14 highlighted physiology papers from IUPS 2005: From 'genomics to functions'

04/03/05

Topics include: anoxia, asthma, burns, NEC, exercise, HIV, Viagra, cranberry juice, satiety, alcohol and gender

San Diego (April 4, 2005) Below are 14 research presentations from the 35th Congress of the International Union of Physiological Sciences held in San Diego, March 31-April 5.

Full press releases on these presentations are available on the American Physiological Society website (http://www.the-aps.org/press/) or on EurekAlert. All abstracts may be accessed at http://www.faseb.org/meetings/eb2005/call/default.htm, through a searchable online program for both IUPS and Experimental Biology 2005.

Statins, other cholesterol depletors, may disrupt hypertension development: UCSD study

Cholesterol-lowering agents, such as statins, and cholesterol-blocking agents may prove to be novel therapeutic agents to modify cellular calcium that contributes to the development of pulmonary hypertension. The UCSD team found a previously unappreciated cellular and molecular mechanism for the disease process that may be amenable to treatment with current and future therapies and might provide more substantial, long-term benefit to those with hypertension.

"Cholesterol-depleting drugs, including statins, lower intracellular Ca2+ and inhibit proliferation in pulmonary artery smooth muscle cells in primary pulmonary hypertension." Physiology 933.6. Hemal H. Patel, Fiona Murray and Paul A. Insel, University of California, San Diego, Department of Pharmacology; Shen Zhang and Jason X-J Yuan, Dept. of Medicine, and Patricia A. Thistlethwaite, Dept. of Surgery.

Featured topic: Patel will participate in Session 898, "Overview: From organelles to organ," IUPS Calcium Signaling Track, Tuesday at 10:30 a.m., room 29C.

Cranberry juice modulates atherosclerotic vascular dysfunction

Taking cranberry juice powder regularly over six months saw a pronounced improvement in vascular function - ability of blood vessels to relax - in subjects with high blood cholesterol and atherosclerosis, a University of Wisconsin study found. With abnormal functioning of blood vessels an important component of heart disease, improving vascular function in patients with high cholesterol and atherosclerosis is critical to protect them from consequences such as heart attack or stroke.

"Cranberry juice modulates atherosclerotic vascular dysfunction." Physiology 387.14. Kris Kruse-Elliott and Jess Reed, University of Wisconsin-Madison School of Veterinary Medicine.

In anoxia, why can't humans be more like western painted turtles?

An oxygen shortage (anoxia) of minutes can quickly cause human death. But the western painted turtle can survive anoxia for months without apparent tissue damage. University of Toronto scientists studied a newly discovered potassium channel (mitochondrial KATP channel) as a possible regulator of NMDA receptor activity. When the channel was inhibited, the protective decrease in calcium influx in the anoxic turtle brain didn't occur, opening a new research direction in this area.

"NMDA receptor regulation by mitochondrial KATP channels and adenosine receptors in cortical neurons of the anoxia-tolerant western painted turtle." Physiology 381.3. Leslie T. Buck, Damian Shin and Matthew Pamenter. University of Toronto Zoology Department.

Featured topic: Buck is also participating in "Mechanisms of metabolic depression: comparative aspects."

'Second messenger' NAADP shows fast, dose-related impact on satiety cycle

An Oxford University study establishes NAADP as new second messenger with potential for treating obesity. Researchers in Antony Galione's lab led by Michiko Yamasaki said, "The existence of the cholecystokinin-A receptor in the brain strongly implies a possible role of NAADP in cholecystokinin-induced satiety." It's the first direct evidence that cholecystokinin elicits a rapid selective increase in NAADP, and unequivocal evidence NAADP is a crucial messenger employed by cholecystokinin.

"Rapid, selective and dose-dependent elevation of the second messenger NAADP." Physiology 932.3. Michiko Yamasaki, Grant Churchill and Antony Galione, Department of Pharmacology, University of Oxford; Sandip Patel, University College London; and Jose M. Cancela, CNRS, Laboratoire de Neurobiologie Cellulaire et Moleculaire, Gif-sur-Yvette, France.

"Controversy" session: Yamasaki, Churchill and Galione are participating in a "controversy" session #654 of the Calcium Signaling Track Monday April 4 room beginning at 10:30.

