Keisuke Miyaji

Cadmium nephrotoxicity and evacuation from the body in a rat modeled subchronic intoxication

Background: Cadmium (Cd) is an important industrial pollutant, although its mechanism of toxicity has not been completely clarified. We studied Cd‐induced subchronic nephrotoxicity and the cadmium evacuation system in rats and cultured human renal tubular cells.

Body mass index for chronic hemodialysis patients: Stable hemodialysis and mortality

Abstract Body mass index (BMI) is used as a reference for weight control programs in the general population and in morbidity and mortality studies in diabetes patients. However, the implications of BMI in chronic hemodialysis patients is unclear. We studied the BMI of chronic hemodialysis patients, focusing on problems encountered during outpatient hemodialysis therapy and on 2‐year mortality. Outpatients with chronic hemodialysis (n = 258; 144 men, 114 women) were divided into four groups: (i) patients with stable hemodialysis; (ii) patients with marked hypotension requiring catecholamine infusion during hemodialysis; (iii) patients with excessive interdialysis weight gain requiring occasional additional hemodialysis; and (iv) patients with troublesome hemodialysis due to other causes. The statistical differences between the average BMI among these groups were evaluated, and were subdivided into sex, age and the duration of hemodialysis history. The 2‐year mortality rates of these patients were also studied according to their BMI. In patients under 60 years of age, those with excessive interdialysis weight gain had statistically larger BMI (23.2; n = 35) compared to patients with good hemodialysis control (20.1; n = 178), regardless of gender and hemodialysis history. The mortality rate was at a minimum at approximately 20 BMI in patients under 60 years of age. However, lower BMI was associated with a greater mortality rate in patients 60 years or over. For chronic hemodialysis patients, the BMI associated with stable hemodialysis and minimum mortality is approximately 20, in those under 60 years of age. The BMI of aged hemodialysis patients should be considered separately in morbidity and mortality studies.

Cadmium-induced testicular damage in a rat model of subchronic intoxication

BackgroundCadmium (Cd)-induced testicular damage in relation to spermatogenesis has not been well studied. We studied the mechanism of Cd-induced testicular damage in a rat model of subchronic intoxication.MethodsMale Sprague-Dawley rats were subcutaneously injected with 0.6 mg Cd/kg per day for 6 weeks. The concentration of Cd in urine, serum and testes was measured by using atomic absorption spectrophotometry. Testicular damage was evaluated by counting the spermatogonia (SG) and spermatocytes (SC) on one cut-surface of five seminiferous tubules in stages VII or VIII of spermatogenesis every week. The location of intratesticular cadmium was determined by using oxine-fluorescent cytochemistry.ResultsThere were no differences in the testes/bodyweight ratio between the study and control groups. The concentration of Cd in the testes increased more than 100-fold that in serum after week 2, suggesting active testicular Cd accumulation (1–3 mg/g tissue). Cadmium accumulation was detected in SG and SC. The number of SG and SC diminished significantly in the study group (week 2: SG 74%, SC 90%; week 4: SG 47%, SC 75%; week 6: SG 30%, SC 54% of the control, respectively).ConclusionsCadmium accumulated in SG and SC, consequently reduced the number of these cells, and disturbed the spermatogenesis in this rat model of subchronic Cd intoxication. Therefore, the number of SG decreased in this rat model of subchronic Cd intoxication.

Improvement of sensitivity and selectivity of high-performance liquid chromatography for anti-retroviral drugs (non-reverse transcriptase inhibitors) by diamond-electrode electrochemical and fluorescence detection

