Elements in Human New Perspectives

7/25/2019 Elements in Human New Perspectives

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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


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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


6/32

Abstracts

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 ' '


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,


7/32

7th International sympo sium on trace elements in huma n: new perspectives October 13th - 15th 2009 Athen s Greece

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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7th International sympos ium on trace elemen ts in hum an: new perspectives October 13th - 15th 2009 Athen s Greece

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


10/32

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


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


11/32

7th International symp osium on trace elements in hum an; new perspectives. October 13th - 15th 2009 Athen s Greece

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'



-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-


12/32

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


^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.


13/32

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


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'*'*


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


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%,


14/32

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


15/32

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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