Natriuretic response to renal medullary endothelin B receptor activation is impaired in Dahl-salt sensitive rats on a high-fat diet.

Renal medullary endothelin B receptors (ET(B)) mediate sodium excretion and blood pressure (BP) control. Several animal models of hypertension have impaired renal medullary ET(B) function. We found that 4-week high-caloric diet elevated systolic BP in Dahl salt-sensitive (Dahl S) rats (126+/-2 vs. 143+/-3 mm Hg, p<0.05). We hypothesized that renal medullary ET(B) function is dysfunctional in DS rats fed a high-caloric diet. We compared the diuretic and natriuretic response to intramedullary infusion of ET(B) agonist sarafotoxin 6c (S6c) in DS rats fed either a normal or high-caloric diet for 4 weeks. Urine was collected during intramedullary infusion of saline for baseline collection followed by intramedullary infusion of either saline or S6c. We first examined the ET(B) function in DS rats fed a normal diet. S6c increased urine flow (2.7+/-0.3 microl/min during baseline vs. 5.1+/-0.6 microl/min after S6c; p<0.05; n=5) and sodium excretion (0.28+/-0.05 vs. 0.81+/-0.17 micromol/min; p<0.05), suggesting that DS rats have renal medullary ET(B) function. However, DS rats fed a high-caloric diet displayed a significant increase in urine flow (2.7+/-0.4 vs. 4.2+/-0.4 microl/min, baseline vs. S6c infusion, respectively; p<0.05, n=6), but no significant change in sodium excretion in response to S6c (0.32+/-0.06 vs. 0.45+/-0.10 micromol/min). These data demonstrate that renal medullary ET(B) function is impaired in DS rats fed a high-caloric diet, which may be contributed to the elevation of blood pressure during high-caloric feeding in this model.

Comparative biological effects and potency of 17α- and 17ß-estradiol in fathead minnows.

17ß-Estradiol is the most potent natural estrogen commonly found in anthropogenically altered environments and has been the focus of many toxicological laboratory studies. However, fewer aquatic toxicological data on the effects of 17α-estradiol, a diastereoisomer of 17ß-estradiol, exists in the literature even though it has been found in the aquatic environment, sometimes at higher concentrations than 17ß-estradiol. The central objective of this study was to determine how the anatomical, physiological, and behavioral effects of exposure to 17α-estradiol compare to the well-documented effects of 17ß-estradiol exposures in aquatic vertebrates. A 21-day flow-through exposure of mature male and female fathead minnows to three concentrations each of 17α- and 17ß-estradiol (averaged measured concentrations 27, 72, and 150 ng/L for 17α-estradiol, and 9, 20, and 44 ng/L for ß-estradiol, respectively) yielded significant, concentration-dependent differences in plasma vitellogenin concentrations among estradiol-exposed males when compared to fish from an ethanol carrier control. Interstitial cell prominence in the testis of fish was elevated in all estradiol treatments. Aggressiveness of male fish to defend nest sites appeared depressed in many of the higher concentration estradiol treatments (albeit not significantly). No clear effects were observed in female fish. Based on plasma vitellogenin data, it appears that 17ß-estradiol is 8-9 times more potent than 17α-estradiol and that the lowest observable effect concentration (LOEC) for 17α-estradiol in fathead minnows is greater than 25 ng/L and may be less than 75 ng/L.

Assessing the effects of exposure timing on biomarker expression using 17beta-estradiol.

