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bstr cts
Trace Elements and E lectrolytes, Vol. 27 - No.3 2010 150-180)
7th International symposium on trace
elements in human: new perspectives
October 13th - 15th 2009 Athens Greece
2010Dustr veragDr.KFeste
O r g a n i z e r s . P o l le t a n d S . E r m i d o u - P o l l e t A t h e n s G r e e c e
ISSN 0946-2104
The diagnosis of trace element
deficiency in iiumans in devel-
oping countries
M. Abdu lia and S. Shukla^
Trace Element Institute for
UNE SCO, Lyon Cedex, France and
^Department of Zo ology, Jiwaji
University, Gwalior, India
From a public health point of view,
it is essential to assure the general
population of all countries in the
world that the intake of all nutrients,
including trace elements, is adequate
in the average, normal daily diet. At
the same time, the ideal diets should
not contain more than the permitted
levels of toxic heavy mlais. Except
for occupational exposure, the main
pathway through which trace ele-
ments enter the human body is via the
food chain. Severe deficiency that re-
quires immediate medical care occurs
rarely in both developed and dev elop-
ing countries. On the other
hand
there
are clear indications that marginal de-
ficiencies of trace elements such as
iron, iodine, zinc and selenium are
fairly common in fast growing coun-
tries in Asia, Africa and South Amer-
ica. According to a recent World
Health Organization (WHO) report,
nearly 2 billion people in developing
countries are affected by iron and io-
dine deficiency alone . The prevalence
of zinc and selenium deficiency may
be of the same magnitude, but unrec-
ognized. Iron and iodine deficiency
can easily be detected by simple labo-
ratory tests and clinical signs. Such
tests are not available for the detec-
tion of other essential trace elements
such as zinc. Even when the dietary
intake is restricted due to starvation
and other socio-economic conditions,
normal body functions are maintained
for a certain period of time by hom eo-
static mechanisms and by making use
of the body reserves. Plasma/serum
levels of trace elements may not al-
ways indicate the body status. Spe-
cific enzyme assays that may reflect
the status of certain trace elements
may not be ideal for the poor popula-
tion of developing countries. Popula-
tion explosion, poverty, pollution and
illiteracy are the major problem s fac-
ing the developing world. Trace ele-
ment problems, as a major health is-
sue have a low priority in many poor
countries. An ideal approach to study
the long-term effect of poverty and
malnutrition that influence trace ele-
ment status is to follow vulnerable
groups such as children and fertile
women in the general population for
extended periods for possible signs
and symptoms of deficiency. Another
important vulnerable group is the el-
derly. By 2050, a third of the popula-
tion of affluent countries will be aged
over 60 years. Once these people re-
tire,
they can expect to live for another
20 years or even more. Growing rank
of senior citizens is a sign of progress
but they also bring a range of prob-
lems. Deficiency of a number of
micronutrients including trace ele-
ments in the elderly has been exten-
sively studied in Sweden by the cur-
rent authors. The intake of a number
of vitamins and trace elem ents are low
in the elderly in Sweden compared
with the current recommendations.
There are a number of social and eco-
nomic problems associated with low
intake levels. Another practical ap-
proach of detecting the existence of
trace element deficiencies rests in
therapeutic trials. Tbe response to
iron supplementation in iron-defi-
ciency anemia is a good illustration
showing the impact of supplemen-
tation. This presentation is aimed at
discussing practicable approaches in
detecting trace element deficiencies
at an early stage in vulnerable g roups
in the general population, especially
in the fast-developing countries in Af-
rica, Asia and South America.
Use
E iearning
technology and
cybernetic methodology for
modern edu cation in the area
of prevention of environmental
health hazard based on
sustainable development
R. Tadeusiewicz and
J.W. Dobrowolski
AGH University of Science and
Technology, Krakow, Poland
Prevention of environmental healtii
hazard as a top priority of sustainable
development requires common action
of experts and knowledge -based soci-
ety. Modem e-leaming is a necessary
tool for adequate life-long learning
about innovative m ethods of early de-
tection e.g. deficiency or excess of
some trace elements in the human en-
vironment, diet and body, as well as
for dissemination of innovative tech-
nologies for more effective primary
prevention. The principles of modem
distance education-including cyber-
netic methodology, modeling leam-
ing, relation between knowledge
sources, leaming environment and
knowledge representation language,
notion and structure are the basic sub-
ject oft is report.
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Abstracts
151
Ethical sustajnability in the
research environment
L.M. Gallicchio
Rutland Institute for Ethics,
Clemson U niversity, Clemson, SC,
USA
Human values are inextricably
part of the successes in scientific re-
search, yet they are not often appreci-
ated enough and focused on. These
values constitute the ethos of the re-
search enterprise within which you
operate your research program. Ethi-
cal sustainability, or EtS, is a way to
enhance y our program to assure that it
endures o ver time. EtS also helps you
impact the next generation of scien-
tific leaders by involving your team
members in defming, maintaining
and teaching EtS to others who join,
or work with, your research p rogram.
F.O.O.D. is a tool to assist in achiev-
ing EtS. Fidelity, Openness, Owner-
ship and Diligence are key values in a
healthy ethos. EtS and F.O.O.D. are
essential to organizational health the
same way trace elements are essential
to human health. Without them, your
research program may not die imme-
diately, but it is more prone to ill-
ness
and a shorter, less optimal life.
Taking the initiative to focus on EtS in
your program will contribute to the
continued longevity of the larger sci-
entific research e nterprise thathasun -
locked innumerable secrets to our ex-
istence.
Metaliomics: a fundamentai
approach in mechanisticaiiy
based metai toxicoiogy
research.
E. Sabbioni
Ageing Research Center (CeSI),
G d'An nunz io University
Foundation, Chietl, Italy
Scientific research on biometals
has generally been carried out sepa-
rately
in
many fields such as biochem -
istry, nutritional science., medicine,
pharmacy, toxicology, agriculture and
environmental science, with me tals
as common factor. However, a better
promotion of the biometals science as
interdisciplinary field to integrate the
metal-related scientific areas requires
a more general approach, in this con-
proposed as a new frontier in the in-
vestigation of trace elements in biol-
ogy [1]. Metal ions are utilized by
fundamental cellular processes. In
this context, transcription, translation
and incorporation of the adequate
metal to function are regulated by the
organism, being synthesis and meta-
bolic function of genes (DNA, R NA)
and proteins not possible without the
aid of metal ions and metalloenzy-
mes.
Thus , the biochemistry ofacell
needs to be characterized not only in
its peculiar genetic (genome) and p ro-
tein (proteome) context but also by
the distribution ofall chemical forms
of the metals/metalloids (metallome)
at different levels of complexity
(whole body, organ., cell and individ-
ual biomoIecule).Thus, the purpose
of metaliomics (study of metals and
metal species and tbeir interactions,
transformations and functions in bio-
logical systems) is to extend and
broaden the bioinorganic chemistry
as a system atic scientific field and
an interdisciplinary science comple-
mentary and in symbiosis with other
om ics such as genom ics, proteo-
mics and metabolomics. From the ex-
perimental point of view, metaliomics
involves the determination ofametal
in whole cells, its distribution over
different cell compartments, its asso-
ciation with particular pools (macro-
molecules, small molecules, free
ions) and the binding to a specific
class of biomo lecules. These versatile
measurements require the availability
of advanced and sophisticated analyt-
ical tools to reach an adequate speci-
ficity of the analytical response with
regard to the identification of a partic-
ular metal species, and enough sensi-
tivity to allow the ultratrace detection
and quantitation of covalently bound
metals in microsamples of proteins
and metal-protein complexes. As
such, metaliom ics, referred to cellular
biochemistry, can be considered a
subset of speciation analysis (distri-
bution of an element among defined
chemical species in a system). The
objectives ofthiswork are to present
examples of an experimental in vitro
mechanistically-based dynamic me-
taliomics research. In particular, the
aims are (i) to highlight the role of nu-
clear and radio analytical techniques
(neutron activation analysis and use
of radiotracers with high specific ra-
dioactivity) in combination with ad-
vanced spectochemical (GF-AAS,
HPLC-ICPMS and EPR techniques)
and bioanalytical techniques (gel fil-
tration, differential centrifugation, ion
exchange chromatography, ultra-
filtration) that allow overcoming of
great analytical difficulties related to
the study of metallomes in micro-
samples of cell culture media, intact
cells,
subcellularfr ctionsand isolated
biomolecules (ii) to show typical re-
sults concerning: (a) cytotoxicity and
carcinogenic potential induced in
mouse fibroblasts Balb/3T3 cell line
by different chemical species Cd, Cr,
Pt and V (b) neurotoxic effects in-
duced by inorganic A s in rat brain re-
aggregates and their individual cell
types as well as by Mn species in rat
pheocromocytoma PC12 cell line in
relation to their uptake, intracellular
distribution, and binding to biomole-
cules. The examples reported show
tbe complexity of metaliomics re-
search and its strong multidisciplinary
characteristic.
References
i ] araguchi
H
Metaliomics as inlegrated
biomdical science, J Anal At Spectrom.
