Materials and Methods The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 233­ 272

Role of melatonin in modulation of oxidative stress induced by delta-
aminolevulinic acid in adult male albino rats.

El-Sawi, MR, Badawy, ME and El-Gharieb, NM.
Zoology Department, Faculty of Science, Mansoura University.


Backgrounds: Delta-aminolevulinic acid (ALA) is a heme precursor that accumulates in
acute intermittent porphyria (AIP) due to enzymatic deficiencies in the heme biosynthetic
pathway, its accumulation has been associated with several symptoms because it works as an
endogenous source of reactive oxygen species, which can exert oxidative damage to cell
structures. The present work was designed to examine the ability of melatonin, a well known
antioxidant and a free radical scavenger secreted from the pineal gland, to revert ALA-promoted
damage in brain, liver and kidney of rats.
Results: The present data demonstrated that chronically ALA-treated rats (40 mg / kg
body wt day after day for 14 days) exhibited very highly significant increases in
malondialdehyde (MDA) and protein carbonyl (PC) whereas the level of glutathione (GSH) was
significantly diminished in the tissue homogenates of all tested organs (brain, kidney & liver).
Among antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione
reductase (GSH-Rd), glutathione-S-transferase (GST) activities were significantly diminished
by ALA treatment. Intraperitoneal injection of melatonin (10 mg / kg body weight, every day
for 14 consecutive days) significantly ameliorated all the tested parameters. Melatonin
moderately increased SOD, CAT, GSH-Rd and GST activities, thereby counteracting the
oxidative stress induced by ALA. Nevertheless, exogenous ALA caused a strong net rise in
MDA and PC and a significant decrease in GSH when given together with ALA, melatonin
antagonized these effects and largely protected the integrity of tissue structures.
From the present data, the protection of melatonin against ALA oxidative stress is
obviously, so it is well recommended to use melatonin in patients suffering from symptoms
related to ALA accumulation.
Key words: Delta-aminolevulinic acid, oxidative stress, melatonin, malondialdehyde,
protein carbonyl, glutathione, superoxide dismutase, catalase, glutathione-reductase,


ALA is the first metabolite of the
sulfhydryl-containing enzyme; consequ-
biosynthetic pathway of the heme group. It
ently, its activity is highly sensitive to the
accumulates in the blood and other tissues;
presence of prooxidant element, which can
mainly the liver and brain of patients with
oxidize its -SH groups (Barbosa et al., 1998
hereditary porphyria (e.g., acute interm-
and Soares et al., 2003). Inhibition of ALA-
ittent porphyria) and acquired porphyria
D activity leads to an accumulation of ALA
(e.g., lead poisoning porphyria), where it
which undergoes auto-oxidation inducing
triggers serious tissue and neurological
free radicals and in this way induced lipid
damage (Bechara et al., 2006).
peroxidation (Hermes-lima et al., 1991).
ALA dehydratase (ALA-D) is an
AIP is an inherited disease, characterized
essential enzyme for all aerobic organisms
by a prophobilinogen deaminase deficiency
because it participates in the biosynthetic
and, as a consequence, accumulation of
pathway of tetrapyrrole molecules, which
ALA, primarily in the liver (Kappas et al.,
constitute prosthetic groups of physiolo-
gically important proteins such as
Pervious studies have shown, both in
hemoglobin and cytochromes (Jaffe et al.,
vitro and in vivo that ALA by it self is a
1995 and Sassa, 1998). ALA-D is a
pro-oxidant (Monteiro et al., 1989 and Neal

Full Paper (vol.28 paper# 1)

Fatma Eid & Amal A The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 237­ 249

Ultrastructural , Histological and Histochemical Study on the Effect of
Electromagnetic Field on the Liver of Pregnant Rats and Their Foetuses.

*Fatma Eid & **Amal A. Al-Dossary
*Faculty of Science , Al-Azhar University
** Faculty of Science, King Faisal University, Dammam K.S.A.


