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Record 1
from database: MEDLINE
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- Title
- HgEDTA complex inhibits GTP
interactions with the E-site of brain
beta-tubulin.
- Author
- Duhr EF; Pendergrass JC; Slevin JT;
Haley BE
- Address
- Division of Medicinal Chemistry and
Pharmaceutics, College of Pharmacy,
University of Kentucky Medical Center,
Lexington.
- Source
- Toxicol Appl Pharmacol, 1993 Oct,
122:2, 273-80
- Abstract
- We have found that EDTA and EGTA
complexes of Hg2+, which conventional
wisdom has assumed are biologically
inert, are potentially injurious to
the neuronal cytoskeleton. Tubulin, a
major protein component of the
neuronal cytoskeleton, is the target
of multiple toxicants, including many
heavy metal ions. Among the mercurials,
inorganic mercuric ion (Hg2+) is one
of the most potent inhibitors of
microtubule polymerization both in
vivo and in vitro. In
contrast to other heavy metals, the
capacity of Hg2+ to inhibit
microtubule polymerization or disrupt
formed microtubules cannot be
prevented by the addition of EDTA and
EGTA, both of which bind Hg2+ with
very high affinity. To the
contrary, the addition of these two
chelating agents potentiates Hg2+
inhibition of tubulin polymerization.
Results herein show that HgEDTA and
HgEGTA inhibit tubulin polymerization
by disrupting the interaction of GTP
with the E-site of brain beta-tubulin,
an obligatory step in the
polymerization of tubulin. Both HgEDTA
and HgEGTA, but not free Hg2+,
prevented binding of [32P]8N3GTP, a
photoaffinity nucleotide analog of GTP,
to the E-site and displaced bound
[32P]8N3GTP at low micromolar
concentrations. This complete
inhibition of photoinsertion into the
E-site occurred in a concentration-
and time-dependent fashion and was
specific for Hg2+ complexes of EDTA
and EGTA, among the chelating agents
tested. Given the ubiquity of Hg2+ in
the environment and the widespread use
of EDTA in foodstuffs and medicine,
these mercury complexes may pose a
potentially serious threat to human
health and play a role in diseases of
the neuronal cytoskeleton.
- Language of Publication
- English
- Unique Identifier
- 94024905
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- MeSH Heading (Major)
- Brain|*DE/ME; Edetic Acid|*PD;
Guanosine Triphosphate|AA/DU/*ME;
Mercury|*PD; Tubulin|*DE/ME
- MeSH Heading
- Affinity Labels|DU; Animal;
Azides|DU; Binding Sites|DE; Human; In
Vitro; Magnesium|PD; Male; Phosphorus
Radioisotopes|DU; Photochemistry;
Protein Binding|DE; Rats; Rats,
Sprague-Dawley; Support, Non-U.S.
Gov't; Support, U.S. Gov't,
Non-P.H.S.; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0041-008X
- Country of Publication
- UNITED STATES
Record 2
from database: MEDLINE
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- Title
- A simple ICP-MS procedure for the
determination of total mercury in
whole blood and urine.
- Author
- Kalamegham R; Ash KO
- Address
- Department of Pathology, University
of Utah Medical Center, Salt Lake City
84108.
- Source
- J Clin Lab Anal, 1992, 6:4, 190-3
- Abstract
- A simple and sensitive procedure for
total mercury in whole blood and urine
using inductively coupled plasma-mass
spectrometry (ICP-MS) is described.
Specimens are prepared by
precipitation-extraction with 50% v/v
hydrochloric acid containing EDTA and
cysteine, centrifuged, and filtered
through fritended screening column;
the filtrates are directly analyzed by
ICP-MS. The method is linear between 2
and 200 micrograms/L in the specimen
with an absolute sensitivity of 0.2
microgram/L in the final supernatant.
The assay variability at various
concentrations (microgram/L) of
mercury are as follows: intra-assay
whole blood (n = 20)-4.6 +/- 0.6 (c.v.
12.3%), 18.3 +/- 1.1 (c.v. 6.1%), 56.4
+/- 2.8 (c.v. 5.0%); inter-assay whole
blood (n = 15)-5.7 +/- 1.0 (c.v.
16.8%), 19.7 +/- 2.7 (c.v. 13.5%), and
50.1 +/- 6.9 (c.v. 13.7%); urine (n =
20)-9.3 +/- 1.2 (c.v. 12.9%), 29.6 +/-
2.2 (c.v. 7.4%). Recovery of organic
and inorganic mercury from blood
samples ranges from 91.6% to 110.2%.
The method is suitable for analysis of
total mercury, both organic and
inorganic, in whole blood and urine.
- Language of Publication
- English
- Unique Identifier
- 93019810
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- MeSH Heading (Major)
- Mercury|*BL/*UR; Spectrum Analysis,
Mass|*MT/SN
- MeSH Heading
- Argon; Cysteine; Edetic Acid; Human;
Hydrochloric Acid; Methylmercury
Compounds|BL/UR; Sensitivity and
Specificity
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0887-8013
- Country of Publication
- UNITED STATES
Record 3
from database: MEDLINE
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- Title
- Inhibition of paraoxonase activity
in human liver microsomes by exposure
to EDTA, metals and mercurials.
- Author
- Gonzalvo MC; Gil F; Hernández AF;
Villanueva E; Pla A
- Address
- Department of Legal Medicine,
Faculty of Medicine, Granada, Spain.
- Source
- Chem Biol Interact, 1997 Aug, 105:3,
169-79
- Abstract
- Inhibition of paraoxon hydrolase (paraoxonase)
activity by 'in vitro' exposure to
EDTA, Mg2+, Co2+, Ba2+, La3+, Zn2+,
Cu2+, Hg2+, p-hydroxymercuribenzoate
(p-OH-MB) and phenyl mercuric acetate
(PMA) was investigated in human liver
microsomes. Enzyme activity was
totally inhibited by 1 mM EDTA in a
time-dependent manner, in contrast to
previous data obtained in rat liver
where an EDTA-resistant fraction was
detected. The possible influence of
postmortem changes in these results
was checked in a parallel experiment
using rat livers with different
postmortem intervals. From our results
the existence in human liver of an
EDTA-resistant fraction cannot be
discarded. Ba, La and PMA showed
immediate inhibition. By contrast the
other compounds tested were
time-dependent inhibitors. Ba and Zn
showed the highest IC50 values. Cu and
mercurials (Hg, p-OH-MB, PMA) were the
most potent inhibitors of human liver
paraoxonase. Kinetic analysis (Lineweaver-Burk
and Dixon plots) indicated that
different inhibitors exhibit different
inhibition patterns: competitive
(EDTA, Ba, La, Cu, p-OH-MB and PMA),
non competitive (Zn) and mixed (Hg).
The pretreatment of sample with
dithiothreitol (DTT) protects against
the inhibitory effect of mercurials.
Furthermore after inhibition by
mercurials the activity was restored
by DTT. These results confirmed the
essential role of the -SH groups to
maintain the catalytic activity of
paraoxonase and suggest the existence
of two types of -SH groups that could
differ in their localization.
- Language of Publication
- English
- Unique Identifier
- 97437462
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- MeSH Heading (Major)
- Edetic Acid|*PD; Enzyme
Inhibitors|*PD; Esterases|*AI/ME;
Mercury Compounds|*PD; Metals|*PD;
Microsomes, Liver|DE/*EN
- MeSH Heading
- Animal; Dithiothreitol|PD; Enzyme
Activation; Human; Kinetics; Rats;
Sulfhydryl Compounds|ME; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0009-2797
- Country of Publication
- IRELAND
Record 4
from database: MEDLINE
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- Title
- Human semen ribonuclease. Location,
properties and inhibition by sodium
dodecyl sulfate, zinc sulfate and
EDTA.
- Author
- Mujica A; Romero G; Hernandez Montes
H
- Address
-
- Source
- Int J Fertil, 1976, :2, 109-13
- Abstract
- Optimal conditions were established
for RNase activity measurement. The
enzyme was measured in human seminal
plasma as well as in spermatozoa.