2004, 19:5-14.
The forensic pharmacoiogy of
inorganic poisons used in the
19th and 20th centuries
N.J.
Birch'-^
'Academic Consultancy Services
Ltd, Codsall, Staffordshire and
-University of Wolverhampton,
England
Inorganic substances have been
used as poisons since early in man's
history. Poisons have always been a
means of injuring or killing an op po-
nent without apparent contact or con-
nection between the assailant and his
(or very often her) victim. Physical
strength is not required and the attack
can be planned according to opportu-
nity, which may be remote in time or
place. Poisoningis ,by definition, pre-
meditated. The pattern of criminal
poisoning has changed over the last
two centuries largely as a conse-
quence of the developments in analyt-
ical techniques, systematic forensic
investigation, knowledge and recog-
nition of natural and unnatural causes
of death and increased regulation of
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7th International sympo sium on trace elemen ts in hum an: new perspectives October 13th - 15th 2009 Athe ns Greece
152
This largely mirrors the progress in
conventional medicine itself where
increasing regulation o fthe practitio-
ners and their materials and tech-
niques has led to an im measurable re-
duction in adverse effects and deaths
caused by the treatment rather than
the disease itself At the commence-
ment of th e 19th Century poisoning
was commonplace using cheap, eas-
ily available m aterials such as arsenic,
sold widely for the killing of vermin,
and detection was unlikely because
systematic investigation of disease
and ofthe causes of death had hardly
begun. decedent was as likely to be
wrongly diagnosed as poisoned.,
when dying of natural causes, as the
converse. The chances of escaping
justice were significant since many
deaths were ascribed to common in-
fectious diseases which were then un-
treatable. However, those punished
were equally likely to be innocent and
wrong ly accused of what w as, in fact,
a natural death. Despite the major
changes in the detection and preven-
tion of poisonings there are still in
present times, very occasionally, no-
torious cases which highlight specific
weaknesses in our present justice and
medical systems, I shall discuss some
interesting cases past and present to
exemplify how regulatory and in-
vestigational change has tried to keep
up with novel poisons and how
poisoners have adapted their methods
accordingly.
Trace elements and alternative
medicine - an awareness
survey
S.N. Rehman
The U niversity o f Texas,
Brownsville, TX, USA
Long before the creation of the
modem medical universities in the
West, the ancient civilizations in
China, India, Southern Europe, Af-
rica, and the Central Americas have
been preventing and treating disease
with natural foods, herbs, roots,
shrubs, and methods other than sur-
gery. This paper compares some of
these ancient practices (now known
as alternative medicine) with our
standard Western medical prac-
tices.
Not only has Western m edicine
ignored the ancient medical practices
ahemative medicine thus giving it
the second class citizen status. Pri-
marily, this paper attempts to accom-
plish three goals: one, it describes the
importance of trace elements in hu-
man health; two, it offers a short de-
scription of alternative medicine in
general and herbal medicine in partic-
ular; and
three,
itpresents the findings
of a pilot study about awareness of
al-
ternative medicine in the United
States of America. Itisthe hope of this
writer that a research agenda would
emerge for developing promotional
campaigns to increase awareness of
trace elements and bene fits, risks, and
availability of herbal alternatives.
Magnesium metabolism and
cardiovascular diseases
K. Kisters', D. Liebscher' and
M. Hausberg'
'Medizinische K linik I, St. Anna
Hospital, Heme, -SHO
Mineralimbalanzen, Berlin, and
^Nphrologie, Stadt. Kliniken,
Karlsruhe, Germany
An overview of magnesium me-
tabolism and the role of magnesium in
development of primary hypertension
is given. Magnesium is an essential
electrolyte in living organisms, which
has to be substituted in a sufficient
amount. The clinical importance of
magnesium overload or magnesium
intoxication is seldom. However, mag-
nesium deficiency is of special impor-
tance in humans, despite normal mag-
nesium supplementation. The primary
effect of a magnesium deficiency re-
sults in a reduction of several enzyme
activities in metabolism and energy
production. The reduced energy pro-
duction can result in a disturbed mem -
brane function, calcium magnesium
antagonism and cell dysfunction.
Thereby consequences may result in
an organ dysfunction and an altered
answer to extemal and internal stress.
The reduced energy status is respon si-
ble for the recovery of unhealthy indi-
viduals, e. g. cardiac arrhythmias, pri-
mary hypertension, pre-eclampsia,
cramps, allergic reactions etc. The
special importance of an oral or intra-
venous supplementation of magne-
sium has often been discribed in a va-
riety of diseases. In an epidemiologic
investigation of 38 patients with m ag-
Mineralimbalancen group in Berlin a
significantly increased risk for stroke
(16 %) was observed. In addition
myocardial infarction (5 %) was less.
A substitution with magnesium im-
proved clinical symptmes in those
magnesium deficient
patients.
In a re-
cent study of our group the benefit of
sartans and the new renin inhibitor
aliskiren was described while show-
ing no negative effect on magnesium
metabolism in hypertensive p atients.
Lithium - still interesting after
all these years
V.S. Gallicchio
Institute for Environmental
Toxicology, D epartment of
Biological Sciences, Clemson
University, Pendleton, S C, USA
Lithium (Li) salts have been
widely used in psychiatry as mood
stabilizing agents for 60 years. Li is
found in variable amounts in foods,
especially grains, vegetables, and in
some areas, the drinking water pro-
vides a significant source of the ele-
ment. Therefore, dietary intake in hu-
mans depends on location, type of
foods consumed, and fiuid intake.
Traces of Li have been detected in hu-
man organs and tissues, leading spec-
ulation that the element was responsi-
ble for specific functions in the hu-
man body. It was not until the 20th
century with studies performed in the
197O's and I990's, primarily in rats
and goats, that maintained on Li-defi-
cient those diets demonstrated higher
mortality, altered reproductive and
behavioral abnormalities. Such defi-
ciencies have not been detected in hu-
mans;
however, studies peribm ied on
populations living in areas with low
Li levels in water supplies have been
associated with higher rates of sui-
cides,
homicides, and the arrest rate
for drug abuse and other crimes. Li
appears to play a significant role in
early fetal development as evidenced
by high Li levels during the early ges-
tational period. Biochemically, the
mechanism of Li action involves
multifactor and interconnected path-
ways with enzymes, honnones, vita-
mins,
and growth and transforming
factors. This body of evidence now
appears sufficient to label Li as an es-
sential element with the recom-
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Abstracts
153
1,000 mg/day. Of extreme importance
for the future is the growing body of
evidence indicating L i can be used ef-
fective for the treatment of acute brain
injuries, e.g., ischemia and chronic
ncurodegenerative diseases such as
Alzheimer's disease, Parkinson's dis-
ease, Tauopathies, and Huntington's
disease. This conclusion is based
upon evidence showing Li is impor-
tant in neurogenesis as well as pro-
tecting neurons from neurotoxicity.
Li influences stem cells, both neu-
ronal and marrow d erived, thus addi-
tional therapeutic implications for
this element in clinical medicine may
be to treat disorders associated with
the faulty production of blood and
nerve cells or as a tool to enhance
blood stem cell mobilization for
transplantation.
Selenium and human cancer
current status and future
perspectives
W. Wasowicz
The Nofer Institute of Occupational
Medicine, D epartment of Toxicol-
ogy and Carcinogenesis, Lodz,
Poland
There is a growing interest in the
biological role of selenium (Se) with
respect to both protection of human
health and prevention of diseases.
Food is a major source of Se and re-
searchers bave a vested interest in Se
status in various p opulations not on ly
because of its deficiency or toxicity
symptom s, but also in view of its po-
tential beneficial effect contributing,
among others, to cancer prevention.
Epidemiological studies, including
retrospective., prosp ective and also in-
tervention, sbow that a low Se level
may increase the risk of certain can-
cers.
However, it should be noted that
there is also a relatively large number
of studies, in which no effect of S e on
cancer has been observed . In the light
of recent studies, it may be assumed
that not only low bu t also high Se sta-
tus may be associated with an ele-
vated cancer risk. Thus, evidence for
thechemopreventiveroleof
Se,
based
on the current epidemiological data,
seems to be conflicting. In order to
find an accurate explanation of this
divergence, researchers have begun
to study the role of
e
in the develop -
As selenium is present in the human
organism mainly in the selenopro-
teins (in the form of the seleno-
cysteine - 21st amino acid encoded
by D NA ), the studies on genetic poly-
morphism of these proteins in terms
of cancer risk assessment are particu-
larly attractive to be condu cted. It has
been found that certain genetic vari-
ants of the selenoproteins' encoding
genes (e.g., GP x i, GP x 4, SeP) may
modify cancer risk. However, the re-
sults of these studies also remain con-
fiicting, and no general conclusions
can be reached on the diet related
carcinogenesis and antioxidant status
(including intervention study) on can-
cer risk. To sum up, the majority of
studies on the relationship between
selenium and cancer, focus either on
the association between Se status and
cancer risk or on the association be-
tween genetic polymorphism of
selenoproteins' genes and cancer risk.
