Correlation Of Plsma C The Egyptian Journal of Hospital Medicine Vol., 12 : 1 ­11 September 2003


Correlation of Serum Concentrations of Soluble
Thrombomodulin, Soluble Vascular Cell Adhesion Molecule-1,
Intracellular Adhesion Molecule -1 And E-Selectin In Patients With
Systemic Lupus Erythematosus

Malak., A. Mohsen*, Magda.A.Gamil*,Maha. I.Shehata*
Boshra.H,El Zawahry **and Salwa.S.I.Afifi***

Clinical Biochemistry,*Microbiology and**Physiology Departments.
Faculty of Medicine for Girls and *** Microbiology Department Faculty of Pharmacy,
Al- Azhar University, Cairo, Egypt.

To date no specific serological parameters are available to assess disease activity in
systemic lupus erythematosus (SLE). The objective of this study was to correlate serum levels
of thrombomodulin (TM), intracellular adhesion molecule-1 sICAM-1, vascular cell adhesion
molecule-1 sVCAM-1, and E-selectin with standard laboratory tests and clinical indices of
disease activity in 40 patients with SLE and 20 apparently healthy persons as controls.
According to British Isles Lupus Assessment Group (BILAG) disease activity index, the 40
patients were divided into two groups, the first consisted of 22 with active disease, and the
second consisted of 18 patients with inactive SLE. Serum sTM, sICAM-1, sVCAM-I, and E-
selectin were measured in their sera, using enzyme linked immuonosorbent assay (ELISA)
technique.C-reactiv protein (CRP), Erythrocyte sedimentation rates (ESR) and serum
creatinines were measured by standard laboratory tests. Total leukocytic count and hemoglobin
concentration were detected by coulter counter. Levels of sTM and sVCAM were highly
elevated in the group of patients with active SLE as compared to the inactive one (P<0.0005)
while sICAM-1 levels were moderately elevated (P<0.005). E-selectin was poorly correlated
with disease activity in SLE (P>0.05). In SLE, the BILAG disease activity index, ESR and
serum creatinine correlated best with sTM, sVCAM-1 and E-selectin levels while there was a
weak association between CRP levels and the adhesion molecules, and no correlation between
CRP level and disease activity.
In conclusion, sTM and sVCAM were the most important serological indices of disease
activity in SLE and might be valuable serological parameters for monitoring therapy.


Systemic lupus erythematosus (SLE)
to blood vessel destruction and organ injury
is an autoimmune disease of unknown
(e.g. glomerulonephritis and vasculitis).It
aetiology affecting multiple organ systems
has been suggested that expression of
.The role of vascular injury in the
adhesion molecules primes the vascular
pathogenesis of SLE has been well
endothelium for subsequent injury, as
described {Belmont et al ; 1999, Cronstein
reflected by increased release of thromb-
omodulin (TM) into the circulation
complexes of auto antibodies and self-
(Belmont et al; 1997 , Boehme et al ;2000).
antigens are deposited in the vascular walls
TM is a cell-surface glycoprotein
of SLE patients and activate the
located at the luminal surface of the
complement pathways .The resulting
vascular endothelium and acts as a
complement products stimulate leucocytes
membrane bound; high-affinity thrombin
to injure the vascular endothelium, leading
receptor (Dittman and Majerus; 1990).It
Refree: Prof; Dr. Azza Shawky Ghanem

Full Paper (vol.13 paper# 1)

Granulocyte macrophage-colony stimulating factor levels in bronchoalveolar lavage fluid from patients with chronic bronchitis The Egyptian Journal of Hospital Medicine Vol., 13 : 14 ­ 21 Dec.2003
I.S.S.N: 12084
1687 -2002

Granulocyte macrophage-colony stimulating factor levels in
bronchoalveolar lavage fluid from patients with chronic bronchitis

Mona Hilmy Alrayes, MD* and Entesar Said Ahmad, MD**,

Department of Clinical and Chemical Pathology* and Department of Chest**.
Girls` Faculty of Medicine- Alazhar University

Background and objectives: Although inflammatory changes are found throughout the
airways of patients with chronic bronchitis (CB), the mechanisms of the pathogenesis of CB are
still unclear. The aim of this study was to investigate airways inflammation in patients with and
without an exacerbation of CB. Granulocyte macrophage-colony stimulating factor (GM-CSF)
levels in serum and bronchoalveolar lavage (BAL) fluid were assayed. Materials and methods:
40 CB patients and 10 never smoking, age and sex matched controls were studied. 20 of the CB
patients were studied under baseline conditions (B), and 20 during an exacerbation (E) of CB.
Bronchoscopy and bronchoalveolar lavage (BAL) with cytological analysis were performed for
7 males from CB(E) group, and 6 males from CB(B) group. The levels of GM-CSF were
determined in sera and in BAL supernatants by a solid phase enzyme immunoassay. Results:
There was high significant elevation of serum GM-CSF in both CB (E) and CB(B) groups in
comparison with the control group (P<0.0001 & P=0.002 respectively). Both serum and BAL
GM-CSF levels were elevated in CB(E) group in comparison with CB(B) group (P=0.0001 &
P=0.009 respectively). Also there was significant elevation of BAL neutrophils, eosinophils and
lymphocytes in CB(E) in comparison with CB(B) (P<0.05, P<0.01 and P<0.01 respectively).
There was only significant positive correlation between BAL GM-CSF and BAL neutrophils
count in CB(E) group, while no significant results were detected in CB(B) group. Conclusion:
During exacerbations of CB there were changes in the cell populations in BAL of patients
consistent with a recruitment of polymorphonuclear leucocytes, eosinophils and lymphocytes in
the airway lumen. These recruited different inflammatory cells could work together toward the
production of airway abnormalities and lung destruction. The locally elevated levels of BAL
GM-CSF might be a cause and /or a result suggesting a role for this cytokine in the
inflammatory processes of chronic bronchitis. The elevated levels of serum GM-CSF in chronic
bronchitis may be due to the interference of other cytokines, microenvironmental factors in bone
marrow and/or other factors.