Results suggest that sperm enzyme may
come from seminal plasma contamination
and that RNase may be used as a marker
enzyme for seminal plasma
contamination. Sodium dodecylsulfate,
a reagent utilized to produce the
solubilization of the spermatozoa,
produced a very strong inhibition of
the RNase at low concentrations (530
muM). Zinc sulfate and EDTA also
produced inhibition of the RNase
activity. Such inhibition may be very
useful in future studies of RNA
metabolism in human spermatozoa.
- Language of Publication
- English
- Unique Identifier
- 76259358
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full text for this document
- MeSH Heading (Major)
- Edetic Acid|*PD; Ribonucleases|*/ME;
Semen|*EN; Sodium Dodecyl Sulfate|*PD;
Zinc|*PD
- MeSH Heading
- Dithiothreitol|PD; Human;
Hydrogen-Ion Concentration; Male;
Mercury|PD; Spermatozoa|EN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0020-725X
- Country of Publication
- UNITED STATES
Record 5
from database: MEDLINE
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- Title
- Effects of plumbous ion on guanine
metabolism.
- Author
- Farkas WR; Stanawitz T
- Address
-
- Source
- J Inorg Biochem, 1979 Aug, 11:1,
31-8
- Abstract
- The enzyme guanine aminohydrolase (guanase)
is inhibited by low levels of Pb2+.
The inhibition is noncompetitive and
the Ki is 3.0 X 10(-6) M. The only
other heavy metals that are inhibitory
at low concentrations are Ag+, which
is 36% more, and Hg2+, which is about
50% less inhibitory than Pb2+. The
inhibition of guanase by Pb2+ and Hg2+
is synergistic and the inhibition of
the enzyme was readily reversed by
EDTA. The relationship of these
studies with guanase and to the
etiology and treatment of saturnine
gout, which appears in humans
suffering from lead poisoning, is
discussed.
- Language of Publication
- English
- Unique Identifier
- 80008188
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- MeSH Heading (Major)
- Aminohydrolases|*AI; Guanine
Deaminase|*AI; Lead|*PD
- MeSH Heading
- Cations, Divalent; Edetic Acid|PD;
Gout|EN/ET; Human; Kinetics; Lead
Poisoning|EN; Mercury|PD; Silver|PD;
Support, U.S. Gov't, P.H.S.; Xanthine
Oxidase|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0162-0134
- Country of Publication
- UNITED STATES
Record 6
from database: MEDLINE
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- Title
- Metal
excretion and magnesium retention in
patients with intermittent
claudication treated with intravenous
disodium EDTA.
- Author
- Guldager B; J‡rgensen PJ;
Grandjean P
- Address
- Department of Surgery, Hiller‡d
Hospital, Denmark.
- Source
- Clin Chem, 1996 Dec, 42:12, 1938-42
- Abstract
- Sixty
patients with intermittent
claudication participated in a
double-blind placebo-controlled trial
of 20 courses of intravenous chelation
therapy with 3 g of disodium EDTA vs
placebo during 5-9 weeks. After the
first infusion, the 24-h urinary
excretion of lead and zinc was
approximately 25-fold higher in the
EDTA-treated group; relative
differences for copper and calcium
were smaller. Urinary magnesium
excretion in the EDTA-treated group
was one-third less than in the control
group. After the treatment period, the
blood lead concentration had decreased
by approximately 73% and the serum
zinc concentration by approximately
34%; other changes in blood
concentrations were negligible. The
loss of essential minerals and the
possible redistribution of lead in the
body may constitute a disadvantage
that should be taken into account in
repeated intravenous EDTA treatment.
- Language of Publication
- English
- Unique Identifier
- 97124459
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- MeSH Heading (Major)
- Edetic Acid|*TU; Intermittent
Claudication|*DT/ME; Magnesium|BL/*ME/UR;
Metals|*UR
- MeSH Heading
- Adult; Aged; Aged, 80 and over;
Calcium|UR; Copper|BL/UR; Double-Blind
Method; Human; Lead|BL/UR; Mercury|BL;
Middle Age; Placebos; Support,
Non-U.S. Gov't; Zinc|BL/UR
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE;
RANDOMIZED CONTROLLED TRIAL
- ISSN
- 0009-9147
- Country of Publication
- UNITED STATES
Record 7
from database: MEDLINE
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- Title
- HgEDTA complex inhibits GTP
interactions with the E-site of brain
beta-tubulin.
- Author
- Duhr EF; Pendergrass JC; Slevin JT;
Haley BE
- Address
- Division of Medicinal Chemistry and
Pharmaceutics, College of Pharmacy,
University of Kentucky Medical Center,
Lexington.
- Source
- Toxicol Appl Pharmacol, 1993 Oct,
122:2, 273-80
- Abstract
- We have found that EDTA and EGTA
complexes of Hg2+, which conventional
wisdom has assumed are biologically
inert, are potentially injurious to
the neuronal cytoskeleton. Tubulin, a
major protein component of the
neuronal cytoskeleton, is the target
of multiple toxicants, including many
heavy metal ions. Among the mercurials,
inorganic mercuric ion (Hg2+) is one
of the most potent inhibitors of
microtubule polymerization both in
vivo and in vitro. In contrast to
other heavy metals, the capacity of
Hg2+ to inhibit microtubule
polymerization or disrupt formed
microtubules cannot be prevented by
the addition of EDTA and EGTA, both of
which bind Hg2+ with very high
affinity. To the contrary, the
addition of these two chelating agents
potentiates Hg2+ inhibition of tubulin
polymerization. Results herein show
that HgEDTA and HgEGTA inhibit tubulin
polymerization by disrupting the
interaction of GTP with the E-site of
brain beta-tubulin, an obligatory step
in the polymerization of tubulin. Both
HgEDTA and HgEGTA, but not free Hg2+,
prevented binding of [32P]8N3GTP, a
photoaffinity nucleotide analog of GTP,
to the E-site and displaced bound
[32P]8N3GTP at low micromolar
concentrations. This complete
inhibition of photoinsertion into the
E-site occurred in a concentration-
and time-dependent fashion and was
specific for Hg2+ complexes of EDTA
and EGTA, among the chelating agents
tested. Given the ubiquity of Hg2+ in
the environment and the widespread use
of EDTA in foodstuffs and medicine,
these mercury complexes may pose a
potentially serious threat to human
health and play a role in diseases of
the neuronal cytoskeleton.
- Language of Publication
- English
- Unique Identifier
- 94024905
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- MeSH Heading (Major)
- Brain|*DE/ME; Edetic Acid|*PD;
Guanosine Triphosphate|AA/DU/*ME;
Mercury|*PD; Tubulin|*DE/ME
- MeSH Heading
- Affinity Labels|DU; Animal;
Azides|DU; Binding Sites|DE; Human; In
Vitro; Magnesium|PD; Male; Phosphorus
Radioisotopes|DU; Photochemistry;
Protein Binding|DE; Rats; Rats,
Sprague-Dawley; Support, Non-U.S.
Gov't; Support, U.S. Gov't,
Non-P.H.S.; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0041-008X
- Country of Publication
- UNITED STATES
Record 8
from database: MEDLINE
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- Title
- Trace element studies in three
patients and a fetus with Menkes'
disease. Effect of copper therapy.
- Author
- Nooijen JL; De Groot CJ; Van den
Hamer CJ; Monnens LA; Willemse J;
Niermeijer MF
- Address
-
- Source
- Pediatr Res, 1981 Mar, 15:3, 284-9
- Abstract
- This paper reports the results of a
multielement analysis of postmortem
samples of Menkes patients, of which
one was untreated and two had been
treated for various lengths of time
with intramuscular injections of
copper-EDTA. The findings have been
compared with data from a Menkes fetus
and from controls. The results confirm
that copper accumulates in various
tissues and demonstrate a further
increase in copper levels as a result
of the treatment with copper-EDTA.
Although no clinical improvement was
observed, the levels of some
copper-containing enzymes normalized
during the copper-therapy.
