Akiko Miki

Decrease of suppressor-inducer (CD4+CD45RA) T lymphocytes and increase of serum immunoglobulin G due to perceived job stress in Japanese nuclear electric power plant workers

To clarify the effects of perceived job stress on the immune system, a cross-sectional study was conducted in 116 male Japanese workers of a nuclear electric power plant (age, 20 to 39; mean, 31 years). Perceived job stress, i.e., psychological job demand, job control, worksite social support, and job strain, was assessed by means of the Japanese version of the Job Content Questionnaire. The job strain score was calculated as the ratio of the job demand score to the job control score. Blood samples were taken from all workers, and numbers of T and natural killer cell subpopulations, B lymphocytes, total lymphocytes and white blood cells, and serum concentrations of immunoglobulins (IgG, IgM, IgA, IgE and IgD) in their blood were measured. The workers were divided into higher and lower strain groups according to their job strain scores. The number of CD4+ CD45RA+ T lymphocytes in the higher strain group having the job strain score of 0.5 or more (41 workers) was significantly smaller than that in the lower strain group having the score of less than 0.5 (75 workers). In contrast, the serum IgG concentration in the former group was significantly higher than that in the latter group (analysis of covariance with age and smoking as covariates). Also, the numbers of total CD4+ T and total T (CD3+) lymphocytes and of white blood cells in the former group were significantly smaller than those in the latter group. After controlling for age and smoking by the partial correlation coefficient in all 116 workers, the number of CD57+ CD16+ natural killer cells was inversely correlated with job demand and with job strain; the number of CD8+ T lymphocytes was positively correlated with worksite social support; and serum IgG and IgM concentrations were positively correlated with job strain. It is suggested that higher job strain decreases the number of CD4+ CD45RA+ T lymphocytes in male Japanese workers but increases serum IgG concentrations.

Warfarin and miconazole oral gel interactions: Analysis and therapy recommendations based on clinical data and a pharmacokinetic model

What is known and Objective:  Miconazole is a strong inhibitor of CYP2C9, one of the main enzymes involved in the metabolism of warfarin. Concurrent use of the two drugs leads to potentially serious adverse effects. Although it is often assumed that use of the oral miconazole gel is acceptable with concomitant warfarin, because of the low bioavailability following buccal administration, drug–drug interactions have been reported following such use. We aimed to investigate case reports of such interactions and develop a pharmacokinetic model to model such interactions.

Effects of smoking and Japanese cedar pollinosis on lymphocyte subpopulations

Approximately 10-30% of the Japanese population suffer from Japanese cedar (Cryptomeria japonica) pollinosis in the spring. To date, the effects of this pollinosis on lymphocyte subpopulations have not been examined epidemiologically. To examine the effects of smoking and Japanese cedar pollinosis on lymphocyte subpopulations, we used flow cytometry to measure CD4+ and CD8+ T-lymphocyte subpopulations, natural-killer cell subpopulations, B(CD19+) lymphocytes, and total lymphocytes in 61 smokers and 51 nonsmokers. Some of these individuals had histories of pollinosis during November 1993-an off-season for Japanese cedar pollination. Our findings suggested that (a) CD4+ T-lymphocyte subpopulations (i.e., CD4+CD29+, CD4+CD45RA+, and CD4+ CD45RO+ cells) together with total CD4+ T, total T, and total lymphocytes, were increased by the effects of smoking; (b) CD8dim+CD11a+T, and CD8+CD11bt, and CD57+CD16+ natural killer cells, together with total CD8+CD11 a+ T and total CD8+ T lymphocytes, were increased by the effects of pollinosis on smokers, even though no lymphocyte subpopulations were increased by only the pollinosis effects; (c) CD4+CD29+T and CD8dimCD11a+ T lymphocytes were increased by the effects of smoking on pollinosis, and (d) CD4+CD29+ T and CD4+CD45RO+ T lymphocytes, CD8dim+CD11 a+ T, and CD8+CD11b+ T lymphocytes and CD57+CD16+ natural killer cells, together with total CD4+ T, total T (CD3+), total CD8+CD11a+, total CD8+ T, and total lymphocytes, were increased by the combined effects of smoking and pollinosis.

