Histamine is a biogenic amine that is biosynthesized by the decarboxylation of the amino acid histidine. Its synthesis and stoarage mainly take place in tissue mast cells and in certain white blood cells, the basophilic granulocytes. In response to some immunological and non-immunological stimuli, histamine is "explosively" released from these cells. ...

Zie: Summary and conclusions

Keyzer, Jules Joseph,

University of Groningen Digital Archive

Determinations of histamine and some of tis metabolites and their clinical applications

Keyzer, Jules Joseph

ARTS repository - University of Groningen

   University of GroningenDeterminations of histamine and some of tis metabolites and their clinical applicationsKeyzer, Jules JosephIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1983Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Keyzer, J. J. (1983). Determinations of histamine and some of tis metabolites and their clinical applications.s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 30-10-2023SUMMARY AND CONCLUSIONSHistamine is a biogenic amine that is biosynthesized by the decarboxyla-t ion of the amino acid hist idine. I ts synthesis and storage mainly take placein t issue mast cel ls and in certain white blood cel ls, the basophil ic granulo-cytes. In response to some immunological and non-immunological st imuli ,histamine is "explosively" released from these cel ls. Histamine release canbe either local or general.  Local ized release leads to i tching and oedema inthe skin or bronchoconstr ict ion in the lung. A general ized, massive hista-mine release causes profound changes in the cardiovascular system and caninduce a l i fe-threatening anaphylactic shock. After i ts release histamine israpidly deactivated by enzymatic transformations. The most importanthistamine metaboli tes are NT-methylhistamine, Nr-methyl imidazoleaceticacid and imidazoleacetic acid. As imidazoleacetic acid also originates fromthe metabolism of hist idine this metaboli te is less useful in studying the roleof histamine. A small  part of the released histamine and the vast majori tyof the histamine metaboli tes leave the body by urinary excretion.For the srudy of the role of histamine in several diseases i t  is necessary t<rdispose of routinely feasible, sensit ive and specif ic techniques, that are ableto measure the low concentrat ions of both histamine and i ts metaboli tes inbody f luids. As these were not avai lable in our laboratory at the start of thisstudy, in this thesis a number of newly developed procedures for the deter-mination of histamine and i ts metaboli tes NT-methylhistamine andN7-methyl imidazoleacetic acid are described.For the determination of histamine and NT-methylhistamine in plasmalnd urine a so-cal led isotope di lut ion technique with mass spectrometricdetection is used. In this technique a f ixed amount of non-radioactivelylabeled hist irmine (c.q. NT-methylhistamine) is added to the samples. Thesestable isotopical ly labeled analog4a re some mass units higher in mass thanthe natural ly occurring compounds. After some extraction andderivatizationprocedures a gas chromatographic separation is performed using capi l larycolumns, fol lowed by mass spectrometric detection. Only the detectionmethod discriminates between the natural ly occurring compound and i tslabeled analog, and the rat io between the amount of both compoundsaccurately ref leccs the amount of the amine present in the original sample.Nr-methylhistamine irnd NT-methyl imidazoleacetic acid in urine canalso be determined by means of a gas chromatographic method with nitro-139gen-phosphorus detection. In this technique a f ixed amount of synthetichomologues of these histamine metaboli tes is added to the urine as internalstandard. After extract ion and derivatization the mixtures are separatedon a capillary column and the nitrogen-containing compounds selectivelydetected. The ratio between the naturally occurring substance and the inter-nal standard is related to the amount of the histamine metaboli te in the urinesample.The normal values of histamine and Nr-methylhistamine in bloodplasma, and those of histamine, NT-methylhistamine and NT-methyl-imidazoleacetic acid in urine have been determined for healthy controlpersons. In contrast to the concentrat ion of histamine and N7-methylhrst-mine in urine, the concentrat ion of NT-methyl imidazoleacetic acid appearedto be strongly dependent on the dietary histamine intake. Therefore, in casethe urinary excretion of the latter metaboli te is used for the determinationof the histamine turnover, histamine containing foodstuffs ( l ike sauerkrautand cheese) have to be avoided. The amount of histamine excreted in theurine is, especial