Exposure of pregnant rats to 50 Hz , 2 mT caused many ultrastructural ,
histological and histochemical changes in liver of pregnant rats and their foetuses . Highly
affected mitochondria , degenerated cristae and rER , decreased ribosomes were observed with
dystrophic changes in cytoplasm and nuclei of foetal & maternal hepatocytes with decreased
glycogen and increased collagenous fibers.
Conclusion: Protein content was highly affected. It is clear that foetal liver is more
sensitive to the electromagnetic field ( EMF ) than maternal ones.
Key words: rats, Electromagnetic Field , Liver , Foetuses.


A significant increase in the quantity
amount of glycogen in hepatocytes of rats
of the magnetic fields is inevitable throngh
exposed to both
10 and
10 T.
the rapidly increasing use of electric power.
They reported that the high level of
Many machines used in the medical field
cortisol in serum of exposed rats suggested
and household produce electromagnetic
that magnetic fields may be a stress
fields in their complex working systems. In
generating factor.
the household and industrial conditions ,
They also noticed a decrease in
human beings are often exposed to
cytoplasmic density of the rat hepatocytes
extremely low frequency ( ELF ) magnetic
exposed to the same field with irregular
fields [ Kang et al., 1993 ]. They added that
distribution of chromatin and increase in
alternating current is more harmful than the
the number of cytoplasmic vacuoles with a
static magnetic fields. There have recently
considerable loss of smooth endoplasmic
been many reports on the potential hazards
reticulum and ribosomes.
of imposed magnetic fields and the
Reduced fertility and / or altered fetal
interactions of magnetic fields with cells,
development as a response to exposure to
tissues and organs [Gorczynska &
electromagnetic fields were studied by
Wegrzynowiczt , 1991 ; Mahmoud , 2005 ;
many authors [Al-Akhras et al., 2001 ;
Frahm et al., 2006 ; Pang et al. , 2007 and
Canedo et al., 2003 ; Hong et al., 2003 ;
Parazzini et al. , 2007 ].
Feychting , 2005 ; Cao et al., 2006 and
According to Veyret ( 2003 ), The
Komazaki &Takano , 2007 ].
three main modes of interactions of the
According to Kheifets et al. ( 2005 )
magnetic fields with the body are:
children are increasingly exposed to elect-
1. direct interaction of the external
romagnetic fields ( EMFs ) at earlier ages.
magnetic fields with biological tissue
They added that the potential
2. electric fields induced in the body by
vulnerability of children to radio frequency
exposure to external electric fields.
(RF) fields have been raised because of the
3. electric fields induced in the body by
potentially greater susceptibility to their
exposure to external magnetic fields.
developing nervous system and their brain
tissue which is more conductive.
Wegrzynowiczt stated that the duration of
Increased frequency of skeletal
exposure and the strength of the magnetic
anomalies among mice foetus was noticed
fields may alter the changes in the liver cell
by Juutilainen (2005), while Frolen et al.
properties. They demonstrated increased
(1993) noticed increased number of dead

Full Paper (vol.28 paper# 2)

Prevalence of Anemia in Egypt The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 295­ 305

Prevalence of Anemia in Egypt (Al-Gharbia Governorate)

1* Ghada Z A Soliman; 2* Magdi N Azmi, & 3** Soha El-S.
1 Biochemistry; 2 Nutrition Education & Ecological Science ; 3 Nutrition.
*National Nutrition Institute, Cairo, Egypt; ** Suez Canal University, Suez, Egypt


Iron deficiency anemia is the most commen type of anemia related to mal
nutrition world wide. It represents a major problem in developing countries, especially in Egypt.
Purpose: The present study was designed to assess the prevalence and status of anemia in
Al-Gharbia Governorate in Egypt.
Material and Methods: 649 mothers and one of their sibling were chosen from different
districts with different food habits and socio-economic status.Hb were determined in mothers
and sibling. Anthropometric measurement includes measurements of height and weight was
done. Age was recorded. Education, Job, income; marital status and number of personal/family
are recorded when possible.
No severe anemia (Hb < 7g/dl) was found in any studied group (mothers or
sibling), only moderate to mild anemia was found ((Hb > 7g/dl). The prevalence of anemia in
mother's is > 47 %, which represent a problem of high degree, while, the prevalence of anemia
in sibling is 52.25 & 54.03 % for male and female respectively which represent a problem of
high degree. The cause of anemia in mothers may be due to menstrual blood loss, increased
duration of menstrual blood flow, while in children may be due to anemic mother, poor, diet,
bad food habit.
Conclusion: To reduce prevalence of anemia and improve anemic mothers, sibling status
in Egypt we needs to improve iron supplementation program
Key Words: Egypt, Anemia, Women,


