Delegation of insulin administration: a survey of community nursing teams in England.

In community nursing, the administration of insulin for people with type 2 diabetes can be delegated by registered nurses to healthcare support workers. Although a voluntary framework in England provides national guidance, little is known about its uptake. The project aim was to determine the roll-out, characteristics and support needs in relation to the delegation of insulin administration in community settings. An online survey was disseminated to community nursing services in England via social media and nursing networks. Of the 115 responding organisations, 81% (n=93) had an insulin delegation programme, with most initiated since 2018. From these services, 41% (n=3704) of insulin injections were delegated daily, with benefits for patients, staff and services reported, along with some challenges. Delegation of insulin administration is an established and valued initiative. Awareness of the national voluntary framework is increasing. National guidance is considered important to support governance arrangements and safety.

Approaches for predicting effects of unintended environmental exposure to an endocrine active pharmaceutical, tamoxifen.

Tamoxifen is an endocrine-active pharmaceutical (EAP) that is used world-wide. Because tamoxifen is a ubiquitous pharmaceutical and interacts with estrogen receptors, a case study was conducted with this compound to (1) determine effects on reproductive endpoints in a nontarget species (i.e., a fish), (2) compare biologically-active metabolites across species, (3) assess whether in vitro assays predict in vivo results, and (4) investigate metabolomic profiles in tamoxifen-treated fish to better understand the biological mechanisms of tamoxifen toxicity. In reproductive assays, tamoxifen exposure caused a significant reduction in egg production and significantly increased ovarian aromatase activity in spawning adult cunner fish (Tautogolabrus adspersus). In plasma from tamoxifen-exposed cunner, the predominant metabolite was 4-hydroxytamoxifen, while in rats it was N-desmethyltamoxifen. Because 4-hydroxytamoxifen is a more biologically active metabolite than N-desmethyltamoxifen, this difference could result in a different level of risk for the two species. The results of in vitro assays with fish hepatic microsomes to assess tamoxifen metabolism did not match in vivo results, indicating probable differences in excretion of tamoxifen metabolites in fish compared with rats. For the first time, a complete in vitro characterization of the metabolism of tamoxifen using fish microsomes is presented. Furthermore, a metabolomic investigation of cunner gonad extracts demonstrates that tamoxifen alters the biochemical profile in this nontarget species. Understanding the consequence of tamoxifen exposure in nontarget species, and assessing the discrepancies between sex- and species-mediated endpoints, is a step toward understanding how to accurately assess the risks posed by EAPs, such as tamoxifen, in the aquatic environment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1834-1850, 2016.

Developing analytical approaches to explore the connection between endocrine-active pharmaceuticals in water to effects in fish.

The emphasis of this research project was to develop and optimize a solid-phase extraction method and high-performance liquid chromatography-electrospray ionization-mass spectrometry method, such that a linkage between the detection of endocrine-active pharmaceuticals (EAPs) in the aquatic environment and subsequent effects on fish populations could eventually be studied. Four EAPs were studied: tamoxifen (TAM), exemestane (EXE), letrozole (LET), anastrozole (ANA); and three TAM metabolites: 4-hydroxytamoxifen, e/z endoxifen, and n-desmethyl tamoxifen. In aqueous matrices, the use of isotopically labeled standards for the EAPs allowed for the generation of good recoveries, greater than 80 %, and low relative standard deviations (% RSDs) (3 to 27 %). TAM metabolites had lower recoveries in the spiked water matrices: 35 to 93 % in waste/source water compared to 58 to 110 % in DI water. The precision in DI water was acceptable ranging from 8 to 38 % RSD. However, the precision in real environmental wastewaters could be poor, ranging from 15 to 120 % RSD, dependent upon unique matrix effects. In plasma, the overall recoveries of the EAPs were acceptable: 88 to 110 %, with %RSDs of 6 to 18 % (Table 3). The spiked recoveries of the TAM metabolites from plasma were good, ranging from 77 to 120 %, with %RSDs ranging from 27 to 32 %. Two of the TAM metabolites, 4-hydroxytamoxifen and n-desmethyl tamoxifen, were confirmed in most of the environmental aqueous samples. The discovery of TAM metabolites demonstrates that the source of the TAM metabolites, TAM, is constant, introducing a pseudo-persistence of this chemical into the environment.