Chronic bronchitis (CB) is a clinical
pathogenetic mechanism of chronic sputum
syndrome defined by cough and chronic
production is still unknown. CB is
sputum production occurring on most days
associated with intermittent exacerbations
of the month for at least 3 months a year
during the two years prior to the study.
exacerbations [CB(E)]) that present with
Sputum is defined as expectorated lower
worsening of the chronic symptoms of
respiratory tract secretions and is composed
productive cough and dyspnea. These
of fluid and cellular components, including
exacerbations cause considerable morbidity
macrophages, bronchial epithelial cells and
and in patients with concomitant airway
inflammatory cells (Seatta et al, 1997). The
obstruction are major causes of mortality.
major risk factor for the development of CB
CB(E) can have one or more of several
is cigarette smoking, but the precise
different etiologies

Full Paper (vol.13 paper# 2)

I.S.S.N: 12084
"Development Of Primary Health Care Based On District Health
System Strategy In Egypt"

Eltobgy A.1, El-Henawy A.2, El-Moselhy E .1, and Osman A.1

1Community Medicine Department, Faculty of Medicine, Al-Azhar University, Egypt.
2Urban Health Department, Ministry of Health and Population, Egypt


The study aimed to improve the qualitative and quantitative aspects of primary health care
(PHC) services within the context of the District Health System (DHS) approach in Egypt. A
cross-sectional analytical research design was chosen to investigate the current research
problem. The study samples included 9 health districts, 35 district hospitals and 201 primary
health care facilities chosen randomly from eight governorates. The results revealed that the
sampled districts (management level) are suffering from many administrative and technical
problems. Analysis of district hospitals and PHC units' data showed that they have a severe
defect in regarding to most of the studied essential elements. The researchers concluded that the
concept of DHS based on PHC as proposed by the WHO is not very clear to the majority of
directors but a very well infrastructure is present allover Egypt that will help in the process of
system development and institution to a great extent if properly planned and organized.


Governmental health care systems are
programs were launched e.g. Extended
normally integrated into the national
Program of Immunization (1977); Selective
administration, thus being characterized by
Primary Health Care (1979); Child Survival
the centralized organizational structures.
and Development Revolution (1982); Safe
Three levels usually describe the providing
Motherhood Initiative (1986); and Better
structures. The Primary Health Care (PHC)
Health through Family Planning (1987).
level comprises basic promotive, preventive
Given that the vertical nature of these
and curative services. The secondary care
programs undermined the holistic idea of
level stands for referral hospitals with broad
the PHC concept, they were heavily
criticized. They were considered as move-
services with high standards can be found
ments, of which "each has characteristics of
in national hospitals on the tertiary care
level. The paradigm of PHC forwarded
simplicity of a program or activity" (Chen,
different strategies e.g. establishment of
community based health care initiatives.
Currently the emphasis of health
These efforts turned out to be rather short
systems development aims at the district
lived due to the lack of a clearly defined
level as an intermediate level between the
framework (Matomora, 1995).
central national structures and the
Since the International Conference on
community based structures of the pure
PHC, held at Alma-Ata in 1979, the call of
PHC approach (WHO, 1987a).
health for all by the year 2000 through PHC
The term "district" denotes a clearly
has provided a motivational and unifying
defined administrative unit of local
concept in international health development
government, which commonly has a
(WHO, 1995a). Murray (1990) clarified
population of between 50,000 and 500,000.
that after the introduction of the primary
Its small enough to allow for clear
health care concept, a variety of vertical
diagnosis of the problems and needs of its

Full Paper (vol.13 paper# 3)

Protective Effect Of Oral And Intranasal Bacterial Lysates In Mice The Egyptian Journal of Hospital Medicine Vol., 13 : 37 ­ 56 Dec 2003


Protective Effect Of Oral And Intranasal Bacterial Lysates In Mice

Hanaa, A. Mansour* and Maha G. Soliman**
*Pharmacology Department (Medical microbiology and immunology unit), National
Organization for Drug Control And Research (NODCAR).
**Zoology Department, Faculty of Science ( girls ) , Al Azhar University.


