DE19719098C1 - Diagnostic determination of labelled nitric oxide in breath - Google Patents
Diagnostic determination of labelled nitric oxide in breathInfo
- Publication number
- DE19719098C1 DE19719098C1 DE1997119098 DE19719098A DE19719098C1 DE 19719098 C1 DE19719098 C1 DE 19719098C1 DE 1997119098 DE1997119098 DE 1997119098 DE 19719098 A DE19719098 A DE 19719098A DE 19719098 C1 DE19719098 C1 DE 19719098C1
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- exhalation
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- therapy
- breath
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- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title 2
- 238000000034 method Methods 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 238000003745 diagnosis Methods 0.000 claims abstract description 4
- 238000005173 quadrupole mass spectroscopy Methods 0.000 claims abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
- 241000195493 Cryptophyta Species 0.000 claims abstract description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims abstract description 3
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 3
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 3
- 239000000700 radioactive tracer Substances 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims description 6
- 239000007789 gas Substances 0.000 claims description 6
- KWTQSFXGGICVPE-WCCKRBBISA-N Arginine hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CCCN=C(N)N KWTQSFXGGICVPE-WCCKRBBISA-N 0.000 claims description 5
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 5
- ODKSFYDXXFIFQN-UHFFFAOYSA-N Arginine Chemical compound OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 239000002243 precursor Substances 0.000 claims description 4
- 230000002685 pulmonary effect Effects 0.000 claims description 4
- 230000024883 vasodilation Effects 0.000 claims description 4
- 208000037849 arterial hypertension Diseases 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 230000002085 persistent effect Effects 0.000 claims description 3
- 238000009423 ventilation Methods 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- MWUXSHHQAYIFBG-OUBTZVSYSA-N nitric-15n oxide Chemical compound O=[15N] MWUXSHHQAYIFBG-OUBTZVSYSA-N 0.000 claims 2
- 241000282412 Homo Species 0.000 claims 1
- 238000007792 addition Methods 0.000 claims 1
- 230000037213 diet Effects 0.000 claims 1
- 235000005911 diet Nutrition 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 abstract 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000004475 Arginine Substances 0.000 description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
- 229930064664 L-arginine Natural products 0.000 description 3
- 235000014852 L-arginine Nutrition 0.000 description 3
- 235000009697 arginine Nutrition 0.000 description 3
- 238000002307 isotope ratio mass spectrometry Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 1
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 1
- VVGPECAOVDZTLZ-UHFFFAOYSA-N [N]NC(N)=N Chemical group [N]NC(N)=N VVGPECAOVDZTLZ-UHFFFAOYSA-N 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000001196 vasorelaxation Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
- A61K51/1206—Administration of radioactive gases, aerosols or breath tests
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/08—Measuring devices for evaluating the respiratory organs
- A61B5/0813—Measurement of pulmonary parameters by tracers, e.g. radioactive tracers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/497—Physical analysis of biological material of gaseous biological material, e.g. breath
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Veterinary Medicine (AREA)
- Pathology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Physiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medical Informatics (AREA)
- Surgery (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Atmospheric Sciences (AREA)
- Dispersion Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Die Erfindung betrifft ein Verfahren zur Bestimmung der 15NO-Exhalation aus L-[guanidino-15N2]Argininmonohydrochlorid zur Diagnostik und Therapie beim Menschen.The invention relates to a method for determining the 15 NO exhalation from L- [guanidino- 15 N 2 ] arginine monohydrochloride for diagnosis and therapy in humans.
NO wird durch die NO-synthase in den Endothelzellen der pulmonalen Arterien gebildet, diffundiert in die glatte Gefäßmuskulatur und wird an der pro sthetischen Gruppe der löslichen Guanylylzyklase gebunden. Dieser Prozeß führt über die Freisetzung von zyclischem Guanosinmonophosphat und Senkung des verfügbaren intrazellulären Kalziums unmittelbar zur NO-induzierten Vasorelaxa tion. Nach neuesten Erkenntnissen gilt NO als bedeutender Regulator des vasku laren Tonus und stimuliert die Vasodilation.NO is produced by the NO synthase in the pulmonary endothelial cells Arteries are formed, diffuses into the smooth vascular muscles and is attached to the pro aesthetic group of soluble guanylyl cyclase bound. This process leads on the release of cyclic guanosine monophosphate and lowering the available intracellular calcium immediately to the NO-induced vasorelaxa tion. According to the latest knowledge, NO is an important regulator of vasku laren tone and stimulates vasodilation.
