Research : Elevated Nitric Oxide In Blood Is Key To High Altitude Function For Tibetans

Cynthia Beall studies adaptation to high altitudes. (Credit: Image courtesy of Case Western Reserve University)

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How can some people live at high altitudes and thrive while others struggle to obtain enough oxygen to function?

The answer for Tibetans who live at altitudes around 14,000 feet is increased nitric oxide (NO) levels. High levels of NO circulate in various forms in the blood and produce the physiological mechanisms that cause the increased blood flow that maintains oxygen delivery despite hypoxia--low levels of oxygen in the ambient air and the bloodstream.

Researchers from Case Western Reserve University and the Cleveland Clinic report that Tibetans have 10 times more NO and have more than double the forearm blood flow of low-altitude dwellers. The findings from a comparison of NO levels in the high and low altitude dwellers are reported in a recent article.*

The low barometric pressure of high altitudes generally causes low arterial oxygen content among Tibetans, yet the researchers have found that Tibetans consume oxygen at normal rates.

"We asked how that could be done," said Cynthia Beall, the S. Idell Pyle Professor of Anthropology at Case Western Reserve University. For two decades, Beall has been one of the world's leading researchers in the studies of high altitude adaptation in different populations in Ethiopia, South America and Tibet.

Beall collected blood samples and blood flow readings from the forearms of 88 Tibetans during a 2002 research trip that was funded by the National Science Foundation. The blood flow data and blood samples were brought back to the United States where Serpil Erzurum, chair of pathobiology, Cleveland Clinic, and the paper's lead author, analyzed the information. In Erzurum's lab, Allison Janocha, a Case Western Reserve graduate, performed many of the technically challenging analyses.

For comparison, the scientists collected the same information from 50 near sea-level dwellers from the United States who participated in the study at the General Clinical Research Center at the Cleveland Clinic.

The combined increase in NO and blood flow levels resulted in double the amount of oxygen delivered to the capillary beds in the Tibetans' arms.

The researchers hypothesize that Tibetans have a genetic mutation that allows high NO production. Genetic studies and comparable data on sea-level populations living at high altitude would be needed to test that hypothesis, said Beall.

During the study, the researchers also recognized another population difference: Tibetan women were found to have higher nitrite and lower nitrate levels than those of Tibetan men, whereas no gender differences were found in sea-level dwellers.

In this research, blood flow is determined by the length, number and width of the diameter of blood vessels. These numbers are determined partly by NO, which is a dilator of the vessels and prevents high blood pressure, which would result from increased blood flow in restricted blood vessels. NO also helps in the release of oxygen to tissues.

NO reacts in the blood to produce nitrite, nitrate, nitrosothiol proteins and á-nitrosyl hemoglobin, which can be used as indicators of NO production. To confirm the increases in NO, the researchers subjected the Tibetan samples to sensitive high performance liquid chromatography, where the results verified the 10-fold increase of NO in the blood.

This study continues to unravel the mysteries of high altitude adaption and follows Beall's 2001 study, published in Nature, on the NO levels in exhaled breath of Tibetans, which were found to be 25 percent greater than that of local Cleveland residents. There was also a related paper on NO and pulmonary blood flow in 2005 in the Journal of Applied Physiology. Brian Hoit of the department of medicine at the Case Western Reserve School of Medicine was the lead author on that paper.

*"The journal article is "Higher Blood Flow and Circulating NO Products Offset High-altitude Hypoxia among Tibetans," published in the current Proceedings of the National Academy of Sciences.

Researchers on the most recent study include Sudhakshina Ghosh, Allison Janocha, Weilin Xu, Dennis Stuehr, and Jesus Tejero from the CCF department of pathobiology; and Selena Bauer, Martin Feelisch, and Nathan Bryan from the Whitaker Cardiovascular Institute in Boston University School of Medicine; and Craig Hemann and Russ Hille from Ohio State University

Technorati : Nitric Oxide In Blood, research

WARNING : Feds List Chemicals That Can Be Misused

The average chicken farmer does not have enough chemicals to make his farm a terrorist target, but many fertilizer wholesalers and paper mills do - and they'll have to tell the government about it as part of new anti-terrorism measures.

On Friday, the Homeland Security Department plans to release a final list of chemicals that businesses must report to keep dangerous materials out of the hands of terrorists. It's part of new authority Congress gave the department to keep an eye on places where hazardous chemicals are kept.

An original list of 344 chemicals - some with specific weight thresholds - was proposed in April and caused an uproar among businesses that had assumed they would be exempt from such terror-related reporting laws. If a facility has a chemical on the department's list, it has to fill out an online form that the Homeland Security Department will use to decide whether the chemical poses enough of a terrorist risk that the facility's security measures should be regulated.

Many chicken farms, for example, keep more than 7,500 pounds of propane, the threshold on the original list. But a new reporting threshold of 60,000 pounds for propane exempts them.

