was performed.

Association between warfarin use and incidence of ischemic stroke in Japanese hemodialysis patients with chronic sustained atrial fibrillation: a prospective cohort study.

Background: Although generally recommended for atrial fibrillation (AF) in the general population, the efficacy and safety of warfarin in hemodialysis patients remains controversial. Warfarin use in hemodialysis patients may confer an additional risk of bleeding that is not appreciated in patients without renal failure because hemodialysis patients have platelet defects and receive anticoagulation agents during dialysis. The incidence of major bleeding was reported to be higher in Japanese AF patients on warfarin therapy compared to patients in other countries, suggesting that racial differences may influence bleeding tendency.

Identification of the long-acting erythropoiesis-stimulating agent darbepoetin alfa in human urine by liquid chromatography-tandem mass spectrometry.

The misuse of recombinant human erythropoietin (rhEPO) increases the proliferation/production of erythrocytes, which enhance oxygen transport capacities, and has grave consequences with respect to human health and fairness in sports. For sports drug testing, the current analytical methods for rhEPOs are mainly gel electrophoretic methods, such as isoelectric focusing-polyacrylamide gel electrophoresis. Mass spectrometry is fundamentally necessary for the reliable identification of rhEPOs in doping control.

UDP-glucuronosyltransferase 2B17 genotyping in Japanese athletes and evaluation of the current sports drug testing for detecting testosterone misuse.

Ethnicity has been found to influence urinary testosterone glucuronide to epitestosterone glucuronide (T/E) ratios among athletes. Uridine diphospho-glucuronosyltransferase 2B17 (UGT2B17) is the most active enzyme in testosterone glucuronidation. UGT2B17 polymorphism analysis is rarely performed in Japanese athletes, and the influence of testosterone administration on steroid profiles and carbon isotope ratios, according to gene polymorphisms, in Asians remains unknown.