ly for females, sometimes increased, without the occurrenceof increased urinary histamine metaboli tes or symptoms associated withenhanced histamine production andf or l iberation. These increases are mostprobably caused by bacterial histamine production in the vagina and/or theurological tract. For this reason, the amount of histamine in urine is not arel iable index for the plasma level of this amine. Under normal circum-stances the histamine production by the bacterial f lora in the gastrointesti-nal tract only contr ibu(es to a l i t t le extent to the amount of histamine andhistamine metaboli tes excreted in urine.The role of histamine in bronchial obstructive reactions of patients withbronchial asthma after al lergen inhalat ion was studied by the determinationof N7-methylhistamine in fract ionated urine samples. I t  was demonstratedthat the urinary excretion of this histamine metaboli te is enhanced after rheearly bronchial obstructive reaction, whereas no increase was observed afterthe late bronchial obstructive reaction. It is concluded that during the earlyreaction mast cel l  degranulat ion does take place, but not cluring the latereaction.Patients with a pathological ly increased number of mast cel ls or basophil icgranulocytes exhibit  a strongly enhanced histamine production. In studyingthe urinary excretion of histamine and i ts metaboli tes i t  became clear thatdeterminations of the metaboli tes of histamine provide a more rel iable para-meter for this enhanced production than the determination of histamine140i tself .  The determinations of Nr-methylhistamine and Nr-methyl imida-zoleacetic acid in urine appear to be useful parameters for the diagnosis andfol low-up of patients with mastocytosis. This is especial ly important becausethis disease often shows no characterist ic symptoms by which the diagnosiscan be stated wirh certainry.The release of histamine occurring during hypersensitivity reactions afrerwasp-st ings or after intravenously administrated iodinated contrast mediawas studied by means of the determination clf  NT-methylhistamine in urine.The urinary excretion of this histamine metaboli te is clearly enhanced inpatients showing the symptoms of a hypersensit iviry reaction, and theamount of this amine in urine correlates well  with the severiw of thefeacrion.Final ly the plasma histamine levels during surgical hip replacemenr weredetermined. I t  was investigated whether cement used for attaching theprothesis to the bone gives rise to histamine release. It was demonstratedthat the plasma histamine levels are about two times enhanced duringcement appl icat ion. However, before i t  can be stated wirh cercainry that rhisincrease is indeed caused by the cement application it will be necessary roinvestigate the plasma histamine levels of a control group of parienrs re-ceiving the same anaesthesia and comparable blood transfusions.ln conclusion it can be -rtated tbat tbe netalT deueloped methods t'or thedeterminatiorz of hi.rtamine and its metabolites lir-methythistanzine dndf, meth1,limidazoleacetic acid are sensitit'e and specific, and offer thepotsibilit,y to mearilre these compound.r in urine routinely. The deter-mination of hittamine and I{ -methylhistanzine in plasma are less easy/ toperform and require, in addition to sample collection according to a strictprotocol. an optimal condit ion of the measuring-instruntent. Tbe deter-mination.r of histamine metabolites in urine collected ouer a certain periodr.,f time prouide a para?r?eter for tbe mean bistamine prodaction- and/orliberation rate duing this time. Because it is possible tbat bacteria in theurological tract and/or tbe uagirza produce histamine, the determination ofhistamine in normalll collected urinet is of linzited aalue. It is pos:ible thaturine collection by catheterization can ouercome this problem. The le"-el ofhittamine in plasma is, etpecially becatse of the uery short half-life time ofthis amine in plasrna, only related to the uerJ/ moment of collection.Generall.1' thit can be considered as a disaduantage. OnlT u'ben rapid andconrecatix)e erents haae to be .rtudied, each possibly inducinB bistamineL 4 lrelease, tbe determination of histamine in pla.rma u'ill be ltreferable to thedetermination of histamine metabolitet in urine.Thu.r, surr-eying the dgnificance of histamine and its metaboliter in clini-cal chemistry. the determination of histamine m.etabolite.r in arine .reems toacquire an important place in the diagnoti.r of patients u'ith mastocyto.ri.r,and in tbe study of mecbanism.r of allergic and other hl,persensitit.'it1'reactions. The determination ot' histamine in pla.rma. hou'eaer, appeart tr.t besuitable only for some specific research quettions.142