Das terminale Guanidino-Stickstoffatom von L-Arginin gilt als Präcursor von NO und wird bei Säugetieren zu Nitrit und Nitrat oxidiert und anschließend renal ausgeschieden.The terminal guanidino nitrogen atom of L-arginine is considered a precursor of NO and is oxidized to nitrite and nitrate in mammals and then renally excreted.
Bisher konnte der Nachweis der endogenen NO-Bildung lediglich indirekt über die Messung von NO3 - im Serum und Harn geführt werden (Castillo et al. Pediatr Res 1995; 38: 17-24).So far, the detection of endogenous NO formation could only be carried out indirectly by measuring N O3 - in serum and urine (Castillo et al. Pediatr Res 1995; 38: 17-24).
Ein direkter Nachweis der Bildung von NO aus L-Arginin in der Exhalati onsluft konnte bisher nicht erbracht werden.Direct evidence of the formation of NO from L-arginine in the exhalati Onsluft could not be provided so far.
Die Isotopenverhältnis-Massenspektrometrie (IRMS) gehört zu den eta blierten Standardmethoden bei der Messung von 15N-Häufigkeiten in festen und flüssigen Proben.Isotope ratio mass spectrometry (IRMS) is one of the established standard methods for measuring 15 N frequencies in solid and liquid samples.
Die Messung von 15N-Anreicherungen in den seltenen Atemgasen N2O und NO ist aufgrund der sehr niedrigen Konzentrationen dieser Gase in der Atemluft mit diesem Verfahren nicht möglich.The measurement of 15 N enrichments in the rare breathing gases N 2 O and NO is not possible with this method due to the very low concentrations of these gases in the breathing air.
Der im Patentanspruch angegebenen Erfindung liegt das Problem zugrun de, ein massenspektometrisches Verfahren zur nicht-invasiven Messung des N- Transfers von L-[guanidino-15N2]Argininmonohydrochlorid und universell 15N- markierten Proteinen aus Hefe und Algen auf 15NO in der Exhalationsluft zu entwickeln, um den klinische Verlauf von Erkrankungen (beispielsweise der persistierenden pulmonalen bzw. arteriellen Hypertension), den Einfluß von Medikamenten, die Wirkung der oralen und intravenösen Zufuhr des NO-Präcur sors Arginin als Agens zur Vasodilation, die Wirkung von NO-Beimengungen zu Beatmungszwecken sowie den Einfluß der Ernährung bei Menschen und Säuge tieren untersuchen zu können. The problem specified in the invention is based on the problem, a mass spectrometric method for the non-invasive measurement of the N transfer of L- [guanidino- 15 N 2 ] arginine monohydrochloride and universally 15 N-labeled proteins from yeast and algae to 15 NO in the To develop exhalation air to determine the clinical course of diseases (e.g. persistent pulmonary or arterial hypertension), the influence of medication, the effect of oral and intravenous administration of the NO precursor arginine as an agent for vasodilation, the effect of NO admixtures to be able to investigate for ventilation purposes and the influence of nutrition in humans and mammals.
Dieses Problem wird durch die im Patentanspruch aufgeführten Merkmale gelöst.This problem is solved by the features listed in the claim solved.
Das Wesen der Erfindung liegt in der Nutzung des NO-Pathways des L- Arginins und der nicht-invasiven Messung von 15NO in der Exhalationsluft mit tels eines Gaschromatographie-Quadrupolmassenspektrometrie-Kopplungssystems (GC-QMS).The essence of the invention lies in the use of the NO pathway of L-arginine and the non-invasive measurement of 15 NO in the exhalation air by means of a gas chromatography-quadrupole mass spectrometry coupling system (GC-QMS).
Bei diesem modifizierten Verfahren dient eine mit flüssigem Stickstoff gekühlte Edelstahlkapillare als Kühlfalle zur Aufkonzentrierung von NO (Kryo trapping). Durch thermische Desorption wird das NO punktuell auf die GC-Säule aufgebracht, gaschromatographisch getrennt und im QMS massenspektrometrisch gemessen.This modified process uses one with liquid nitrogen cooled stainless steel capillary as a cold trap for concentrating NO (cryo trapping). The NO is selectively applied to the GC column by thermal desorption applied, separated by gas chromatography and mass spectrometry in the QMS measured.
Es wurde gefunden, daß die Verabreichung von 7,5 mg/kg L-[guanidino- 15N2]Argininmonohydrochlorid (95 Atom-%) an 3 Erwachsene nach 30 bis 45 Minuten zu einer maximalen 15NO-Markierung von 4,4 bis 6,1 Atom-%-exzess in der Atemluft führte.It was found that the administration of 7.5 mg / kg L- [guanidino- 15 N 2 ] arginine monohydrochloride (95 atomic%) to 3 adults after 30 to 45 minutes to a maximum 15 NO label of 4.4 to 6.1 atomic% excess resulted in the air we breathe.
