Assessment of Vitamin A Body Stores by Stable Isotopes

The first study in human subjects to directly compare measured liver vitamin A content with the predictions of isotope dilution was performed in the laboratory of Prof James Olson at Iowa State University.

 

In the well nourished individual, some 80 to 90% of total body vitamin A is in the liver, so the usual validation of isotope dilution estimates is by comparison with the vitamin A content of the liver.

Ideally, the mass of tracer should be very low, so that it does not perturb vitamin A metabolism.

For assessment of vitamin A status, a dose of vitamin A labelled with a stable isotope is administered after a baseline blood sample has been collected. A period of equilibration of the dose with the vitamin A body pool is necessary before the follow-up blood sample is taken for analysis by mass spectrometry. From the dilution of the precisely measured dose of isotope labelled vitamin A, it is possible to calculate the total quantity of exchangeable vitamin A in the body. This is the most sensitive way to non-invasively estimate vitamin A status over the whole range, from deficient to normal to excessive

 

 

 

 

 

References:

1.     Harold C. Furr, Isotope Diluti on Assessment of Vitamin A Status,  James A Olson Memorial Lecture -CARIG Workshop at Experimental Biology 2011

2.                IAEA Bulletin 55-1-March 2014, a small part can reveal the whole: How isotope technique help nutrition

 

 

 

Assessment of Total Energy Expenditure by Stable Isotopes

Stable isotopes of hydrogen and oxygen have been recently used to measure energy expenditure in free-living humans. The doubly labeled water method using these isotopes is a form of indirect calorimetry which has been extensively validated in animals and humans. The method is completely safe, requires only periodic sampling of body fluids, and is ideally suited for measurement of energy expenditure in free-living or hospitalized patients.

After the administration of doubly labeled water (D₂¹⁸O), the labeled hydrogen (D₂) would be eliminated as water (D₂O), corresponding to water output, whereas the oxygen isotope would be eliminated as water (H₂¹⁸O) and as expired carbon dioxide (C¹⁸O₂). By measuring the difference between the elimination rates of labeled oxygen and hydrogen, the carbon dioxide production rate can be calculated. The carbon dioxide production rate is converted into energy expenditure by knowing the respiratory quotient of the food ingested during the observation period.

The advantage of this technique is that sample collection only involves urine collection at timed intervals following initial dosing. These samples are then analyzed using isotope ratio mass spectrometry (IRMS) to determine the stable isotope remaining in the body.

 

Reference:

Measuring Energy Expenditure Using the Doubly Labeled Water Method Technical Paper 905.

Stable Isotope Application in Medical Diagnostic

Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine. When PAH activity is reduced, phenylalanine accumulates in blood and can lead to serious medical problems. Therefore, newborn babies are screened for PKU or other metabolic diseases soon after birth. Screening for PKU is done with various techniques. actual concentration of phenyl alanine/tyrosine ratio is determined using tandem mass  spectrometry (MS-MS). The use of stable isotope labeled standards is a key component of the MS-MS analysis of extracted metabolite from blood samples.

In addition, the in vivo assay of phenylalanine hydroxylase was carried out by injection a solution of L-phenylalanine-D6 and in various times after injection, the blood samples were collected and analysed using tandem mass spectrometry (MS-MS). Phenyl alanine hydroxylase activity determined by measuring the labeled phenylalanine to labeled tyrosine ratio.

1. R. Matalon, D. E. Matthews, K. Michals, D. Bier, The use of deuterated phenylalanine for their vivo assay of phenylalanine hydroxylase activity in children, Journal of Inherited Metabolic Diseases, 1982, Vol. 5, 17-19.

2. N. Koklolish, I. Ziegler, on the level of phenylalanine, tyrosine and tetrahydrobioprotein in the blood of tumor-bearing organisms, cancer bichem. Biophys., 1977, Vol. 2, 79-85.  

3. D. E. Matthews, an overview of phenylalanine and tyrosine kinetics in humans, J. Nutr., Vol. 137, 2007, 1575s-1594s.

Stable Isotope in Optical Fiber industry

To reliably support many decades of revenue generating services the optical loss in fibers should not degrade with time. For some fibers, however, there is a significant risk that the optical loss could increase due to the chemical reactions between the atomic defects in fibers and the trace amounts of molecular hydrogen inevitably present in or around optical cables.

Selecting the right fibers made with the proper process and high purity silica material can guard against hydrogen aging loss increases and help ensure decades of reliable network service. There are basically three types of hydrogen aging losses that must be avoided in Ge-doped silica fibers to help ensure reliability in optical transmission over an expected service lifetime of 25 years or more. These hydrogen aging losses are caused by different types of atomic defects or impurities present in the silica fibers. The severity of hydrogen aging loss degradation is dependent on the fiber manufacturing process and the purity of the

silica material involved.

Replacing hydrogen with deuterium improves the function of the optical fibers by serving as a passivating agent at this interface.

 

References:

K. Chang, The Importance of Minimizing Hydrogen Aging Losses and Alkali Impurities OFS AllWave® Zero Water Peak (ZWP) Fiber.

 

Stable Isotopes in Oil Industry

Mud tracing is utilized in a variety of drilling fluid systems to help define the amount of filtrate invasion throughout coring operations. It is used to achieve more accurate oil and water saturations during the formation evaluation.