English

   University of GroningenDeterminations of histamine and some of tis metabolites and their clinical applicationsKeyzer, Jules JosephIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1983Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Keyzer, J. J. (1983). Determinations of histamine and some of tis metabolites and their clinical applications.s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 20-06-2022SUMMARY AND CONCLUSIONSHistamine is a biogenic amine that is biosynthesized by the decarboxyla-t ion of the amino acid hist idine. I ts synthesis and storage mainly take placein t issue mast cel ls and in certain white blood cel ls, the basophil ic granulo-cytes. In response to some immunological and non-immunological st imuli ,histamine is "explosively" released from these cel ls. Histamine release canbe either local or general.  Local ized release leads to i tching and oedema inthe skin or bronchoconstr ict ion in the lung. A general ized, massive hista-mine release causes profound changes in the cardiovascular system and caninduce a l i fe-threatening anaphylactic shock. After i ts release histamine israpidly deactivated by enzymatic transformations. The most importanthistamine metaboli tes are NT-methylhistamine, Nr-methyl imidazoleaceticacid and imidazoleacetic acid. As imidazoleacetic acid also originates fromthe metabolism of hist idine this metaboli te is less useful in studying the roleof histamine. A small  part of the released histamine and the vast majori tyof the histamine metaboli tes leave the body by urinary excretion.For the srudy of the role of histamine in several diseases i t  is necessary t<rdispose of routinely feasible, sensit ive and specif ic techniques, that are ableto measure the low concentrat ions of both histamine and i ts metaboli tes inbody f luids. As these were not avai lable in our laboratory at the start of thisstudy, in this thesis a number of newly developed procedures for the deter-mination of histamine and i ts metaboli tes NT-methylhistamine andN7-methyl imidazoleacetic acid are described.For the determination of histamine and NT-methylhistamine in plasmalnd urine a so-cal led isotope di lut ion technique with mass spectrometricdetection is used. In this technique a f ixed amount of non-radioactivelylabeled hist irmine (c.q. NT-methylhistamine) is added to the samples. Thesestable isotopical ly labeled analog4a re some mass units higher in mass thanthe natural ly occurring compounds. After some extraction andderivatizationprocedures a gas chromatographic separation is performed using capi l larycolumns, fol lowed by mass spectrometric detection. Only the detectionmethod discriminates between the natural ly occurring compound and i tslabeled analog, and the rat io between the amount of both compoundsaccurately ref leccs the amount of the amine present in the original sample.Nr-methylhistamine irnd NT-methyl imidazoleacetic acid in urine canalso be determined by means of a gas chromatographic method with nitro-139gen-phosphorus detection. In this technique a f ixed amount of synthetichomologues of these histamine metaboli tes is added to the urine as internalstandard. After extract ion and derivatization the mixtures are separatedon a capillary column and the nitrogen-containing compounds selectivelydetected. The ratio between the naturally occurring substance and the inter-nal standard is related to the amount of the histamine metaboli te in the urinesample.The normal values of histamine and Nr-methylhistamine in bloodplasma, and those of histamine, NT-methylhistamine and NT-methyl-imidazoleacetic acid in urine have been determined for healthy controlpersons. In contrast to the concentrat ion of histamine and N7-methylhrst-mine in urine, the concentrat ion of NT-methyl imidazoleacetic acid appearedto be strongly dependent on the dietary histamine intake. Therefore, in casethe urinary excretion of the latter metaboli te is used for the determinationof the histamine turnover, histamine containing foodstuffs ( l ike sauerkrautand cheese) have to be avoided. The amount of histamine excreted in theurine is, especial ly for females, sometimes increased, without the occurrenceof increased urinary histamine metaboli tes or symptoms associated withenhanced histamine production andf or l iberation. These increases are mostprobably caused by bacterial histamine production in the vagina and/or theurological tract. For