Combining both types of data (con-
cerning both dietary and genetic fac-
tors) would be more informative and
valuable in the assessment of cancer
risk development, which was indi-
cated in recent studies. On the basis o f
recent findings, I would like to con-
clude that studies on the relationship
between diet and cancer should focus
on the interactions between dietary
and genetic factors rather than on the
study of each factor separately. Data
from such studies would be especially
interesting in view ofthe intervention
trial planning. Prior to supplemen-
tation, DNA genotyping should be
first performed in order to select indi-
viduals with certain genetic back-
ground. This wo uld allow to avoid (at
least to some exten t) the study bias as-
sociated with genetic variation and to
identify individuals who, due to the
specific gene and nutrient interaction,
are more orlesssu sceptibletocancer.
Acknowledgment
This study was supported by
ECNIS Network of Excellence (Con-
tract No. 513943/UE).
Trace elements in health and
diseases: cancer/inflammation
T. Westermarck', T. Tallberg-,
V.M. Ab dulla\ M. Crohns' and
F.Atroshi
'Rinnekoti Research Centre, Espoo,
'The Helsinki Institute for
Bio-Immunotherapy, Helsinki,
Finland, 'UNESCO, Lyon, France,
and -^Pharmacology and Toxicology
(ELTDK), University of Helsinki,
Helsinki, Finland
Inflammation and cancer.
New
cancer incidence remains high w orld-
wide. Onco logists are paying more at-
tention to the role of inflammation in
chronic diseases. The possibility that
mutation and inflammation are mutu-
ally reinforcing processes that, left
unchecked, can transform normal
cells into potentially deadly tumors
through macrophages and other in-
flammatory cells with oxygen free
radicals. Inflammation may develop
into a systemic response character-
ized by changes that include fluctua-
tions in the levels of plasma proteins,
trace metal, hormones, and electro-
lytes.
A number of pathologic, envi-
ronmental, psychological, and nutri-
tional factors have been associated
with chemotherapy-related fatigue. In
people with cancer, three major
mechanisms may be involved: alter-
ation in the body's ability to process
nutrients efficiently, increase in the
body's energy requirements, and de-
crease in intake of energy sources.
Tbe trace elements play their most im-
portant role as cofactors in enzymes.
It can play a role in tumor su ppression
by stimulating an antitumor immune
response, but more often it appears to
stimulate tumor development.
Can
cer patients should avoid ingesting
certain natural dietary compo
nents.
Certain amino acids and essen-
tial metal ions may act as growth fac-
tors for primitive malignant cells.
Cancer patients should therefore
avoid ingesting everything bought
from the health food shop since that
could introduce specific cancer
growth factors. The metabolic defi-
ciency to be corrected in cancer is not
caused by starvation but actually d ue
to the lack of a few very specific di-
etary com ponents forming the regula-
tory complexes in the patients' serum
(Figure). Recommended duration
for dietary measures and the use of
7/25/2019 Elements in Human New Perspectives
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7th Internationai sympo sium on trace elements in human: new perspectives, October 13th - 15th 2009 , Athen s, Greece
154
Figure 1. Westerma rck et ai.)
bolic deficiency causing cancer
seems to exacerbate as a function of
time,consequently requiring slightly
increased dosages ofthe dietary sup-
plementation, for every decade in
therapy. This may then sustain the pa-
t ients '
health. Efforts to compensate
the etiologic metabolic deficiency in
cancer patients' should preferably
start before surgery, since it can pre-
vent spread and implantation mtasta-
ses.
It also seems to shorten the con-
valescence. The administration of a
small surplus of certain essential nat-
ural food components can also com-
pensate genetic weaknesses, as has
been sho wn in cases suffering from
e.g. HN PCC , or BRCA. The possibil-
ity to compensate an inherited w eak-
ness by biological means should ac-
tively be taken into accoun t, and acted
on. Active biological compensation
trials, instead of attempts to correct
inherited genetic ailments, deserve
more clinical studies. If gene thera-
pies ever become successful in adults
it would be too expensive of a treat-
ment modality for world populations,
presently suffering from ever in-
creasing cancer incidences [I]. Ex
planation for the complete regres
sion of tumors following bio
therapy. No consistent tumor-spe-
cific immunological reaction could be
found which could explain the CR ob-
served. Inconclusive evidence was
obtained from ex tensive immunologi-
cal screening for circulating and/or
cell-bound immunity, cytolytic anti-
8v n chmlcBl groups of amIno add
we d as dietary supplment:
Ala,
It,Lflu.Val Arg,His, Lye I
TTir, Si r I Glu, Atp Met, Cye Try. Phe I Pro
Practicable Radioisotopes
N.V. Phlllps-Duphar, compiled by J .JJ ^m en
V VI VH VUI
1
2
3
4
5
1
H
U
Ha
K
Cu
Rb
Ag
II
B
Sr
6 C
Tl V Cr Mn Fe,Co
Sn Mo
W
inhibitor factor, natural killer cells,
killer cell indexes, tumor cell lysis,
apoptosis, phospholipase or comple-
ment activation, enhanced interferon
production or chalone reactions etc.
During the healing reaction obtained,
it was found that organ-specific mito-
chondria were activated [1]. Certain
test-animals have not been able to
sustain health if fed only specific gen e
manipulated food-items possibly
since mitochondria do not recognize
them as belonging to their phylogen-
etic repertoire. Radiation as a means
to preserve food may also be deleteri-
ous since it kills the mitochondria in
our diet - the grass-roots on which we
thrive?Alow temperature inactivates
also regulatory mitochondria. In for-
mer times, blood donors were trans-
ferring warm blood to the recipient,
and surgeons observed then that the
cancer growth stopped forawhile. As
we are wann-blooded the mito-
chondrial function also seems to re-
quire a body temperature to act prop-
erly?
References
[1 ] allbergT h WestermarckT AtroshiF A
possibility to prevent recurrent mela-
noma.renal. breast and prostate cancer J.
Trends in Biomedicine. 2008; 3 :44-54.
Complementary and alternative
medicine CAM) used in termi-
nal ill patients
J. Bntzel'^ H. BntzeF, O. Micke^-
^K. Kisters^^F. Bruns-^,
M. GIa t z e l ' ' \ R . Mc ke ' ,
K.G Schnekaes** and U. Schfer'-^
'Department of Otolaryngology,
Head Neck Surgery,
^Department of Palliative Medicine,
Sdharz-Krankenhaus Nordhausen
gGmbH , Nordhausen, 'Department
of Radiotherapy, Franziskus-Hospi-
tal,
Bielefeld, Department of Inter-
nal Medicine I, St. Ann a-Hospital,
Hem e, ^Department of R adiother-
apy, Special Oncology, Medical
School Hannover, Hannover,
Department of Radiotherapy,
Zentralklinikum Suhl gGmbH, Suhl,
^Department of Radiotherapy,
Klinikum Lemgo-Lippe, Lemgo,
and AKTE - The German Working
Group Trace Elements and
Electrolytes in Oncology
Objective: The use of comp lemen-
tary and alternative methods is com-
mon in oncology, but nothing is known
about the role of CAM in the last days
of a patient's life. Material and Meth-
od x Between1 2007and 10-2008 the
palliative care team treated 85 pa-
tients (50 male, 35 female, median
age 62 years) on out-door basis. All
families were asked to complete a
structured questionnaire regarding
the use of CAM during the last period
of a patient's life. Patients suffered
from cancer in 83/85 patients (98%),
two patients had neurologic disor-
ders.
Resu lts: Only 2 0 families 31%)
have not used any CAM. Spiritual
support (praying, hospice services)
was for asked by 60/85 families
71
% ).
25/85 families (29%) reported
drug
use.
Favorite methods w ere vita-
mins (n = 11, 13%), trace elements
(n - 9, 11% ), and mistletoe (n - 8,
9%). 30 patients (35%) were treated
by physiotherapy (28 oncology pa-
tients,
2 neurology patients). Logo-
pedy and ergotherapy w ere used in 10
patients (12%). 12 families (14%) re-
ported aroma-therapy in patient's care.
Main information source was the GP
(house physician) (45/85, 53%)), fol-
lowed by the palliative care team
(30/85,
35% ) and pharmacies (27/85,
32%).
Internet, journals or self-ser-
vice information were used by only
25/85 families (29%). The effectivity
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155
mated between I and 5 (very good -
worthy) by the patients or their fami-
lies.
The following ranking w as regis-
tered: spiritual support 2.4; physical
therapy 2.7, Iogopedy/ergotherapy
3.1, drugs 3.3. 65/85 families (76%)
were satisfied with the information
received from the health care practi-
tioners. Conclusion: Complementary
methods are often practiced during
the last days of a patient. Fam ilies and
friends are looking for valid informa-
tion and need help by the profession-
als.
The different methods have to be
evaluated regarding effectivity as
well as acceptance by the patients.