Der Vorteil des erfindungsgemäßen Verfahrens liegt in der Möglichkeit auf nicht-invasivem Wege mittels in vivo Bestimmungen der endogenen NO-Produk tion den klinischen Verlauf von Erkrankungen (beispielsweise der persistierenden pulmonalen bzw. arteriellen Hypertension), den Einfluß von Medikamenten, die Wirkung der oralen und intravenösen Zufuhr des NO-Präcursors Arginin als Vasodilationsagens, die Wirkung von NO-Beimengungen zu Beatmungszwecken sowie den Einfluß der Ernährung bei Menschen und Säugetieren untersuchen zu können.The advantage of the method according to the invention lies in the possibility non-invasive way by means of in vivo determinations of the endogenous NO product tion the clinical course of diseases (for example the persistent pulmonary or arterial hypertension), the influence of drugs that Effect of oral and intravenous administration of the NO precursor arginine as Vasodilation agent, the effect of NO admixtures for ventilation purposes as well as investigating the influence of nutrition in humans and mammals can.
Ein Ausführungsbeispiel wird im folgenden näher beschrieben.An exemplary embodiment is described in more detail below.
Gesunden Erwachsenen im Alter von 28 bis 56 Jahren mit einem Körper gewicht von 54 bis 84 kg werden nach dem Frühstück um 08.00 Uhr 7,5 mg/kg L-[guanidino-15N2]Argininmonohydrochlorid (95 Atom-%) oral verabreicht.Healthy adults aged 28 to 56 years with a body weight of 54 to 84 kg are orally administered after breakfast at 8:00 a.m. 7.5 mg / kg L- [guanidino- 15 N 2 ] arginine monohydrochloride (95 atom%).
Die Ausatemluft wird im 30- bzw. 60-Minuten Rhythmus in 2-Liter Atemgasbeuteln über 12 Stunden fraktioniert gesammelt.The exhaled air becomes 2-liter every 30 or 60 minutes Breathing gas bags collected fractionally over 12 hours.
Zusätzlich wird der Harn zur Bestimmung der 15 N-Häufigkeiten im Ge samtstickstoff, Harnstoff, Ammoniak, Nitrit und Nitrat im 2- bzw. 4-Stunden Rhythmus über 24 Stunden quantitativ gesammelt.In addition, the urine is used to determine the 15 N frequencies in the Ge Velvet nitrogen, urea, ammonia, nitrite and nitrate in 2 or 4 hours Rhythm collected quantitatively over 24 hours.
Die 15N-Häufigkeiten im NO, N2O, NO2- und NO3 werden mittels GC- QMS gemessen (QP 2000, Shimadzu, Japan), während die 15N-Häufigkeiten in den Harnfraktionen Gesamt-N, Harnstoff und Ammoniak mittels IRMS (Europa Scientific, Crewe, U. K.) ermittelt werden.The 15 N frequencies in NO, N 2 O, NO 2 - and NO 3 are measured using GC-QMS (QP 2000, Shimadzu, Japan), while the 15 N frequencies in the urine fractions total N, urea and ammonia using IRMS (Europa Scientific, Crewe, UK) can be determined.
Die orale Verabreichung des 15N-markierten Arginins führt nach 30 bis 45 Minuten in der Atemluft zu maximalen 15NO-Markierungen von 4, 4 bis 6,1 Atom-%-exzess während die 15N-Markierungen im N2O erst nach 45 bis 90 Minuten mit 0,78 bis 1,43 Atom-%-exzess ihr Maximum erreichen. Die kumula tive 15NO-Exhalation liegt im Mittel bei 0,09 Promille während die renalen Gesamt-15N-Exkretionen zwischen 24 und 36% beträgt.Oral administration of the 15 N-labeled arginine leads to a maximum of 15 NO-markings of 4.4 to 6.1 atom% excess in the breathing air after 30 to 45 minutes, while the 15 N-markings in the N 2 O only after 45 up to 90 minutes with 0.78 to 1.43 atomic% excess. The cumulative 15 NO exhalation is on average 0.09 per thousand, while the total renal 15 N excretion is between 24 and 36%.