Viagra shows selective effects in hypertensive pregnancy on mother, fetus

Although it didn't lower pregnant mothers' blood pressure, Viagra produced an "intriguing" array of significant benefits to both mother and fetus, researchers at the University of Vermont College of Medicine found. Viagra seemed to improve uterine and placental blood flow measured by arterial diameter along with a corresponding increase of birth weight to normal levels, up 25%. Most surprising effect: total elimination of fetal death, versus 11% in the untreated hypertensive group.

"Beneficial effects of Viagra on fetal and vascular parameters in hypertensive pregnancy in the rat." Physiology 909.9. George Osol, Gerard Celia and Natalia I. Gokina, Department of Obstetrics and Gynecology, University of Vermont College of Medicine.

Growth factor in baby formula could reduce NEC, most devastating GI disease in preemies

NEC incidence among breast-fed babies is a little as 10% of formula-fed. University of Arizona researchers found adding one protein found in mother's milk (EGF) to formula cut incidence of NEC in half. Importantly, EGF altered the balance between gene expression of cell death and cell survival, protecting the intestine from developing NEC.

"Epidermal growth factor reduces intestinal apoptosis in an experimental model of necrotizing enterocolitis." Physiology 400.1. Jessica A. Clark, Tara A. Saunders, Sarah M. Doelle, Hana Holubec, Robert H. Lane, Melissa D. Halpern and Bohuslav Dvorak, Department of Pediatrics, University of Arizona.

Pediatric burn victims' recovery, diabetes, metabolism aided by fenofibrate (Tricor)

Increasing cell fat metabolism with fenofibrate (Tricor) in seriously burned children also improved glucose metabolism to nearly normal levels, according to clinical work at University of Texas Medical Branch and Shriners Hospital for Children. With diabetes a common reaction to trauma and surgery, directly treating insulin resistance could speed recovery. The researchers found that a surprising 70% of victims 4 to 14 with over 40% surface burns suffered insulin sensitivity about half of healthy children.

"Fenofibrate improves glucose metabolism in pediatric burns patients." Physiology 361.2. Melanie Green Cree, Alse Aarsland, David Chinkes, David N. Herndon and Robert R. Wolfe from the University of Texas Medical Branch and Shriners Hospital for Children, Galveston.

Moderate aerobic exercise improves cardiovascular and nervous system function in HIV+

First study to demonstrate the profound effects of aerobic fitness on pre-clinical manifestations of cardiovascular and autonomic dysfunction in HIV was conducted at Teachers College/ Columbia University, and Coler Goldwater Specialty Hospital, New York. Moderate exercise was 10 weeks, 3 times a week, 45 minutes/session. Cardio-vascular and autonomic profiles of the fit HIV+ subjects were significantly improved compared to a similar group that didn't exercise -- regardless if they had HIV or not.

"Fitness is associated with improved arterial compliance and parasympathetic modulation in HIV," Physiology 347.11. David K. Spierer, Adrienne Zion, Gregory Gates and Ronald De Meersman, Dept. of Biobehavioral Sciences, Teachers College, Columbia University and at Coler Goldwater Specialty Hospital: Spierer, Augusta Alba, Jay Kleinfeld, Eugene McPherson and Julie Romero.

In asthma, it's not the drugs but the inflammation that increases cardiovascular risk, damage

East Carolina University researchers discovered that the inflammation associated with asthma directly affects the heart's recovery from a heart attack, confirming growing evidence that asthma may directly, and negatively, impact the cardiovascular system. If the clinically important findings are confirmed, asthma could be identified as a potential risk factor for post-operative complications and recurrent events following such cardiology interventions as angioplasty. It also should lead to better management of CVD patients with asthma.

"Airway inflammation increases infarction after myocardial ischemia-reperfusion in mice," Physiology 389.21. "Neutrophil degranulation and ischemia-induced expression of neutrophil chemotactic molecules are enhanced in a murine model of asthma." Physiology 691.4. Surovi Hazarika, Michael R. Van Scott and Robert M. Lust, Department of Physiology Brody School of Medicine, East Carolina University.

SERPINE2 identified as novel candidate gene for COPD, especially with smoking

Brigham and Women's Hospital/ Harvard Medical School researchers said their studies strongly suggest SERPINE2 is a gene capable of modifying COPD risk, particularly in response to smoking. The major tissue, cell protease inhibitor's role in the lung was previously unrecognized. But now it's seen as a most promising susceptibility candidate due to its biologic relevance, its expression correlation with disease characteristics, and the allelic association in COPD families and replication in non-familial COPD patients.

