Hypertension and type II diabetes are co-morbid diseases that lead to the development of nephropathy. Soluble epoxide hydrolase (sEH) inhibitors are reported to provide protection from renal injury. We hypothesized that the sEH inhibitor 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) protects the kidney from the development of nephropathy associated with hypertension and type II diabetes. Hypertension was induced in spontaneously diabetic Goto-Kakizaki rats using angiotensin II and a high salt diet. Hypertensive Goto-Kakizaki rats were treated for two weeks with either AUDA or its vehicle added to drinking water. Mean arterial pressure increased from 118 ± 2 mmHg to 182 ± 20 and 187 ± 6 mmHg for vehicle and AUDA treated hypertensive Goto-Kakizaki rats, respectively. AUDA treatment did not alter blood glucose. Hypertension in Goto-Kakizaki rats resulted in a 17-fold increase in urinary albumin excretion that was decreased with AUDA treatment. Renal histological evaluation determined that AUDA treatment decreased glomerular and tubular damage. In addition, AUDA treatment attenuated macrophage infiltration and inhibited urinary excretion of MCP-1 and kidney cortex MCP-1 gene expression. Taken together, these data provide evidence that sEH inhibition with AUDA attenuates the progression of renal damage associated with hypertension and type II diabetes.
Contrast-enhanced 3D GRE T1-weighted imaging is superior to SE T1-weighted imaging for the detection of dural venous sinus thrombosis and TS stenosis but does not substitute for dedicated MRV. Hyperintensity on unenhanced SE T1-weighted imaging is unreliable for the detection of dural venous sinus thrombosis.
Wise medical practice requires balancing the idealistic goals of medicine with the physical and economic realities of their application. Clinicians should know and employ the rules, maxims, and heuristics that summarize these goals and constraints. There has been little formal study of rules or laws pertaining to therapeutics and prognosis, so the authors postulate four physical and four economic laws that apply to health care: the laws of (1) finitude, (2) inertia, (3) entropy, and (4) the uncertainty principle; and the laws of (5) diminishing returns, (6) unintended consequences, (7) distribution, and (8) economizing. These laws manifest themselves in the absence of health, the pathogenesis of disease, prognosis, and the behaviors of participants in the health care enterprise. Physicians and the public perilously disregard these laws, frequently producing misdiagnoses, distraction, false expectations, unanticipated and undesirable outcomes, inequitable distribution of scarce resources, distrust, and cynicism: in short, quixotic medicine. The origins and public reinforcement of quixotic medicine make it deaf to calls for pragmatism. To achieve the Accreditation Council of Graduate Medical Education competency of systems-based practice, the authors recommend that premedical education return to a broader liberal arts curriculum and that medical education and training foster didactic and experiential knowledge of these eight laws.
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