this reason, the amount of histamine in urine is not arel iable index for the plasma level of this amine. Under normal circum-stances the histamine production by the bacterial f lora in the gastrointesti-nal tract only contr ibu(es to a l i t t le extent to the amount of histamine andhistamine metaboli tes excreted in urine.The role of histamine in bronchial obstructive reactions of patients withbronchial asthma after al lergen inhalat ion was studied by the determinationof N7-methylhistamine in fract ionated urine samples. I t  was demonstratedthat the urinary excretion of this histamine metaboli te is enhanced after rheearly bronchial obstructive reaction, whereas no increase was observed afterthe late bronchial obstructive reaction. It is concluded that during the earlyreaction mast cel l  degranulat ion does take place, but not cluring the latereaction.Patients with a pathological ly increased number of mast cel ls or basophil icgranulocytes exhibit  a strongly enhanced histamine production. In studyingthe urinary excretion of histamine and i ts metaboli tes i t  became clear thatdeterminations of the metaboli tes of histamine provide a more rel iable para-meter for this enhanced production than the determination of histamine140i tself .  The determinations of Nr-methylhistamine and Nr-methyl imida-zoleacetic acid in urine appear to be useful parameters for the diagnosis andfol low-up of patients with mastocytosis. This is especial ly important becausethis disease often shows no characterist ic symptoms by which the diagnosiscan be stated wirh certainry.The release of histamine occurring during hypersensitivity reactions afrerwasp-st ings or after intravenously administrated iodinated contrast mediawas studied by means of the determination clf  NT-methylhistamine in urine.The urinary excretion of this histamine metaboli te is clearly enhanced inpatients showing the symptoms of a hypersensit iviry reaction, and theamount of this amine in urine correlates well  with the severiw of thefeacrion.Final ly the plasma histamine levels during surgical hip replacemenr weredetermined. I t  was investigated whether cement used for attaching theprothesis to the bone gives rise to histamine release. It was demonstratedthat the plasma histamine levels are about two times enhanced duringcement appl icat ion. However, before i t  can be stated wirh cercainry that rhisincrease is indeed caused by the cement application it will be necessary roinvestigate the plasma histamine levels of a control group of parienrs re-ceiving the same anaesthesia and comparable blood transfusions.ln conclusion it can be -rtated tbat tbe netalT deueloped methods t'or thedeterminatiorz of hi.rtamine and its metabolites lir-methythistanzine dndf, meth1,limidazoleacetic acid are sensitit'e and specific, and offer thepotsibilit,y to mearilre these compound.r in urine routinely. The deter-mination of hittamine and I{ -methylhistanzine in plasma are less easy/ toperform and require, in addition to sample collection according to a strictprotocol. an optimal condit ion of the measuring-instruntent. Tbe deter-mination.r of histamine metabolites in urine collected ouer a certain periodr.,f time prouide a para?r?eter for tbe mean bistamine prodaction- and/orliberation rate duing this time. Because it is possible tbat bacteria in theurological tract and/or tbe uagirza produce histamine, the determination ofhistamine in normalll collected urinet is of linzited aalue. It is pos:ible thaturine collection by catheterization can ouercome this problem. The le"-el ofhittamine in plasma is, etpecially becatse of the uery short half-life time ofthis amine in plasrna, only related to the uerJ/ moment of collection.Generall.1' thit can be considered as a disaduantage. OnlT u'ben rapid andconrecatix)e erents haae to be .rtudied, each possibly inducinB bistamineL 4 lrelease, tbe determination of histamine in pla.rma u'ill be ltreferable to thedetermination of histamine metabolitet in urine.Thu.r, surr-eying the dgnificance of histamine and its metaboliter in clini-cal chemistry. the determination of histamine m.etabolite.r in arine .reems toacquire an important place in the diagnoti.r of patients u'ith mastocyto.ri.r,and in tbe study of mecbanism.r of allergic and other hl,persensitit.'it1'reactions. The determination ot' histamine in pla.rma. hou'eaer, appeart tr.t besuitable only for some specific research quettions.142