The new non-reversed transcriptase inhibitor (NRTI) drugs for treatment of acquired immunodeficiency syndrome (AIDS) are reported. An improvement in the sensitivity and selectivity of high-performance liquid chromatography was obtained by diamond electrode-electrochemical detector and fluorescence detector owing to different structural information. The four anti-retroviral NRTI drugs (abacavir, didanosine, lamivudine and zidovudine) were separated on a CapcellPak C18 UG120 column (250 mm x 4.6 mm I.D., 5 microm) with an acetonitrile-25 mM potassium dihydrogenphosphate buffer (pH 8.0; 1:9, v/v) as the mobile phase. We applied dual detection (electrochemical detection and florescence detection) for improving the peak identification and also for improved selectivity, which assisted monitoring by trace-volume samples (e.g., plasma). The electrochemical detector, equipped with a diamond electrode, was set at 2000 mV (applied voltage) and the fluorescence detector was set at excitation wavelength 275 nm and emission wavelength 315 nm. The detection limits of the four NRTIs in spiked plasma were 1-100 ng/ml by electrochemical detection and 5-10 pg/ml by fluorescence detection. The calibration graphs were linear up to 20 microg/ml by electrochemical detection and 10 microg/ml by fluorescence detection. This is the first report of LC analysis of NRTIs by electrochemical detection, also combined with fluorescence detection. The detection limits of didanosine, lamivudine and zidovudine were improved 20-fold by electrochemical detection and 500-fold by fluorescence detection compared to previous reports on UV detection. The selectivity was also improved by dual detection. The proposed method was applied to the preliminary monitoring of NRTIs in plasma.

Cryopreservation of human sperm in patients with malignancy: First 2 years’ experience

BackgroundPatients with malignancy (n = 130) participated in the sperm cryopreservation program.MethodsAfter washing and concentrating, sperm was cryopreserved using KS-VIm cryoprotectant medium. Participant background factors such as age, marital status, underlying disease, presence or absence of previous treatment and semen findings (concentration, motility and morphology) were analyzed to determine parameters associated with the program.ResultsPatients in their 20s were most common (64 cases) and 94 cases were unmarried at the first visit. The main underlying diseases were testicular tumor (53 cases), leukemia (43 cases) and malignant lymphoma (13 cases). The program was completed for 118 cases. For leukemia, all semen parameters were closer to normal in patients without previous treatment (untreated group, UG) compared with the treated group (TG). When semen findings in the UG were classified according to underlying disease, sperm concentration was lower in patients with testicular tumor compared with those who had leukemia or malignant lymphoma. Four couples underwent reproductive therapies with the cryopreserved sperm through assisted reproductive technology, and three babies were born to two couples.ConclusionSperm cryopreservation liberates patients with malignancy from iatrogenic infertility as a consequence of intensive therapy, allowing them to retain reproductive ability.

Prostate cancer with multiple lung metastases in a hemodialysis patient

Abstract In hemodialysis patients, few cases of prostate cancer have been reported until recently. We present a case of prostate cancer with multiple lung metastases in a chronic hemodialysis patient. A 65‐year‐old Japanese man who had maintained hemodialysis for 5 years was referred to our hospital with multiple metastatic lung tumors. Serum prostate tumor markers were highly elevated although his plasma testosterone level was within the normal range. A transrectal needle prostate biopsy confirmed a histologic diagnosis of moderately differentiated adenocarcinoma. Androgen blockade therapy was very effective as evidenced by a quick decrease of serum tumor markers. The follow‐up computed tomography scan of the chest performed 3 months later showed a complete disappearance of the coin lesions. The early detection of prostate cancer in hemodialysis patients is difficult because of a lack of urologic symptoms, which indicate the importance of periodic screening by serum tumor markers. Combined androgen blockade is effective even in hemodialysis patients. However, close follow up is necessary because long‐term results and prognoses are still unknown.

Kidney autotransplantation in a patient with renal pelvic and bladder carcinomas

A 66‐year‐old Japanese woman, whose left kidney was non‐functioning, was referred to us with a diagnosis of invasive bladder carcinoma and right renal pelvic carcinoma. The latter tumor was clearly packed in the renal calyx and was considered to be of low‐grade malignancy. Nephron preserving surgery of the right kidney was performed, followed by radical cystectomy and construction of an ileal conduit. The postoperative course was good, without significant complications. Renal function was restored and a postoperative imaging study showed a well‐functioning transplanted kidney. At present (20 months after surgery), the patient is doing well and has presented no signs of recurrence of the disease.