The World Bank estimates that one-
cut-off hemoglobin level used to define
half of the world's population suffers from
anemia in infancy (Florentino & Guirriec
malnutrition and that two million people
1984; deMeyer & Adiels-Tegman 1985;
suffer from diseases related to iron, iodine
UNAC1 1987; and Stolitzfus 2001 a & b).
and vitamin A deficiency (World Bank
In developing countries, 40­45% of
1996). These deficiencies affect women,
children aged 0­4 y old suffer from anemia
infants and children especially those of
(ACC/SCN 2000). The main cause of ane-
developing countries. Poor eating habits
mia is iron deficiency (ACC/SCN 2000).
play a major role in the development of iron
Severe anemia increases mortality; iron
deficiency anemia that is an important
deficiency impairs behavioral and cognitive
indicator of poor health status. Children and
development and reduces fitness and work
adolescent are at increased risk of
capacity (Stoltzfus 2001 a & b).
developing iron deficiency anemia because
Anemia is caused either by limited
of their increased demand for iron during
dietary intake, excessive loss of nutrients or
growth and puppetry. In most cases, they
excessive utilization. The anemia is
are undiagnosed because of irregular, far
associated with a number of sequelae
visiting of heath clinics, doctors, and
including both structural chan-ges, like
hospitals (World Bank 1996).
mitochondrial swelling and mucosal
Iron-deficiency anemia (IDA) in infa-
atrophy, and functional abnor-malities, such
nts is a common problem worldwide and an
as cardiac failure, decre-ased work output,
enormous public health risk in developing
countries. The prevalence of anemia in

infants varies between 5% and 43%
1 UNAC: United Nations Administrative
according to the population studied and the

Full Paper (vol.28 paper# 3)

Fatma Eid & Amal A The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 306 ­ 326

Ultrastructural , Histological and Histochemical Study on the Effect of
Electromagnetic Field on the Kidney cortex of Pregnant
Rats and Their Foetuses.

*Fatma Eid & **Amal A. Al-Dossary
*Faculty of Science , Al-Azhar University
**Faculty of Science King Faisal University, Dammam K.S.A.


Results: Exposure to 50 Hz 2 mT caused dystrophic changes in kidney cortex of maternal
& foetal rats. Large degenerated areas , internal bleeding and highly affected glomeruli were
detected. Epithelial cells of distal convoluted tubules (ds) were highly sensitive to EMF than
proximal convoluted tubules (px).foetuses were more sensitive than maternal ones. Golgi
apparatus was more resistant than mitochondria .
Conclusion: Altered polysaccharides , protein and collagen were noticed in kidney of
exposed pregnant rats and their foetuses.
Key words: Rrats, Electromagnetic Field , Kidney , Foetuses.


Electromagnetic fields are a type of
terminals, microw-ave ovens, overhead
low-level radiation generated by computer
lights, power lines, and the hundreds of
terminals, microwave ovens, and other elec-
motors that can generate higher than normal
tronic devices. The Earth itself produces
gauss strengths (magnetic energy meas-
some energy fields that are detrimental to
uring unit). EMFs interact with living
human health as well, commonly referred to
systems, affecting enzymes related to
as geopathic stress. While the intensity of
growth regulation, pineal gland metabolism
these fields is small, studies show that they
(regulation of the sleep hormone, melat-
may have a role in development of a
onin), and cell division and multiplication.
number of chronic illnesses, including
In 1997, kang et al. , studied the
cancer, heart disease, and sleep disorders.
biological affect, of magnetic field 0-5 T at
Researchers once thought EMFs,
7 Hz on murine brain and kidney of mice
especially at very low and extremely low
and they noticed eosinoplilic change of
frequencies EMFs, were safe because they
cytoplasm and immunohistochemical react-
were of such low strength compared to
ion to amyloid precursor protein in the
other forms of radiation, such as those from
neurons of the cerebal cortex. They added
a nuclear reactor or X rays machimes. Now,
that thalamus and brain stem were less
as technology proliferates and people are
affected than renal tubular epithelium. They
using more electronic devices, some
observed degenerated tubules scattered in
researchers suspect EMFs are contributing
cortical area where little changes were
to a subtle assault on people's immune
observed in glomeruli and collecting
systems and overall health.
tubules in the medulla.
Electromagnetic changes in the
Ivldashev and Zufarova (2002)
environment can adversely affect the
recorded variation in the ratio of the total
energy balance of the human organism and
area of glomerular capillaries to glomerular
contribute to disease. We are surrounded by
area, indicating the asynchronism of their
stress-producing electro-magnetic fields
filling with blood.
generated by the electrical wiring in homes
In 2004, Somosy et al., proved that 50
and offices, televisions, computers, video
Hz magnetic field affected the cell

