Excretion Profiles of the Mycotoxin Deoxynivalenol, following Oral and Intravenous Administration to Sheep

Excretion Profiles of the Mycotoxin Deoxynivalenol, followingOral and Intravenous Administration to Sheep. PRELUSKY, D. B.,VEIRA, D. M., TRENHOLM, H. L., AND HARTIN, K. E. (1986). Fundam.Appl. Toxicol. 6, 356–363. The excretion profiles of deoxynivalenol(DON) and metabolites (DON glucuronide conjugate, 3,715-trihydroxytrichothec-9,12-diene-8-one(DOM-1), and DOM-1 glucuronide conjugate) were defined in malesheep following either intravenous (iv) or oral administrationof the toxin at levels of 0.5 and 5.0 mg DON/kg body wt, respectively.After iv dosing, urinary DON levels declined in a biphasic fashionwith an average elimination half-life (terminal phase) of 1.2hr. diminishing to baseline concentrations by 8 hr. Maximumurinary excretion rates for the two major metabolites identified(conjugated DON, conjugated DOM-1) occurred 0.5–1.5 hrafter dosing, exhibiting elimination half-lives of 2.2 and 3.1hr, respectively. Total recovery accounted for only about 66.5%of the dose: 63.0% in the urine (24.1% DON, 21.2% conjugatedDON, 0.5% DOM-1, 17.2% conjugated DOM-1) and 3.5% in bile (madeup almost completely of conjugated DOM-1). The peak biliaryexcretion rate for conjugated DOM-1 was found to occur within1 hr postdosing, which rapidly declined to baseline levels by5 hr. Following oral administration, urinary excretion ratesof the major metabolites (DON, conjugated DON, conjugated DOM-1)reached maximum 6–9 hr post-treatment, and declined exponentiallywith t values of 3.2, 4.0, and 5.0 hr, respectively. Urinaryand biliary recovery of administered DON averaged approximately7.1%: 7.0% in urine (2.1% DON, 3.6% conjugated DON, 0.06% DOM-1,1.2% conjugated DOM-1) and 0.11% in bile (predominately conjugatedDOM-1). Between 54 and 75% of the oral dose was recovered inthe feces. These findings indicate that DON and metabolitesdo not persist in the body following either a single oral orintravenous dose of DON and are rapidly excreted. However, followingiv administration, a portion of the dose (33.5%) remained unaccounted,presumably converted to unidentified metabolites. Based on theseresults it appears that metabolism is the major process of eliminationof DON in sheep.     

Expression of cathepsin D and epidermal growth factor receptor in stage III cervical carcinomas

Cathepsin D and epidermal growth factor receptor (EGFR) antigens are related to tumor invasion, metastasis, progression, and recurrence. To assess the prognostic significance of the expression of these two antigens, biopsy specimens consecutively obtained from 216 patients with stage III cervical carcinomas (191 with squamous cell carcinomas and 25 with adenocarcinomas), who were treated with radiotherapy, were investigated immunohistochemically. The positive rate of cathepsin D expression in squamous cell carcinomas was 74%, significantly higher than the 47% observed in adenocarcinomas ( P  = 0.015). The EGFR positive rate in squamous cell carcinomas was 33%, somewhat higher than the 16% in adenocarcinomas ( P  = 0.088). The chi-square test and Kaplan–Meier method showed no significant relationship between the expression of either cathepsin D or EGFR and the prognosis in these patients. These results indicate that in stage III cervical carcinomas cathepsin D and EGFR expression do not correlate with prognosis.     

Transcapillary ultrafiltration and peritoneal equilibration test in pediatric patients

The usefulness of the peritoneal equilibration test (PET) in children is unknown. The relationship between transcapillary ultrafiltration and PET was investigated in order to evaluate the usefulness of PET in children. PET was performed on 14 patients undergoing peritoneal dialysis. Their age and bodyweight ranged from 3.8 to 23.6 years and 10.2 to 55.8 kg, respectively. The patients were divided into two groups according to bodyweight; group A patients weighed ≤ 40 kg (n = 7) and group B patients weighed > 40 kg (n = 7). There was no significant difference in the mean infusion volume per bodyweight between the two groups, but the mean infusion volume per body surface area was smaller in group A than in group B. Group A showed a more rapid equilibration of dialysate glucose and creatinine than group B. Higher normalized mass transfer area coefficients were evident in group A. In spite of the lower effective glucose gradient in group A, the transcapillary ultrafiltration capacity (TUFC) showed no difference between the two groups. When the slope indices of the regression equations between the two groups were compared, the slopes of the regression in the relationship between TUFC and dialysate (D) ratios D/D₀ glucose or D/P creatinine in group A were steeper than those in group B. Results of the present study indicate that the larger peritoneal area to infusion volume in patients with smaller body size results in both a rapid equilibration of solutes and sufficient transcapillary ultrafiltration.