Furthermore, in agreement with the
identification of the copper-binding
protein in the kidney as
metallothionein, it was found that not
only copper, but also zinc, cadmium,
and mercury are trapped in this
tissue. A low copper concentration in
the brain was also found in a Menkes
fetus, indicating that brain damage
might already have occurred before
birth. Speculation Until recently,
Menkes' disease was considered to be
due to copper deficiency. However, the
symptoms are more typical of a storage
disease in which copper is
irreversibly trapped in some tissues,
in particular in the kidneys, by
metallothionein. This abnormal storage
pattern gives rise to copper
deficiency elsewhere in the organism,
particularly in the brain where it may
cause irreversible damage in the
foetus. Parenteral administration of
copper does not lead to clinical
improvement. The only
"therapy" that seems
feasible at present is tracing the
carriers of the disease and advising
abortion when prenatal diagnosis
indicates a male fetus carrying the
disease.
- Language of Publication
- English
- Unique Identifier
- 81174435
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- MeSH Heading (Major)
- Brain Diseases, Metabolic|*DT;
Copper|AN/*TU; Menkes Kinky Hair
Syndrome|DI/*DT; Trace Elements|*AN
- MeSH Heading
- Arsenic|AN; Cadmium|AN; Case Report;
Cobalt|AN; Comparative Study; Edetic
Acid; Female; Fetal Diseases|DI;
Human; Infant; Iron|AN; Male;
Mercury|AN; Molybdenum|AN; Pregnancy;
Selenium|AN; Tissue Distribution;
Zinc|AN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0031-3998
- Country of Publication
- UNITED STATES
Record 9
from database: MEDLINE
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- Title
- Monoglyceride and diglyceride
lipases from human platelet microsomes.
- Author
- Chau LY; Tai HH
- Address
- Division of Medicinal Chemistry and
Pharmacognosy, College of Pharmacy,
University of Kentucky, Lexington
405367-0082.
- Source
- Biochim Biophys Acta, 1988 Dec,
963:3, 436-44
- Abstract
- In the present study, we have
characterized the properties of both
diglyceride lipase (lipoprotein
lipase, EC 3.1.1.24) and monoglyceride
lipases (acylglycerol lipase, EC
3.1.1.23) in an attempt to assess the
potential roles of these two enzymes
in the release of arachidonate in
activated human platelets. Diglyceride
lipase exhibited maximal activity at
pH 3.5, whereas monoglyceride lipase
showed optimal activity at pH 7.0.
Neither of the lipases were inhibited
by EDTA or stimulated by Ca2+, Mg2+ or
Mn2+. Both enzymes, however, were
strongly inhibited by Hg2+ and Cu2+,
indicating the involvement of
sulfhydryl groups in catalytic
activity. This suggestion was further
supported by their sensitivity toward
sulfhydryl inhibitors, with
monoglyceride lipase being more
susceptible to inhibition. Both
lipases were found to be inhibited to
a different degree by a variety of
antiplatelet drugs blocking
aggregation and arachidonate release.
Kinetic studies indicated that
dichotomous metabolism of
diacylglycerol to monoacylglycerol and
to phosphatidic acid could occur
concurrently, since the apparent Km
values for diglyceride lipase and for
diglyceride kinase were comparable.
Further studies showed that the
specific activity of monoglyceride
lipase was at least 100-fold higher
than that of diglyceride lipase,
indicating that the rate-limiting step
in the release of arachidonate was the
reaction catalyzed by diglyceride
lipase.
- Language of Publication
- English
- Unique Identifier
- 89062521
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- MeSH Heading (Major)
- Blood Platelets|*EN; Carboxylic
Ester Hydrolases|*BL; Lipoprotein
Lipase|*BL; Monoacylglycerol
Lipases|*BL
- MeSH Heading
- Calcium|PD; Copper|PD; Edetic
Acid|PD; Heat; Human; Hydrogen-Ion
Concentration; Kinetics; Magnesium|PD;
Manganese|PD; Mercury|PD;
Microsomes|EN; Platelet Aggregation
Inhibitors|PD; Substrate Specificity;
Sulfhydryl Reagents|PD; Support,
Non-U.S. Gov't; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
Record
10 from database: MEDLINE
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- Title
- Differential metal response and
regulation of human heavy
metal-inducible genes.
- Author
- Murata M; Gong P; Suzuki K; Koizumi
S
- Address
- Division of Hazard Assessment,
National Institute of Industrial
Health, Kawasaki, Japan.
- Source
- J Cell Physiol, 1999 Jul, 180:1,
105-13
- Abstract
- A number of heavy metal-inducible
genes have been reported, but their
ranges of response to various metal
species are not well known. It is also
unclear if these genes are regulated
through common mechanisms. To answer
these questions, we compared induction
kinetics of human metal-inducible
genes including the MT-IIA (coding for
a metallothionein isoform), hsp70
(coding for the 70-kDa heat-shock
protein), and c-fos genes in HeLa
cells exposed to Zn, Cd, Ag, Hg, Cu(II),
Co, or Ni ions. Transcripts from these
three genes were increased after
exposure to wide ranges of metals, but
each gene was unique in its induction
kinetics. Generally, induction was
observed at lower metal concentrations
in the order of MT-IIA, hsp70, and c-fos.
These genes also showed differential
responses in time course: more rapid
induction was observed in the order of
c-fos, hsp70, and MT-IIA after
exposure to Zn or Cd. Since the
metal-responsive element (MRE) and
heat shock element (HSE) of the MT-IIA
and hsp70 genes, respectively, are
thought to be the cis-acting DNA
elements that mediate metal response,
we compared the properties of proteins
that specifically bind to these
elements. MRE-binding activity was
detected only in the extract from
cells exposed to Zn. By contrast, HSE-binding
activity was detected in extracts from
cells treated with Zn, Cd, Ag, and Cu.
The former was also activated by Zn in
vitro, while the latter was not. Each
of these DNA-binding activities showed
no affinity to the recognition
sequence of the other. These results
demonstrate that the human
metal-inducible genes have broad
ranges of response to a variety of
heavy metals, but suggest that they
are probably regulated through
independent mechanisms.
- Language of Publication
- English
- Unique Identifier
- 99288869
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- MeSH Heading (Major)
- Heat-Shock Proteins 70|*GE;
Metallothionein|*GE; Metals,
Heavy|*PD; Proto-Oncogene Proteins c-fos|*GE
- MeSH Heading
- Blotting, Northern; Cadmium|PD;
Chelating Agents|PD; Cobalt|PD;
Copper|PD; Dose-Response Relationship,
Drug; DNA-Binding Proteins|ME; Edetic
Acid|PD; Gene Expression|DE; Gold|PD;
Hela Cells; Human; Mercury|PD;
Nickel|PD; Nuclear Proteins|ME;
Oligonucleotide Probes; RNA,
Messenger|AN; Transcription Factors|ME;
Transcription, Genetic|PH; Zinc|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9541
- Country of Publication
- UNITED STATES
Record
11 from database: MEDLINE
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- Title
- Mobilisation of heavy metals into
the urine by CaEDTA: relation to
erythrocyte and plasma concentrations
and exposure indicators.
- Author
- Araki S; Aono H; Murata K
- Address
-
- Source
- Br J Ind Med, 1986 Sep, 43:9, 636-41
- Abstract
- To
investigate the effects of calcium
disodium ethylenediamine tetra-acetate
(CaEDTA) on the urinary excretion,
erythrocyte, and plasma concentrations
and exposure indicators of seven heavy
metals, CaEDTA was administered by
intravenous infusion to 20 workers
exposed to lead, zinc, and copper. The
workers' blood lead concentrations
ranged from 22 to 59 micrograms/dl
(mean 38 micrograms/dl (1.8 mumol/l].
The 24 hour urinary excretion of
metals after CaEDTA administration (mobilisation
yield) was on average 13 times the
background excretion for lead, 11
times for zinc, 3.8 times for
manganese, 3.4 times for cadmium, 1.3
times for copper, and 1.1 times for
chromium; no significant increase was
found for mercury. The mobilisation
yield of lead (MPb) was significantly
correlated with whole blood and
erythrocyte concentrations and the
urinary excretion of lead but not with
its plasma concentration; similarly,
the mobilisation yield of cadmium was
significantly correlated with its
erythrocyte concentration. In
addition, MPb was significantly
correlated with intra-erythrocytic
enzyme delta-aminolaevulinic acid
dehydratase activity and urinary
coproporphyrin excretion. The relation
between the mobilisation yield of
heavy metals and their body burden
(and toxic signs) is discussed in the
light of these findings.