Dosage adjustment of quinolone antibiotics and angiotensin-converting enzyme inhibitors in patients with renal dysfunction

The aim of this study was to verify an approach for calculating pharmacokinetic parameters suitable for adjusting dosage regimens in patients with renal dysfunction. We carried out a retrospective analysis of the pharmacokinetic profiles of 12 new quinolone antibiotics and 11 angiotensin-converting enzyme inhibitors (ACEIs) in patients with normal and impaired renal function to obtain the renal excretion ratio (R(renal)) of each drug. We demonstrated that the pharmacokinetics of each drug in a patient with renal dysfunction can be adequately estimated using the R(renaI) value of each drug together with the creatinine clearance as an index of the individuals renal function. Using the R(renaI) value obtained, we could successfully simulate pharmacokinetic profiles of the drugs in publications other than that used to obtain the R(renal) values. On the other hand, age-related changes in the pharmacokinetics of new quinolone antibiotics are not always adequately predicted using the R(renal) value compared to using creatinine clearance alone as an index, and the reasons for this are not fully understood. These results demonstrate that dosage regimens of quinolone antibiotics and ACEIs in patients with renal dysfunction can be adequately optimized using the R(renal) value for each drug using the present approach.

Immunological effects of CaEDTA injection: Observations in two lead workers

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) injection on human immune system in relation to exposure to lead, we administered CaEDTA by intravenous injection for 1 hr three times (three consecutive days) a week to two male lead workers. They had been engaged in recycling lead for 31 and 22 years, aged 61 and 53 years (workers 1 and 2), respectively. Before the treatment of CaEDTA, their blood lead concentrations (PbB) were 81 and 68 micrograms/dl, respectively. The administration of CaEDTA had been carried out to worker 1 for 10 weeks and to worker 2 for 6 weeks. A significant decrease in PbB between before and after three-times CaEDTA injection was found in both workers. Significant increases in IgG, IgA, IgM, CD8+, and CD57+ cells were found in worker 1. A significant increase in IgD was found in worker 2. During the study period, IgG in worker 1 and CD4+ cells in worker 2 were gradually increasing. There was a significant negative correlation between IgG and PbB in worker 1. It is suggested that the immunological function such as antibody formation in lead workers might be improved by CaEDTA injection.

Induced next-day somnolence in an elderly patient taking suvorexant concomitantly with diltiazem.

OBJECTIVE To present the first case of induced next-day somnolence in a patient taking suvorexant concomitantly with diltiazem. CASE SUMMARY The patient was an 88-year-old female who had suffered from insomnia and anorexia, for which a psychiatric clinic had prescribed 1.5 mg/day aripiprazole and 15 mg/day suvorexant (both once daily at bedtime), which cured her insomnia. Subsequently, a different hospital prescribed diltiazem hydrochloride (100 mg, sustained-release, daily after breakfast) for treatment of hypertension. After starting diltiazem, the patient was unable to wake up in the morning and overslept by ~ 3 hours. On the third day of taking diltiazem, the patient, on the basis of her own judgment, took only half a tablet of suvorexant, and found that she was able to sleep, and there was no somnolence the following morning. As halving suvorexant tablets is an off-label usage, and lower-dose tablets are not available, her prescription was switched to 1-mg rilmazafone hydrochloride. Since then, her sleep disorder has not recurred. DISCUSSION Because suvorexant is metabolized by CYP3A4, next-day somnolence could have occurred as a result of increased plasma suvorexant concentration due to CYP3A4 inhibition by diltiazem. CONCLUSION Elderly patients may suffer next-day somnolence if they concomitantly take suvorexant and sustained-release diltiazem hydrochloride, even if the diltiazem dose is low and there is a significant interval between the administration times of the two drugs. In order to avoid drug interaction, it may be desirable to switch from suvorexant to a different soporific that is not metabolized by CYP3A4.