NARCIS 

University of Groningen Research Database

  
 University of Groningen
Determinations of histamine and some of tis metabolites and their clinical applications
Keyzer, Jules Joseph
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from
it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date:
1983
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Keyzer, J. J. (1983). Determinations of histamine and some of tis metabolites and their clinical applications
s.n.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the
author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately
and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the
number of authors shown on this cover page is limited to 10 maximum.
Download date: 10-02-2018
SUMMARY AND CONCLUSIONS
Histamine is a biogenic amine that is biosynthesized by the decarboxyla-
t ion of the amino acid hist idine. I ts synthesis and storage mainly take place
in t issue mast cel ls and in certain white blood cel ls, the basophil ic granulo-
cytes. In response to some immunological and non-immunological st imuli ,
histamine is "explosively" released from these cel ls. Histamine release can
be either local or general.  Local ized release leads to i tching and oedema in
the skin or bronchoconstr ict ion in the lung. A general ized, massive hista-
mine release causes profound changes in the cardiovascular system and can
induce a l i fe-threatening anaphylactic shock. After i ts release histamine is
rapidly deactivated by enzymatic transformations. The most important
histamine metaboli tes are NT-methylhistamine, Nr-methyl imidazoleacetic
acid and imidazoleacetic acid. As imidazoleacetic acid also originates from
the metabolism of hist idine this metaboli te is less useful in studying the role
of histamine. A small  part of the released histamine and the vast majori ty
of the histamine metaboli tes leave the body by urinary excretion.
For the srudy of the role of histamine in several diseases i t  is necessary t<r
dispose of routinely feasible, sensit ive and specif ic techniques, that are able
to measure the low concentrat ions of both histamine and i ts metaboli tes in
body f luids. As these were not avai lable in our laboratory at the start of this
study, in this thesis a number of newly developed procedures for the deter-
mination of histamine and i ts metaboli tes NT-methylhistamine and
N7-methyl imidazoleacetic acid are described.
For the determination of histamine and NT-methylhistamine in plasma
lnd urine a so-cal led isotope di lut ion technique with mass spectrometric
detection is used. In this technique a f ixed amount of non-radioactively
labeled hist irmine (c.q. NT-methylhistamine) is added to the samples. These
stable isotopical ly labeled analog4a re some mass units higher in mass than
the natural ly occurring compounds. After some extraction andderivatization
procedures a gas chromatographic separation is performed using capi l lary
columns, fol lowed by mass spectrometric detection. Only the detection
method discriminates between the natural ly occurring compound and i ts
labeled analog, and the rat io between the amount of both compounds
accurately ref leccs the amount of the amine present in the original sample.
Nr-methylhistamine irnd NT-methyl imidazoleacetic acid in urine can
also be determined by means of a gas chromatographic method with nitro-
139
gen-phosphorus detection. In this technique a f ixed amount of synthetic
homologues of these histamine metaboli tes is added to the urine as internal
standard. After extract ion and derivatization the mixtures are separated
on a capillary column and the nitrogen-containing compounds selectively
detected. The ratio between the naturally occurring substance and the inter-
nal standard is related to the amount of the histamine metaboli te in the urine
sample.
The normal values of histamine and Nr-methylhistamine in blood
plasma, and those of histamine, NT-methylhistamine and NT-methyl-
imidazoleacetic acid in urine have been determined for healthy control
persons. In contrast to the concentrat ion of histamine and N7-methylhrst-
mine in urine, the concentrat ion of NT-methyl imidazoleacetic acid appeared
to be strongly dependent on the dietary histamine intake. Therefore, in case
the urinary excretion of the latter metaboli te is used for the determination
of the histamine turnover, histamine containing foodstuffs ( l ike sauerkraut
and cheese) have to be avoided. The amount of histamine excreted in the
urine is, especial ly for females, sometimes increased, without the occurrence
of increased urinary histamine metaboli tes or symptoms associated with
