Xiang, Lusha, Jay S. Naik, Benjamin L. Hodnett, and Robert L. Hester. Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 290: R134 -R138, 2006. First published September 15, 2005 doi:10.1152/ajpregu.00295.2005.-These studies tested the hypothesis that in obese Zucker rats (OZRs), a model of metabolic syndrome, the impaired functional vasodilation is due to increased thromboxane receptor (TP)-mediated vasoconstriction and/or decreased prostacyclin-induced vasodilation. Spinotrapezius arcade arterioles from 12-wk-old lean (LZR) and OZR were chosen for microcirculatory observation. Arteriolar diameter (5 LZR and 6 OZR) was measured after 2 min of muscle stimulation in the absence or presence of 1 M SQ-29548 (TP antagonist). Additionally, arteriolar diameter (6 for each group) was measured after application of iloprost (prostacyclin analog; 0.28, 2.8, and 28 M), arachidonic acid (10 M), and sodium nitroprusside (0.1, 1, and 10 M) in the absence or presence of 1 M SQ-29548. A 10 M concentration of adenosine was used to induce a maximal dilation. Basal diameters were not different between LZRs and OZRs. Functional hyperemia and arachidonic acid-mediated vasodilations were significantly attenuated in OZR compared with LZR, and treatment with 1 M SQ-29548 significantly enhanced the dilations in OZRs, although it had no effect in LZRs. Vasodilatory responses to iloprost and sodium nitroprusside (1 and 10 M) were significantly reduced in OZR. Adenosine-mediated vasodilation was not different between groups. These results suggest that the impaired functional dilation in the OZR is due to an increased TP-mediated vasoconstriction and a decreased PGI2-induced vasodilation.obese Zucker rat; prostacyclin; thromboxane; vasoconstriction IT IS WELL ESTABLISHED THAT, during periods of increased skeletal muscle metabolism (such as during exercise), blood flow to the muscle increases (functional hyperemia) because of dilation of local arterioles (functional dilation), and this vasodilatory response is dependent, in some part, on endothelial function (22). However, in patients and animals with metabolic syndrome, endothelial dysfunction may occur early in the pathology of this syndrome (4), possibly contributing to the impaired functional hyperemia seen in metabolic syndrome. For example, patients with type 2 diabetes exhibit an impaired endothelial-dependent vasodilatory response to ACh and a significant impairment of the functional hyperemic response to leg cycle ergometer exercise (14). Our laboratory and others (8,32) have demonstrated that the obese Zucker rat (OZR), a model of metabolic syndrome, have both an attenuated functional and ACh-induced vasodilation in skeletal muscle arterioles. Although the mechanism(s) responsible for the impaired functional dilation remains unclear, these studies reveal a possible relationship between the endothelial dysfunction and the impaired functional vasodilation.The determination of the mechanism(s) responsible...

Advances in transoral surgical techniques have helped identify occult oropharyngeal malignancies that traditionally have been treated with comprehensive radiation to the entire pharyngeal axis. We demonstrate the efficacy of a TORS-assisted approach to identify and surgically treat the primary tumor in patients presenting with CUP. In addition, patients managed with the TORS-assisted endoscopic approach benefit from surgical and pathological triage, which in turn results in deintensification of treatment by eliminating the need for chemotherapy in the majority of patients, as well as avoiding radiation therapy in select patients.

We have developed Quantitative Circulatory Physiology (QCP), a mathematical model of integrative human physiology containing over 4,000 variables of biological interactions. This model provides a teaching environment that mimics clinical problems encountered in the practice of medicine. The model structure is based on documented physiological responses within peer-reviewed literature and serves as a dynamic compendium of physiological knowledge. The model is solved using a desktop, Windows-based program, allowing students to calculate time-dependent solutions and interactively alter over 750 parameters that modify physiological function. The model can be used to understand proposed mechanisms of physiological function and the interactions among physiological variables that may not be otherwise intuitively evident. In addition to open-ended or unstructured simulations, we have developed 30 physiological simulations, including heart failure, anemia, diabetes, and hemorrhage. Additional stimulations include 29 patients in which students are challenged to diagnose the pathophysiology based on their understanding of integrative physiology. In summary, QCP allows students to examine, integrate, and understand a host of physiological factors without causing harm to patients. This model is available as a free download for Windows computers at http://physiology.umc.edu/themodelingworkshop.

Obesity has been shown to impair muscle blood flow in humans. Vasodilatory control mechanisms such as metabolic control, myogenic mechanisms, conducted vasodilation, and release of endothelium-derived factors may be impaired in obesity due to insulin resistance, hyperglycemia, dyslipidemia, inflammation, oxidative stress, and endothelial dysfunction. The physiological importance of these blood flow control mechanisms has predominately been determined during the increase in blood flow (functional hyperemia) that occurs in response to the increased metabolism associated with exercise. This review examines the mechanisms by which functional hyperemia may be impaired in obesity and indicates areas where further studies are needed. The most extensively studied area of obesity-induced changes in muscle blood flow has been the role of endothelium-derived mediators during resting blood flow and exercise-induced hyperemia. Elevations in oxidative stress alter endothelium-derived factors, resulting in impaired vasodilatory responses. Alterations in metabolic and conducted vasodilatory regulation of blood flow have not been extensively studied in obesity, providing a potential area of research.