Full Paper (vol.28 paper# 4)

The role of black seed and/ or bees honey in modulating heart disorder induced by food additives in male rats The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 327 ­ 341

The role of black seed and/ or bees honey in modulating the heart disorder
induced by food additives in male rats.

Wafaa M. El-Kholy; Hanaa A. Hassan and Samar E. Nour
Zoology Department, Faculty of Science, Mansoura University


Background: The present study aimed to throw the light on the potential hazards of some
food additives whether preservatives such as sodium nitrite or colors as sunset yellow on the
heart disorders through their own effect or the interaction between them. The study also,
investigated the possible protective role of black seed and/ or bees honey against such risks.
Results: Herein, the mentioned food additives caused significant elevations in serum and
cardiac total lipids (TL), total cholesterol (TC), triglycerides (TG) and phospholipids (PL) levels
as well as serum LDL-c, VLDL-c levels and LDL-c/HDL-c ratio. Meanwhile, significant
decrements were shown in serum HDL-c level and HDL-c/TC ratio. Additionally, creatine
kinase (CK) and aspartate transferase (AST) enzymes activity were increased significantly in
serum and cardiac tissue.
Moreover, oxidative stress markers; lipid peroxidation product (MDA) and protein
carbonyl group (PC) were increased significantly in the cardiac tissue. Regarding, antioxidants;
glutathione (GSH) content, glutathione -S -transferase (GST) and catalase (CAT) enzymes
activity were decreased significantly in the cardiac tissue.
Conclusion: However, the use of black seed and/ or bees honey ameliorated the
disturbances observed indicating remarkable protection against the toxic effects of these food
additives on the heart and offers more safety. Overall, here with the most pronounced effect was
achieved by the combined treatment. In addition, the treatment by bees honey was more
effective than black seed.
Keywords: Food additives,sunset yellow,sodium nitrite,rats.


Food additives are common in our life
inflammatory response and tissue injury
and play an important role in human being's
life. They are substances that not normally
carcinogenesis (Choi, 1985) and endocrine
consumed as a food by itself and not
disturbance (Jahries et al., 1986).
normally used as a typical ingredient of the
Alternatively, food colors are an
food, whether or not it has a nutritive value
important characteristic and selection
(Ismail et al., 2003). The principle classes
criterion for food choice. Among these
of food additives are preservatives, coloring
colors is sunset yellow which is used in the
agents, flavours, emulsifiers and stabilizers
textile, printing, paper manufacturing,
(Lindsay, 1985).
pharmaceutical and food industries (Chung
Among these food preservatives is
et al., 1992). Many of synthetic food
sodium nitrite which is used in preservation
colorants have side effects such as urticaria,
of cured meat, fish and milk. Although
genotoxic, clastogenic and carcinogenic
small doses of nitrite (0.25 mg/kg/day)
effects (Combes and Haveland­Smith,
were recommended by Egyptian standard
1982) and behavioral disorders in children
(1989) in preserved food yet, nitrite can be
(Pollock and Warner, 1990), endocrinal
changed in stomach into nitrosamine
disturbances (Jennings et al., 1990).
(Furukawa, 2000). The toxicological effects
However, several natural antioxidants
of nitrite in different mammalian species
co-administrated with food additives in
are well documented including impairment
order to ameliorate the adverse effects of
of certain defense mechanisms like to the
food additives (Merken and Beecher, 2000).

