Research Project:
OM-00113/2000
THE
HISTAMINE DEPENDENT PATHOMECHANISM, EARLY
DIAGNOSIS
AND
PREVENTION OF OSTEOPOROSIS
BACKGROUND
There are three main
factors that are related to the increasing frequency of the
osteoporosis in the
elderly population:
- postmenopausal oestrogen deficiency in women,
- aging related metabolic alterations, in both women and men,
- side
effects of the corticosteroid treatments.
Research on the basic
mechanism and treatment of osteoporosis that represents one of the most
serious, most expensive epidemiological problem – is extensively
investigated
in the industrialized countries. Our research project addresses the
basic
questions of the pathomechanism of osteoporosis, a disorder that
affects larger
segment of population than any other illness.
This project is based on the observation
that
the oestrogen depletion did not cause development of severe
osteoporosis in the
bones of a genetically histamine deficient (histidine decarboxylase
(HDC)
knock-out) mice. Based on this finding, it is assumed that the bone
protecting
effect of the histamine deficiency might be an important component
among the
risk factors of osteoporosis in humans as well.
OBJECTIVES
The primary goal of the project is to
develop a diagnostic
method that is able to predict the risk for osteoporosis prior to the
menopause. The current research focuses on revealing new relations
among the
results of cell analytical, cytofluorimetric, clinical and laboratory
diagnostic findings. The thoroughly designed network of investigation
was
designed to investigate postmenopausal women – the population segment
having
the highest risk for osteoporosis – with special attention to those
individuals
suffering from allergic diseases as well. In longer run, our results
may
contribute to the development of a complementary therapeutic treatment
of
osteoporosis disorders by selectively affecting the 'remodelling'
process of
the bone tissue.
DESCRIPTION,
RESULTS
The patient
groups were formed according to the
results of gynecological investigations, anamnesis, clinical laboratory
parameters and the hormonal status of the patients.
The gynecological status of the patients is
determined by physical, cytological and infectological investigations.
By the time being, 150 patients have been
investigated. The summary of the results is shown in the following
table. Based
on the cytological and infectological findings, 32 woman were excluded
from the
further research.
|
|
Number of patients |
|
Negative |
128 |
|
Anamnesis |
0 |
|
Physical investigation
|
18 |
|
Cytology |
4 |
|
Infectology |
10 |
|
Total: |
150 |
The
patients excluded due to infectological
disorders suffered from either fungal or bacteriological infections.
The
cytology related exclusions were made because of inflammation (P3
cytology) and
in situ carcinoma (P4 cytology).
There were
no exclusions due to the results of the clinical laboratory
measurements.
RESULTS
Histamine receptor expression:
- Anti-histamine-receptor
antibodies: were developed against three oligopeptides corresponding to
the
extracellular, histamine binding fragments of the human histamine
receptors,
H1R, H2R and H3R. The developed antibodies were successfully used to
determine
the level of expression of these receptors on all identified leukocyte
populations by means of flow cytometry.
- The
H1R and H2R receptor expression tend to be relatively high on the
surface of
monocytes isolated from peripheral blood samples of allergic patients.
- A
higher histamine receptor expression is associated to the increase of
the bone
related alkalic phosphatse activity.
- The
increased serum Ca++ concentration is inversely related to the
histamine
receptor expression.
- The
serum inorganic phosphate concentration has inverse relation with the
histamine
receptor expression.
HDC content in leukocytes:
The HDC
content
was higher in the peripheral blood lymphocytes (PBL) of the allergic
patients
as compared to the healthy control group.
No
significant differences were
found among the following parameters of the patients:
Laboratory
data of the
bone metabolism:
The following
routine laboratory measurements were
made: Serum and urine Ca++ and phosphorus concentration, serum total
and bone
related alkalic phosphatase concentration. The measured values were not
significantly different among the patient groups selected according to
the
duration of the post menopause.
Ratio of the lymphocyte
subpopulations:
Aging and
allergy has no significant influence on the number and ratio of
lymphocyte
subpopulations as determined by flow cytometry measurements.
Histamine content of the
leukocytes:
The histamine
content was not significantly different in the cytoplasm of the
peripheral
blood leukocytes of the various patient groups.
COORDINATOR:
Dr. György
Lustyik
Soft Flow
Hungary Kft.
H-7628
Pécs, Kedves u. 24.
Tel.: +36
72 240064, Fax: +36 72 240065
CONTRIBUTORS
Prof. Dr.
András Falus, aMember of Hungarian Academy of Sciences
Semmelweis University
Institute of Genetics, Cell- and Immuno Biology
1089 Budapest, Nagyvárad tér 4.
Tel.: +36 1 210 2929
|
Prof. Dr.
Csaba Horváth
Semmelweis University
1st Department of Medicine
1083 Budapest, Károlyi Sándor u. 2/a.
Tel.: +36 1 210 0278/1509 |
Dr.
Éva Pállinger
Semmelweis University
Institute of Genetics, Cell- and Immuno Biology
1089 Budapest, Nagyvárad tér 4.
Tel.: +36 1 210 2929
|
Dr. Attila
Kiss
Central Hospital of Hungarian Defense Forces
1126 Budapest, Királyhágó u. 1-3.
Tel.: +36 1 356 6522/354
|
Dr.
Emilia Kormányos
Central Hospital of Hungarian Defense Forces
1126 Budapest, Királyhágó u. 1-3.
Tel.: +36 1 356 6522 |
|