Medical Pharmacology and Physiology

Columbia, MO, United States

Medical Pharmacology and Physiology

Columbia, MO, United States
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News Article | May 4, 2017

VIDEO:  The fight against skin cancer just got a new weapon. For years, melanoma researchers have studied samples that were considered uniform in size and color, making them easier to examine... view more The fight against skin cancer just got a new weapon. For years, melanoma researchers have studied samples that were considered uniform in size and color, making them easier to examine by more conventional means. But melanomas don't always come in the same shape and hue; often, melanomas are irregular and dark, making them difficult to investigate. Now, researchers at the University of Missouri have devised a new tool to detect and analyze single melanoma cells that are more representative of the skin cancers developed by most patients. The study, recently reported in Analyst published by the Royal Society of Chemistry, outlines the new techniques that could lead to better and faster diagnoses for the life-threatening disease. "Researchers often seek out the types of cancerous cells that are homogenous in nature and are easier to observe with traditional microscopic devices," said Luis Polo-Parada, an Associate Professor of Medical Pharmacology and Physiology and an investigator at Mizzou's Dalton Cardiovascular Research Center. "Yet, because the vast amount of research is conducted on one type of cell, it often can lead to misdiagnosis in a clinical setting." The team that included Gary Baker, an assistant professor of chemistry in the MU College of Arts and Science and Gerardo Gutierrez-Juarez, a professor and investigator at the University of Guanajuato in Mexico, decided to supplement an emerging technique called photoacoustic (PA) spectroscopy, a specialized optical technique that is used to probe tissues and cells non-invasively. Current systems use the formation of sound waves followed by the absorption of light which means that the tissues must adequately absorb the laser light. This is why, up until now, researchers have focused only on strong-light-absorb cells melanoma cells, Polo-Parada said. The team modified a microscope that was able to merge light sources at a range conducive to observing the details of single melanoma cells. Using the modified system, human melanoma and breast cancers as well as mouse melanoma cells were diagnosed with greater ease and efficiency. The team also noted that as the cancer cells divided, they grew paler in color but the system was able to detect the newer, smaller cells as well. "Overall, our studies show that by using modified techniques we will be able to observe non-uniform cancer cells, regardless of their origin," Polo-Parada said. "Additionally, as these melanoma cells divide and distribute themselves throughout the blood, they can cause melanomas to metastasize. We were able to observe those cancers as well. This method could help medical doctors and pathologists to detect cancers as they spread, becoming one of the tools in the fight against this fatal disease." The study, "Spectrophotometric analysis at the single-cell level: elucidating dispersity within melanic immortalized cell populations," was supported in part by the Mizzou Advantage program, an initiative that fosters interdisciplinary collaboration among faculty, staff, students and external partners to solve real-world problems in four areas of strength identified at the University of Missouri, including Food for the Future, One Health/One Medicine, Sustainable Energy and Media of the Future. Ellison Gordon from the Mizzou Machine Shop was involved in the manufacturing of components for the microscope setup.

Young C.N.,Medical Pharmacology and Physiology | Deo S.H.,Medical Pharmacology and Physiology | Chaudhary K.,Harry uman Va Medical Center | Thyfault J.P.,Nutrition and Exercise Physiology | And 3 more authors.
Journal of Physiology | Year: 2010

Recent animal studies indicate that insulin increases arterial baroreflex control of lumbar sympathetic nerve activity; however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, muscle sympathetic nerve activity (MSNA) and arterial blood pressure were measured in 19 healthy subjects (27 ± 1 years) before, and for 120 min following, two common methodologies used to evoke sustained increases in plasma insulin: a mixed meal and a hyperinsulinaemic euglycaemic clamp. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. Plasma insulin was significantly elevated within 30 min following meal intake (Δ34 ± 6 uIU ml-1; P < 0.05) and remained above baseline for up to 120 min. Similarly, after meal intake, arterial baroreflex-MSNA gain for burst incidence and total MSNA was increased and remained elevated for the duration of the protocol (e.g. burst incidence gain: -3.29 ± 0.54 baseline vs.-5.64 ± 0.67 bursts (100 heart beats)-1 mmHg-1 at 120 min; P < 0.05). During the hyperinsulinaemic euglycaemic clamp, in which insulin was elevated to postprandial concentrations (Δ42 ± 6 μIU ml-1; P < 0.05), while glucose was maintained constant, arterial baroreflex-MSNA gain was similarly enhanced (e.g. burst incidence gain: -2.44 ± 0.29 baseline vs.-4.74 ± 0.71 bursts (100 heart beats)-1 mmHg-1 at 120 min; P < 0.05). Importantly, during time control experiments, with sustained fasting insulin concentrations, the arterial baroreflex-MSNA gain remained unchanged. These findings demonstrate, for the first time in healthy humans, that increases in plasma insulin enhance the gain of arterial baroreflex control of MSNA. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.

Fairfax S.T.,Biomedical science | Holwerda S.W.,Medical Pharmacology and Physiology | Credeur D.P.,Medical Pharmacology and Physiology | Zuidema M.Y.,Internal Medicine | And 7 more authors.
Journal of Physiology | Year: 2013

Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra-arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P= 0.016) and then robustly decreased to a nadir of -5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (-2.1 ± 0.7% and -0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors. © 2013 The Physiological Society.

Padilla J.,E102 Veterinary Medicine | Simmons G.H.,E102 Veterinary Medicine | Fadel P.J.,Medical Pharmacology and Physiology | Fadel P.J.,University of Missouri | And 4 more authors.
Hypertension | Year: 2011

Aging has been recently associated with increased retrograde and oscillatory shear in peripheral conduit arteries, a hemodynamic environment that favors a proatherogenic endothelial cell phenotype. We evaluated whether nitric oxide (NO) bioavailability in resistance vessels contributes to age-related differences in shear rate patterns in upstream conduit arteries at rest and during rhythmic muscle contraction. Younger (n=11, age 26±2 years) and older (n=11, age 61±2 years) healthy subjects received intra-arterial saline (control) and the NO synthase inhibitor N-Monomethyl-l-arginine. Brachial artery diameter and velocities were measured via Doppler ultrasound at rest and during a 5-minute bout of rhythmic forearm exercise. At rest, older subjects exhibited greater brachial artery retrograde and oscillatory shear (-13.2±3.0 s and 0.11±.0.02 arbitrary units, respectively) compared with young subjects (-4.8±2.3 s and 0.04±0.02 arbitrary units, respectively; both P<0.05). NO synthase inhibition in the forearm circulation of young, but not of older, subjects increased retrograde and oscillatory shear (both P<0.05), such that differences between young and old at rest were abolished (both P>0.05). From rest to steady-state exercise, older subjects decreased retrograde and oscillatory shear (both P<0.05) to the extent that no exercise-related differences were found between groups (both P>0.05). Inhibition of NO synthase in the forearm circulation did not affect retrograde and oscillatory shear during exercise in either group (all P>0.05). These data demonstrate for the first time that reduced NO bioavailability in the resistance vessels contributes, in part, to age-related discrepancies in resting shear patterns, thus identifying a potential mechanism for increased risk of atherosclerotic disease in conduit arteries. © 2011 American Heart Association, Inc.

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