Full Paper (vol.28 paper# 5)

Serological evidence of The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 342 ­ 346

Serological evidence of antibodies to certain
arboviruses in desert rodent sera in Egypt

Nour El.Din H. Sherif
Zoology Department , Faculty of Science, Suez Canal University, Ismailia, Egypt


Introduction : Small rodents inhabiting the wadis close to St Katherine in the mountains
of the Sinai Peninsula, Egypt, were trapped and antibodies to Sindbis (SIN) , West Nile (WN)
and Quaranfil (QRF) viruses in their sera were studied.
Materials and Methods One mouse had Haemagglutination­inhibition (HI) antibodies
against SIN antigen in his serum, 3 mice had HI antibodies against WN antigen in their sera.
The titers is low to be of any significance.
Conclusion: It seems that natural cycle of transmission of SIN and WN viruses involving
rodents does not exist. Seven mice had Complement-fixation (CF) antibodies in their sera
against Quaranfil antigen. Conclusion, the CF test results suggest the existence of another
mammal vector cycle.
Keywords: Sindbis, West Nile and Quaranfil viruses (rodent), HI, CF.


Like several other mammals rodents
1955) ,West Nile (Taylor et al .,1956),
get natural infection with an arthropod-
Sandfly (Schmidt et al., 1966), The tick
borne viruses (arboviruses) without show-
borne Quaranfil, Chenuda and Nyamanini
ing apparant ill health, and natural infection
viruses (Taylor et al.,1966c) .Sandfly virus
is detected during surveys accidentally by
infects humans only, but the other viruses
virus isolation or serologic tests. Rodents
most probably are mainly zoonosis .
act as a subsidiray natural host for the tick-
This paper describes antibody studies
borne group of viruses (Kuceruk , 1963&
on desert rodent sera collected in various
Webb, 1965) and were thought to play a
regions of St Katherine's Protectorat, Egypt,
role in the natural cycle of propagation of
to investigate the occurrence of natural
Rift valley fever virus (Weinbren and
infection of these rodents with Sindbis,
West Nile or Quaranfil viruses.

encephalitis virus and group C arboviruses
Materials and Methods
(Jonkers et al., 1968). Experimental virus

infection of rodents lead to the development
Study sites:
of viremia, some animals died while the
The study was carried out in the St
majority survived and acquired antibodies
Katherine's Protectorate , southern Sinai, an
to the arbovirus used (Simthburn &
arid montane region characterized by
Haddaw, 1949 Weinbern & Mason , 1957
complex systems of dry valleys (Wadis)
Simpson, 1965 and ,1966).
and plains (Hobbs, 1995; Zalat & Gilbert,
In Egypt the prevelant species of
1998; Behnke et al., 2000). Four wadies
rodents (Hoogstraal, 1963) live in close
were choosen: El Arbaein and Tofaha, close
association of human population in the
to the Suez Canal University Environmental
cultivation fields.Their relation to the
Research Centre (ERC) at St Katherine
natural cycles of propagation of arboviruses
(Behnke et al., 2000) and Abu Seila and
known to be in active circulation in Sinai,
Boqueia, some 5 km to the north across the
Egypt was not studied. The viruses
Plain of El Raha (Barnard et al., 2003b) .
recognized as endemic in Egypt are
Collection of rodents :
mosquito-borne Sindbis (Taylor et al.,

Full Paper (vol.28 paper# 6)

L- carnitine is a naturally occurring substance required The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 347 ­ 354

The effect of L-Carnitine on Sodium Valproate-Induced Physiological
Disturbances in Rats

Fahmy G. Elsaid1,2 and Fawzya E. Zeghiebr1
1Zoology Department, Faculty of Science, Mansoura University, Egypt.
2Life Science Department, Faculty of Science, King Khalid University, KSA