Colleges and universities that keep chemicals in many of their laboratories were spun up over the proposed list as well. The final list will only affect universities that carry large amounts of a certain chemical and small amounts of chemicals that could be used as weapons.

However, just because a business is required to fill out the government's online questionnaire does not necessarily mean that they'll be regulated by the government, said a Homeland Security official who spoke on the condition of anonymity, because the final list had not yet been published.

"Once we assess that they have large amounts of chemicals of consequence, then what we will do is work with them on a plan so that they can secure a facility," the official said.

The potential to use certain chemicals as weapons is one of the reasons the government came up with the list. For example:

_Hydrogen peroxide, commonly used to bleach paper, can also be used in liquid explosives - the weapon of choice in at least two foiled terror plots. Those plots led to prominent airport security measures, including restrictions on how much liquid passengers can carry on planes and the screening of shoes.

_Ammonium nitrate, used in most fertilizers, has been a main ingredient in bombs used in attacks across the world. The 1995 Oklahoma City bombing, which killed 168 people, involved 2 tons of ammonium nitrate.

_Chlorine, which is generally used as a disinfectant, has been a popular explosive ingredient in attacks in Iraq.

As a result, businesses with more than 500 pounds of chlorine that could potentially be stolen, and businesses with 2,500 pounds of chlorine that could be hazardous if released, will be subject to reporting requirements.

Most businesses with these amounts of chlorine are water treatment facilities or specialty chemical manufacturers, said Scott Jensen, spokesman for the American Chemistry Council, which represents about 90 percent of the nation's chemical makers.

Facilities with at least 2,000 pounds of ammonium nitrate used in fertilizers that could be easily stolen and potentially used to make a bomb must also fill out the online forms. These include producers and wholesalers, according to the Fertilizer Institute, a Washington-based trade group.

And businesses that have hydrogen peroxide at a 35 percent concentration will also be subject to regulations. Many paper mills and water treatment facilities use this grade of hydrogen peroxide, Jensen said.

Dropped from the list entirely were acetone and urea. Acetone is commonly used in nail polish remover, and urea is used in fertilizer.

Technorati : Fertilizer, chemical

Toxic Releases Down From North American Industry Leaders

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Pollution , and purification is always a burning question , awaring the CEC's goal ,The latest Taking Stock report from the Commission for Environmental Cooperation (CEC) reveals that a continued decline in releases of toxic chemicals to the environment--15 percent for the United States and Canada from 1998 to 2004--is being driven by a group of industrial facilities that are the largest generators of emissions
The CEC report, however, also reveals that the leading role of the largest waste-producing facilities stands in stark contrast to a substantial increase in chemical releases and transfers by a much larger group of industrial facilities that report lower volumes of emissions.

Released October 18, the annual report compares industrial pollution from a matched set of facilities in Canada and the United States--three million tonnes of chemicals released or transferred in the two countries in 2004. Over one-third of that amount was released at the location of reporting facilities, including over 700,000 tonnes released to the air, with another third transferred to recycling. For the first time, the CEC report also provides data from Mexico. Across the three countries, metals and their compounds--lead, chromium, nickel and mercury--were reported by the highest proportion of facilities.

"The evidence is clear that industry and government action to limit chemical releases is showing steady progress," said Adrián Vázquez-Gálvez, CEC's executive director. "It is equally clear that a large number of small and medium-size industrial facilities need to do a better job in reducing their waste and emissions if we are going to see even greater progress in North America. We trust the progress shown by industry leaders and the fact that pollution prevention is a proven strategy will encourage everyone to tackle pollution issues at the source."

The CEC's analysis demonstrates that facilities from Canada and the United States that reported pollution prevention activities--product and process redesign, spill and leak detection, and substituting raw materials--showed reductions from 2002--2004. Facilities not engaged in these activities did not show similar progress.

A new chapter provides a detailed look at industrial recycling, finding that over one-third of US and Canadian releases and transfers reported in 2004--more than 1 million tonnes--were recycled. Recycling has increased in recent years due to increases in production and in scrap metal prices. Most of the materials were metals, including copper, zinc, lead and their compounds.

The trilateral analysis is based on matched data from some 9 industrial sectors, 56 chemicals, and 10,000 facilities, comparing releases and transfers for similar facilities in Canada, Mexico and the United States. The report identifies a different pattern of releases and transfers in each of the three countries.

Comparisons of the three countries' industrial emissions will continue to improve as the CEC works with governments, industry and NGOs to expand the number of chemicals and facilities that are comparable.

Taking Stock compiles data from Canada's National Pollutant Release Inventory, the United States' Toxics Release Inventory, and, starting with its first year of mandatory reporting in 2004, Mexico's pollutant release and transfer register, the Registro de Emisiones y Transferencia de Contaminantes

Technorati : CEC’s goal .toxic