1,721,129 research outputs found

    Diabetes mellitus and hypertension: a physiologic basis for a rational therapeutic approach.

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    The basic mechanisms that initiate and sustain hypertension in the diabetic population are poorly understood. Obesity, insulin, genetic factors, and abnormalities in calcium homeostasis may contribute, and could be related to an elevated Na+/H+ antiport activity. In the first study described in this investigation, hypertensive subjects with insulin-dependent diabetes mellitus (IDDM) who had an elevated Na+/Li+ countertransport activity were found to have a lower whole body glucose utilization, a lower insulin-stimulated forearm carbohydrate oxidation, larger ultrasound kidney volume, and increased left ventricular mass index when compared with hypertensive IDDM subjects with a normal Na+/Li+ countertransport activity or normotensive IDDM subjects. Thus an elevated Na+/Li+ countertransport activity appears to identify a subset of IDDM patients who are more susceptible to the development of the renal and cardiac complications associated with hypertension. This underlines the importance of choosing an appropriate antihypertensive therapy that will not produce a deterioration in glucose and lipid metabolism. In the second part of the report, results are presented for the treatment of hypertensive patients with non-insulin-dependent diabetes mellitus with doxazosin. The selective alpha 1-inhibitor produced a significant reduction in blood pressure, together with favorable changes in the serum lipid profile. As a result, the calculated risk of developing coronary heart disease was significantly reduced. Throughout the study no patients required a dose reduction or discontinuation of doxazosin because of side effects, and no clinically significant changes in laboratory tests were apparent. Thus doxazosin could be considered a useful antihypertensive agent in hypertensive patients with IDDM who are insulin-resistant and who have renal and cardiac abnormalities

    Models to interpret kinetic data in stable isotope tracer studies.

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    In contrast to "weightless" radioactive tracers, stable isotope tracers have nonnegligible mass and are naturally present in the system, and the measured variable is a ratio of two isotopic species. These features do not allow stable isotopic tracer data analysis using straightforward analogy with radioactive tracer approaches, even though this practice is common. In this study, we present kinetic variables, models, and measurements for the analysis and interpretation of stable isotope tracer data. Assumptions and mathematical techniques for modeling the data when perturbation is both nonnegligible and negligible are discussed. Emphasis is placed on the rich information content of the dynamic portion of a stable isotope tracer curve and on the role of compartmental and noncompartmental modeling approaches for its interpretation. A presumed and commonly used analogy between the radioactive specific activity and stable isotopic enrichment is shown to be incorrect. We show that the proper analogue of specific activity is the tracer-to-tracee molar ratio. This variable is not a directly measurable one, but a formula is derived that allows its computation from the data. A method for reconstructing the time course in blood of the concentration component due to endogenous synthesis is presented. This allows measurement of the extent of the perturbation in the case where a nonweightless tracer is used. Special attention is given to data analysis originating from a multiple tracer experiment, a configuration necessary for studying more complex systems, e.g., the kinetics of interacting substrates
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