enhanced histamine production andf or l iberation. These increases are most
probably caused by bacterial histamine production in the vagina and/or the
urological tract. For this reason, the amount of histamine in urine is not a
rel iable index for the plasma level of this amine. Under normal circum-
stances the histamine production by the bacterial f lora in the gastrointesti-
nal tract only contr ibu(es to a l i t t le extent to the amount of histamine and
histamine metaboli tes excreted in urine.
The role of histamine in bronchial obstructive reactions of patients with
bronchial asthma after al lergen inhalat ion was studied by the determination
of N7-methylhistamine in fract ionated urine samples. I t  was demonstrated
that the urinary excretion of this histamine metaboli te is enhanced after rhe
early bronchial obstructive reaction, whereas no increase was observed after
the late bronchial obstructive reaction. It is concluded that during the early
reaction mast cel l  degranulat ion does take place, but not cluring the late
reaction.
Patients with a pathological ly increased number of mast cel ls or basophil ic
granulocytes exhibit  a strongly enhanced histamine production. In studying
the urinary excretion of histamine and i ts metaboli tes i t  became clear that
determinations of the metaboli tes of histamine provide a more rel iable para-
meter for this enhanced production than the determination of histamine
140
i tself .  The determinations of Nr-methylhistamine and Nr-methyl imida-
zoleacetic acid in urine appear to be useful parameters for the diagnosis and
fol low-up of patients with mastocytosis. This is especial ly important because
this disease often shows no characterist ic symptoms by which the diagnosis
can be stated wirh certainry.
The release of histamine occurring during hypersensitivity reactions afrer
wasp-st ings or after intravenously administrated iodinated contrast media
was studied by means of the determination clf  NT-methylhistamine in urine.
The urinary excretion of this histamine metaboli te is clearly enhanced in
patients showing the symptoms of a hypersensit iviry reaction, and the
amount of this amine in urine correlates well  with the severiw of the
feacrion.
Final ly the plasma histamine levels during surgical hip replacemenr were
determined. I t  was investigated whether cement used for attaching the
prothesis to the bone gives rise to histamine release. It was demonstrated
that the plasma histamine levels are about two times enhanced during
cement appl icat ion. However, before i t  can be stated wirh cercainry that rhis
increase is indeed caused by the cement application it will be necessary ro
investigate the plasma histamine levels of a control group of parienrs re-
ceiving the same anaesthesia and comparable blood transfusions.
ln conclusion it can be -rtated tbat tbe netalT deueloped methods t'or the
determinatiorz of hi.rtamine and its metabolites lir-methythistanzine dnd
f, meth1,limidazoleacetic acid are sensitit'e and specific, and offer the
potsibilit,y to mearilre these compound.r in urine routinely. The deter-
mination of hittamine and I{ -methylhistanzine in plasma are less easy/ to
perform and require, in addition to sample collection according to a strict
protocol. an optimal condit ion of the measuring-instruntent. Tbe deter-
mination.r of histamine metabolites in urine collected ouer a certain period
r.,f time prouide a para?r?eter for tbe mean bistamine prodaction- and/or
liberation rate duing this time. Because it is possible tbat bacteria in the
urological tract and/or tbe uagirza produce histamine, the determination of
histamine in normalll collected urinet is of linzited aalue. It is pos:ible that
urine collection by catheterization can ouercome this problem. The le"-el of
hittamine in plasma is, etpecially becatse of the uery short half-life time of
this amine in plasrna, only related to the uerJ/ moment of collection.
Generall.1' thit can be considered as a disaduantage. OnlT u'ben rapid and
conrecatix)e erents haae to be .rtudied, each possibly inducinB bistamine
L 4 l
release, tbe determination of histamine in pla.rma u'ill be ltreferable to the
determination of histamine metabolitet in urine.
Thu.r, surr-eying the dgnificance of histamine and its metaboliter in clini-
cal chemistry. the determination of histamine m.etabolite.r in arine .reems to
acquire an important place in the diagnoti.r of patients u'ith mastocyto.ri.r,
and in tbe study of mecbanism.r of allergic and other hl,persensitit.'it1'reac
tions. The determination ot' histamine in pla.rma. hou'eaer, appeart tr.t be
suitable only for some specific research quettions.
142