Background: Chronic treatment with sodium valproate (VPA) can lead to elevation of
specific oxidative metabolites that associated with the drug's toxicity.
Results: Valproate exposure leads to an increase in reactive oxygen species (ROS). The levels
of lipid peroxidation (malondialdehyde), and lipid profile variables (cholesterol, phospholipids,
triglycerides and free fatty acids) were significantly increased (p<0.001) in orally administrated rats
with sodium valproate at 400 mg/kg body weight/day. Also the deflection in the activities of
catalase (CAT), lactate dehydrogenase (LDH) and Na,K-ATPase was registered where CAT, LDH
and Na-K, ATPase activities were decreased (p<0.001) in rats under VPA treatment compared to
the controls. These changes were more pronounced in valproate 60 days treated group than in
valproate 30 days treated group. Oral administration of l-carnitine (L-CAR) at 300 mg/kg b. w. /day
showed alleviation in all metabolic and physiologic changes in rats treated with sodium valproate.
L-CAR supplementation might be recommended for human especially for epileptic persons
subjected for long term to sodium valproate treatment.
Key words: Sodium valproate, L-carnitine, epilepsy, lipid profile, Malondialdehyde, catalase,
Lactate dehydrogenase and Na, K- ATPase activities, muscle, brain, bone and liver.


Sodium valproate (VPA) is a major
anti-epileptic drug with a broad spectrum of
(DeVane, 2003). Several findings and
anti-epileptic activity. It has been the drug of
investigations are in favor of oxidative stress
choice in the treatment of most forms of
mechanism playing a role as a result of
primary generalized epilepsies and is also
reactive oxygen species (ROS) over
efficient against partial seizures (Rowan,
production and/or compromised antioxidant
1997). The mechanism of action of valproate
capacity (Sabayan et al., 2007). A study
has yet to be fully elucidated. Much attention
demonstrated that a single dose of VPA in
has been focused on the inhibitory central
rats led to a dose-dependent elevation in
nervous system neurotransmitter -aminob-
plasma and liver levels of the endogenous
utyric acid (GABA).VPA pharmacological
lipid peroxidation marker (Tong et al,. 2003).
action includes increase of - aminobutyric
Oxidative stress is the cytotoxic conseq-
acids levels (Loscher and Vetter, 1985) and
uences of ROS which are generated as by
decrease of repetitive firing of action
prevented by simultaneous administration of
potentials (MacLean and Macdonald, 1986).
free-radical scavengers and support the
Moreover, antiepileptic drugs may cause the
concept that VPA hepatotoxicity is due to
changes in the oxidant/antioxidant system of
lipid peroxidation (Buchi et al., 1984). Also
the body. Valproic acid exposure leads to an
increased oxidative stress is associated with
increase in reactive oxygen species (ROS)
hypercholesterolemia (Dhalla et al., 2000).
(Defoort et al., 2006).
Oxidative damage to lipid, protein and DNA
The main issues of concern with VPA
in the neuronal system may cause dysregu-
have been hematological toxicity, teratoge-
lation of membrane transport mitochondrial

Full Paper (vol.28 paper# 7)

THE ROLE OF MELATONIN IN ALUMINUM INDUCED GENOTOXICITY IN ALBINO RATS The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 355 ­ 362

The Role Of Melatonin In Aluminium Induced Genotoxicity In
Female Albino Rats

Zeinab E. Hanafy
Department of Zoology, Faculty of Science (Girls), Al-Azhar University.


Aim of the work,
In spite of the wide range of use of aluminium. With the increasing
awareness of possible health hazards associated with their use, more attention have been
focused on their biological and biochemical activity. Aluminium salts are used as the active
antiperspirant in under cosmetics, but the effects of widespread, long term and increasing use
remain unknown. Aluminium is known to have genotoxic profile, capable of causing both DNA
alterations and epigenetic effects. Melatonin reduces the free radical generation and metal
detoxification .This study was planned to determine the effects of melatonin on aluminium
induced toxicity in the chromosomes of bone marrow cell .
Material and Methods ,Forty female albino rats were used in the present work for the
chromosomal analysis. Four groups of adult female albino rats were used in the following way:
Group -I, control group; Group-II,50 mg /kg b.wt aluminium orally; Group-III, 50g / kg b.wt
melatonin orally and Group- IV, 50 mg /kg b.wt aluminium orally (am) +50 g / kg b.wt
melatonin orally(pm). Doses were given 30 days. All animals were sacrificed and the bone
marrow of femur bones was taken for subsequent cytogenetic studies.
The results
, Aluminium treatment induced a significant increase in the structural as well
as numerical chromosomal aberrations . The frequency of chromosomal aberrations showed
significant decrease when rats treated with melatonin and aluminium .In conclusion, the results
indicated that melatonin showed a significant improvement of genetic damages induced by