In this study albino mice were used to test the beneficial effect of bacterial lysates
vaccination against lethal dose of Pseudomonas aeroginosa. Escherichia coli lysate,
Pseudomonas aeroginosa lysate, Staphylococcus aureus lysate
and mixed bacterial lysates were
administered through the oral and the intranasal routes, both in the presence and absence of
Freund's adjuvant versus a placebo. Pseudomonas aeroginosa fifty percent lethal dose ( LD50 )
was injected intraperitonealy following intranasal and oral vaccination. The placebo and the
four bacterial lysates were also used in association with Freund's adjuvant. The results of
the LD50 in intranasal vaccinated groups were 50%, 37.5%, 100%, 0% and 12.5%, and
those with Freund's adjuvant were 25%, 25% , 12.5%, 62.5%, 0% and 0% respectively. The
results of LD50 in oral vaccination were 50%, 25%, 62.5% 0% and 37.5%, and those treated
with Freund's adjuvants were 12.5%, 12.5 %, 12.5%, 37.5 %, 0% and 25% respectively. The
bacterial lysates vaccinated groups were studied for the total body weight (T), liver (L),
spleen (S), thymus (Th) weights and the L+S+Th/T ratio. Besides, the peripheral blood and
the peritoneal fluid total and differential leucocytic counts were determined and the
bone marrow lymphocyte percentage. The serum immunoglobulins G and M were
assessed using the immundiffusion plates. Our conclusion is: Bacterial lysates can play an
important role as immunomodulators when used by oral or intranasal routes.


Few substances have a greater
and safe even in young or pregnant animals
positive impact upon health care mana-
,an example is Leptospira vaccines
gement than antibodies, vaccines and
(Kurstak, 1994).
adjuvants . For most of this century, these
Rutishauser et al. (1998) showed
immunological agents have enjoyed wides-
that the use of an oral bacterial lysate
pread medical applications, predominantly
was effective in patients with recurrent
for the treatment, prevention of infectious
respiratory tract bacterial infections. Their
diseases. Technologies are evolving that are
study demonstrated that the use of an oral
leading to safer, more effective and more
bacterial lysate consisting of the antigens of
cost- efficient vaccines. In Europe, a killed
seven bacteria commonly involved in
bacterial is referred to as a bacterial
respiratory tract infections has been
vaccine, while in the United States a killed
developed for the induction of specific and
bacterial product is referred to as a
non specific immune responses of the
bacterin and the term vaccine is reser-
mucosa ­associated lymphoid tissue. Tablet
ved for an immunizing agent that
formulation were taken once daily during
contains live inactivated microbial compo-
two periods of four weeks each. The
nents (Bey et al, 1997) . Inactivated
clinical severity score was significantly
whole bacterial cell suspensions are
lower in patients treated with bacterial
probably the most common type of
lysate compared to patients given placebo.
vaccine used in domestic animals. These
The infection rates revealed reduction of
vaccines proved to be extremely effective
39% in children and reduction of 44% in

Full Paper (vol.13 paper# 4)

ABSTRACT The Egyptian Journal of Hospital Medicine Vol., 13: 57- 65 Dec.2003
I.S.S.N: 12084

Evaluation Of The Potential Mutagenic Effects Of Ginseng On Maternally
Treated Postimplanted Mouse Foetuses

H.M. El Ashmaoui, S. M. Girgis and Abd El Raouf, A.
Cell Biology Department, National Research Centre, 12622 ­ Dokki, Cairo, Egypt

The aim of this study was to evaluate the potential mutagenic effects of ginseng (herbal
medicine) on maternally treated postimplanted mouse foetuses. A total of 60 adult albino female
mice were used and divided into 6 groups (10 females each). The first group (I) served as a
control group and received oral doses of the vehicle (0.5 ml disteled water ) for 60 days before
pregnancy to 13th day of pregnancy. The rest 5 groups received orally 4mg/ of ginseng
for 7, 14, 30, 45 and 60 days before day 0 of gestation and extended to 13th day of pregnancy.
Then 6 females of each group were sacrificed, feotuses sample from each female were taken and
subjected to cytogenetic analysis. The rest females of each group (4 females) were continuously
treated and sacrificed at day 17 of getation, foetuses were examined morphologically and for
different features such as implanation sites, living feotuses, resorbed foetuses and foetus body
weight. Chromosome analysis of the present study (Table 1) revealed that there were numerical
aberrations (peridiploidy). There was a difference only between group II and III in respect to
hypodiploid (2n-), meanwhile, hyperdiploid (2n+) were more frequent in group IV and VI than
that in control group (group I). For the total numerical aberrations, there were significant
differences between groups II, VI compared to the control group. All groups had little
frequencies of structural aberrations especially for chromatid gaps, breaks and fragments. There
were a significant differences between group IV and VI compared with the control group for the
deletions. Chromosome breaks were more frequent in the groups III and IV compared to the
control group, whereas groups V, VI had more frequencies of centromeric attenuations than the
control group. There were no differences between control group and the rest of all groups
investigated for implantation sites, living foetuses and resorbed foetuses (Table 2), whereas for
gross malformation, 5.41 % of group VI where abnormal and the rest of all groups had no
malformations. For the mean fetal body weight, there was a significant difference among the
control group (I) and the groups number II, III and VI. We conclude that treatment with ginseng
as a herbal medicine may cause fetal chromosomal aberrations as well as gross malformation
especially when taken for a long time and extended during pregnancy. So, we recommend that
the use of ginseng during first trimester of pregnancy should be with caution.