- Language of Publication
- English
- Unique Identifier
- 87000506
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- MeSH Heading (Major)
- Edetic Acid|*PD; Erythrocytes|*ME;
Metals|*ME
- MeSH Heading
- Adult; Cadmium|ME; Chromium|ME;
Copper|ME; Environmental Exposure;
Human; Lead|ME; Male; Manganese|ME;
Mercury|ME; Middle Age; Zinc|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0007-1072
- Country of Publication
- ENGLAND
Record
12 from database: MEDLINE
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- Title
- Cyclic adenosine 3':5'-monophosphate
phosphodiesterase activity in
malignant and cyclic adenosine
3':5'-monophosphate-induced
"differentiated"
neuroblastoma cells.
- Author
- Kumar S; Becker G; Prasad KN
- Address
-
- Source
- Cancer Res, 1975 Jan, 35:1, 82-7
- Abstract
- The regulation of cyclic adenosine
3:5-monophosphate (cyclic AMP)
phosphodiesterase activity in
homogenates of malignant and cyclic
AMP-induced "differentiated"
neuroblastoma cells was studied.
Neuroblastoma cells of at least three
mouse and one human clone had both the
low (2 to 4 muM) and the high (66 to
106 muM) Km phosphodiesterase. In
cyclic AMP-induced differentiated
cells the values of Km were decreased,
whereas the values of Vmax appeared to
be slightly increased. Magnesium and
manganese stimulated phosphodiesterase
activity. Calcium, zinc, copper,
mercury, ethylenediaminetetraacetic
acid, and imidazole completely
inhibited phosphodiesterase activity
in malignant cells, whereas the above
agents, except
ethylenediaminetetraacetic acid, only
partially inhibited enzyme activity in
differentiated cells.
Ethylenediaminetetraacetic acid
completely reduced phosphodiesterase
activity in differentiated cells. The
pH optimum for phosphodiesterase
activity was about 8 in both malignant
and differentiated cells. The present
studies show that the values of Km and
Vmax and the sensitivity of
phosphodiesterase activity to divalent
ions change in cyclic AMP-induced
differentiated neuroblastoma cells,
and therefore we propose that the
reverse may be true during malignant
transformation of nerve cells.
- Language of Publication
- English
- Unique Identifier
- 75074120
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- MeSH Heading (Major)
- Cell Differentiation|*; Cyclic
AMP|ME/*PD; Neuroblastoma|*EN;
Phosphoric Diester Hydrolases|*ME
- MeSH Heading
- Adenylate Cyclase|ME; Animal;
Calcium|PD; Caudate Nucleus|EN; Clone
Cells; Copper|PD; Depression,
Chemical; Edetic Acid|PD; Human;
Hydrogen-Ion Concentration;
Imidazoles|PD; Magnesium|PD;
Manganese|PD; Mercury|PD; Mice;
Stimulation, Chemical; Support, U.S.
Gov't, Non-P.H.S.; Time Factors;
Zinc|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-5472
- Country of Publication
- UNITED STATES
Record
13 from database: MEDLINE
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- Title
- Erythrocyte porphobilinogen synthase
(delta-aminolaevulinate dehydratase)
activity: a reliable and quantitative
indicator of lead exposure in humans.
- Author
- Mitchell RA; Drake JE; Wittlin LA;
Rejent TA
- Address
-
- Source
- Clin Chem, 1977 Jan, 23:1, 105-11
- Abstract
- We assessed optimal conditions for
assay of porphobillinogen synthase (EC
4.2.1.24) activity in human blood
containing abnormally high
concentrations of lead. Zn2+and -SH,
both required for complete activation
of the enzyme, had additive effects.
Using a modified method based on these
studies, we found blood lead
concentration to be strictly
proportional to ln(activated/nonactivated)
enzyme activity. One brand of
commercially available
"lead-free" tubes contained
a substance that interfered with this
relationship. In vitro studies, with
the modified assay, showed ALAD to be
activated by low concentrations but
inactivated by high concentrations of
Hg2+, Cd2+, and
ethylenediaminetetraacetate. We fouund
no genetically influenced differences
among unexposed individuals when
in(activated/nonactivated) enzyme
activities were compared. The
technique is suitable for use in
screening for lead poisoning in
humans.
- Language of Publication
- English
- Unique Identifier
- 77089786
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- MeSH Heading (Major)
- Erythrocytes|*EN; Hydro-Lyases|*BL;
Lead Poisoning|*DI/*EN;
Porphobilinogen Synthase|*BL
- MeSH Heading
- Cadmium|PD; Edetic Acid|PD; Enzyme
Activation|DE; Glutathione|PD; Human;
Kinetics; Lead|BL/PD; Mercury|PD;
Sodium|PD; Zinc|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0009-9147
- Country of Publication
- UNITED STATES
Record
14 from database: MEDLINE
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- Title
- Comparative studies on cholesterol
oxidases from different sources.
- Author
- Noma A; Nakayama K
- Address
-
- Source
- Clin Chim Acta, 1976 Dec, 73:3,
487-96
- Abstract
- 1. Comparison of the characteristics
of cholesterol oxidases from different
sources was made by a new
polarographic method for measurement
of the oxygen-consumption rate. 2. A
pH optimum of 7.0 was observed for
cholesterol oxidases isolated from
Nocardia and Brevibacterium, pH 5.0
for the enzyme from Schizophyllum and
pH 7.5 for the enzyme from
Streptomyces. 3. In the system used in
the present study, Ca2+ and Mg2+ had
no effect on these enzyme activities.
On the other hand, the Schizophyllum
enzyme was strongly inhibited by
increasing concentrations of Cu2+,
whereas the brevibacterium enzyme was
slightly activated by them and
Nocardia and Streptomyces enzymes were
not affected. Hg2+ strongly inhibited
the activities of enzymes the
Schizophyllum enzyme. 4. Using serum
as substrate, the cholesterol oxidases
employed, except for the enzyme from
Streptomyces, were not active without
detergent in the reaction mixture.
Effects of various detergents at
various concentrations on the enzyme
activities were studied. 5. Results of
studies on the reaction of cholesterol
oxidases on free cholesterol in
low-and high-density lipoproteins were
also compared.
- Language of Publication
- English
- Unique Identifier
- 77067450
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- MeSH Heading (Major)
- Cholesterol|*BL; Hydroxysteroid
Dehydrogenases|*ME
- MeSH Heading
- Brevibacterium|EN; Calcium|PD;
Comparative Study; Copper|PD;
Detergents|PD; Edetic Acid|PD; Human;
Hydrogen-Ion Concentration; Kinetics;
Magnesium|PD; Mercury|PD; Nocardia|EN;
Osmolar Concentration;
Schizophyllum|EN; Species Specificity;
Streptomyces|EN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0009-8981
- Country of Publication
- NETHERLANDS
Record
15 from database: MEDLINE
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- Title
- Cathepsins B1 from human fetal
membranes.
- Author
- Warwas M; Dobryszycka W
- Address
-
- Source
- Biochim Biophys Acta, 1976 Apr,
429:2, 573-80
- Abstract
- Cathepsins B1 (EC 3.4.22.1) were
isolated from fetal membranes of human
placenta, i.e. amnion and
chorion-decidua. Purification of the
enzymes was achieved by the
freezing-thawing technique, ammonium
sulphate fractionation and Sephadex
gel filtration. Cathepsis B1 separated
either from amnion or from
chorion-decidua exhibited optimum
activity at pH 6.2, and an optimum
temperature between 42-45 degrees C.
They were inhibited by heavy metals,
and compounds which react with the
thiol groups. Isoelectric focusing
demonstrated three isoenzymes of
cathepsin B1 originating from
chorion-decidua, while only one band
was found for the enzyme from amnion.