Trace elements selenium and
zinc as tumour markers in pa
tients witii advanced head and
neck cancer
J .B nt ze l ' ^U. Knol le ' ,
A. Garayev', R.
U. Schfer^ \K. ^
K.G Schnekaes^ R. Hunger**,
F.Br un s' ' ' , M. GlatzeH and
O. Micke ' '
'Department of Otolaryngology,
Head Neck Surgery, Sdharz-
Krankenhaus Nordhausen gGmbH,
Nordhausen, -Department of Radio-
therapy, Klinikum Lippe-Lemgo,
Lemgo, ^Department of Intemal
Medicine I, St Anna H ospital,
Hem e, ^AKTE - The German
Working Group Trace Elements
and Electrolytes in Oncology ,
^Department of Radiotherapy,
Special Oncology, Medical School
Hannover, Hannover, ''Department
of Radiotherapy, Zentralklinikum
Suhl gGm bH, S uhl, and ^Depart-
ment of Radiotherapy, Franziskus-
Hospital, Bielefeld, G ermany
During the last years we have col-
lected data showing a relation be-
tween the status of the disease and the
serum concentrations of different
trace elements. Are they able to moni-
tor the disease as tumor m arkers? In a
first study 100 untreated head/neck
cancer patients were characterized by
decreased levels of selenium , zinc and
iron. Only copper was increased.
During the radiotherapy no changes
of serum concentrations were seen. A
further analysis had shown the differ-
ences between resectable and non-
resectable tum ors. The larger the pri-
creased the concentration of selenium
in the serum of our patients was.
These fmdings are supported by new
data of NMR-tumor volumetry and
trace elements concentrations in 21
patients. The relation between se-
rum-selenium and tumor volume is
stronger than between classical tumor
markers (SCC; CEA, CYFRA 21-1)
and the tumor v olume. A last investi-
gation has suggested that a destroyed
homeostasis of trace elements is a
sign of pre-terminal ill patient. When
the destroyed homeostasis is ob-
served, the patient has a window of
4 - 6 weeks of remaining life time.
Conclusions: Trace element status of-
fers a lot of information about the
course of the disease and the individ-
ual. But environmental factors have
more impact on this trace elemen t sta-
tus than on other classical tumor
markers.
Rare Earth m etal compiexes
with 4 hydroxycoumarins are
more active againstHIV 1in
cell culture
P.
Genova-Kalou', S. Raleva^,
A. Hinkov\ 1. ManoloV,
S. Gurkova^ and R. Argirova^
'National Centre of Infectious and
Parasitic Diseases, D epartment of
Virology, Laboratory of Cell cul-
tures,
-National Centre of Infectious
and Parasitic Diseases, Department
of Virology, Laboratory of
Retroviruses, ^Sofia University
St. Kliment Ohridski , Faculty of
Biology, Laboratory of Virology
and, 'Sofia Medical University,
Faculty of Pharmacy, Department of
Chemistry, Sofia, Bulgaria
Introduction: Coumarine deriva-
tives have a broad spectrum of biolog-
ical activities, including anti-HIV ef-
fect (anti-integrase-lN) recently re-
ported. Their potential to form com-
plexes, esp. with some lanthanides
showed antitumor and other biologi-
cal activities. Seventeen bis-(4-hy-
droxycoumarin) (4-hc) derivatives
were synthesized in Bulgaria and later
used as ligands. First anti-HIV assays
were performed in cell culture in
non-toxic concentrations showing
that three out of seventeen 4-hc had
anti-HIV activity (IM-7, IM-8 and
IM-1 0)(IM -7, IM-8 and lM-10). This
with - Ce(III), lanthanum - La(III)
and neodymium - Nd(III) and to eval-
uate the cytotoxicity ofth active de-
rivatives and their complexes on
MT-4 cells and to study for anti-HIV
activity in cell cultures. Materials and
methods: Cell toxicity (CC50) and
maximal non-toxic concentrations
(MNCs) were performed in MT-4
cells on 72h by MTT-test. The MNC
and CC50 for each compound were
calculated from dose-response curves.
Reverse transcriptase (RT) activity
and RT processing (PCR) were stud-
iedtosee the impactonearly stages of
HIV-1 replication. Results: The less
cytotoxic compound, according to
^4NC,
was IM-8, whose MNC values
were higher than those of IM-7 and
IM-10. The less cytotoxic co mpoun d,
according to CC50 values, was IM-8
for all derivatives. Six out of seven-
teen complexes showed higher HIV-1
inhibition compared to that of the lig-
ands.
Ce(lll) complexes were more
prone to inhibit the HIV-activity in
cell culture than La(I[I) and Nd(III)
complexes. Conclusions: Rare-earth
metal complexes are readily formed
with 4-hc. Complexes with Ce(III)
show higher anti-HIV activity than
those with La(llf) and Nd(III). Fur-
ther studies are in progress to detect
the target and mechanism of action.
Trace element disturbances in
platelets of juvenile and infan
tiie NCL patients
T. Westermarck', E. Johansson' and
F.Atroshi^
'Rinnekoti Research Center, Espoo,
and -Dep. Pharmacology and
Toxicology, ELTDK, U niversity o f
Helsinki, Finland
Depletion of ATP/PC stores is an
essential trigger for all subsequent
cytotoxic events in focal cerebral
ischemia formed e.g. during seizures.
Maintenance of ionic gradients re-
quires significant energy; with the re-
duction in ATP, there is a gradual in-
crease in intracellular Na+ and Ca-H-,
resulting in cell depolarization, and
release of glutamate, which second-
arily stimulates the AMPA and
NMMDA receptors, opening ionic
channels allowing a rapid influx of
Ca++ into the
cell.
This increase stim-
ulates the initiation of proteolysis,
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156
if continued, produces cell death and
neurological injury associated with
cerebral ischemia, and probably pre-
aging degenerative changes seen in
Batten's disease (NCL). Disorders in
which free radicals and antioxidants
are implicated include Batten s dis-
ease.
Recent evidence has shown the
importance of diet in delaying the ag-
ing process and in protecting against
several degenerative and chronic dis-
eases. Recent cortieosteroid trial
(Prednison 40 mgx 1 ofNCL patients
has increased the need of checking the
trace element levels of the treated
NCL patients, when corticosteroids
may result in increased need of
supplementation of calcium, magne-
sium and zinc; and speed up the cog-
nitive deterioration. We have exam-
ined trace element levels in platelets
of infantile and juvenile NCL pa-
tients.
Metal ions from platelets were
analyzed by micro-PIXE; metal ions
from erythrocytes by ICP-MS. The
concentration of Ca was significantly
increased, and Zn significantly de-
creased in the throbomcytes in juve-
nile,
but not in infantile NC Lpatien ts.
Therapeutic metabolic and
kinetic aspects of ianthanum
carbonate: a new phosphate
binder in chronic renal failure
patients
P C . D'Haese, A.J. Bervoets,
M.E. De Broe and GJ. Behets
Laboratory of Pathophysiology,
Faculties of Medicine and Bio-
medical and Pharmaceutical and
Veterinary Sciences, University of
Antwerp, Antwerp, Belgium
In the search for safe alternatives
for calcium- and aluminum-based
agents lanthanum carbonate has re-
cently been introduced as a new phos-
phate binder in chronic renal failure
patients. Clinical studies showed the
com pou nd to be highly efficient for
phosph ate binding. In view ofthe past
experience with aluminum however,
some concerns have been raised as to
whether lanthanum treatment might
go along with some toxic side effects,
particularly at the level of the bone.
Clinical as well as experimental stud-
ies indicated that although there is
some minor deposition ofthe element
in bone, long-term treatment is not ac-
fect or the development of a low bone
turnover disease. Moreover, in con-
trast to aluminum, ultrastructural lo-
calization studies revealed lanthanum
deposition not to be associated with
any type of renal bone disea se. As lan-
thanum is mainly excreted by tbe
liver, patients with chronic renal fail-
ure are not at an increased risk for ac-
cumulation of the element as com-
pared to subjects with nonnal renal
function. After oral treatment how-
ever, we and others noticed 2 - 3 fold
higher lanthanum levels in the livers
of rats with chron ic renal failure com -
pared to rats with normal renal func-
tion. Studies dealing with the kinetics
and tissue distribution, absorption,
and subcellular localization of lantha-
num in the liver using transmission
electron microscopy, electron energy
loss spectrometry, and X-ray fiuores-
cence showed that in the liver lantha-
num w as located in lysosomes and in
the biliary canal, but not in any other
cellular organelles. This suggests that
lanthanum is transported and elimi-
nated by the liver via a transcellular,
endosomal-lysosomal-biliary canicu-
lar transport route. Feeding rats with
chronic renal failure orally with Ian-
thanum resulted in a doubling ofthe
liver levels compa red to rats with nor-
mal renal fiinction, but the serum lev-
els were similar in both animal
groups. These levels plateaued after 6
weeks ataconcentration below3jig/g
in both groups. When lanthanum w as
administered intravenously, thereby
bypassing the gastrointestinal tract-
portal vein pathway, no difference in
liver levels was found between rats
with and without renal failure. This
suggests that there is an increased
gastrointestinal permeability or ab-
sorption of oral lanthanum in uremia.