Modulation of aromatase activity as a mode of action for endocrine disrupting chemicals in a marine fish.

The steroidogenic enzyme aromatase catalyzes the conversion of androgens to estrogens and therefore plays a central role in reproduction. In contrast to most vertebrates, teleost fish have two distinct forms of aromatase. Because brain aromatase activity in fish is up to 1000 times that in mammals, fish may be especially susceptible to negative effects from environmental endocrine-disrupting chemicals (EDCs) that impact aromatase activity. In this study, the effects of estradiol (E2), ethynylestradiol (EE2), octylphenol (OP), and androstatrienedione (ATD) on reproduction and aromatase activity in brains and gonads from the marine fish cunner (Tautogolabrus adspersus) was investigated. The purpose of the study was to explore the relationship between changes in aromatase activity and reproductive output in a marine fish, as well as compare aromatase activity to two commonly used indicators of EDC exposure, plasma vitellogenin (VTG) and gonadosomatic index (GSI). Results with E2, EE2, and ATD indicate that aromatase activity in cunner brain and ovary are affected differently by exposure to these EDCs. In the case of E2 and EE2, male brain aromatase activity was signficantly increased by these treatments, female brain aromatase activity was unaffected, and ovarian aromatase activity was significantly decreased. Treatment with the aromatase inhibitor ATD resulted in significantly decreased aromatase activity in male and female brain, but had no significant impact on ovarian aromatase activity. Regardless of test chemical, a decrease or an increase in male brain aromatase activity relative to controls was associated with decreased egg production in cunner and was also correlated with significant changes in GSI in both sexes. E2 and EE2 significantly elevated plasma VTG in males and females, while ATD had no significant effect. Treatment of cunner with OP had no significant effect on any measured endpoint. Overall, results with these exposures indicate EDCs that impact aromatase activity also affect reproductive output in spawning cunner.

Chlorotriazine herbicides and metabolites activate an ACTH-dependent release of corticosterone in male Wistar rats.

Previously, we reported that atrazine (ATR) alters steroidogenesis in male Wistar rats resulting in elevated serum corticosterone (CORT), progesterone, and estrogens. The increase in CORT indicated that this chlorotriazine herbicide may alter the hypothalamic-pituitary-adrenal axis. This study characterizes the temporal changes in adrenocorticotropic hormone (ACTH), CORT, and P4 in male Wistar rats following a single dose of ATR (0, 5, 50, 100, and 200 mg/kg), simazine (SIM; 188 mg/kg), propazine (PRO; 213 mg/kg), or primary metabolites, deisopropylatrazine (DIA; 4, 10, 40, 80, and 160 mg/kg), deethylatrazine (DEA; 173 mg/kg), and diamino-s-chlorotriazine (DACT; 3.37, 33.7, 67.5, and 135 mg/kg). The maximum dose for each chemical was the molar equivalent of ATR (200 mg/kg). Significant increases in plasma ACTH were observed within 15 min, following exposure to ATR, SIM, PRO, DIA, or DEA. Dose-dependent elevations in CORT and progesterone were also observed at 15 and 30 min post-dosing with these compounds indicating an activation of adrenal steroidogenesis. Measurement of the plasma concentrations of the parent compounds and metabolites confirmed that ATR, SIM, and PRO are rapidly metabolized to DACT. Although DACT had only minimal effects on ACTH and steroid release, dosing with this metabolite resulted in plasma DACT concentrations that were 60-fold greater than that observed following an equimolar dose of ATR and eightfold greater than equimolar doses of DIA or DEA, indicating that DACT is not likely the primary inducer of ACTH release. Thus, the rapid release of ACTH and subsequent activation of adrenal steroidogenesis following a single exposure to ATR, SIM, PRO, DIA, or DEA may reflect chlorotriazine-induced changes at the level of the brain and/or pituitary.