Key words:
Panax ginseng, mutagenicity, maternally treated, foetus, chromosomal aberration,


Ginseng (Panax ginseng) is a commonly
and Canada; and 3) P. notoginseng, grown
used herbal medicine world-wide (one
in southwest China. Siberian ginseng is not
meant to be taken regularly that has
ginseng at all, although it is in the same
cumulative strengthening effects). There are
family (Araliaceae) and is also used for its
several varieties of ginseng . The three
tonic effects.
Panax species commonly used in herbal
medicine are: 1) P. ginseng, grown in
(ginsenoynes A-K) and sesquiterpenes.
P.quinquefolius, grown in the United States
Ginsenosides are believed to be major

Full Paper (vol.13 paper# 5)

Immuno-histochemical study of the expression of Bcl2 in the skin of mice under the effect of exposure to ultra violet rays type-B, before and after local Rotinoic acid The Egyptian Journal of Hospital Medicine Vol., 13 : 66 ­74 Dec 2003


Immuno-histochemical study of the expression of ICAM-1 in the skin
of mice under the effect of exposure to ultra violet rays type-B, before
and after topical Retinoic acid

Somaya H. Mohamed*, Fouad M. Badr*, Howayda Abed El-Aal,Rushdy W.
Mohamed, and Bassem S. Ahmed

From Departments of Histology*, Pathology and Dermatology Suez Canal Faculty of
Medicine and Histology department Al-Azhar Faculty of Medicine - Assuit

The exposure to ultraviolet radiations (UVR) become a medical problem, not just
cosmetics or aesthetic concern, but for their skin photoaging and photodamage.
The naturally and synthetic derivatives of vitamin A (Retinoids) may have a role in
treatment and prophylaxis against skin photodamage.
The current work studied the effect of ultraviolet-B rays on the ICAM-1 expression of
mice's skin, before and after topical retinoids acid.
Thirty-six mice were subjected to ultraviolet-B rays in dose of 1.4J/cm2 for 15minutes
every other day for 10weeks. The mice were subdivided into 3 equal groups; Radiated,
Prophylactic, Treated, besides the non-exposed skin samples, which considered as control
group. The prophylactic mice were subjected to topical Retinoic acid one day before UVR
exposure, the mice of treated groups were subjected to topical Retinoic acid after the last UVR
exposure 3times weekly for 10weeks.
Paraffin sections slides were prepared and stained with Hematoxylin and eosin stains for
study the morphology.
The immuno-histochemical study for detection of ICAM-1 expression was performed
using labeled streptavidin biotin technique (Dako) with the monoclonal antibody {ICAM-1 (G-
The ICAM-1 expression was evaluated as optical density, and the obtained data was statistically
analyzed by using student's t-test.
The study revealed a clinical signs of photodamaged skin only in radiated group mice.
Histologically epidermal thickness associated with keratinocytic atypia, and necrotic cells were
observed in radiated group mice. There was a statistically significant increase in the optical
density of ICAM-1 expression in radiated and prophylactic groups mice (p<0.001 and p< 0.005
The study concluded that retinoic acid given after UVB completely reversed the
morphological, histological and ICAM-1 expression changes induced by UVB exposure and
retinoic acid given before UVB prevented some of the morphological, histological and ICAM-1
expression changes induced by UVB exposure.

Repeated exposure to UVR leads to
beds have become a popular source of
chronic changes in the appearance and
artificial UVR (Fitzpatrick, 1997).
function of the skin described as
Photoaging and photodamage include;
Photoaging and photodamage (Kaminar,
wrinkles (fine and coarse), roughness,
1995). The most prevalent and well-known
source of UVR is the sun. Phototherapy is
(lentigines and keratosis), scaling, xerosis
an additional potential source and tanning
and telangiectasia (Leyden, 2001).

Full Paper (vol.13 paper# 6)

Quantitative microscopical and histochemical study of the skin of mice under the effect of exposure to ultra violet rays type- The Egyptian Journal of Hospital Medicine Vol., 13 : 75 ­ 89 Dec 2003


Quantitative microscopical and histochemical changes in the Liver and
Testis of adult rabbit under the effect of oral intake
of cotton seeds Gossypol

Hassan S. El-Dawi, Ahmed N. Al-Kasaby, Bassem S. Ahmed*
and Amir M. Al-Nagar*
Histology Department, Faculty of Medicine Al-Azhar University Cairo and Assuit*

