The objective of this study was to explore the challenges faced by parents of former neonatal intensive care unit (NICU) patients in transitioning home from parents' and healthcare providers' perspective. We conducted semistructured individual and group interviews with parents of former NICU patients and healthcare providers. Themes from the individual interviews framed the group interviews' contents. The group interviews were recorded and transcribed, and thematic analysis was performed to identify themes. We conducted individual and group interviews with 16 parents and 33 inpatient and outpatient providers from November 2017 to June 2018. Individual interview participants identified several barriers experienced by parents when transitioning their infant home from the NICU including parental involvement and engagement during NICU stay and during the discharge process. Further exploration within group interviews revealed opportunities to improve discharge communication and processes, standardization of parental education that was lacking due to NICU resource constraints, support for parents' emotional state, and use of technology for infant care in the home. Parents of NICU patients face serious emotional, logistical, and knowledge challenges when transitioning their infant home from the NICU. Understanding and mitigating the challenges of transitioning infants from NICU to home require multistakeholder input from both parents and providers.
Metabolites of propylthiouracil (PTU) appearing in rat bile and urine were compared after administration of 14C-PTU or 35S-PTU. Chromatography of 24-hr urines on Bio Gel P-2 columns resulted in the separation of several peaks of radioactivity. Each peak was subjected to further study. The results demonstrated that the most abundant component of urine was unaltered PTU and confirmed that PTU-glucuronide was a major urinary metabolite. These compounds accounted for 42.3 and 16%, respectively, of the total urinary radioactivity. Three metabolites heretofore unreported in rat urine, sulfate, propyluracil (PU) and S-methyl propylthiouracil (S-rhethyl PTU), were identified and comprised 7, 5.1 and 3.5%, respectively, of the total radioactivity. The major metabo- lite (22%) was not identified but appeared to be an S-conjugate of PTU or a PTU metabolite. Several radioactive PTU metabolites were also observed i n 6-hr bile. The most abundant metabolite was PTU-glucuronide comprising 41.9% of the total with small amounts of unaltered PTU and of sulfate also being observed. Two other substances were glucuronides of unidentified PTU metabolites and 3 unidentified compounds appeared to be S-conjugates of PTU or a PTU metabolite. The variety of metabolites observed suggests that several pathways are involved in PTU metabolism in the rat and that a major site of biological alteration in the PTU molecule is the S group. (Endocrinology94: 1689, 1974)
Abstract Unopposed estradiol and obesity are known risk factors for endometrial adenocarcinoma (EC). Endometrium from women with obesity was found to have an increase in mutations relative to tissue from normal weight women, indicating DNA damage may be accelerated in the setting of obesity. Since obesity is associated with high levels of insulin and anovulatory cycles, we sought to mimic these conditions in a mouse model. We previously found that hyperinsulinemic MKR mice, without the confounder of obesity, have an increased incidence of nuclear atypia in endometrial glands. We hypothesized that hyperinsulinemia and unopposed estradiol have a synergistic effect on inducing abnormal architecture and DNA damage in the endometrium, than either alone. At 8-10 weeks old, cohorts of MKR (n=20) and WT (n=20) mice underwent ovariectomy and placement of either an estradiol (E2) or placebo (P) pellet. Metabolic profiling included insulin tolerance testing and MR for body composition. At 3 months post-implantation, mice received a partial hysterectomy and second pellet replacement. At 6 months, the remaining uterus was bisected into pieces. A blinded histological analysis was conducted by a gynecology pathologist. A marker of DNA damage due to oxidative stress, 8-oxoguanine-DNA-glycosylase (8-OHdG), was quantified by ELISA. Data was analyzed using Kruskal-Wallis test with multiple test correction, or Fischer’s exact test. By 6 months, MKR-E2 treated mice had a 27% lower body weight than MKR-P mice (p<0.05), and 31% lower than WT-E2 mice (p<0.01). WT-E2 and WT-P had similar weight, and were similar to MKR-P (p=ns). Percent body fat was similar across all 4 cohorts of mice (p=ns). Since placebo-treated mice had small, atrophied uteri with minimal gland formation, E2 pellet failure was determined by the presence of small, atrophied uteri and occurred in 4 MKR and 3 WT mice at either 3 or 6 months. All other MKR and WT E2 treated mice had enlarged uteri. The frequency of endometrial gland dilation was similar in MKR-E2 and WT-E2 uteri (p=ns), but all MKR mice had moderate-severe dilation, whereas WT mice had 50% mild and 50% moderate-severe dilation (p=0.07). Focal hyperplasia was present in one MKR-E2 mouse, and nuclear atypia was present in one WT-E2 mouse. MKR-P uteri had a 7-fold higher mean 8-OHdG relative to MKR-E2 uteri (5.0±3.7 vs 0.7±1.6, p<0.002). WT-E2 and WT-P uteri had similar 8-OHdG (1.6±0.8 vs 1.8±0.6, p=ns), as did MKR-E2 and WT-E2 uteri (p=ns). Our findings show that hyperinsulinemia exacerbates the cystic dilation induced by chronic unopposed estradiol, indicating a synergy of insulin and estradiol in promoting abnormal glandular growth in the endometrium. Surprisingly, uterine DNA damage was highest in the setting of hyperinsulinemia alone, in a hormonal state mimicking post-menopause. Further work is needed to understand the effect of estradiol on intrauterine oxidative stress-induced damage.
The identities and relative amounts of the major metabolites in rat thyroids 6 h after the administration of [14C]propylthiouracil ([14C]PTU) have been investigated. Rat thyroid extracts were chromatographed on columns of Bio-Gel P-2 and DEAE-Sephadex and in various thin layer chromatography systems. The extracts contained protein-bound PTU metabolites; an unknown peak 3; peak 1, which was chromatographically similar to PTU—SO2H; peak 2, which was similar to PTU—SO3H; PTU; and small amounts of 6-n-propyluracU (PU). The major metabolites were isolated and purified by column chromatography. On the basis of chromatographc properties identical to cochromatographed standards in seven different systems and the products formed after treatment with various reagents, peak 1 was identified as PTU—SO2H and peak 2 as PTU—SO3H. Peak 3 was seen only on Bio-Gel P-2 columns, was very unstable, and was not similar to any known PTU standard. The properties of this compound suggest that it may be a thiolsulfonic ester 1686_1_iimg, but the data are insufficient for positive identification. Approximately 85% of the radioactivity in the protein peak was bound to thyroglobulin. HC1 converted 86.5% of the protein-bound radioactivity to PU, and H2S converted 91% to PTU, indicating that an oxidized S was involved in the linkage to protein. Dithiothreitol released 23.6% of the protein-bound radioactivity as PTU, and mercaptoethanol released 32.5%, indicating that 25–35% of the PTU is bound in disulfide linkage. Approximately 50% of the radioactivity released by mercaptoethanol was S-ethanol PTU, which suggests a PTU-protein bond similar to a thiolsulfonic ester. Quantitation of the metabolites revealed that protein-bound metabolites accounted for 21–29% of the total radioactivity, unknown peak 3 accounted for 7.1%, PTU—SO2H for 48–50%, PTU—SO3H for 8–10%, and PTU for 10.7–16.5%. Only traces of PU were observed. These data demonstrate that PTU—SO2H is the major PTU metabolite in rat thyroid and must be the compound X.observed by other investigators and that all metabolites identified are oxidative products of PTU. These findings support the earlier conclusion of Taurog and Riesco that protein binding of PTU occurs as a consequence of oxidation.