Characterization of the hypothalamic-pituitary-adrenal axis response to atrazine and metabolites in the female rat.

Atrazine (ATR) has recently been shown to activate the hypothalamic-pituitary-adrenal (HPA) axis in rodents. The current study investigated the effect of ATR and two of its chlorinated metabolites, desisopropylatrazine (DIA) and diamino-s-chlorotriazine (DACT), on the HPA axis in the Long-Evans female rat. A single oral gavage administration of 75 mg/kg ATR or 60.2 mg/kg DIA (a dose equimolar to the applied ATR dose) during the morning of proestrus resulted in significant, acute increases in circulating adrenocorticotropic hormone (ACTH), corticosterone, and progesterone. Oral doses of ATR or DIA were given daily over the course of the 4-day ovarian cycle starting on the day of vaginal estrus, resulted in a similar, dose-responsive activation of the HPA axis. The increase in ACTH, corticosterone, and progesterone by these compounds was of a similar magnitude to that produced by 5-min restraint stress. Single or multiple oral exposures to DACT, on the other hand, did not significantly alter pituitary-adrenal hormone release. These results were observed despite plasma levels of DACT being higher than any other metabolite at the time of hormone measurement. Overall, circulating metabolite concentrations following equimolar dosing were much higher than those observed after ATR administration. Additional studies indicated that the activation of the HPA axis by oral exposure to ATR and DIA was not due simply to the stimulation of gastrointestinal afferents. Similar responses were observed in rats which received an oral dose of ATR following bilateral subdiaphramatic vagotomy and following intravenous administration of DIA in jugular vein catheterized animals. We conclude that ATR and the metabolite DIA significantly activate the HPA axis following oral exposure in the female rat. Activation of this endocrine axis by these chlorotriazines could contribute to the induced changes of female reproductive function reported previously.

Individual effects of estrogens on a marine fish, Cunner (Tautogolabrus adspersus), extrapolated to the population level.

Endocrine-disrupting chemicals (EDCs) in the environment may alter the population dynamics of wildlife by affecting reproductive output. This study describes a matrix modeling approach to link laboratory studies on endocrine disruption with potential ecological effects. The experimental model used is cunner (Tautogolabrus adspersus), which inhabit estuarine and marine areas where sewage treatment and other discharges containing estrogenic EDCs are likely. To test the effects of estrogenic exposures on fecundity, reproductively active cunner were exposed in three separate experiments by implanting 17beta-estradiol, estrone, or 17alpha-ethynylestradiol subcutaneously in a slow-release matrix at 0.05, 0.5, and 2.5 mg/kg. Egg production per gram female and egg viability were determined daily for a 1-week preexposure period and then for a 2-week exposure period. The mean number of eggs produced per gram female and egg viability (%) were calculated for the initial preexposure period and the 2-week exposure period for each experiment. Significant changes were observed in egg production per gram female in the high-17beta-estradiol treatment (P = 0.07) and high-17alpha-ethynylestradiol treatment (P = 0.04). A significant increase was observed in egg viability (%) in the low-17alpha-ethynylestradiol treatment (39.0%; P < or = 0.05). Cunner population response was projected using an age-structured matrix population model parameterized with published survival and fecundity estimates. By incorporating reproductive response data from laboratory exposures, model projections were used to describe how reproductive changes by estrogen treatment could alter cunner population growth rate (lambda). Published by Elsevier Inc.

Review of evidence: are endocrine-disrupting chemicals in the aquatic environment impacting fish populations?

