fIn this study, we assessed the effects of the prevaccination titer and age on the immunogenicity of a low dose of influenza vaccine in children less than 4 years of age. A total of 259 children received two vaccine doses (0.1 ml for 0-year-olds and 0.2 ml for children 1 year of age or older) 4 weeks apart during the 2005/2006 season. The hemagglutination inhibition antibody titers were measured before vaccination and 4 weeks after the first and second doses. The geometric mean titer, mean fold rise, seroresponse proportion (>4-fold rise in titer), and seroprotection proportion (titer >1:40) were calculated for the prevaccination titer and age categories. A multivariate logistic regression analysis was performed using the seroresponse and seroprotection proportions as dependent variables and the prevaccination titer and age as explanatory variables. As for the seroresponse against the H1 antigen after the first dose, the adjusted odds ratios of the prevaccination titers (versus <1:10) were 2.2 (95% confidence interval, 0.8 to 5.8) at 1:10 to 1:20 and 0.14 (0.04 to 0.49) at >1:40. The corresponding figures for ages were 0.03 (0.01 to 0.07) for the 0-year-olds and 0.17 (0.08 to 0.34) for the 1-year-olds compared with the 2-to 3-year-olds (P trend < 0.001). Similar results were also obtained for the H3 and B strains. Significantly elevated odds ratios for seroprotection were observed with greater prevaccination titers and older ages for all strains. The prevaccination titer and age were independently associated with the antibody response in young children. The immune response was weaker in the younger children and those without preexisting immunity. Influenza is a vaccine-preventable disease. The rate of seasonal influenza infection is highest among children, and children less than 2 years of age are at high risk of influenza-associated hospitalization (1, 2). The Advisory Committee on Immunization Practices routinely recommends that children 6 months to 8 years of age receive two doses of influenza vaccine during their first season of vaccination in order to optimize the immune response (3). This recommendation is based on data showing that vaccine effectiveness and immunogenicity are lower among young children treated with one dose of the vaccine, whereas two doses of vaccine provide substantial protection against influenza-like illness (ILI) (4-6) and induce a protective level of antibodies, even in young children (7-15).The factors affecting low immune responses to the influenza vaccine among children are supposed to include immature immunity function due to age, infrequency of opportunity for exposure to influenza virus through vaccination and/or infection, thus resulting in a lack of induced priming, and a low-volume dose of the vaccine. As the subjects get older, it has been reported that their prevaccination titer (pretiter) increases (16-19), but there has been very little detailed research that considered the predictive factors in the immune response (20,21).In this report, we present the immunogenicity o...

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The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.

ObjectivesCreatine and creatine phosphate act as a buffer system for the regeneration of ATP in tissues with high and fluctuating energy demands. Total creatine content of the rat testis is high compared to all other tissues except skeletal muscle and creatine excretion in rat urine has been shown to increase following testicular damage caused by toxicants. Because the use of biomarkers in toxicology is becoming increasingly important, we investigated whether urinary creatine might be a useful marker for testicular damage in human.MethodsIn a retrospective study, the records of 22 male patients with urological malignancies treated with cisplatin, leuprorelin or goserelin at 4‐week intervals between October 2005 and October 2015 were evaluated. Urinary creatine and serum follicle‐stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels were assessed in all patients. Single‐voided urine samples were collected to determine urinary creatine‐to‐creatinine ratios. Blood sample collection was done in the morning when serum testosterone levels are around their peak: such morning time sampling for testosterone measurements is recommended in the clinical setting and routinely used in epidemiological studies.ResultsSeven patients with urothelial carcinoma treated with cisplatin based chemotherapy (mean age, 64.1 years) showed no significant changes in urine creatine/creatinine ratio during treatment and had a significant increase in FSH and LH levels and a significant decrease in testosterone levels compared to those at baseline. Similarly, no significant changes in urine creatine/creatinine ratio occurred in patients with prostatic carcinoma treated with leuprorelin (n=8; mean age, 70.0 years) or goserelin (n=7; mean age, 70.4 years), both of whom had castrate levels of testosterone (≤0.5 ng/mL) and suppressed levels of FSH and LH during treatment.ConclusionsOur data demonstrate that testicular damage could not be detected by urinary creatine in patients treated with drugs showing testicular toxicity. Two major testicular functions, i.e., the production of testosterone and formation of haploid germ cells, are generally considered to be regulated by pituitary gonadotrophins, with LH acting on the testosterone‐producing Leydig cells located in the interstitium and FSH affecting Sertoli cells in the seminiferous tubules. Thus, our hormonal data may indicate the presence of cisplatin‐induced Sertoli cell dysfunction and inhibition of Leydig cell function by LH‐RH analogues.Support or Funding InformationNoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

BackgroundClinical laboratory values are critical indicators for clinical trials from beginning of enrolments for rightful subjects to monitoring the subject's safety. However, actual values may vary significantly due to differences in assay methodologies and standardization even within a country. Therefore, when conducting clinical trials with Caucasian subjects in non-Caucasian native countries such as Japan, it is even more important to understand and consider the ethnicity differences in laboratory values to minimize bias and obtain the best results. In this study, to define the reference ranges for Caucasian healthy subjects for clinical trials in Japan, we reviewed and analyzed clinical laboratory data from our healthy Caucasian studies. The characteristics of clinical laboratory reference intervals were evaluated and compared between Caucasian and Japanese volunteers. Methods Clinical laboratory data for Caucasian volunteers (524 Males, 29 Females) from the screening tests for clinical trials at SOUSEIKAI Sumida Hospital from Jan 2017 to Dec 2017 and assessed hematological and clinical chemistry data with a focus on Hepatic and Lipid Panels. The clinical laboratory reference intervals were compared to the values for same age and gender group of Japanese volunteers. Also, we evaluated the values in different age groups to investigate the impact of age factors over ethnicity factors. Results A total data of 524 healthy Caucasian volunteers aged 20 to 45 years for 11 parameters were reviewed and analyzed; AST, ALT, ALP, T-Bil, LDH, gamma-GT, TG, LDL-C. HDL-C, Creatine, TCh, There were statistically significant differences between Japanese and Caucasian data in CK and LDL-C for male volunteers whereas other indicators showed similar ranges. The laboratory values for ALT, ALP, in Caucasian males were somewhat higher than those from Japanese males and TG was higher in Japanese males compare to Caucasian males. Also, our reference ranges for Caucasian volunteers were consistent with established intervals from the US (Massachusetts General Hospital, MGH-USA) ConclusionBy defining and understanding the right clinical laboratory reference intervals for Caucasian healthy subjects, it is possible to assess participant's eligibility and safety for clinical trials, avoiding unnecessary exclusion of eligible participants and over-reporting of adverse events (AEs) for Caucasian studies in Japan.