It is known that the secretion of PTH is often impaired in association with aluminum (Al3+) accumulation in patients with renal failure. The mechanisms involved remain ill defined. Since adenylate cyclase plays a role in the regulation of PTH secretion, these studies examine the effects of Al3+ on parathyroid adenylate cyclase. In membranes from normal bovine parathyroid glands, basal adenylate cyclase activity, in the presence of 0.2 mM ATP and 20 mM Mg2+, increased by 22% as Al3+ was raised from 0-10 microM. Higher Al3+ concentrations caused a progressive decrease in adenylate cyclase activity, reaching 68% inhibition of control activity at 2 mM Al3+. Since adenylate cyclase activation is influenced by the interaction of multiple sites within the adenylate cyclase complex, the nature of the inhibition by Al3+ was explored by examining the interaction of Al3+ with substrate ATP and with Mg2+, an allosteric activating metal ion. In the presence of 20 mM Mg2+, Al3+ concentrations of 1-2 mM resulted in noncompetitive inhibition with respect to ATP [decrease in maximum velocity (Vmax) from 4176 in the absence of Al3+ to 1106 pmol cAMP/mg protein X 15 min; Michaelis Menten constant (Km) for ATP was unchanged]. In contrast, at fixed ATP (0.2 mM), 0.5 mM resulted in competitive inhibition of adenylate cyclase with respect to Mg2+, whereas at higher Al3+ concentrations the inhibition was noncompetitive. When Mg2+ was replaced by Mn2+ (enzyme activity reflects the activity of the catalytic unit), the inhibitory effect of Al3+ on adenylate cyclase activity was abolished. These data suggest that the inhibition of parathyroid adenylate cyclase by Al3+ occurs at the level of the allosteric metal activating site. These data provide a potential mechanism for the inhibition of PTH secretion by Al3+.
Purpose/Objectives To examine partner involvement in treatment decision making for localized prostate cancer, congruence between partner involvement and patient preference, reasons for partner noninvolvement, and partner satisfaction with patient treatment. Design Cross-sectional exploratory study. Setting 100 counties in North Carolina. Sample 281 partners of men with newly diagnosed localized prostate cancer. Methods Participants completed a phone survey. Logistic regression analyses were used. Main Research Variables Partners’ involvement in treatment decision making, partner satisfaction with treatment, activities of partner involvement, and reasons for noninvolvement. Findings Two hundred twenty-eight partners (81%) related to decision making, 205 (73%) were very satisfied with the treatment the patients received, and partner involvement was congruent with patient preference in 242 partners (86%). Partners reported several reasons for noninvolvement: agreeing with whatever the patient decides, trusting the doctor’s decisions, believing that the patient should make the decision, respecting the patient’s decision, and being concerned with the impact on their relationship if they chose the wrong treatment. Conclusions Most partners engaged in multiple activities during treatment decision making for localized prostate cancer and were satisfied with the patient’s treatment. Partner involvement was mostly congruent with patient preference. Implications for Nursing Partners’ active involvement in treatment decision making for localized prostate cancer (e.g., being involved in patients’ conversations with doctors) should be encouraged and facilitated for those who prefer this type of decision making.
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