In this paper, evidence from the current literature is presented that addresses either of two questions: 1) do EDCs in the aquatic environment have the potential to impact the reproductive health and survival of various fish species, and 2) are EDCs in the aquatic environment actually impacting the reproductive health and sustainability of indigenous populations of fish? Overall, data from laboratory experiments support the hypothesis that EDCs in the aquatic environment can impact the reproductive health of various fish species, but evidence that EDCs in the aquatic environment are actually impacting the reproductive health and sustainability of indigenous fish populations is less convincing. The scarcity of evidence linking impacts of environmental EDCs with changes in reproductive success of indigenous fish populations may reflect a critical need for a dependable method or indicator to assess reproduction of fish in situ. In addition, more studies that investigate whether fish populations routinely exposed to EDCs in situ are experiencing changes in population structure are needed. Linking endocrine disruption and reproductive impairment with an ecologically relevant impact on the sustainability of real fish populations remains, with few exceptions, an open challenge.

Relationship between reproductive success and male plasma vitellogenin concentrations in cunner, Tautogolabrus adspersus.

The gene for vitellogenin, an egg yolk protein precursor, is usually silent in male fish but can be induced by estrogen exposure. For this reason, vitellogenin production in male fish has become a widely used indicator of exposure to exogenous estrogens or estrogen mimics in the aquatic environment. The utility of this indicator to predict impacts on fish reproductive success is unclear because information on the relationship between male plasma vitellogenin and reproductive end points in male and female fish is limited. In the research reported in this article, we investigated whether the presence of male plasma vitellogenin is a reliable indicator of decreased reproductive success in mature fish. Adult and sexually mature male and female cunner (Tautogolabrus adspersus) were exposed to 17ss-estradiol, ethynylestradiol, or estrone, three steroidal estrogens that elicit the vitellogenic response. Data were gathered and pooled on egg production, egg viability, egg fertility, sperm motility, and male plasma vitellogenin concentrations. All males, including two with plasma vitellogenin levels exceeding 300 mg/mL, produced motile sperm. Neither percent fertile eggs nor percent viable eggs produced by reproductively active fish demonstrated a significant correlation with male plasma vitellogenin concentrations. Male gonadosomatic index and average daily egg production by females showed significant, but weak, negative correlation with male plasma vitellogenin concentrations. Results suggest that male plasma vitellogenin expression is not a reliable indicator of male reproductive dysfunction in adult cunner exposed to estrogens for 2-8 weeks during their reproductive season, at least in relation to capacity to produce motile sperm or fertilize eggs. Male plasma vitellogenin expression may serve as an indicator of reduced female reproductive function caused by estrogen exposure.

A temperate reef fish, Tautogolabrus adspersus, (Walbaum) as a potential model species for laboratory studies evaluating reproductive effects of chemical exposure.

In ecotoxicological testing, there are few studies that report on reproductive output (egg production) of marine or estuarine fish. Cunner (Tautogolabrus adspersus) were studied as a potential model species to evaluate the impact of pollutants with estrogenic activity on reproduction in estuarine fish populations. Cunner inhabit marine and estuarine areas where contaminant discharges are likely. Baseline values for cunner gonadosomatic index (GSI), hepatosomatic index (HSI), and plasma vitellogenin (VTG) were determined in a field reference site (April 1999-December 1999). Male and female GSI indicated that cunner spawning is synchronized. Female HSI and VTG increased prior to GSI. From our laboratory observations, cunner are suitable for conducting experiments with reproductive endpoints indicative of both exposure (vitellogenin levels) and effects (egg production). However, cunner are not sexually dimorphic and stripping ripe fish is the only method to distinguish sex. In preparation for laboratory exposure studies with cunner, we designed a laboratory experimental holding system to accommodate cunner's reproductive behavior, a vertical spawning run to the water surface. Cunner were successfully acclimated from overwintering torpor to spawning condition in the laboratory by gradually changing the environmental conditions of fish held at winter conditions (4 degrees C and 9:15-h light:dark photoperiod) to spawning condition (18 degrees C and 15:9-h light:dark photoperiod). Our results show that cunner successfully spawned daily in the laboratory. They produced fertile eggs in our experimental system designed to accommodate cunner's vertical spawning runs, demonstrating that male and female reproductive behavior was synchronized in the laboratory. Our observations indicate that cunner would be a useful model species for evaluating reproductive effects of environmental contaminants in laboratory studies.