- Language of Publication
- English
- Unique Identifier
- 76161400
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- MeSH Heading (Major)
- Amnion|*EN; Cathepsins|IP/*ME;
Chorion|*EN; Fetal Membranes|*EN
- MeSH Heading
- Cations, Divalent; Edetic Acid|PD;
Female; Human; Hydrogen-Ion
Concentration;
Hydroxymercuribenzoates|PD;
Iodoacetates|PD; Kinetics; Mercury|PD;
Organ Specificity; Pregnancy
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
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16 from database: MEDLINE
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- Title
- Lead poisoning from Indian herbal
medicine (Ayurveda) [see comments]
- Author
- Dunbabin DW; Tallis GA; Popplewell
PY; Lee RA
- Address
- Flinders Medical Centre, Bedford
Park, Sa.
- Source
- Med J Aust, 1992 Dec, 157:11-12,
835-6
- Abstract
- OBJECTIVE:
To present a case of lead poisoning
following ingestion of Indian herbal
medicine. CLINICAL FEATURES: A
37-year-old man presented with a
history of abdominal pain, anorexia
and malaise. He had recently returned
from a trip to India where he had been
taking two different herbal tonics.
Investigation revealed low-grade
hepatitis and normocytic anaemia with
prominent basophilic stippling. The
blood lead concentration was high, and
analysis of the herbal tablets
revealed a very high lead content.
INTERVENTION AND OUTCOME: The patient
required narcotic analgesia for
abdominal pain and was treated with
chelation therapy with calcium
ethylenediaminetetra-acetate (calcium
EDTA) for five days which resulted in
a high urinary excretion of lead and
resolution of his symptoms over a
period of several days. CONCLUSION:
Lead poisoning in Australia is usually
the result of chronic industrial
exposure, but practitioners should be
aware of the possibility of poisoning
from other domestic sources such as
unglazed pottery, cosmetics and herbal
remedies, especially those from Asia
and India, in which lead may be
present in high concentration.
Patients from Asia who present with
unexplained anaemia or abdominal
symptoms should be asked about
exposure to such sources.
- Language of Publication
- English
- Unique Identifier
- 93086568
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- MeSH Heading (Major)
- Lead Poisoning|*ET; Medicine,
Ayurvedic|*; Medicine, Herbal|*;
Plants, Medicinal|*/CH
- MeSH Heading
- Adult; Arsenic|AN; Case Report;
Human; Lead|AN; Male; Mercury|AN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0025-729X
- Country of Publication
- AUSTRALIA
Record
17 from database: MEDLINE
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- Title
- High-performance liquid
chromatographic determination of
N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine,
the active plasma metabolite of a
prodrug atriopeptidase inhibitor (SCH
42495), using a thiol selective
(Au/Hg) amperometric detector.
- Author
- Alton KB; Hernandez A; Alvarez N;
Patrick JE
- Address
- Department of Drug Metabolism and
Pharmacokinetics, Schering-Plough
Research Institute, Bloomfield, NJ
07003.
- Source
- J Chromatogr, 1992 Sep, 579:2,
307-17
- Abstract
- A high-performance liquid
chromatographic assay for the
determination of
N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine
(SCH 42354; II), the active metabolite
of the atriopeptidase inhibitor
prodrug,
N-[2(S)-(acetylthiomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methi
onine ethyl ester (SCH 42495; I), in
human plasma was validated for use in
clinical pharmacokinetic studies.
Plasma (200 microliters) was processed
by protein precipitation with acetone
containing the internal standard,
N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-
ethionine (III). Compound II was
recovered (ca. 90%) in the supernatant
after centrifugation and prepared for
injection by the addition of 0.15 M
monochloroacetic acid containing 0.2
mM EDTA. Separation of II and III was
accomplished on commercially available
reversed-phase C8 columns designed for
the separation of basic compounds.
Both compounds were detected using
amperometric detection (+0.125 V
versus Ag/AgCl) on a thin-layer Au/Hg
amalgam electrode. The lower limit of
quantitation was 10 ng/ml, where the
inter-assay precision (coefficient of
variation) was +/- 11.4% and the
inter-assay accuracy (bias) was +1.0%.
No endogenous interferences were
observed in the extracts obtained from
drug-free plasma. The detector
response (using either peak area or
height ratios of II to III) was linear
from 0.01 to 1.0 micrograms/ml.
Compound II was stable in plasma
supplemented with EDTA and sodium
hydrogensulfite for at least 3 months
when stored frozen at -78 degrees C;
no significant decomposition of II was
observed following three freeze-thaw
cycles. The feasibility of this liquid
chromatographic assay with
electrochemical detection was
demonstrated with plasma samples from
hypertensive subjects administered 100
mg of compound I.
- Language of Publication
- English
- Unique Identifier
- 93055121
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- MeSH Heading (Major)
- Chromatography, High Pressure
Liquid|*MT; Methionine|*AA/BL/ME;
Neprilysin|*AI/BL/ME
- MeSH Heading
- Gold; Human; Hypertension|BL;
Mercury; Sulfhydryl Compounds
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9673
- Country of Publication
- NETHERLANDS
Record
18 from database: MEDLINE
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- Title
- Phosphorylation of the Ca2+ pump
intermediate in intact red cells,
isolated membranes and inside-out
vesicles.
- Author
- Szász I; Hasitz M; Sarkadi B; Gárdos
G
- Address
-
- Source
- Mol Cell Biochem, 1978 Dec, 22:2-3,
147-52
- Abstract
- Ca2+-entry into intact red cells
containing [32P]-ATP increases the
phosphorylation of the 150 000 dalton
polypeptide of the membrane. This
phosphorylation occurs even in
Mg2+-depleted red cells. Extracellular
lanthanum applied during ATP-depletion
further increases the Ca2+-induced
phosphorylation. In fragmented
membranes or resealed insideout
vesicles (IOVs) membrane bound Mg2+ is
sufficient to catalyze the
phosphorylation of spectrin 2 and Band
3 polypeptides with low concentrations
(less than micron of [32P]-ATP. In
Ca-EDTA buffers one single polypeptide
is phosphorylated which is located in
the 150 000 molecular weight region.
KmCa for phosphorylation is much lower
(0.2 micron) than for active Ca2+
transport (40 micron) in IOVs.
Lanthanum induced phosphorylation (up
to 250 micron Lafree) is significantly
greater than Ca2+-induced
phosphorylation. Hg2+ inhibits both
Ca2+ and La3+ induced phosphorylation.
Ca2+-induced labelling can be rapidly
"chased" by unlabelled
ATP+Mg2+, but not with EGTA+Mg2+.
Dephosphorylation in Ca2+
phosphorylated membranes and IOVs is
significantly inhibited by La3+. It
can be concluded that the mechanism of
La3+ and Hg2+ inhibition of the Ca2+
pump is different in intact cells and
isolated membranes or Iovs.
- Language of Publication
- English
- Unique Identifier
- 79134711
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- MeSH Heading (Major)
- Calcium|*BL/PD; Erythrocyte
Membrane|DE/*ME; Erythrocytes|DE/*ME;
Membrane Proteins|*BL; Phosphoproteins|*BL
- MeSH Heading
- Biological Transport, Active|DE;
Human; Lanthanum|PD; Mercury|PD;
Phosphorylation
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0300-8177
- Country of Publication
- NETHERLANDS
Record
19 from database: MEDLINE
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- Title
- A novel approach for heavy metal
poisoning treatment, a model. Mercury
poisoning by means of chelating
microspheres: hemoperfusion and oral
administration.
- Author
- Margel S
- Address
-
- Source
- J Med Chem, 1981 Oct, 24:10, 1263-6
- Abstract
- The chelating drugs BAL
(2,3-dimercaptopropanol), EDTA
(ethylenediaminetetraacetic acid), and
penicillamine
(2-amino-3-mercapto-3-methylbutanoic
acid), which are used for metal
poisoning, are toxic and there is a
real need for alternatives, especially
for severe cases. A novel approach for
treatment of heavy-metal poisoning is
under investigation in our group. The
approach utilizes the synthesis of
chelating microspheres specific for
the desired metallic compound. The
microspheres are suggested for use in
severe cases by means of hemoperfusion,
as a first aid, and then by oral
administration. As a model this
approach was tried for mercury
poisoning. Polymercaptal microspheres
of 0.8 micrometer average size were
synthesized. The microspheres have a
high surface area, have a high
affinity toward organic and inorganic
mercury compounds, and can compete
easily with albumin and cysteine in
the ability to bind mercury compounds.