Gossypol is a natural yellowish phenolic compound (dimeric or bis-naphthalene) isolated from
the seeds of cotton plants (Gossypium species).
The aim of the present work was to study the possible microscopical and histochemical
changes in the liver and testis of adult rabbit under the effect of oral intake of cotton seeds
Eighteen 6month age adult male rabbits were subdivided into 3 equal groups (control,
experimental and recovery). The experimental and recovery groups were subjected to 1.05mg/day
Gossypol suspended in olive oil intubation for 9weeks and the recovery rabbits were left 9weeks
after last dose.
Liver and testis paraffin sections were processed and stained with Hematoxylin and eosin stain
for morphological changes. Glycosaminoglycans in the seminiferous tubules were stained by PAS
technique. Studying of the nucleic DNA in the spermatogenic cells was done by Feulgen technique.
Quantitative study included seminiferous tubules thickness; spermatogonia and primary
spermatocytes cell areas. Also the distribution of PAS positive materials analyzed as area percent
and nucleic DNA as optical density. All analysis was done by the aid of image analysis System.
The study showed that liver was affected by gossypol administration. The changes appeared as
distinct pinpoint foci of coagulative necrosis, vacuolar degeneration of hepatocytes and dilation of
the sinusoids with mild perivascular lymphoid aggregation.
The testis showed distortion loss of spermatogenic cells, Sertoli and germ organization under
the effect of gossypol. Sertoli cells showed an intracellular vacuolization. Also, there were luminal
multinucleated giant cells as well as a prominent DNA fragmentation in the spermatogonia nuclei.
The quantitative study showed statistically significant decrease in the mean thickness of
seminiferous tubules , the mean area of spermatogonia, and primary spermatocyte , mean area
percent of distribution of PAS positive materials of seminiferous tubules and a significant increase
in the mean optical density of nucleic DNA of spermatogonia affinity to Feulgen stain in
experimental group, (p<0.001). After 9weeks recovery periods most of the morphological and
quantitative changes were still present.
The study concluded that gossypol has a toxic effect on the liver and testis of rabbits and their
toxicity may be more prominent in humans.
The study recommend restriction of uses of cotton seed oil in human uses and further study on the
possible risk of uses of cattle fed on cottonseed meals.


Full Paper (vol.13 paper# 7)

Indices of Free Testosterone And Hyperandrogenemia in Relation The Egyptian Journal of Hospital Medicine Vol., 13 : 90 ­ 98 Dec 2003


Indices of Free Testosterone And Hyperandrogenemia in Relation
To Hirsutism in Middle Aged Egyptian females

*Kandil H.T., * Hassan Z.A., * Abaza D.M. ** Abd. El Fattah . A.M.

* Endocrinology and ** clinical pathology
Departments- Al- Azhar university (Girls)

Hirsutism is an androgen excess related disorder that commonly affects women causing a
variety of negative metabolic disturbances. Early and accurate diagnoses of androgen over-
production or hypersensitivity to normal circulating androgen have an important implication for
treatment and follow up of patients.
The aim of this work is to study the validity of hyperandrogonemic index (HAI) and index
of free testosterone (IFT) in, diagnosis of hirsute Egyptian women, and its correlation to hair
score as a clinical marker for hirsutism.
Twenty-four hirsute women aged 19-32 y's, median (24.25 ± 4.3) were studied. Ten age
matched nonhirsute females, were studied as controls. Patients and control were subjected to the
following, full history and clinical examination. Biochemical and hormonal parameters were
measured, fasting blood sugar (FBLS), 2 hours post prandial blood sugar (2h pp BL. S), serum
total testosterone (TT), free testosterone (FT), dihydroepiandrosterone (DHEA),
Dihydroepiandrosterone sulphate (DHEAS) androstenedion (ADION), prolactin (PL) and sex
hormone binding globulin (SHBG). Index of free testosterone (IFT) and index of
hyperandrogenemia (IHA) were calculated. Results showed significant higher BMI (P< 0.009),
2hrs PPBLS. (P< 0.001), TT (P< 0.005), FT (P< 0.000), SHBG (P< 0.02) and (ADION) (P<
0.000) in hirsute females compared to controls. Hair score was positively correlated with IFT
only while it was not correlated with all of the measured hormones.
FT was positively correlated with BMI (P< 0.004), FBLS (P< 0.001) and 2hrs PPBL.S (P<
0.000). While TT was positively correlated with BMI (P< 0.001). Androstenedion was
positively correlated with systolic BL.P (P< 0.000), diastolic BL.P (P< 0.02), FBL.S (P< 0.001)
and 2hrs PPBL.S (P< 0.000). IFT was positively correlated with hair score (P< 0.05), BMI (P<
0.01), systolic BL.P (P< 0.004), FBL.S (P< 0.001) and 2hrs PPBL.S (P< 0.01).
SHBG was negatively correlated with systolic BL.P (P< 0.04), FBL.S (P< 0.05) and 2hrs
PPBL.S (P< 0.03).

Hirsutism is a clinical symptom associated with hyperandrogenism. It must be diagnosed
accurately, and as early as possible. The most accurate diagnostic measurement is IFT rather
than IHA or other hormones individually.
Hirsutism must be studied in depth not as a simple complaint, as it may be the entrance to the
more complex metabolic syndrome.
IFT is beneficial in diagnosis of borderline hirsute women.


Hirsutism is one of the most common
more likely, a nonserious medical problem;
endocrine disorders in women of fertile age.
(George et al 2003).
In these women, the hairiness implies the
Increased androgen production causes well-
presence of abnormal androgen level / or
documented negative metabolic changes,
action, which may represent a serious or,
(Conway et al 1992). Those women are at

Full Paper (vol.13 paper# 8)

Influence of ionizing radiation on Cobra (Naja haje) and Cerastes cerastes venoms: Toxicological and immunological aspects The Egyptian Journal of Hospital Medicine Vol., 13 :99 ­ 111 Dec 2003


Influence of ionizing radiation on Cobra (Naja haje) and Cerastes
cerastes venoms: Toxicological and immunological aspects.