Lanthanum levels in the brain and
heart fluctuated near its detection
limit with long-term treatment (20
weeks) having no effect on organ
weight, liver enzyme activities, or
liver
histology.
We suggest that the ki-
netics of lanthanum in the liver is
consistent with a transcellular trans-
port pathway, with higher levels in the
liver of uremic rats due to higher
intestinal absorption.
Se Pb and Cd ieveis in renal
failure patients in China
B.Chen' L.V.Lamberts ' ,
G.J. Behets', T.-t. Zhao^ L. Gang-,
X.-h. Hou ' G- j. Guan^ and
P C .
D'Haese '
'Laboratory of Pathophysiology,
Faculties of M edicine and Bio-
medical and Pharmaceutical and
Veterinary Sciences, University of
Antwerp, Antwerp, Belgium,
-Department of Nephrology,
The Second Affiliated Hospital,
Shandong University, and
'Department of Respiratory
Medicine, Shandong Provincial
Chest Hospital Jinan, P. R. China
Whole blood and serum samples
of Chin ese stable chron ic renal failure
(CRF) patients (n ^81),hemo dialysis
patients (n = 135), post-transplant pa-
tients (n = 60) and subjects with nor-
mal renal function (NRF) (n = 42)
were collected, as well as water and
dialysate sam ples from5dialysis cen-
ters.
The concentration of selenium
(Se),
lead (Pb) and cadmium (Cd ) was
measured by atomic absorption spec-
trometry. The mean serum Se levis in
patients with different degrees of re-
nal failure were significantly lower
than those of subjects with NRF (p 30 kg/m- (n =
141) and diabetic women (n = 93,
BMI 18 - 24 (19 ), 25 - 30 (38 )
and > 30 (43 )). Multielement hair
analysis was conducted by ICP-AES,
ICP-MS methods. Obese women
were found to have elevated hair Hg,
K, and decreased Ca, Mg, Zn and io-
dine as compared to control subjects.
In the diabetic group similar devia-
tions were found: elevated hair
K
Hg,
Na and decreased Ca, Mg, Zn, Co
compared to control. The only differ-
ence between obese and diabetic
women was Na level, which was sig-
nificantly higher in Type 2 diabetic
patients as compared to the control
and obese ones. It is interesting to
note that hair iodine was low er only in
obese patients, but not in diabetics.
Thus,
in Type 2 diabetes there are
more numerous and serious changes
inmineral metabolism as compared to
obesity impairing anabolic processes
and w ater-salt balance regu lation; Zn
imbalance can play an important role
in pathogenesis of both obesity and
Type 2 diabetes. The obtained data
also suggests that muhielement hair
analysis is tbe useful diagnostic tool
in prevention and treatment of exces-
sive weight gain, obesity and meta-
bolic syndrome in women.
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158
Trace element imbalances role
in pathogenesis of fetal
alcohol syndrome
A.V. Skalnya
ANO Centre for Biotic Medicine,
Moscow, Russia
Alcoholism and related hereditary
consequ ences, including fetal alcohol
syndrome, are one of the dramatic
problems in Russian public health.
The severity of alcohol related de-
rangements are also due to malnutri-
tion, micronutrient deficiencies and
ecological pollution. In a series of ex-
perimental investigations, the role of
Cu/Zn imbalance in the whole body
and numerous deficiencies of macro
and trace elements with simultaneous
Pb,
Cd accumulation in central nervous
system were demonstrated (Skalny,
1985 - 2008). We have found the co r-
relation between trace element imbal-
ances and behavioral deviations in ex-
perimental animals, and protective ef-
fects of zinc in offspring of alcoho-
lized rats due to normalization of
trace element ratios in brain struc-
tures.
Preliminary data from clinical
nutritional studies, which are ongoing
as a part of the international Collabo-
rative Initiative on Fetal Alcohol
Spectrum Disorders (CIFASD, Prof
C.L. Keen et al.) suggests a potential
role of zinc and choline in develop-
ment/prevention of fetal alcohol spec-
trum disorders.
Acknowledgment
The author gratefully acknowl-
edges Dr. Christina D. Chambers,
Prof Carl. L. Keen (University of
California) and Elena S. Vyatchanina
(Russian Society of Trace Elem ents in
Medicine) for collaboration in FASD
studies.
The content of trace elements
in aerial parts of plants of
Genus Pulmonaria
D. Kj-uglov
Novosibirsk State Medical Univer-
sity, Department of P harmacognosy,
Novosibirsk, Russia
Herbal remedies produced from
the aerial parts of plants ofthegenus
Pulmonaria have anti-anemic activ-
ity. A similar pharmacological activ-
taining an herbal raw. The trace ele-
ments composition of five species of
Pulmo naria Pulmo naria officinalis
L.,
P. obscura
Dumort.,
P mollis
Wulf ex Homem.,
P angustifolia
L.
andP . rubra Schott) was researched
by means of inductively coupled
plasma mass-spectroscopy. It was es-
tablished that trace elements compo-
sition of researched plants is similar.
Biogenic trace elements (B, K, P, V,
Ca, Co, Cu, Fe, Mg, Mn, M o, Na, Si,
Zn) have a smaller variability in con-
trast to 47 o thers trace elements. Evi-
dently, the content of biogenic trace
elements define the homeostasis of
vegetable organism, and variability of
this content has to be smaller than the
other elements. Accumulating of the
other elements has a random charac-
ter. Different p arts ofaplant (genera-
tive shoots and rosellate leaves) have
a different relative amount of bio-
genic trace elemen ts, and different ra-
tio of contents of m anganese and iron.
Therefore, herbal remedies produced
from different parts of a plant can
have a different pharmacological ac-
tivity - antianemic and expectorant
conformably.
Magnesium deficiency and in-
creased fractional magnesium
excretion in insulin-dependent
diabetes mellitus - magnesium
loading test and blood
pressure
K. Kisters', M. Schildheuer^
A. Bauer^, K. Dick-, A. Peters^,
B. Gremmler*, M. Hausberg\
M. Quang Ng uyen ' and P.M. Rob^
'Medical C linic I, St. Anna-Ho spital,
^Medical Clinic , Un iversitts-
klinikum Lbeck, IMedical Clinic I,
Stadtisches K linikum, Karlsruhe,
and ""Cardiology, M arienh ospital,
Bottrop, Germany
Background: There is experimen-
tal and clinical evidence giving im-
portance to the relationship between
magnesium (Mg) and diabetes mel-
litus.The American Diabetes Society
suggested that attention be given to
the diagnostic significance of a Mg
deficiency in diabetes mellitus. Be-
cause of regional differences in Mg
suppply, we studied Mg status in the
surroundings of Lbck in healthy per-
sons as compared to diabetics. Patients
and 27 inpatients with an insulin-
dependent diabetes mellitus (DM ) and
bad metabolic control were studied.
Mg++wasmeasured by atomic absorp-
tion spectroscopy (Video 12 appara-
tus) in serum and erythrocytes; basic
24-hour urinary Mg excretion
(b-Mg-u), fractional Mg excretion
(f-Mg-u) were calculated. In addition
the Mg loading test (Mg-It) was ap-
plied. Results: In diabetics a hypo-
magnesaemia was observed as com-
pared to healthy subjects both in se-
rum (0.73 0.04 vs. 0.83
0.04
mm ol/l, means SD , p < 0.05) and in
red blood ce l Is (1 .43 0.16 vs . l .84
0.10 mmol/l) (p < O.OI). The b-Mg-u
was 2.75 3.62 mmol/d in DM as
compared to 5.84 2.21 mmol/d in
controls (p
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Abstracts
159
However, whether changes in trace
element metabolism or distribution
participate in the pathogenesis of iron
overload tissue damage is not known.
The aim ofthiswork is to study how
trace elements homeostasisisaffected
by the bloodletting used to treat
heniochromatosis. We recruited out-
patients from the Hemochromatosis
Clinic at the D epartment of M edicine.
After genotyping we measured iron
status and common clinical chemistry
tests,
and trace element profiles were
studied before and after treatment for
iron overload. According to prelimi-
nary results, serum co ncentrations of
aluminium, boron, selenium, stron-
tium and zinc decline after blood-
letting. The pathophysiological con-
sequence ofthisis not kn own.
Serum trace elements and
brain atrophy in aicohoiics
E. Gonzalez-Reimers',
C. Martin-Gonzalez',
L. G alindo-M artin',
E. Garcia-Valdecasas',
I. Hemn dez-Betancor',
C. Fernandez-Rodriguez',
P.Abre-Gonzlez'
and N. Faria
'Servicio de Medicina Interna,
Hospital Un iversitario de Can arias,
^Dpto de Quimica Analitica, and
^Dpto. De Fisiologia, Universidad de
La Laguna, La Laguna, Tenerife,
Canary Islands, Spain
Chronic alcoholics are at risk of
developing several neurological al-
terations, the so-called alcoholic de-
mentia, related to brain atrophy, and
cerebel lar atrophy , together w ith thia-
mine deficiency related Wemieke's-
Korsakoff encephalopathy, being the
most frequently reported alterations.
