Chronic amphotericin B nephrotoxicity in the rat, protective effect of prophylactic salt loading

Amphotericin B (AMPHO) is the most effective and widely used antifungal agent for the treatment of systemic fungal disease in man. Its use is frequently limited by the development of nephrotoxicity, including renal vasoconstriction with depressed glomerular filtration rate (GFR) and renal plasma flow (RPF), inability to concentrate the urine, and renal potassium wasting. We investigated the effects of oral NaCl loading during chronic administration of AMPHO, on renal function in the rat. Rats were provided 150 mmol/L NaCl (AMPHO plus NaCl) or tap water (AMPHO plus H2O) as drinking water, 3 days prior to, and during chronic AMPHO (5 mg/kg/d intraperitoneal [IP] for 21 days). At the end of the experimental period, renal functional parameters were determined, including serum creatinine, urinary volume and electrolyte excretion rates, ability to maximally concentrate the urine after water deprivation, and renal hemodynamics. NaCl supplementation prevented the rise in serum creatinine (AMPHO plus NaCl, initial v final, 0.39 +/- 0.03 v 0.40 +/- 0.03 mg/dL [34.6 +/- 2.7 v 35.4 +/- 2.7 mumol/L], P = NS) seen in AMPHO plus H2O (0.34 +/- 0.01 v 0.51 +/- 0.04 mg/dL [30.0 +/- 0.9 v 45.2 +/- 3.5 mumol/L], P less than 0.05)

Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses

An endothelium-derived relaxing factor (EDRF) has recently been identified as nitric oxide (NO), originating from endothelial cell metabolism of L-arginine. In vitro studies suggest that EDRF/NO stimulates soluble guanylate cyclase and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels in vascular smooth muscle cells, resulting in the vasorelaxant effects of endothelium-dependent vasodilators such as acetylcholine (ACh). The importance of EDRF/NO in normal physiology or disease states remains uncertain. We therefore investigated the relationship between ACh-induced hemodynamic responses, synthesis of EDRF/NO, and changes in the rate of urinary cGMP excretion in the anesthetized rat in vivo. Intravenous infusion of ACh resulted in hypotension, maintenance of glomerular filtration rate, and renal vasodilatation. ACh induced a dose-dependent increase in urinary cGMP excretion, an effect that was not observed with equihypotensive doses of the endothelium-independent vasodilator, prostacyclin. Rates of cGMP excretion were significantly correlated with the fall in systemic blood pressure induced by ACh. Treatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of enzymatic synthesis of nitric oxide from L-arginine, prevented the ACh-induced increase in urinary cGMP excretion as well as the systemic and renal hemodynamic effects of ACh. Plasma levels of atrial natriuretic peptide were unchanged by ACh infusion. Intravenous infusion of L-NMMA was associated with increased blood pressure and decreased basal rates of urinary cGMP excretion. This hypertensive effect was reversed by administration of L-arginine

Two Techniques for Assessing Virtual Agent Personality

Personality can be assessed with standardized inventory questions with scaled responses such as "How extraverted is this character?" or with open-ended questions assessing first impressions, such as "What personality does this character convey?" Little is known about how the two methods compare to each other, and even less is known about their use in the personality assessment of virtual agents. We tested what personality virtual agents conveyed through gesture alone when the agents were programmed to display introversion versus extraversion (Experiment 1) and high versus low emotional stability (Experiment 2). In Experiment 1, both measures indicated participants perceived the extraverted agent as extraverted, but the open-question technique highlighted the perception of both agents as highly agreeable whereas the inventory indicated that the extraverted agents were also perceived as more open to new experiences. In Experiment 2, participants perceived agents expressing high versus low emotional stability differently depending on assessment style. With inventory questions, the agents differed on both emotional stability and agreeableness. With the open-ended question, participants perceived the high stability agent as extraverted and the low stability agent as disagreeable. Inventory and open-ended questions provide different information about what personality virtual agents convey and both may be useful in agent development

Two Techniques for Assessing Virtual Agent Personality

Personality can be assessed with standardized inventory questions with scaled responses such as "How extraverted is this character?" or with open-ended questions assessing first impressions, such as "What personality does this character convey?" Little is known about how the two methods compare to each other, and even less is known about their use in the personality assessment of virtual agents. We tested what personality virtual agents conveyed through gesture alone when the agents were programmed to display introversion versus extraversion (Experiment 1) and high versus low emotional stability (Experiment 2). In Experiment 1, both measures indicated participants perceived the extraverted agent as extraverted, but the open-question technique highlighted the perception of both agents as highly agreeable whereas the inventory indicated that the extraverted agents were also perceived as more open to new experiences. In Experiment 2, participants perceived agents expressing high versus low emotional stability differently depending on assessment style. With inventory questions, the agents differed on both emotional stability and agreeableness. With the open-ended question, participants perceived the high stability agent as extraverted and the low stability agent as disagreeable. Inventory and open-ended questions provide different information about what personality virtual agents convey and both may be useful in agent development

Abnormal renal hemodynamic response to reduced renal perfusion pressure in diabetic rats: role of NO

Diabetic rats manifest abnormal renal hemodynamic responses, with persistent renal vasodilation at reduced renal perfusion pressures. We hypothesized that in diabetes, renal hemodynamics are modulated by increased activity of the endogenous vasodilator, NO. In anesthetized Munich-Wistar rats, after 6 wk of streptozotocin-induced, insulin-treated diabetes, and in age-matched, nondiabetic littermates (n = 7-8), basal renal hemodynamics and responses to graded reductions in renal perfusion pressure were determined before and after intrarenal arterial infusion of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). An identical protocol was followed in a second cohort of rats pretreated with indomethacin (4 mg/kg iv). Diabetic rats demonstrated hyperglycemia, renal enlargement, hyperfiltration, and increased urinary excretion of the stable NO metabolites, NO2 and NO3. L-NAME eliminated basal hyperfiltration in diabetic rats, and L-NAME, but not indomethacin, also eliminated persistent renal vasodilation at reduced renal perfusion pressure. We conclude that in a rat model of diabetes, increased endogenous NO activity may play a role in basal hyperfiltration and in the persistent renal vasodilatation manifested at reduced renal perfusion pressures