Claims (2)
- 1. 1.1. als Tracersubstanzen universell 15N-markierte Proteine aus Hefe und Algen, vorzugsweise L-[guanidino-15N2]Argininmonohydrochlorid (95 Atom-%), ver wendet werden,
- 2. 1.2. die Messung der 15N-Häufigkeiten des NO im Atemgas mit einer Gaschro matographie-Quadrupolmassenspektrometrie Kopplung mit kryogener NO-Anrei cherung erfolgt.
- 1.1.1. 15 N-labeled proteins from yeast and algae, preferably L- [guanidino- 15 N 2 ] arginine monohydrochloride (95 atom%), are used universally as tracer substances,
- 2. 1.2. the 15 N frequencies of the NO in the breathing gas are measured using a gas chromatography-quadrupole mass spectrometry coupling with cryogenic NO enrichment.
- 1. 2.1. mittels in vivo Bestimmungen der endogenen 15NO-Produktion auf nicht- invasivem Weg der klinische Verlauf von Erkrankungen vorzugsweise der persi stierenden pulmonalen bzw. arteriellen Hypertension beurteilt wird,
- 2. 2.2. der Einfluß von Medikamenten auf die 15NO-Produktion ermittelt wird,
- 3. 2.3. die Wirkung der oralen und intravenösen Zufuhr des NO-Präcursors Argi nin als Vasodilationsagens bestimmt wird,
- 4. 2.4. die Wirkung von NO-Beimengungen zu Beatmungszwecken gemessen wird und
- 5. 2.5. der Einfluß der Ernährung bei Menschen und Säugetieren auf die endogene 15NO-Produktion untersucht wird.
- 1. 2.1. the clinical course of diseases, preferably persistent pulmonary or arterial hypertension, is assessed by means of in vivo determinations of endogenous 15 NO production in a non-invasive way,
- 2. 2.2. the influence of drugs on 15 is determined NO production,
- 3. 2.3. the effect of oral and intravenous administration of the NO precursor arginin is determined as a vasodilation agent,
- 4. 2.4. the effect of NO additions for ventilation purposes is measured and
- 5. 2.5. the influence of diet in humans and mammals on endogenous 15 NO production is investigated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1997119098 DE19719098C1 (en) | 1997-05-06 | 1997-05-06 | Diagnostic determination of labelled nitric oxide in breath |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1997119098 DE19719098C1 (en) | 1997-05-06 | 1997-05-06 | Diagnostic determination of labelled nitric oxide in breath |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19719098C1 true DE19719098C1 (en) | 1999-05-12 |
Family
ID=7828770
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1997119098 Expired - Fee Related DE19719098C1 (en) | 1997-05-06 | 1997-05-06 | Diagnostic determination of labelled nitric oxide in breath |
Country Status (1)
| Country | Link |
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| DE (1) | DE19719098C1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001031334A1 (en) * | 1999-10-26 | 2001-05-03 | Diabact Ab | Method and means for detecting inflammatory processes |
| EP1380838A3 (en) * | 2002-07-11 | 2004-09-08 | Ralph Gäbler | Method of gas analysis for determining the reaction of a biological system |
| DE102004035916A1 (en) * | 2004-07-23 | 2006-03-16 | Prof. Dr. Karl-Heinz Gericke Technische Universität Braunschweig Institut für Physikalische und Theoretische Chemie | Device, useful for isotopically determining nitrogen monoxide concentration in e.g. breathing air, comprises a UV source of light (emits a light of wavelength and electronically energizes isotope of nitrogen monoxide) and a light detector |
-
1997
- 1997-05-06 DE DE1997119098 patent/DE19719098C1/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| Castillo et al. Pediatr. Res. 1995, 38 S.17-24 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001031334A1 (en) * | 1999-10-26 | 2001-05-03 | Diabact Ab | Method and means for detecting inflammatory processes |
| EP1380838A3 (en) * | 2002-07-11 | 2004-09-08 | Ralph Gäbler | Method of gas analysis for determining the reaction of a biological system |
| DE102004035916A1 (en) * | 2004-07-23 | 2006-03-16 | Prof. Dr. Karl-Heinz Gericke Technische Universität Braunschweig Institut für Physikalische und Theoretische Chemie | Device, useful for isotopically determining nitrogen monoxide concentration in e.g. breathing air, comprises a UV source of light (emits a light of wavelength and electronically energizes isotope of nitrogen monoxide) and a light detector |
| DE102004035916B4 (en) * | 2004-07-23 | 2007-10-18 | Prof. Dr. Karl-Heinz Gericke Technische Universität Braunschweig Institut für Physikalische und Theoretische Chemie | Method for the isotope-selective determination of nitrogen monoxide concentrations |
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