Esmat A. Shaban
Assistant Professor, Drug Research Departement,
National Center for Radiation Research and Technology,
Atomic Energy Authority.

The effect of gamma irradiation (15 KGy) on the Cobra Naja haje and Cerastes cerastes
venoms toxicity and immunogenicity was evaluated. Irradiated venoms were at least 28.1% less
toxic than non-irradiated venoms. However the antigenic response was not changed as judged
by the capacity of irradiated venoms to react with polyvalent antivenom horse serum. The
immunodiffusion method showed identity between irradiated and non-irradiated samples.
The effect of gamma radiation on some venom enzymes and venoms profile was studied.
Proteolytic, phospholipase A2 and hemorrhagic activities were inhibited by irradiation.
Irradiation with gamma rays resulted in structural changes in the venoms as indicated by the
changes in their molecular weights.
The results indicated that irradiation of toxic protein -using suitable dose- can promote
significant detoxification but still retaining many of the original antigenic and immuonological
properties of native venom.


Venoms in general are weakly
physicochemical changes that can alter their
immunogenic, yet fairly toxic (Magalhaes,
primary , secondary or tertiary structures,
1986). This causes problems because
while keeping many of their native
serotherapy is the treatment of choice in
immunological properties intact (Shalka
snake bite-accidents and horse antisera
and Antoni , 1970). Lauhatirananda et al.,
availability is dependent upon venom
(1970) observed that several functions of a
immunogenicity. To improve antisera
protein have different radio-sensitivity and
production and extend the useful life of
that its antigenic properties are the most
immunized horses much effort has been
radioresistant. Hati et al., 1990 showed that
devoted to decrease chronic venom toxicity.
Russell viper venom was detoxified by
Several techniques have been used to
gamma radiation (100 Krad or 200 Krad)
detoxify venoms such as mixing the venom
and used for active immunization of rabbits.
with carboxymethlycellulose (Moroz et
Shaban (1990) found that irradiation of
al.,1963), irradiation by gamma rays
Androctonus amorexia scorpion venom
(Baride et al ., 1980), adding formaldehyde,
with gamma rays in dry state (15 and 30
(Costa et al., 1985), controlled iodination
KGy) decreased its lethal and toxic activity
(Daniel et al., 1987) and encapsulation of
while retaining its antigenicity. Therefore,
purified toxins in liposomes (Freitas and
irradiation of toxic proteins can promote
Frezard, 1997).
g n i f i c
n t
d e t
xi f i
a t i
but still retain
One method that has been shown to
many of the original antigenic and immuno-
be effective for attenuating venom toxicity
logical properties of native venom.
and maintaining immunogenicity is gamma
Snake venoms are complex mixtures
radiation (Baride et al., 1980; Hati et
which may show qualitative differences in
al.,1990; Shaban, 1990; Mandal et al.,
their composition not only between species
1993, Nascimento et al., 1996).
but also from individual to another
Proteins irradiated either in the dry
(Tu,1977). Cerastes cerastes and Naja haje
state or in solution undergo chemical and
snakes one belong to family Viperidae and

Full Paper (vol.13 paper# 9)

Hormonal Profile And Histopathological Study On The Influence Of Silymarin On Both Female And The Egyptian Journal of Hospital Medicine Vol., 13 :112 ­ 122 Dec


Hormonal Profile And Histopathological Study On The Influence Of
Silymarin On Both Female And Male Albino Rats

Enas A.M.Khalil

National Organization for Drug control and Research


Silymarin is a mixture of flavonoids extracted from seeds of milk thistle (Silybum
marianum [L] Gaertn ). Extracts of S. marianum have been used in the treatment of liver
diseases for more than 2000 years.
Flavonoids are a large group of polycyclic phenols of plant origin. Flavonoids displaying
estrogenic effects (phytoestrogen).
Phytoestrogens show an estrogenic activity owing to the structural similarity with the
estrogen skeleton ,mimicking natural estrogens, it binds to estrogen receptor and modulates its
activity . These effects cause complex changes inducing a shift in an overall hormonal balance
of the individual. Long term intake of feeds with a higher content of phytoestrogens can induce
transient or permanent infertility.
Silybum marianum leaves have been traditionally used in Egypt for their antifertility
effects .Also, the antifertility property of silybum marianum leaves was investigated in female
albino rats. This property highlights the impotance to clarify the role of silymarin (420mg /day )
a human therapeutic dose on both female and male albino rats.
Silymarin (151.2 mg/kg BW) prevented pregnancy in adult female albino rats on days 1-5
post coitum. In female rats the follicle stimulating hormone (FSH) displayed marked increase,
while the luteinizing hormone (LH) and estradiol remained within normal levels. These results
showed a distinct increase in number and size of ovarian growing follicles while the effect of
silymarin on the uterine wall was in the form of hypertrophy of endometrial epithelium, also
increase in the number of uterine glands. Ovaries taken from females treated with silymarin for
one and two months contained a large number of growing follicles.
In male rats treated with silymarin (151.2 mg/kg BW) for one month, testosterone and LH
were increased significantly, meanwhile estradiol not changed. Testes of rats treated with
silymarin for one month showed well developed spermatogenesis with lot of sperms. The
epididymis of the same group contained a heavy number of sperms. While rats treated with
silymarin for two months displayed significant decrease in serum testosterone levels, while LH
and estradiol not changed. These rats displayed some tubules contained well developed
spermatogenic layer and normal leyding cells, others appeared moderated by affected. The
epididymis contained less number of sperms.
These results indicated that silymarin (151.2mg /kgBW) a dose equivalent to human
therapeutic dose (420mg/ day) prevented pregnancy in female rats and caused some histological
changes in the ovary and uterus, while it has biological benefits for male rats during short