University of Groningen

   University of GroningenDeterminations of histamine and some of tis metabolites and their clinical applicationsKeyzer, Jules JosephIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:1983Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Keyzer, J. J. (1983). Determinations of histamine and some of tis metabolites and their clinical applications.s.n.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 12-11-2019SUMMARY AND CONCLUSIONSHistamine is a biogenic amine that is biosynthesized by the decarboxyla-t ion of the amino acid hist idine. I ts synthesis and storage mainly take placein t issue mast cel ls and in certain white blood cel ls, the basophil ic granulo-cytes. In response to some immunological and non-immunological st imuli ,histamine is "explosively" released from these cel ls. Histamine release canbe either local or general.  Local ized release leads to i tching and oedema inthe skin or bronchoconstr ict ion in the lung. A general ized, massive hista-mine release causes profound changes in the cardiovascular system and caninduce a l i fe-threatening anaphylactic shock. After i ts release histamine israpidly deactivated by enzymatic transformations. The most importanthistamine metaboli tes are NT-methylhistamine, Nr-methyl imidazoleaceticacid and imidazoleacetic acid. As imidazoleacetic acid also originates fromthe metabolism of hist idine this metaboli te is less useful in studying the roleof histamine. A small  part of the released histamine and the vast majori tyof the histamine metaboli tes leave the body by urinary excretion.For the srudy of the role of histamine in several diseases i t  is necessary t<rdispose of routinely feasible, sensit ive and specif ic techniques, that are ableto measure the low concentrat ions of both histamine and i ts metaboli tes inbody f luids. As these were not avai lable in our laboratory at the start of thisstudy, in this thesis a number of newly developed procedures for the deter-mination of histamine and i ts metaboli tes NT-methylhistamine andN7-methyl imidazoleacetic acid are described.For the determination of histamine and NT-methylhistamine in plasmalnd urine a so-cal led isotope di lut ion technique with mass spectrometricdetection is used. In this technique a f ixed amount of non-radioactivelylabeled hist irmine (c.q. NT-methylhistamine) is added to the samples. Thesestable isotopical ly labeled analog4a re some mass units higher in mass thanthe natural ly occurring compounds. After some extraction andderivatizationprocedures a gas chromatographic separation is performed using capi l larycolumns, fol lowed by mass spectrometric detection. Only the detectionmethod discriminates between the natural ly occurring compound and i tslabeled analog, and the rat io between the amount of both compoundsaccurately ref leccs the amount of the amine present in the original sample.Nr-methylhistamine irnd NT-methyl imidazoleacetic acid in urine canalso be determined by means of a gas chromatographic method with nitro-139gen-phosphorus detection. In this technique a f ixed amount of synthetichomologues of these histamine metaboli tes is added to the urine as internalstandard. After extract ion and derivatization the mixtures are separatedon a capillary column and the nitrogen-containing compounds selectivelydetected. The ratio between the naturally occurring substance and the inter-nal standard is related to the amount of the histamine metaboli te in the urinesample.The normal values of histamine and Nr-methylhistamine in bloodplasma, and those of histamine, NT-methylhistamine and NT-methyl-imidazoleacetic acid in urine have been determined for healthy controlpersons. In contrast to the concentrat ion of histamine and N7-methylhrst-mine in urine, the concentrat ion of NT-methyl imidazoleacetic acid appearedto be strongly dependent on the dietary histamine intake. Therefore, in casethe urinary excretion of the latter metaboli te is used for the determinationof the histamine turnover, histamine containing foodstuffs ( l ike sauerkrautand cheese) have to be avoided. The amount of histamine excreted in theurine is, especial ly for females, sometimes increased, without the occurrenceof increased urinary histamine metaboli tes or symptoms associated withenhanced histamine production andf or l iberation. These increases are mostprobably caused by bacterial histamine production in the vagina and/or theurological tract. For this reason, the amount of histamine in urine is not arel iable index for the plasma level of this amine. Under normal circum-stances the histamine production by the bacterial f lora in