These microspheres also were
encapsulated with agarose--a blood
compatible polymer--and were tried
successfully for plasma perfusion (in
10 min, 40% of CH3HgCl and of HgCl2
were removed from 20 ppm of poisoned
plasma).
- Language of Publication
- English
- Unique Identifier
- 82122390
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- MeSH Heading (Major)
- Chelating Agents|*AD/ME;
Hemoperfusion|*; Mercury Poisoning|*TH
- MeSH Heading
- Administration, Oral; Human;
Mercury|ME; Microspheres; Models,
Biological
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2623
- Country of Publication
- UNITED STATES
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20 from database: MEDLINE
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- Title
- No evidence of renal toxicity from
amalgam fillings [see comments]
- Author
- Sandborgh Englund G; Nygren AT;
Ekstrand J; Elinder CG
- Address
- Department of Dental Toxicology,
Karolinska Institute, Huddinge,
Sweden.
- Source
- Am J Physiol, 1996 Oct, 271:4 Pt 2,
R941-5
- Abstract
- Dental
amalgam continuously releases mercury.
Studies of sheep [Boyd et al., Am. J.
Physiol. 261 (Regulatory Integrative
Comp. Physiol. 30): R1010-R1014, 1991]
showed decreased renal function after
placement of amalgam fillings. In this
study, renal function was investigated
in 10 healthy volunteers before and
after amalgam removal. The subjects
had an average of 18 tooth surfaces
filled with amalgam, which was removed
during one dental session. One week
before and sixty days after removal,
the glomerular filtration rate (GFR)
was determined by 51Cr-EDTA clearance
technique. Blood and urine samples
were collected for analysis of
mercury, creatinine, beta
2-microglobulin, N-acetyl-beta-glucosaminidase
(NAG), and albumin 1 wk before and 1,
2, and 60 days after amalgam removal.
The plasma mercury concentration
increased significantly 1 day after
removal. Sixty days later,
significantly lower mercury levels
were found in blood, plasma, and
urine. The GFR values were similar
before and after mercury exposure
(mean 94 and 94 ml/min per 1.73 m2,
respectively). No detectable effects
occurred on excretion of NAG, beta
2-microglobulin, or albumin. It is
concluded that no signs of renal
toxicity could be found in conjunction
with mercury released from amalgam
fillings.
- Language of Publication
- English
- Unique Identifier
- 97053473
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- MeSH Heading (Major)
- Dental Amalgam|*AE; Kidney|*DE;
Mercury|*AE/BL
- MeSH Heading
- beta 2-Microglobulin|UR;
Acetylglucosaminidase|UR; Adult;
Albuminuria|UR; Creatinine|ME; Female;
Glomerular Filtration Rate|DE; Human;
Male; Middle Age; Support, Non-U.S.
Gov't; Time Factors
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0002-9513
- Country of Publication
- UNITED STATES
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21 from database: MEDLINE
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- Title
- The effect of zinc and other
divalent cations on the structure and
function of human alpha
2-macroglobulin.
- Author
- Pratt CW; Pizzo SV
- Address
-
- Source
- Biochim Biophys Acta, 1984 Dec,
791:2, 123-30
- Abstract
- Zinc binding to human alpha
2-macroglobulin was studied to assess
its involvement in the structure and
function alpha 2-macroglobulin.
Equilibrium dialysis experiments
indicated multiple classes of
zinc-binding sites, the one of highest
affinity having a site number of 20
and a Kd value of 8 X 10(-7) M. Native
alpha 2-macroglobulin and alpha
2-macroglobulin-trypsin complexes
bound comparable amount of zinc. The
proteinase inhibitory activity of
alpha 2-macroglobulin was not affected
by zinc binding at physiological
concentrations nor by the removal of
zinc by EDTA. Above 25 microM zinc,
alpha 2-macroglobulin activity
decreased, although binding of
[125I]trypsin was not affected. When
nondenaturing gel electrophoresis was
performed, the preparation of alpha
2-macroglobulin migrated as
half-molecules at increasing zinc
concentration. Experiments with other
divalent cations correlated decreases
in alpha 2-macroglobulin activity with
apparent dissociation of the alpha
2-macroglobulin tetramer in the
presence of copper and mercury, but
not barium, cadmium or nickel. While
zinc binding to alpha 2-macroglobulin
does not function in proteinase
inhibition, it might be involved in
zinc transport in vivo. At
nonphysiological concentrations, zinc
and other divalent cations are useful
as probes of protein quaternary
structure.
- Language of Publication
- English
- Unique Identifier
- 85072921
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- MeSH Heading (Major)
- alpha-Macroglobulins|AI/*ME/PD;
Zinc|ME/*PD
- MeSH Heading
- Binding Sites; Cations, Divalent;
Copper|PD; Dialysis; Electrophoresis,
Polyacrylamide Gel; Human;
Macromolecular Systems; Mercury|PD;
Protease Inhibitors|PD; Support, U.S.
Gov't, Non-P.H.S.; Support, U.S.
Gov't, P.H.S.; Trypsin|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
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22 from database: MEDLINE
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- Title
- Stereoselective hydrolysis of soman
in human plasma and serum.
- Author
- De Bisschop HC; De Meerleer WA; Van
Hecke PR; Willems JL
- Address
- Technical Division of the Army,
Department for Nuclear, Biological and
Chemical Protection, Vilvoorde,
Belgium.
- Source
- Biochem Pharmacol, 1987 Nov, 36:21,
3579-85
- Abstract
- The contribution of various human
serum and plasma fractions to the
total hydrolysis rate constants of the
four isomers of soman is studied.
Spontaneous hydrolysis (as measured in
buffer) occurs at a faster rate for
the C(+)P(+)- and C(-)P(-)-isomers. A
stereoselectively catalyzed hydrolysis
of soman occurs in serum fractions IV
and V (albumin). In fraction V the
C(+)P(+)- and C(-)P(-)-isomers are
hydrolyzed at a faster rate than their
respective epimers, while in fraction
IV-1 a stereoselective effect towards
C(+)P(+)-soman is found. All the
forementioned contributions, however,
are negligible in comparison with the
stereoselective enzymatic hydrolysis
of the P(+)-isomers. The latter
reaction is characterized by a
significant lowering of the activation
energy as compared with the
spontaneous hydrolysis of the
P(+)-isomers. Such a lowering in
activation energy is not found for the
hydrolysis of the P(-)-isomers in
whole serum or plasma; hence it can be
concluded that a phosphorylphosphatase
hydrolyzes the P(+)-isomers in a
stereoselective way, the P(-)-isomers
either not being affected by this
(these) enzyme(s) or the mechanism of
catalysis being fundamentally
different. This conclusion is in
agreement with the observations on the
influence of Hg2+ on the hydrolysis of
soman in serum; the hydrolysis of the
P(+)-isomers is significantly
inhibited by 1 mM of Hg2+ while the
P(-)-hydrolysis is unaffected by this
concentration of Hg2+. The action of
some potential inhibitors on this
phosphorylphosphatase activity was
studied. Iodoacetate did not inhibit
nor did Ba2+, Sr2+, Co2+ or Mn2+ show
a significant effect on the hydrolysis
of the P(+)-isomers. On the other hand
the hydrolytic activity in serum was
nearly completely inhibited by EDTA
but restored upon addition of Ca2+.
These findings suggest that this
enzymatic activity can be classified
as an arylesterase (paraoxonase).
Finally, the influence of pH on the
hydrolytic activity shows a different
pattern for C(+)P(+)- and C(-)P(+)-soman,
which may suggest that more than one
enzyme is involved in the degradation
of soman.
- Language of Publication
- English
- Unique Identifier
- 88049757
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- MeSH Heading (Major)
- Soman|*BL
- MeSH Heading
- Calcium|PD; Human; Hydrogen-Ion
Concentration; Hydrolysis; Mercury|PD;
Stereoisomerism; Tromethamine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2952
- Country of Publication
- ENGLAND
Record
23 from database: MEDLINE
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- Title
- Mobilization of heavy metals by
newer, therapeutically useful
chelating agents.