Although pathogenesis is still ob-
scure, cytokine-mediated neuroin-
flammation and oxidative damage
may play a role in brain atrophy of un-
complicated alcoholics. Therefore,
alterations in trace elements, such as
selenium and zinc deficiency, in-
volved in antioxidative capacity, or
iron exce ss, frequently o bserved in al-
coholics, acting as a pro-oxidant, m ay
be all involvedas pathogenic factors.
In order to deepen our knowledge
about the relation between brain atro-
phy and trace elements and o xidative
the present study, including 61 alco-
holic patients and 12 age and sex-
matched controls, all of them sanitary
workers w ho had undergone a cranial
scan because of minor symptoms. Pa-
tients showed a more intense degree
of atrophy, differences being ob-
served in Huckmann (t ^ 2.95), bi-
cauda (t - 3.93) and celia index (t -
3.75) and cortical atrophy (t ^ 5.45,
p < 0.001 in all cases). Statistically
significant differences between pa-
tients with cerebellar atrophy and
those without cerebellar atrophy were
observed regarding copper (854 |ig/I
181 ^ig/l vs. 1088
[ig \
269 ng/l,
p = 0.014), and zinc (971 ^g/1 69 6
Hg/1 vs. 1817 \ig/\ 1298 \ig/lp =
0.03). On the contrary, serum ferritin
was h igher among patients with cere-
bellar atrophy (529 370 ng/ml vs.
308 209 ng/ml p - 0.044). Serum
ferritin also showed a significant cor-
relation with bicaudate index (rho ^
0.3, p =0.029 and Huckmann's in-
dex (rho = 0 .32, p = 0.02), and serum
transferrin, an inverse one with Huck-
mann s index (rho ^ -0.30 ,p=0.031).
However, selenium showed a direct
(opposite of what was expected) sig-
nificant correlation with Huckmann
index (rho = 0.35, p - 0.046). No rela-
tion was observed betw een trace ele-
ments and age, amount of ethanol
consumed, years of consumption,
malondialdehyde (only 12 cases), or
proinfiammatory cytokines (TNF-a,
IL-6).
Thus, besides ferritin, higher
among those with more intense atro-
phy, trace elements are only poorly re-
lated to brain atrophy, but patients
with cerebellar atrophy do have low er
serum copper and zinc levels.
Dietary bio moduiation
schedule for treatment of
prostate cancer patients
T. Tallberg', T. Westermarck' and
F.Atroshi
'The Helsinki Institute for
Bio-Immunotherapy Ltd., and
^Pharmacology and T oxicology,
ELTDK, University of Helsinki,
Helsinki, Finland
Prostate cancer (CaP) is a hor-
mone-dependent disease based on
Huggins and Hobbs orchiectomy
studies in 1941 [1]. As CaP regularly
recurred, it led to bilateral adrenai-
tients died in a short time since adre-
nal glands actually had a central regu-
latory position in this endocrine dis-
ease [3]. CaP still lacks a definitive
comprehensible etiology. t isin many
cases a potentially incurable age-
linked disease. Several clinical obser-
vations designate that a regulatory
function is performed by the adrenal
glands linked to a feed-back effect ac-
tivated by its zona-reticularis (ZR)
cells.
This positive clinical effect is
promulgated by specific dietary meta-
bolic factors in all stages of CaP [4].
These nutritional factors have been
found to cure CaP even in cases suf-
fering from multiple bone mtastases
[5] - to avoid hormone refractory
states (HRPC), and stop the progress
of the disease in patients on Watchful
Waiting [6]. We have used dietary
bio-modulation schedule for treat-
ment of prostate cancer patients (Ta-
ble 1). This complex dietary formula
has been developed empirically over
two decades according to the aeno-
carcinoma code for CaP [4, 6]. The
amino acids, trace-element ions and
CNS lipids tested w ere fed according
to the code while constantly monitor-
ing the effect on the patients' hor-
mone balance and clinical features.
Dietary bio modulation schedule for
treatment of prostate ca ncer patients.
1) Oral administration of each ( 2 - 5
g/day) of respective L-amino acids;
Arg, Asp, Glu, Gly, Lys, and Ser,
eventually also His, all in connection
with meals. 2) Essential trace-element
salts prescribed orally as biologically
active ions, at dose levels of some
milligrams ( 1 - 3 m g/day); Chromium
(CrCl2.6H:O) 6 mg (- 1.17 mg Cr),
Tinn (SnCl4.5H2O) 4 mg (= 1.35 mg
Sn),
Strontium (SrC b) 1 - 7mg { 1
mg
Sr),
Vanadine (Na:
VO.,.
4
H2O),
6
mg (- 2.5 mg V), Wolfram ( Na. WO4.
2 H :0) , 4 mg (- 2.3mg W). 3) Small
physiologic amounts of vitamins; A,
B,C, D, E, K, folie acid (2 m g/d) and
lycopene. To improve lymphopoiesis
and the immune-defence of patients a
diet containing prion-free neurogenic
lipids (Neurofood Ltd. Finland). All
these dietary ingredients can be m ixed
together in yogurt or ice-cream, or as a
daily nutritional ration utilizing pre-
packed powders. Dose-levels are ad-
justed based on the clinical response
as measured during the therapy, and
correlated to the patients' body
weight. A good pro gnosis caused by
adrenal ZR feedback activation can
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160
rapidly be accessed by standard labo-
ratory tests, evidenced by increased
FSH, PRL , SHBG levels and the free
% of PSA, wh ile a decrease is seen in
the levels of; DHEA , DHE AS , and to-
tal PSA-levels.
References
[11 Huggins C. Hodges
CV
Studies on pros-
tate cancer: I. Effect of castration, estro-
geti. and androgen injection on serum
phosphatases in metastatic carcinoma of
the prostate. Cancer Research. ')4I; I:
[2 ] Huggins C. Scon WW Bilateral adrenal-
ectomy iti prostate cancer. Ann Surg.
\945\ 122:1031-1041.
[3] Tallherg T.Cancer treatment, based on
active nutritional bio-modulation, hor-
mottal therapy and specific autologous
immunotherapy. J Aust Coll Nutr and
EnvMed. N96; 15:5-2^.
[4] Tallbei gT Studies on cancer of tlie Pros-
tate Gland, a search for Aetiological and
Prognostic Factors. J Aust Coll Nutr and
EnvMed.
2003;
22.- 11-16.
[5] Tallherg TRegu lation of cancer by ther-
apeutic vaccination and dietary bio-mod-
ulation involving organ specific mito-
chondria. Int J Biotechnology. 2007;9 :
391-410.
[6] Tallherg T. Dahek M. Prostate cancer,
aetiological, therapeutic, prognostic and
prophylactic factors. Anticancer Re-
search. 2008;
2 8:
3507-3508.
Bio-Immunotherapy can
prevent recurrent prostate -
renal cancer and melanoma
T. Tallberg, T. Westermarck and
F.Atroshi
The Institute for Bio-Immunotherapy,
Helsinki, F inland
Tumors may spontaneously re-
gress which implies that mammals
possess a natural intrinsic regulatory
capability to control the de-differenti-
ation of specialized organ cells, "The
metabolic triumph of the host" (Dr.
W.M. Cole 1974). Thus this novel
paradigm is that cancer represents a
complex chronic metabolic defi-
ciency disease which can be com pen-
sated by biological dietary means.
The aim was consequen tly to analyze
if the disturbed interior milieu can be
corrected /compensated and lead to a
biological cu re without side-effects in
prostate cancer patients. Randomized
clinical studies with hundreds of can-
cer patients, over 35 years, showed
provement in the survival rate by
feeding renal cancer, and melanoma
patients a specific combination of nu-
tritional amino acids, trace-element
ions,
inductional central nervous sys-
tem lipids (CNS), plus supporting the
hormonal balance, and specifically in
renal cancer and melanoma by activa-
tion of the patients autologous im-
mune-defense. The composition of
these natural etioiogical bio-modulat-
ing factors regulating our three major
forms of cancer; leukemia, adeno-
carcinoma, and sarcoma have primar-
ily been outlined. Significantly better
disease-fiee intervals extending over
decades, were achieved utilizing pow-
ders containing these vital dietary sup-
plements to correct the complex etio-
iogical metabolic deficiency causing
cancer. This is the "intellectual prop-
erty" of this Institute. Ready-made
powders complied to treat prostate
cancer, (decreasing Gleason scores)
are available from our Institute, at a
cost of only 2 - 4 /day. In a random-
ized study with 127 patients suffering
from metastasized renal cancer, di-
etary supplements could also arrest
recurrent disease. Pertinent bio-mod-
ulating dietary components were;
L-amino acids; Ala, Arg, Asp, Lys,
plus trace-elements; Cr, Mo, Se, Sn,
V, and central nervous system CNS-
lipids,
and physiologic doses of vita-
mins.