Silymarin is a mixture of flavonoids
Bombardelli,1995). Silymarin is a hepatop-
extracted from seeds of milk thistle
rotective (Schriewer et al.,1975), cytopro-
(silybum marianum [ L.] Gaertn ) which
tective (Valenzuela et al. ,1985; Valenzuela
contains silybin, silydianin , and silychristin
et al. ,1987; Muriel et al.,1992 ; Schonfeld
as the major constituents. (Morazzoni and
et al. ,1997; Sonnenbichler et al. , 1999),

Full Paper (vol.13 paper# 10)

A Six -Year Clinical, Microbiological and Radiological Study Outcome Following Treatment of Peri-implantitis The Egyptian Journal of Hospital Medicine Vol., 13 :123 ­ 134 Dec


A Six -Year Clinical, Microbiological and Radiological Study Outcome
Following Treatment of Peri-implantitis

Abeer, S. Gawish* and Susan, A. Hassan**

Lecturer of Oral Medicine, Periodontology, Oral Diagnosis and Oral Radiology, **
Associate Professor of Oral Maxillofacial Surgery,
Faculty of Dentistry, for Girls, Al Azhar University


The present study evaluated the long-term outcome of a combined surgical and
composite graft (bovine porous bone mineral BPBM and autogenous bone) in the
treatment of peri-implantitis. Six individuals with titanium implants demonstrating a
marginal bone loss. Baseline ,1 and 6 years measurements, including introral digital
radiographs, gingival index (GI), probing depth(PD) and probing bone level (BL) were
performed. In each implant subgingival bacterial samples were obtained and subjected
to microbiological analysis by culture. Surgical exposure of the lesions and cleaning of
the implants using hydrogen perioxide and2% aqueous solution of chlorohexidine
gluconate were performed. The autogenous bone was harvested from the chin combined
with BPBM and packed into the bony defects. The treatment was evaluated clinically,
microbiologically and radiographically at 1 and 6 years. Results: revealed a significant
reduction in plaque and gingival bleeding. The mean probing depth was 6.94+ 1.16 at
the baseline and it was 1.91 + 1.21 at the end of the study period. All treated implants
showed bonegain. The mean gain in bone level was 5.12 + 0.5 and radiological
evaluation of bone density was measured at crest, mid-implant and lateral apical area of
interest AOI 32.0 + 0.87, 72.91 +0.83, 63.0 + 0.94 at baseline and it reached 109.5 +
0.53, 141.63 + 1.19 and 144.0 + 0.47 respectively. The presence of putative periodontal
pathogens significantly declined at the end of the study period.
The results of the study suggest that the use of composite bone grafts as the treatment
strategy for peri-implantitis lesions with maintenance of good oral hygiene appears to be an
efficacious treatment approach for restoring hard tissue support of dental implants during the 6
year follow-up period.


Implant dentistry is a relatively new
negative bacteria similar to periodontitis
and fast growing area of oral health services
(5). Peri-implantitis has been associated
(18). Successful treatment results and
with gram- negative bacteria similar to
patient satisfaction with dental implant
periodontitis (20). The goal of implant
dentistry today should be the control of
prevention and treatment of peri-implant
periodontal pathogens in the oral cavity.
Once a peri-implant inflammatory process
periodontitis are often described as
starts, implant sites get compromised by
inflammatory diseases with oral pathogens
severe loss of peri-implant supported bone.
emerging either at implants, within the
Meffert et al, (21) classified implants
intraimplant components or teeth. Peri-
with complication into three types: Ailing
implantitis has been associated with gram-
implant in which bone loss accompanies

Full Paper (vol.13 paper# 11)

Ability of Gamma-Irradiated Polyvalent Antivenin to Neutralize the Toxicity of the Egyptian Cobra (Naja haje) Venom The Egyptian Journal of Hospital Medicine Vol., 13 :135 ­ 152 Dec


Ability of Gamma-Irradiated Polyvalent Antivenin to Neutralize the
Toxicity of the Egyptian Cobra (Naja haje) Venom

Esmat A. Shaban* and Manar N. Hafez**

*Drug Rad. Res. Dept. and **Rad. Biol. Res. Dept.
National Center for Radiation Research and Technology,
Atomic Energy Authority, Cairo.