the gastrointesti-nal tract only contr ibu(es to a l i t t le extent to the amount of histamine andhistamine metaboli tes excreted in urine.The role of histamine in bronchial obstructive reactions of patients withbronchial asthma after al lergen inhalat ion was studied by the determinationof N7-methylhistamine in fract ionated urine samples. I t  was demonstratedthat the urinary excretion of this histamine metaboli te is enhanced after rheearly bronchial obstructive reaction, whereas no increase was observed afterthe late bronchial obstructive reaction. It is concluded that during the earlyreaction mast cel l  degranulat ion does take place, but not cluring the latereaction.Patients with a pathological ly increased number of mast cel ls or basophil icgranulocytes exhibit  a strongly enhanced histamine production. In studyingthe urinary excretion of histamine and i ts metaboli tes i t  became clear thatdeterminations of the metaboli tes of histamine provide a more rel iable para-meter for this enhanced production than the determination of histamine140i tself .  The determinations of Nr-methylhistamine and Nr-methyl imida-zoleacetic acid in urine appear to be useful parameters for the diagnosis andfol low-up of patients with mastocytosis. This is especial ly important becausethis disease often shows no characterist ic symptoms by which the diagnosiscan be stated wirh certainry.The release of histamine occurring during hypersensitivity reactions afrerwasp-st ings or after intravenously administrated iodinated contrast mediawas studied by means of the determination clf  NT-methylhistamine in urine.The urinary excretion of this histamine metaboli te is clearly enhanced inpatients showing the symptoms of a hypersensit iviry reaction, and theamount of this amine in urine correlates well  with the severiw of thefeacrion.Final ly the plasma histamine levels during surgical hip replacemenr weredetermined. I t  was investigated whether cement used for attaching theprothesis to the bone gives rise to histamine release. It was demonstratedthat the plasma histamine levels are about two times enhanced duringcement appl icat ion. However, before i t  can be stated wirh cercainry that rhisincrease is indeed caused by the cement application it will be necessary roinvestigate the plasma histamine levels of a control group of parienrs re-ceiving the same anaesthesia and comparable blood transfusions.ln conclusion it can be -rtated tbat tbe netalT deueloped methods t'or thedeterminatiorz of hi.rtamine and its metabolites lir-methythistanzine dndf, meth1,limidazoleacetic acid are sensitit'e and specific, and offer thepotsibilit,y to mearilre these compound.r in urine routinely. The deter-mination of hittamine and I{ -methylhistanzine in plasma are less easy/ toperform and require, in addition to sample collection according to a strictprotocol. an optimal condit ion of the measuring-instruntent. Tbe deter-mination.r of histamine metabolites in urine collected ouer a certain periodr.,f time prouide a para?r?eter for tbe mean bistamine prodaction- and/orliberation rate duing this time. Because it is possible tbat bacteria in theurological tract and/or tbe uagirza produce histamine, the determination ofhistamine in normalll collected urinet is of linzited aalue. It is pos:ible thaturine collection by catheterization can ouercome this problem. The le"-el ofhittamine in plasma is, etpecially becatse of the uery short half-life time ofthis amine in plasrna, only related to the uerJ/ moment of collection.Generall.1' thit can be considered as a disaduantage. OnlT u'ben rapid andconrecatix)e erents haae to be .rtudied, each possibly inducinB bistamineL 4 lrelease, tbe determination of histamine in pla.rma u'ill be ltreferable to thedetermination of histamine metabolitet in urine.Thu.r, surr-eying the dgnificance of histamine and its metaboliter in clini-cal chemistry. the determination of histamine m.etabolite.r in arine .reems toacquire an important place in the diagnoti.r of patients u'ith mastocyto.ri.r,and in tbe study of mecbanism.r of allergic and other hl,persensitit.'it1'reactions. The determination ot' histamine in pla.rma. hou'eaer, appeart tr.t besuitable only for some specific research quettions.142

https://pure.rug.nl/ws/files/3414736/Keyzer.PDF

Determinations of histamine and some of tis metabolites and their clinical applications

Abstract

Similar works

Full text

Available Versions

University of Groningen Digital Archive

ARTS repository - University of Groningen

ARTS repository - University of Groningen

NARCIS

University of Groningen Research Database

University of Groningen