Significantly improved clinical
results were also obtained with cuta-
neous (103 cases) and Uveal mela-
noma (54 patients) ingesting; Gty,
Glu, Ala, Asp, He, Lys, + Cr, Se, Sn,
V, W, and CNS-lipids. Strontium is
important to cure prostate cancer. In
bio-immunotherapy significant clini-
cal improvement has been achieved
for dietary correction alone in renal
cancer (p ^ 0.04), and high risk (T3)
uveal melanoma (p ^ 0.001
),
but clin-
ical results are usually further im-
proved if the therapy is combined
with active specific immunotherapy
utilizing polymerized autologous tu-
mor tissue. Tumor tissue should
therefore always be saved at surgery
to facilitate the prepa ration o f individ-
ual vaccines since patients' m alignant
cells contain a fingerprint of antigenic
tumor-markers. Similar good thera-
peutic results have also been obtained
with other forms of cancer. This heal-
ing reaction does not involve
apoptosis or lysis of tumor cells as
they regain normal healthy function,
with complete regression {CK ,even
of big tumors, without a scar. Regular
immune reactions do not have such a
capacity. Actually activated regula-
tory organ-specific mitochondria
have been found to be involved in the
healing process. Metabolic bio-mod-
ulation can also prevent recurrent
cancer because it actively strives to
correct the etioiogical deficiency. Our
standard therapy is primarily extract-
ing only symptoms of this metabolic
deficiency disease. It is as if only the
loose teeth ofth scurvy patient w ere
removed instead of giving him vita-
min-C.
Malignant transformation
caused by genetic weakness (e.g.
HNPCC) is out of reach for gene ther-
apy, since it involves aberrations in
several genes, but malignant transfor-
mation can be prevented by dietary
supplementation administering small
amounts of pertinent essential meta-
bolic components aimed to regain the
physiologic internal milieu in the pa-
tients'
body. Healthy persons attain
this balance from their normal diet.
All bio-modulating components in-
volved are natural substances, and
thus ethical, inexpensive, easy to ad-
minister and have a long shelf life.
Bio-immunotherapy entails no side
effects, but also harbor prophylactic
potentials.
Cancer is regulated by organ-
specific mitochondria via
genomics proteomics and
lipidomics
T. Tallberg', T Westermarck' and
F.Atroshi'
'The Helsinki Institute for
Bio-Immunotherapy, Helsinki,
-Rinnekoti Research Centre, Espoo,
and 'Pharmacology and Toxicology
(ELTDK ), University of H elsinki,
Finland
Mammalian cancer control is de-
pendent on a complex metabolic phy-
siologic bodily balance. Normaliza-
tion of malignant gene transcription
in an organ requires dietary co rrection
of the etiologic long-standing meta-
bolic deficiency involving six or more
inter-linked natural factors aided by
hormonal equilibrium, enhanced by
specific autologous immunotherapy.
In bio-immunotherapy this therapeu-
tic bio-modulation is aimed to simu-
late specific leukemia, adenocarcino-
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Abstracts
161
ing to a cancer cure by forcing tumor
cells back into healthy gene tran scrip-
tion, without apoptosis. M itochondria
are thus transformed and become
electron-dense as their cristae and
matrix gather metal-enzymes (Cr, Fe,
Ti,
Zn) and appear in the vicinity of
the intact tumor cell nucleus. This
inductional signal is transferred to
chromosomes by strontium thru the
nuclear membrane. This physiologic
mammalian healing in hundreds of
patients resembles mysterious sponta-
neous cures. Immunobiology forms a
vital paradigm shift over prevailing
cancer therap ies; "to kill cancer cells".
Mammalian genes (22 - 60.000) are
too few to explain the complex,
time-linked physiological expression
leading to health and senescence. The
human chromosomal nucleotide se-
quence analogy with monkeys and
rats (99%; 96%) is surprising, sug-
gesting that chromosomes were cre-
ated by mitochondria during eons of
their phylogenetic toil, representing a
"memory of evolution" rather than
the "secret oflife".Mitochondrial ac-
tion in cancer seems primarily to be
gene-regulatory and reparative, plus
its energy production for the nucleus.
They are also involved in digestive
and decay processes, with program-
med cell death and ending in senes-
cence. Organ-specific mitochondria
act as one operator in the supercom-
puter every cell symbolizes, where
chromosomal DNA forms the mem-
ory unit. The billions of nucleotide
chemical letters between genes are
not "junk-sequences", but they pin-
point species' specific genes during
embryogenesis. Proteomies shapes a
hundred-thousand proteins conformed
into active quaternary molecules. The
importance of the lipidome, with its zil-
lions of "functional lipids" in our cen-
tral nervous system (CNS) linked to
gestational embryonic induction, is
usually overlooked. Inductional Con-
trol and Lipidomics also functions in
the adult body but less conspicuously.
Blood-brain barrier lesions with CNS-
lipid loss curtail axonal cell-control in
that enervated area, espousing malig-
nant transformation. Ingested CNS-
lipids stimulate lymphopoiesis, and can
alleviate diverse neurog enic ailments;
stress and pain ^ the warning signal
that CNS cannot cope with demands
from its crucial inductional signal-
system for a steady state healthy func-
tion etc. A marked depletion of CNS
lipids in affecting three specific seg-
mentai areas of the spinal cord is pos-
sibly also linked to different forms of
clinical atherosclerosis. Mitochon-
dria regulation is related to lipido-
mics, genomics and proteomies, and
it may lead to the future use of
schooled organ-specific mitochon-
dria as genuine cancer remedies.
Prostate cancer depends on
adrenal gland functions and
mitochondrial regulation. A
study over three decades
analyzing etiological
therapeutic and prognostic
factors
T. Tallberg', T. Westermarck^ and
Faik Atroshi^
'The Institute for
Bio-Immunotherapy, Helsinki,
^Rinnekoti Research Cen tre, Espoo,
and 'Pharmacology and Toxicology,
University of Helsinki, Helsinki,
Finland
Epidemiology studies indicate that
dietary habits have a pronounced ef-
fect on the incidence of prostate can-
cer (CaP). Latent disease, which in
autopsies is found in 80% of male pa-
tients over 80 years, suggests that
metabolic factors are involved. The
aim for this study, over 30 years, was
therefore to search for metabolic
compo nents which could reverse, and
arrest the progress of
CaP.
Methods:
To facilitate the dietary treatmen t and
improve compliance of ready-made
powders containing all pertinent met-
abolic factors procured and fed to pa-
tients. These powders contain spe-
cific amino acids, trace element ions
and central nervous system lipids. In
search for etiological factors 70 dif-
ferent cases of CaP were followed,
with informed consent, for over 10
years, recounting their clinical and
laboratory responses to this biologi-
cal treatment m odality. As only physi-
ologic natural non-toxic and inexpen-
sive metabolic components were uti-
lized, no side-effects were encoun-
tered, but prognostic clinical features
were found. C linical results: Follow-
ing this biological treatment, trans-
formed organ-specific mitochondria
were seen to surround the tumor cell
nucleus and empty their elec-
tron-dense material irough the nu-
were cured without apoptosis. Conse-
quently "Watchful waiting" even as
active surveillance is unethical since
no attempt is made to stop CaP from
becoming more aggressive. In a case
found by screening the Gleason score
declined from 8 - 4 in six years. M ul-
tiple bone mtastases regressed in a
patient wh ile strontium w as adminis-
tered, now without recurrence for
over 18 years. Hormone refractory
(HRPC) states have been evaded by,
"short time" intermittent LHRH treat-
ment (3.6mgZoladex And rocur), in
synergy with CaP powders. Further
hormone injections have been possi-
ble to be extended to intervals of 3 - 6
mon ths. Prognostic features were de-
fined based on uctuations in FSH,
DHEAS, PRLand PSA-levels. Addi-
tional clinical cases will be described
in detail. Conclusions: This biologi-
cal non-invasive therapyisan altema-
tive to our standard treatment modali-
ties as it does not cause grav e
side ef
fects and deterioration of the patien ts'
life-quality. Activated transformed
mitoch ond ria are involved in the heal-
ing. Improved diagno stic tests should
decrease the need for excessive
( 1 2 -2 4) biopsy co res. If the Gleason
score is 7 - 10. bloody biopsies may
actually spread m alignant
cells
into the
circulation and cause the high inci-
dence of recurrent disease (30 - 40% )
following prostatectomy. Screening
for CaP is important since there is
now a realistic possibility to stop the
progress of
CaP
in the early phase of
the disease. The clinical effect of di-
etary sup plementation, activating ad-
renal zona reticularis cells, can rap-
idly be evaluated using standard labo-
ratory tests, and the prognostic man-
agement of prostate cancer assessed.