D₂O is a water-soluble tracer used to treat the water phase of the drilling fluid. As it is non-radioactive and harmless to the environment, it will not hinder disposal or recycling of the drilling fluid. D₂O is used to elevate the natural background level of deuterium, which generally ranges from 130 - 150 ppm throughout the world. D₂O found in the core during analysis is easily distinguished by its mass from any other water extracted from the sample. The amount introduced to the drilling mud can be manipulated to reflect certain concentrations targeted for the determination of fluid saturations.

 

Reference:

Weatherford Laboratories, well site services brochure.

Stable Isotope Application in Nutrition Studies

Nutrition plays a vital role in early child development. Isotope techniques can help determine if a baby is exclusively breastfed or not, as well as how much human milk the baby consumes.

 

A mother drinks a dose of deuterium oxide that is distributed throughout her body and is incorporated into her milk. The deuterium gradually disappears from her body and appears in the body of the baby.

Over a period of 14 days, samples of saliva or urine are collected from the mother and child, revealing the changes in isotope concentration.

A mathematical model is used to determine how much of the deuterium given to the mother appears in the baby’s saliva. This gives insight into the baby’s intake of human milk and whether the baby has consumed water from other sources, as well as the body composition of the mother.

 

1.                IAEA Bulletin 55-1-March 2014, a small part can reveal the whole: How isotope technique help nutrition

Stable Isotopes as internal standard

Stable Isotopes as internal standard

An internal standard is used when performing bioanalysis with mass spectrometry detection. The best internal standard for bioanalysis is an isotopically labeled version of the molecule you want to quantity. Internal standards should contain enough mass increase to show a signal outside the natural mass distribution of the analyte.

Generally, because of the abundance of hydrogen in organic molecules, the use of deuterium is proffered compared to 13C and 15N, which are generally more expensive solution for stable isotope labeled internal standards.

A deuterated internal standard will have the same extraction recovery, ionization response in ESI mass spectrometry and the same chromatographic retention time, and therefore deuterated standards are ideal for bioanalysis.

  goldbook.iupac.org

 

Stable Isotopes in Hydrology Studies

Isotopes, when used in groundwater hydrology give a direct insight into the movement and distribution processes within aquifers. Techniques used in hydrology may be classified into three groups: environmental isotopes, artificial isotopes, and application of sealed radioactive sources. Isotope hydrology provides complementary information on the type, origin and age of groundwater. If the isotope content does not change within the aquifer, it will reflect the origin of the water, particularly the location, period and processes of recharge. If the isotope content changes along groundwater paths, this will reflect the history of the water, particularly the mixing, salinization and discharge processes.

The isotopes commonly employed in groundwater investigations are the heavy stable isotopes of the water molecule, deuterium and oxygen-18 and the radioactive isotopes, tritium and carbon-14.

As there are no harmful chemicals associated with deuterium oxide and deuterium oxide is a stable isotope, it’s hydrology application cause no environmental hazards.

References:

1. J.L. Terwey, 1984, Isotopes in groundwater hydrology.

2. R. Letolle, Ph.Olive, 2003, A short history of isotopes in hydrology.

stable isotope Heavy Water Reactors

Heavy- water reactor programs were started in Canada, France, Germany, Italy, Japan, Sweden, Switzerland, the United Kingdom, the United States of America and the former USSR. Each country built research and prototype power reactors, some operating successfully for a number of years, but only the heavy water moderated, heavy water cooled version developed in Canada (also known as CANDU) proceeded to the stage of commercial implementation to become one of the three internationally competitive reactor types available at the end of the 20th century and which has been exported to a number of countries.

Heavy-water reactor (HWR) is a nuclear reactor, commonly using unenriched natural uranium as its fuel, that uses heavy water (deuterium oxide D₂O) as its coolant and neutron moderator. the heavy water coolant is kept under pressure, allowing it to be heated to higher temperatures without boiling. While heavy water is significantly more expensive than ordinary light water, it creates greatly enhanced neutron economy, allowing the reactor to operate without fuel-enrichment facilities and enhancing the ability of the reactor to make use of alternate fuel cyles.

HWR technology offers fuel flexibility, low operating costs and a high level of safety, and therefore represents an important option for countries considering nuclear power programmes.

-         Heavy water reactors: status and projected development: IAEA, 2002.

stable isotope (Heavy Water )Application in Fusion reactor

Fusion is the process which powers the sun and the stars. It is energy that makes all life on earth possible. It is called “fusion” because the energy is produced by fusing together light atoms, such as hydrogen, at the extremely high pressure and temperatures which exist at the center of the sun. at the high temperatures experienced in the sun any gas becomes plasma.

A fusion reaction is about four million times more energetic than a chemical reaction such as the burning of coal, oil or gas. With current technology, the reaction most readily feasible is between the nuclei of the two heavy forms of hydrogen- deutrium (D)  and tritium(T). On a mass basis, the D-T fusion reaction release over four times as much energy as uranium fission.

In a fusion reactor, the concept is that neutrons generated from the D-T fusion reaction will be absorbed in a blanket containing lithium which surrounds the core. The lithium then transformed into tritium (which is used to fuel the reactor) and helium. The blanket must be thick enough to slow down the high-energy neutrons. The kinetic energy of the neutrons is absorbed by the blanket, causing it to heat up. The heat energy is collected by the coolant flowing through the blanket and, in a fusion power plant this energy will be used to generate electricity by conventional methods.

-         Fusion as an energy source, W.J. Nuttal. 2008