- Author
- Aposhian HV; Maiorino RM; Gonzalez
Ramirez D; Zuniga Charles M; Xu Z;
Hurlbut KM; Junco Munoz P; Dart RC;
Aposhian MM
- Address
- Department of Molecular and Cellular
Biology, University of Arizona, Tucson
85721, USA.
- Source
- Toxicology, 1995 Mar, 97:1-3, 23-38
- Abstract
- Four chelating agents that have been
used most commonly for the treatment
of humans intoxicated with lead,
mercury, arsenic or other heavy metals
and metalloids are reviewed as to
their advantages, disadvantages,
metabolism and specificity. Of these,
CaNa2EDTA and dimercaprol (British
anti-lewisite, BAL) are becoming
outmoded and can be expected to be
replaced by
meso-2,3-dimercaptosuccinic acid
(DMSA, succimer) for treatment of lead
intoxication and by the sodium salt of
2,3-dimercapto-1-propanesulfonic acid
(DMPS, Dimaval) for treating lead,
mercury or arsenic intoxication.
Meso-2,3-DMSA and DMPS are
biotransformed differently in humans.
More than 90% of the DMSA excreted in
the urine is found in the form of a
mixed disulfide in which each of the
sulfur atoms of DMSA is in disulfide
linkage with an L-cysteine molecule.
After DMPS administration, however,
acyclic and cyclic disulfides of DMPS
are found in the urine. The Dimaval-mercury
challenge test holds great promise as
a diagnostic test for mercury
exposure, especially for low level
mercurialism. Urinary mercury after
Dimaval challenge may be a better
biomarker of low level mercurialism
than unchallenged urinary mercury
excretion.
- Language of Publication
- English
- Unique Identifier
- 95232791
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- MeSH Heading (Major)
- Chelating Agents|*TU; Metals|PK/*PO
- MeSH Heading
- Animal; Dimercaprol|ME/TU; Edetic
Acid|ME/TU; Human; Succimer|ME/TU;
Support, U.S. Gov't, P.H.S.;
Unithiol|ME/TU
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW,
TUTORIAL
- ISSN
- 0300-483X
- Country of Publication
- IRELAND
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24 from database: MEDLINE
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- Title
- A structural role for metal ions in
the "wild-type" conformation
of the tumor suppressor protein p53.
- Author
- Hainaut P; Milner J
- Address
- Department of Biology, University of
York, Heslington, United Kingdom.
- Source
- Cancer Res, 1993 Apr, 53:8, 1739-42
- Abstract
- In human tumors, many different
point mutations of the p53 gene knock
out suppressor function and induce the
p53 polypeptide to adopt an
immunologically distinct,
"mutant" conformation. Here
we show that exposure to the metal
chelator 1,10-phenanthroline induces
wild-type p53 to adopt the mutant
conformation and that this process is
reversible. Conversion to mutant
phenotype also occurs after exposure
to (a) an organic mercurial reagent
targeting cysteinyl residues and (b)
low concentrations of mercury or
cadmium. We propose that binding of
metal ions, most probably zinc, to
conserved cysteinyl residues
stabilizes the tertiary structure of
wild-type p53.
- Language of Publication
- English
- Unique Identifier
- 93223179
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- MeSH Heading (Major)
- Metals|*PD; Protein p53|*CH
- MeSH Heading
- Amino Acid Sequence; Animal;
Cysteine|CH; Edetic Acid|PD; Egtazic
Acid|PD; Human; Mice; Molecular
Sequence Data; Protein Conformation|DE;
Rabbits; Support, Non-U.S. Gov't;
Zinc|ME/PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-5472
- Country of Publication
- UNITED STATES
Record
25 from database: MEDLINE
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- Title
- A structural role for metal ions in
the "wild-type" conformation
of the tumor suppressor protein p53.
- Author
- Hainaut P; Milner J
- Address
- Department of Biology, University of
York, Heslington, United Kingdom.
- Source
- Cancer Res, 1993 Apr, 53:8, 1739-42
- Abstract
- In human tumors, many different
point mutations of the p53 gene knock
out suppressor function and induce the
p53 polypeptide to adopt an
immunologically distinct,
"mutant" conformation. Here
we show that exposure to the metal
chelator 1,10-phenanthroline induces
wild-type p53 to adopt the mutant
conformation and that this process is
reversible. Conversion to mutant
phenotype also occurs after exposure
to (a) an organic mercurial reagent
targeting cysteinyl residues and (b)
low concentrations of mercury or
cadmium. We propose that binding of
metal ions, most probably zinc, to
conserved cysteinyl residues
stabilizes the tertiary structure of
wild-type p53.
- Language of Publication
- English
- Unique Identifier
- 93223179
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- MeSH Heading (Major)
- Metals|*PD; Protein p53|*CH
- MeSH Heading
- Amino Acid Sequence; Animal;
Cysteine|CH; Edetic Acid|PD; Egtazic
Acid|PD; Human; Mice; Molecular
Sequence Data; Protein Conformation|DE;
Rabbits; Support, Non-U.S. Gov't;
Zinc|ME/PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-5472
- Country of Publication
- UNITED STATES
Record
26 from database: MEDLINE
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- Title
- Lead poisoning with pigmentation of
the oral mucosa. Review of the
literature and report of a case.
- Author
- ten Bruggenkate CM; Lopes Cardozo E;
Maaskant P; van der Waal I
- Address
-
- Source
- Oral Surg Oral Med Oral Pathol, 1975
May, 39:5, 747-53
- Abstract
- Some general aspects of the
pathogenesis and the clinical and oral
symptoms of chronic lead intoxication
are presented. Treatment procedures
are briefly discussed. The case of a
patient suffering from plumbism is
described. A typical Burtonian line
was present in the mouth. By electron
microprobe analysis, it was shown that
this line was mainly the result of
lead and, to a minor extent, the
result of mercury-, copper-, and
iron-bearing pigment in the
subepithelial tissue.
- Language of Publication
- English
- Unique Identifier
- 75195263
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- MeSH Heading (Major)
- Gingival Diseases|*CI; Lead
Poisoning|*CO/DI/DT; Pigmentation
Disorders|*CI
- MeSH Heading
- Adult; Biopsy; Calcium|AD/TU; Edetic
Acid|AD/TU; Human; Injections,
Intravenous; Male
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0030-4220
- Country of Publication
- UNITED STATES
Record
27 from database: MEDLINE
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- Title
- Human erythrocyte pyrimidine
nucleoside monophosphate kinase.
Partial purification and properties of
two allelic gene products.
- Author
- Teng YS; Chen SH; Scott CR
- Address
-
- Source
- J Biol Chem, 1976 Jul, 251:14,
4179-83
- Abstract
- Human pyrimidine nucleoside
monophosphate kinase is a polymorphic
enzyme having two allelic gene
products, UMPK 1 and UMPK 2, in
several populations. A procedure is
described for the partial purification
of this enzyme from human red blood
cells resulting in a 1500-fold
purification of the enzyme for UMPK 1
and 583-fold for UMPK 2. The purified
enzyme preparation catalyzed the
phosphorylation of UMP, CMP, and dCMP,
and used ATP as the preferred
phosphate donor. The heavy metals,
mercury, and copper, were found to be
strong inhibitors of pyrimidine
nucleoside monophosphate kinase
activity. EDTA was found to protect
the enzyme from inactivation by the
heavy metals, and 2-mercaptoethanol
stabilized the enzyme during
purification. UMPK 1 and UMPK 2 were
found to have similar kinetic
properties; however, UMPK 2 had a
slower electrophoretic mobility and
greater thermolability than UMPK 1.
- Language of Publication
- English
- Unique Identifier
- 76213295
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- MeSH Heading (Major)
- Alleles|*; Erythrocytes|*EN;
Isoenzymes|*BL; Phosphotransferases|*BL/IP;
Polymorphism (Genetics)|*
- MeSH Heading
- Cations, Divalent; Drug Stability;
Heat; Human; Kinetics;
Structure-Activity Relationship;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record
28 from database: MEDLINE
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- Title
- Recent advance in the therapy of
metal poisonings with chelating
agents.