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7th Intemational symposium on trace elements in hum an: new perspectives October 13th - 15th 2009 . Athe ns Greece
162
Selenium in radiation oncology
- an update
O. Micke', L. Schomburg^,
J. Bu entz el\ K. Kisters and
R. Muecke^
'Department of Radiotherapy and
Radiation Oncology, Franziskus
Hospital, Bielefeld, ^Institute for
Experimental Endocrinology,
Charit Berlin, 'Department of
Otolaryngology, Sdharz Hospital
No rdha usen , Department of Internal
Medicine, St. Anna Hospital, Heme,
and ^Department of Radiotherapy,
Lippe Hospital Lemgo, Germany
(on behalf of the German Working
Group Trace Elements and
Electrolytes in Oncology (AKTE))
Tbe essential trace element Sele-
nium, wbich is a crucial cofactor in
the most important endogenous anti-
oxidative systems of the human body,
attracts more and more attention of
lay and expert group s. The interest of
oncologist mainly focuses in tbe
following clinical aspects: Radiopro-
tection of normal tissues, radiosensitiz-
ing in malignant
tumors,
antiedematous
effect, prognostic impact of selenium
and effects in primary and secondary
cancer prevention. Selenium is a con-
stituent of the small group of seleno-
cysteine-containing selenoproteins
and elicits important structural and
enzymatic functions. Selenium defi-
ciency has been linked to increased
infection risk and adverse mood
states.
Se has been shown to possess
cancer-preventive and cytoprotective
activities in both animal models and
humans. It is well established that Se
has a key role in redox regulation and
antioxidant function, and hence in
membrane integrity, energy metabo-
lism and protection against DNA
damage. Recent clinical trials showed
tbe importance of selenium for clinical
oncology. Our own clinical study in-
volving 48 patients suggest that sele-
nium has a positive effect on radia-
tion-associated secondary lym phedema
in patients with limb edemas as well
as in the head and neck reg ion, includ -
ing endolaryngeal edema. Another
randomized Phase III study of our
group was performed to examine the
cytoprotective properties of selenium
in radiation oncology. The aim was to
evaluate, whether sodium selenite is
able to compensate a preexisting sele-
nium deficiency and to prevent radia-
tion induced diarrhea in adjuvant ra-
diotherapy for pelvic gynecologic
malignancies. By this study, for the
first
time,
the significant b enefit ofso-
dium selenite supplementation with
regard to selenium deficiency and ra-
diotherapy induced diarrhea in pa-
tients with cervical and uterine cancer
has been shown in a prospective ran-
domized trial. Disease free survival
and overall survival data implies tbat
supplementation with Se does not in-
terfere witb the positive biological ef-
fects of radiation treatm ent, and m ight
constitute a valuable adjuvant therapy
option especially in marginally sup-
plied individuals. More recently there
were emerging concerns coming up
from two large clinical preven tion tri-
als (NPC , SELECT) that selenium in-
creases the possible risk of develop-
ing diabetes Type 2. Despite obv ious
flaws of both studies and good
countearguments, a controversial de-
bate remains on the possible advan-
tage and risks of selenium in cancer
prevention. However, in the light of
the recent clinical trials, the potential
benefits of selenium supplementation
in tumor patients are undeniable even
so further research is needed.
Selenium substitution during
radiotherapy in head and neck
cancer
J. BntzeI '^O.
M.Gl a t zeP \ U. Sch fe r ' ^
D.Riesenbeck\ K. Kiste rs ' ' \
F. Bmns^\ K.G Schnekaes ,
H. Daw czynski^ and R. Mcke'*'*
'Department of Otolaryngology,
Head Neck Surgery, Sdharz-
Krankenhaus Nordhausen gGmbH ,
Nordhausen, -Department of Radio-
therapy, Franziskus-Hospital,
Bielefeld, -Department of Radio-
therapy, Zentralklinikum Suhl
Gm bH , Suhl, ^Department of Radio-
therapy, Klinikum Lippe-Lemgo,
Lem go, ^Department of Radiother-
apy, Prosper-Hospital, Reckling-
hausen, ^Department of Internal
Medicine I, St Anna Hospital,
Hem e, ^Department of Radiother-
apy, Special Oncology, Medical
School Hannover, Hannover,
AKTE, Tbe German Working
Group Trace Elements and
Electrolytes in Oncology , and
^Pharmaceutical company biosyn,
Fellbach, Germany
Objective: The substitution of
sele-
nium effects in activation of the sele-
nium dependent enzyme glutathione
peroxidase is important for scaveng-
ing free
radicals.
Until today only lim-
ited datawasavailable about the clini-
cal impact of selenium regarding tbe
toxicities due to free radical produc-
ing therapies, e.g. irradiation or che-
motherapy. Material and methods: 39
patients (8 female, 31 male) witb ad-
vanced head/neck cancer were in-
cluded in a randomized Phase II
study. The mean age was 63.52 9.31
years. Tumor localizations: oral can-
cer 15 patients, oropharynx 19 pa-
tients,
hypopharynx5patients, CUP
patient. Group A (n ^ 22) received
500 |ig sodium selenite at the days of
radiotherapy and 300 ^g sodium sele-
nite at holidays or weekend. G roup B
(17) was irradiated without any sele-
nium substitution. Both groups were
well balanced according age, gender,
localization and stage of the tumor.
We evaluated the RTOG grade of
radit ion-associated toxicities onc e
per week. Results: We observed the
following serious toxicities (Group A
versus Group B): dysphagia 22.7%
vs . 35.3%,
loss of taste 22.7% vs.
47.1%,dry mouth 22.7% vs. 23.5%,
7/25/2019 Elements in Human New Perspectives
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Abstracts
163
statistical trend {F isher's exact-test) is
only seen in the area of loss of taste
(p = 0.172). The analysis per week
(Student t-test) had shown a signifi-
cant reduction of dysphagia in the se-
lenium group at the last week of irra-
diation. Conclusion: The small ran-
domized trial has shown limited ef-
fects of selenium in the prevention of
ageusia (loss of taste) and dysphagia
due to radiotherapy hecause of head
and neck cancer.
Tobacco smo king during preg
nancy affected Pro Hepcidin
levels in serum
M. Chelchowska', J. Ambroszkiewicz',
J. Gajewska', T. Maciejewski- and
T. Laskowska-Klita'
'Department of Newborn Screening,
and -Department of Obstetrics and
Gynecology, Institute of Mother and
Child, Warsaw, Poland
Maternal smoking is associated,
probably through a hypoxic effect on
the fetus, with stimulation of fetal
erythropoiesis and with increased fe-
tal iron requirements. Recently as a
central mediator of iron metabolism, a
pcptidc hormone producedbythe hver
known as pro-hepcidin has emerged. It
isknown that anemia and hypoxiasup-
press hepcidin mRNA expression. The
effect of tobacco smoking on serum
concentration of pro-hepcidin and
some iron parameters in pregnant
women and their newbom s were stud-
ied. Healthy matched-maternal cord
pairs (n ^ 60) were divided into non-
smoking and smoking groups accord-
ing to questionnaire declaration. In
the smoking group, lower concentra-
tions of pro-hepcidin in serum of
mothers and in cord blood were ob-
served. It amounted respectively tto
only 85% (p < O.OI) and 70% (p 30 jam in
diameter) in AA women was lower
than in healthy subjects (265 3 .4 vs.
320 2.5, p < 0.001). In AA group,
20 3.4% of hair in parietal zon e was
fuzz-like
vs .
1 2 0.5 % in control. AA
women were also characterized by in-
creased level of androstendion (24%
vs .18% in control, p < 0.001), DHT
(47.7%
vs. 25% , p
7/25/2019 Elements in Human New Perspectives
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7th International sympo sium on trace elements in huma n: new perspectives October 13th - 15th 2009 Athen s Greece
164
The significance of b lood
urine and hair multielement
analysis in estimation of
human elemental status
A.V. Skalny and M.G Skalnaya
ANO Centre for Biotic Medicine,
Moscow, Russia
The estimation of buman elemen-
tal status is a very important diagnos-
tic problem because of differences in
reflection of macro and trace ele-
ments metabolism in different diag-
nostic biosubstrates (laboratory sam-
ples). The comparative study of si-
multaneous determination of ca. 20
macro and trace elements in scalp
hair, whole blood and urine of practi-
cally healthy persons was conducted
using ICP-OES/ICP-MS. Positive
correlations between the majority of
trace elements, Ca and Mg were
found, but neg ative correlations in the
case of K and Na in human hair and
wbole blood samples were found. The
strongest correlations were observed
for heavy metals. The anthropomtrie
and physiological parameters ofinves-
tigated individuals correlated much
better
to
whole blood macro and trace
element concentrations as compared
to bair content, probably because of
strong hom eostatic regulation. S o, si-
multaneous determination of macro
and trace elements in different diag-
nostic biosubstrates provides more
proper information about elemental
status of humans, useful for nutri-
tional, ecological and physiological
investigations.
Hair trace element profiles in
autistic children
T.G Vizel' and A.A. Skalny^
'Research Institute of Psychiatry and
^People Friendship U niversity of
Russia, Moscow, Russia
Examined clinically and labora-
tory were 38 children (30 boys and 8
girls) with autism (varying d egrees of
severity) and 38 healthy children (20
boys and 18 girls) aged 2-10 years.
ICP-MS analysis of autistic children's
hair sbowed the decreased content of
Se (0.36 0,3 vs. 1.05 0.2 mcg /g in
control,
p
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