Temporal and spatial variability in estrogenicity has been documented for many treated wastewater effluents with the consequences of this variability on the expression of biomarkers of endocrine disruption being largely unknown. Laboratory exposure studies usually utilize constant exposure concentrations which may produce biological effects that differ from those observed in organisms exposed in natural environments. In this study, we investigated the effects of differential timing of exposures with 17beta-estradiol (E2) on a range of fathead minnow biomarkers to simulate diverse environmentally relevant exposure profiles. Two 21-day, replicate experiments were performed exposing mature male fathead minnows to E2 at time-weighted mean concentrations (similar average exposure to the contaminant during the 21-day exposure period; 17ng E2/L experiment 1; 12ng E2/L experiment 2) comparable to E2 equivalency values (EEQ) reported for several anthropogenically altered environments. A comparable time-weighted mean concentration of E2 was applied to five treatments which varied in the daily application schema: E2 was either applied at a steady rate (ST), in a gradual decreasing concentration (HI), a gradual increasing concentration (LO), applied intermittently (IN), or at a randomly varying concentration (VA). We assessed a range of widely used physiological (vitellogenin mRNA induction and plasma concentrations), anatomical (body and organ indices, secondary sex characteristics, and histopathology), and behavioral (nest holding) biomarkers reported to change following exposure to endocrine active compounds (EACs). All treatments responded with a rise in plasma vitellogenin concentration when compared with the ethanol carrier control. Predicatively, vitellogenin mRNA induction, which tracked closely with plasma vitellogenin concentrations in most treatments was not elevated in the HI treatment, presumably due to the lack of E2 exposure immediately prior to analysis. The ability of treatment male fish to hold nest sites in direct competition with control males was sensitive to E2 exposure and did yield statistically significant differences between treatments and carrier control. Other biological endpoints assessed in this study (organosomatic indices, secondary sex characteristics) varied little between treatments and controls. This study indicates that a broad suite of endpoints is necessary to fully assess the biological consequences of fish exposure to estrogens and that for at least field studies, a combination of vitellogenin mRNA and plasma vitellogenin analysis are most promising in deciphering exposure histories of wild-caught and caged fishes.

Immunolocalization of Na+/K+-ATPase and Na+/K+/2Cl- cotransporter in the tubular epithelia of sea snake salt glands.

The sublingual salt gland is the primary site of salt excretion in sea snakes; however, little is known about the mechanisms mediating ion excretion. Na(+)/K(+)-ATPase (NKA) and Na(+)/K(+)/2Cl(-) cotransporter (NKCC) are two proteins known to regulate membrane potential and drive salt secretion in most vertebrate secretory cells. We hypothesized that NKA and NKCC would localize to the basolateral membranes of the principal cells comprising the tubular epithelia of sea snake salt glands. Although there is evidence of NKA activity in salt glands from several species of sea snake, the localization of NKA and NKCC and other potential ion transporters remains unstudied. Using histology and immunohistochemistry, we localized NKA and NKCC in salt glands from three species of laticaudine sea snake: Laticauda semifasciata, L. laticaudata, and L. colubrina. Antibody specificity was confirmed using Western blots. The compound tubular glands of all three species were found to be composed of serous secretory epithelia, and NKA and NKCC were abundant in the basolateral membranes. These results are consistent with the morphology of secretory epithelia found in the rectal salt glands of marine elasmobranchs, the nasal glands of marine birds and the gills of teleost fishes, suggesting a similar function in regulating ion secretion.

Nurses' experience of violence in Alberta and British Columbia hospitals.

This study examined responses to a survey on violence in the workplace from a sample of 8,780 registered nurses practising in 210 hospitals in the Canadian provinces of Alberta and British Columbia. Findings relate to the frequency of violence against nurses, reported as the number of times they experienced a violent incident in the workplace. Nearly half (46%) of those surveyed had experienced 1 or more types of violence in the last 5 shifts worked. Frequency varied by type: emotional abuse 38%, threat of assault 19%, physical assault 18%, verbal sexual harassment 7.6%, sexual assault 0.6%. Further, 70% of those who had experienced violence indicated they had not reported it. Patients constituted the main source of all types of violence. The most prevalent type, emotional abuse, was further explored for its possible determinants. This was also the type of violence most evenly distributed among sources (patients, families, co-workers, physicians). Multiple regression modelling using the individual nurse as the unit of analysis showed the significant predictors of emotional abuse to be age, casual job status, quality of care, degree of hospital restructuring, type of unit, relationships among hospital staff, nurse-to-patient ratios, and violence-prevention measures; using the hospital as the unit of analysis the predictors were found to be quality of care, age, relationships with hospital staff, presence of violence-prevention measures, and province. These findings illustrate important differences in models that use the individual and the institution as the unit of analysis. Implications include targeting prevention strategies not only at the nurse but, perhaps more importantly, at the hospital. Overall, the findings suggest that health-care institutions are not always healthy workplaces and may increasingly be stressful and hazardous ones.