- Author
- Aaseth J
- Address
-
- Source
- Hum Toxicol, 1983 Apr, 2:2, 257-72
- Abstract
- 1 A survey is given of the use of
chelating agents in the treatment of
metal poisonings. 1 The complexing
agents in established clinical use are
the polyaminopolycarboxylic acid EDTA
(ethylenediamine tetraacetate) and the
thiols BAL (2, 3-dimercaptopropanol)
and D-penicillamine. Desferrioxamine
is useful in the treatment of iron
overloading. 2 The theoretical
foundation of the metal-ligand
interaction and some general
principles of value in the search for
new metal antidotes are outlined. 3
Recent research has shown that 2,
3-dimercaptosuccinic acid (DMS) and 2,
3-dimercaptopropane-1-sulphonate (DMPS)
are effective in mercury and arsenic
poisonings. 4 DMS and DMPS are of
significantly lower toxicity than BAL,
and they can be administered orally or
intravenously. 5 A particularly low
toxicity of DMS is reported from
clinical and experimental studies, and
this agent may be useful against
several metal poisonings including
mercury, lead and gold.
- Language of Publication
- English
- Unique Identifier
- 83236439
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- MeSH Heading (Major)
- Chelating Agents|ME/TO/*TU;
Metals|*PO
- MeSH Heading
- Animal; Brain|ME; Chemistry; Drug
Stability; Human; Kinetics; Support,
Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE; REVIEW
- ISSN
- 0144-5952
- Country of Publication
- ENGLAND
Record
29 from database: MEDLINE
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- Title
- Prevention by chelating agents of
metal-induced developmental toxicity.
- Author
- Domingo JL
- Address
- Laboratory of Toxicology and
Biochemistry, School of Medicine,
Rovira i Virgili University, Reus,
Spain.
- Source
- Reprod Toxicol, 1995 Mar, 9:2,
105-13
- Abstract
- Chelating agents such as calcium
disodium ethylenediaminetetraacetate
(EDTA), 2,3-dimercaptopropanol (BAL),
or D-penicillamine (D-PA) have been
widely used for the past 4 decades as
antidotes for the treatment of acute
and chronic metal poisoning. In recent
years, meso-2,3-dimercaptosuccinic
acid (DMSA), sodium
2,3-dimercapto-1-propanesulfonate (DMPS)
and sodium
4,5-dihydroxybenzene-1,3-disulfonate (Tiron)
have also shown to be effective to
prevent against toxicity induced by a
number of heavy metals. The purpose of
the present article was to review the
protective activity of various
chelating agents against the
embryotoxic and teratogenic effects of
well-known developmental toxicants
(arsenic, cadmium, lead, mercury,
uranium, and vanadium). DMSA and DMPS
were found to be effective in
alleviating arsenate- and arsenite-induced
teratogenesis, whereas BAL afforded
only some protection against
arsenic-induced embryo/fetal toxicity.
Also, DMSA, DMPS, and Tiopronin were
effective in ameliorating methyl
mercury-induced developmental
toxicity. Although the embryotoxic and
teratogenic effects of vanadate were
significantly reduced by Tiron, no
significant amelioration of
uranium-induced embryotoxicity was
observed after treatment with this
chelator.
- Language of Publication
- English
- Unique Identifier
- 95315648
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- MeSH Heading (Major)
- Abnormalities, Drug-Induced|*PC;
Chelating Agents|*TU; Fetal
Development|*DE; Metals|*PO/TO
- MeSH Heading
- Animal; Female; Human; Pregnancy
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW,
TUTORIAL
- ISSN
- 0890-6238
- Country of Publication
- UNITED STATES
Record
30 from database: MEDLINE
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- Title
- Determination of intracellular
levels of 6-mercaptopurine metabolites
in erythrocytes utilizing capillary
electrophoresis with laser-induced
fluorescence detection.
- Author
- Rabel SR; Stobaugh JF; Trueworthy R
- Address
- Department of Pharmaceutical
Chemistry, University of Kansas,
Lawrence 66045.
- Source
- Anal Biochem, 1995 Jan, 224:1,
315-22
- Abstract
- Capillary electrophoresis proved to
be a useful technique for the analysis
of intracellular levels of
6-thioguanosine mono-, di-, and
triphosphate with analysis times of 20
min. Conditions required for baseline
separation of the thioguanine
nucleotides consisted of a 25 mM
KH2PO4 (pH 8.0) buffer and a
separation voltage of +28 kV.
Laser-induced fluorescence detection
(lambda ex = 325 nm, lambda em = 410
nm) of the thioguanine nucleotide
metabolites of 6-mercaptopurine (6-MP)
was possible following oxidation of
the thiol functionality. Tedious
extraction procedures involving
mercury cellulose resins or phenyl
mercury adduct formation, which had
been required previously for the
selective extraction of thiopurines
from erythrocytes, were unnecessary
due to the overall specificity of the
approach. However, the inclusion of 50
mM EDTA in the sample preparation was
required to inhibit the
anabolic/catabolic enzymatic activity,
which was responsible for the
degradation of the analytes. The
method demonstrated linearity from 5
to 1700 pmol/100 microliters red blood
cells for the three analytes (RSDs
< or = 8%). The feasibility of the
method was demonstrated for the
quantitation of 6-thioguanine
nucleotides in patients receiving
either oral or intravenous 6-MP
therapy.
- Language of Publication
- English
- Unique Identifier
- 95225456
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- MeSH Heading (Major)
- Erythrocytes|*CH; Guanine
Nucleotides|*BL; Guanosine Diphosphate|*AA/BL;
Guanosine Triphosphate|*AA/BL;
Thionucleotides|*BL;
6-Mercaptopurine|*ME
- MeSH Heading
- Electrophoresis; Fluorescence;
Human; Support, Non-U.S. Gov't;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-2697
- Country of Publication
- UNITED STATES
Record
31 from database: MEDLINE
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- Title
- Metal-binding characteristics of the
parotid salivary protein gustin.
- Author
- Shatzman AR; Henkin RI
- Address
-
- Source
- Biochim Biophys Acta, 1980 May,
623:1, 107-18
- Abstract
- Metal binding characteristics of the
parotid salivary protein gustin have
been examined. When purified to
apparent homogeneity, gustin contains
1 gatom Zn/mol which is tightly bound
(Kd at pH 7.2, 4.5--10(-11) M). This
tightly bound zinc can be removed with
strong chelators such as
diethyldithiocarbamic acid and
1,10-o-phenanthroline at pH 4.5, but
not with EDTA or Chelex 100. Removal
of the metal ion causes no appreciable
conformational change in the protein.
The apoprotein can be reconstituted by
dialysis against Zn2+-containing
buffer, a process favored by pH
greater than 6.0. Only cobalt is able
to bind to the apoprotein at this
strong binding site. Cobalt binding is
appreciably weaker than that of zinc (Kd
at pH 7.2, 1.3--10(-7) M) and is
maximal at pH 7.0. The weaker binding
of cobalt is also illustrated by the
loss of 37% of bound cobalt after 96 h
of dialysis at pH 7.2, conditions
under which the zinc content of gustin
does not change. A second gatom Zn/mol
may be loosely bound to gustin, but is
easily removed by dialysis against
metal ion-free buffer. Other metal
ions such as copper, nickel, iron or
manganese, but not cadmium or mercury,
bind loosely to this second zinc site
and are removed with ease. Zinc
appears to be involved in the
formation of the complex between
gustin and glycoproteins which are
present in human parotid saliva in
vivo.
- Language of Publication
- English
- Unique Identifier
- 80198516
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- MeSH Heading (Major)
- Parotid Gland|*ME; Salivary
Proteins|*ME; Zinc|*ME
- MeSH Heading
- Ageusia|PP; Apoproteins|ME;
Chromatography, Gel; Circular
Dichroism; Cobalt|ME; Glycoproteins|ME;
Human; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-3002
- Country of Publication
- NETHERLANDS
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