"Expression of Serine Proteinase Inhibitor E2, a novel candidate COPD susceptibility gene, in the lung." Physiology 936.4. Sorachai Srisuma, Dawn L. DeMeo, Brigham H. Mecham, Edwin K. Silverman, Scott T. Weiss, Kathleen J. Haley, John J. Reilly, Steven D. Shapiro, and Thomas J. Mariani, Brigham and Women's Hospital/ Harvard Medical School, Boston.

Feature topic presentation: Srisuma is participating in session #477, "Receptors and signaling pathways in lung injury and repair."

Estrogen, SERMS reduce asthma impact by halting constriction

Medical College of Georgia scientists showed that elevated estrogen levels reduce the severity of asthma and perhaps of other diseases involving airway constriction. They report estrogen, as well as selective estrogen receptor modifiers (SERMs), completely abolished abnormal tracheal constriction. The researchers found that hyperresponsiveness of tracheal rings to carbachol was completely prevented with only 30 minutes of estrogen treatment. SERMs such as tamoxifen equally prevented the exaggerated constriction to allergen seen in asthmatic-induced airways.

"Estrogens prevent the tracheal hyper-responsiveness to carbachol in asthma." Physiology 375.5. Christiana Dimitropoulou, Shu Zhu, Richard E. White and John D. Catravas of the Department of Pharmacology & Toxicology, Medical College of Georgia, Augusta, and Dennis Ownby of the Department of Pediatrics; Catravas also is with the MCG Vascular Biology Center.

'Mandela's Paradox' may show that osteoporosis propensity starts in pre-teen years

Halfway through a large 20-year study of South African youth, researchers discovered a counterintuitive finding that may lead to rethinking the development of osteoporosis, the roots of which may well lie in the childhood years. Despite less activity and calcium intake in their youth, adult black South Africans have very low hip fracture rates. As blacks' lifestyles change will their genetic advantages be lost to Western influences?

"Physical activity and bone mass accumulation patterns differ in black and white South African children," Joanne A. McVeigh, Shane A. Norris and John M. Pettifor, MRC Mineral Metabolism Research Unit, Dept. of Paediatrics, and School of Physiology, University of Witwatersrand Medical School, Johannesburg. Physiology 347.8

15 generations of untrained jocks, couch potatoes show big physiological adaptations

Exercise research usually keys on training effects, but UCSD physiologists studied underlying genetic mechanisms through 15 generations of untrained rats from a single strain. Large physiological adaptations resulted in the oxygen delivery system, supporting the theory that over time animal systems will maximize efficiency. The key result showed the oxygen system maximization was independent of training or environment. Human benefits could come from learning the prompts to exercise and mechanisms of system improvement.

"VO2max and muscle O2 transport in rats continue to diverge with further selective breeding for endurance running." Richard A. Howlett, University of California, San Diego. 936.2.

"Cardiovascular differences between rats selectively bred for endurance running capacity." Scott David Kirkton, UCSD, 936.3. "

15 generations of selective breeding for endurance running capacity in rats is associated with enhanced lung structure and function not seen at generation 7." Patrick G. Giuliano (this paper only), UCSD. 936.1.

Others involved in all three papers: Peter D. Wagner, Harrieth E. Wagner, UCSD Department of Medicine, Division of Physiology (as are Howlett, Kirkton and Giuliano); Norberto C. Gonzalez, University of Kansas Medical Center, Dept. of Molecular and Integrative Physiology; Steven L. Britton and Lauren G. Koch, University of Michigan Dept. of Physical Medicine and & Rehabilitation.

Alcoholism reduces male heart's ability to synthesize protein; possible therapy target?

Researchers at Penn State College of Medicine's Cellular and Molecular Physiology Department confirmed that defects in myocardial protein metabolism contributed to alcoholic heart muscle disease. After six months of high alcohol consumption, the heart muscle's ability to synthesize proteins was compromised in males, but not females. One altered step in protein synthesis in males mirrored alcohol-induced defects in ventricular function. The defect resulted from altered phosphorylation of a particular protein factor.

"Gender modulates the response to chronic alcohol intoxication in the heart." Physiology 909.5. Thomas C. Vary, Joseph M. Leese and Scot R. Kimball, Pennsylvania State University College of Medicine Cellular and Molecular Physiology Department.

Source: Eurekalert & others

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