In this study, the lethality as well as the biochemical and histological effects of Cobra
(Naja haje) envenomation at a sublethal dose has been investigated in mice and rats.
The venom injected intraperitoneally in rats (0.2 mg/kg) produced marked increase in the
activities of ALT, AST, ALP and LDH. Also, serum glucose, urea and creatinine levels were
significantly elevated. These results are in accordance with the histological findings of the liver
that showed vacuolated hepatocytes and scattered necrotic and haemorrhagic areas together with
congestion and dilatation of blood vessels and sinusoids. The spleen also displayed small
diffuse white pulps with ill-defined outlines and extravasation of blood that extended to
infiltrate the widened sinusoids. The venom also produced severe degeneration of the cardiac
muscle with loss of striations and extensive haemorrhage inbetween the myocardial bundles.
These biochemical and histological envenomation disorders, were markedly and
effectively neutralized by the polyantivenins (non-irradiated and gamma-irradiated in a
sterilizing dose of 25 kGy). The neutralization ability of both antivenins was the same against a
lethal dose of the venom (2.5 LD50). The minimal protective dose of the polyantivenins was
calculated to be 16000 µg/20 gm mouse. Rats injected with mixtures of venom and antivenins
(non-irradiated and irradiated) showed a decrease in all elevated biochemical parameters
investigated. The histological examination also showed less severe injuries in all organs
examined (liver, spleen and heart) which appeared more or less normal with very few
abnormalities remaining.
Comparative study was also done on these antivenins using immunodiffusion technique
which showed the same precipitin bands with the tested venom. Thus, it can be concluded that
both antivenins (non irradiated and 25 KGy gamma-irradiated) have similar immunoglobulins
and have no differences in their antilethal and enzymatic neutralizing ability as well as in
ameliorating the degree of tissue damage induced by the venom.


Poisoning by snake bite is a real clinical
Cerastes cerastes, etc.... A polyvalent
problem, espesially in tropical areas, and
antivenin prepared against Naja haje,
efficacious treatment should, therefore, be
Cerastes cerastes, Cerastes viper and Naje
available. Since the beginning of this
nigrocolus is widely used in Egypt in the
century, antivenom serotherapy constitutes
the major therapeutic approach (Chippaux,
vaccines and sera are prepared under
aseptic conditions and filtered through
In Egypt, there are many varieties of
bacterial filters. This procedure involves an
snakes, some of them cause severe damage
extensive and strict aseptic conditions
to snake bite victims like Egyptian Cobra,
which makes the product very expensive.

Full Paper (vol.13 paper# 12)

ž’ The Egyptian Journal of Hospital Medicine Vol., 13 :153 ­161 Dec 2003


Interleukin ­18 and other inflammatory cytokines as independent predictors
of diabetic nephropathy in patients with type 2 diabetes mellitus.

Sahar M.Shawky *; and Eman A. Ismail**

Internal Medicine* and Clinical Pathology ** Departments.
Faculty of Medicine, Ain Shams University


Diabetes Mellitus is a very common cause of glomerular disease in adults and is a very
common cause of end stage renal failure. The pathogenesis of diabetic nephropathy is not
completely understood dispite extensive investigations. Involvement of the kidneys in patients
with diabetes mellitus includes not only hyperglycemia, advanced glycosylation products but
also activation of proinflammatory cytokines. Data about the relationship of inflammation to
nephropathy in type 2 diabetes mellitus are scarce.
Our study was conducted to compare levels of interleukin - 18 ( IL- 18), tumor necrosis
factor-alpha.( TNF- ) and interleukin- 6 (IL-6) in serum of diabetic patients with various
degrees of nephropathy. The study included 50 patients and 35 normal control subjects
presented at Ain Shams University Hospitals. The diabetic subjects were divided into 3groups
according to urinary albumin excretion ( UAE):
o Group I : included 22 subjects with UAE < 30 g/mg creatinine i.e diabetic patients
with normoalbuminuria.
o Group II : included 20 subjects. with UAE 30 to 300 g/mg creatinine i.e. diabetic
patients with microalbuminuria .
o Group III : Included 8 subjects with UAE > 300 g/mg creatinine i.e. diabetic patients
with macroalbuminuria.
The serum levels of IL­18, TNF- and IL-6 were measured for the control group to
determine the normal values and for all diabetic subjects with various degrees of nephropathy .
The results revealed highly significant statistical differences in serum levels of IL-18,
TNF- and IL-6 between the patients and control subjects. In addition, IL-18 levels were
increased in diabetic patients with proteinuria as compared with those without proteinuria. Also
TNF- and IL-6 in diabetic patients with microalbuminuria and clinical albuminuria were
significantly increased as compared with diabetic patients without albuminuria.
These results suggest that serum levels of IL-18, TNF- and IL-6 may have
etiopathogenic roles in diabetic nephropathy and are independent predictors of UAE in type 2
diabetes mellitus. So, in addition to metabolic and hemodynamic factors, it is possible to
consider the participation of inflammation on the pathogenesis of diabetic nephropathy.


Nephropathy is a major contributor to
arterial blood pressure ( Timothy et al.,
overall morbidity and mortality in diabetic
2000 )
patients( Dipetrillo et al., 2003 ).
Diabetic nephropathy is one of the
Diabetic nephropathy is a clinical
leading causes of chronic renal failure.
syndrome characterized by persistent
Although both type I diabetes mellitus and
albuminuria > 300 mg/day, with a decline
type 2 diabetes mellitus lead to end stage
in glomerular filteration rate, and elevated
renal disease, the great majority of patients
Refree : Prof ; Dr. Badowi Labib.
Refree : Prof ; Dr. Salwa Aboul-Hana.

Full Paper (vol.13 paper# 13)