targets within the cell similar to those of
industrial are capable of causing cytoge-
known toxic metals , such as cadmium
netic damage in experimental animal and
[Nieboer and Richardson 1980 and Muller
human [Heddle et al., 1983]. Aluminium
and Wilhelm 1987 ].
( Al ) chloride ( 10 ­ 200 µ M ) increased
Melatonin is the principal secretary
the aluminium content in hepatocytes
product of the pineal gland . The molecule
isolated from fed male rats in a time -and
endocrine actions on other glands, but it
concentration - dependent manner . After
also has been shown to function as a free
60 min of incubation with 100 µ M
radical scavenger, antioxidant and in
aluminium about 45 % of cellular alumi-
immunomodulation [Conti and Maestroni
nium was found each in the mitoch-
1995 ; Reiter et al.,1995 and Vijayalaxmi
ondrial and the post mitochondrial
et al., 2004]. Melatonin is highly lipid
fraction of hepatocytes , whereas about 5%
soluble and enters cells and subcellular
of aluminium sedimented with nuclei
compartments with ease [Reiter 1991] ;
and cell debris. [ Muller and Wilhelm
melatonin has not been shown to be toxic .
1987]. Aluminium linked inhibition of
Melatonin and its precursors, tryptophan
several enzymes, such as ATP ase,
and serotonin, were examined for their
metal binding affinities for both essential
lactate dehydrogenase ( LDH ) in brain
and toxic metals : aluminium , cadmium ,
fractions [Riedel and Christensen 1979:
copper , iron, lead and zinc [ Limson et al.,
Bock and Ash 1980 ; Lai and Blass, 1984
1998 ] .
and Ganrot , 1986 ] .
Melatonin, together with other free
Aluminium is known to react with
radical scavenger in the brain, reduces the

Full Paper (vol.28 paper# 8)

Electron Microscopic study of Desmosomes and Tonofilaments in Lichen Planus The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 363­ 370

Electron Microscopic study of Desmosomes and
Tonofilaments in Lichen Planus

Sawsan Khalifa EL- Sayed* and Hossam El- Dein Hussin Osman **.
From Department of Dermatology and Venereology,
Al- Azhar University for Girl, Cairo and Anatomy Department,
Al- Azhar University for Boys, Cairo **.


Lichen planus (L.P) is an idiopathic inflammatory disease of the skin and
mucous membrane.
Desmosomes are responsible for the adhesion of keratinocytes. Tonofilaments are one
of the major cytoskeleton structure in mammalian epidermis.
Patients and Methods: Six patients complained from Lichen planus are included in this
study for the study of ultrastructure of both desmosomes & tonofilaments .
Results: revealed an increase in the size and numbers of both of them which can be
explained as a one of the defensive mechanism of the cells against frequent rubbing which is
accompanied L.P. which is considered as a resistance mechanism of keratinocytes.


Lichen planus is an idiopathic
seen by light microscope (Carr and Tover,
inflammatory disease of the skin & mucous
membrane. It is characterized by pruritic

Patients and Methods
extremities (Boyd and Neldner, 1991).

Although its etiology and pathog-
Six patients examined clinically &
enesis are not fully understood, L.P has
pathologically (by H&E) & proved to have
been associated with multiple disease pro-
lichen planus are involved in this study
cess and agents, such as viral infections,
from the period of 12/ 2005 up to 3/ 2006
autoimmune disease, medications, vaccin-
from out patient clinic of dermatology &
ations and dental restorative material
Venereology department of El Zahraa
(Shiohara and Kana, 2003).
hospital. Detailed history of the disease was
Desmosomes are the major adhesion
taken from the patients & then sent
complex in epidermis anchoring keratin
speciemens to the Electron microscopy unit
intermediate filaments to the cell membrane
in anatomy department in Al Azhar faculty
& bridging adjacent keratinocytes and
of medicine (Boy branch, Cairo) for
allowing cells to withstand trauma
preparation to be examined by Electron
(Nickoloff et al., 2002). Desmosomes serve
in maintain cellular integrity and they are

also postulated to have a function in
Steps used for the preparation of
transducing signals (Cowin and Burre,
specimen were:

Tonofilaments are a complex of
1- Obtaining materials:
network of bundles of cytoplasmic keratin
Punch biopsy was used in our study after
filaments which link both desmosomes &
injection of the lesion with lidocain Hcl as a
hemidesmosomes. Tonofilaments appear to
local anesthesia.
form an elaborate network of guyropes

which distribute mechanical forces evently
2- Fixation:
throughout the epidermis. These bundles
The specimens fixed using double
are so coarse in case of skin that can be
procedures with the following steps:

Full Paper (vol.28 paper# 9)

Introduction The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 371­ 396

The Effect Of Losartan On The Kidney Of Adult Female Albino Mice And
On The Renal, Hepatic And Pulmonary Tissues Of Their Fetuses

Iman Zakaria
Department of Zoology, Faculty of Science, Ain Shams University


Angiotensin receptor blockers as well as angiotensin-converting
enzyme inhibitors are antihypertensive medications prescribed by a wide variety of physicians.
Blocking of angiotensin II (ANG II) mainly through angiotensin II type I receptor (AT1) has
been implicated in mediating the angiotensin-converting enzyme (ACE) inhibition. The present
study was designed to investigate the effects of an AT1 antagonist, losartan, on the renal tissues
of adult and fetus as well as the hepatic and pulmonary tissues of fetuses histologically and
Materials and Methods: Pregnant CD-1 mice were used in this study and they were
administered losartan orally through gastric tube. Animals were divided into three groups; the
first group served as control, while the second and third groups were administered losartan (10
mg/kg/day) during the second and third weeks of pregnancy respectively. At the end of
pregnancy, the pregnant females were sacrificed and the fetuses were removed where the kidney
of both adult and fetuses as well as the liver and lung of fetuses were removed.
Results: Light and electron microscopic examination of the selected tissues revealed
conspicuous pathological lesions especially in the second group. Renal lesions were represented
by hypertrophied glomeruli with a marked increase in mesangial cells, interstitial fibroblasts
proliferation and haemorrhage. Ultrastructural changes were represented by thickening of the
glomerular basement membrane, fusion of foot processes and tubular necrosis in both adult and
fetuses. Moreover, the fetal liver of the second group showed marked accumulation of glycogen
contents, fatty degeneration, necrosis and nuclear pyknosis.
The fetal lung revealed remarkable damage of the epithelial cells lining the respiratory
bronchioles, focal areas of cellular necrosis, moderate increase in pneumocytes type II and
macrophages. A marked increase in number of alveolar fibroblasts was also observed.
Conclusion: Consequently, such pathological lesions induced by losartan-treatment might
lead to renal dysfunction, hepatic injury and chronic lung inflammation. Thus, extreme caution
seems to be necessary in losartan treatment during pregnancy. It is essential to balance the risks
of toxicity from drug treatment, the hazards of the fetus against the risks of non treatment during
the second trimester of pregnancy.
Key words: Losartan- Adult- fetus- kidney ­ liver- lung.


Hypertension presents a unique
from coronary heart disease, chronic heart
problem in therapeutics. It is usually a
failure, stroke and kidney failure.
lifelong disease that causes few symptoms
until the advanced stage. Sustained arterial
antagonists are effective monotherapeutic
hypertension damages blood vessels in
agents for treatment of mild to moderate,
kidney, heart and brain and leads to an
and severe hypertension (Nelson et al.,
increased incidence of renal failure,
1991 and Heger et al., 1997). Losartan is
coronary disease and stroke (Benowitz,
the first of a new class of agents orally
1995). Mensah (1999) reported that
active nonpeptidal antihypertensive agent
hypertension is the leading preventable
that specifically blocks the angiotensin II
cause of premature morbidity and mortality
type I receptors and has undergone

Full Paper (vol.28 paper# 10)

Alteration of Oxidative Status in Rats Following Administration of Acrylamide The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 397 ­ 403

Alteration of Oxidative Status in Rats Following Administration of

Hanaa H. El-Sayed1, Shawkia S. Abd El- Halim1,
Gehan M. Morsy2 and Ayman El-Sayed El- Adawi3
1- National Nutrition Institute. 2- Women's college- Ain Shams University.
3- Home Economics college- Minufiya University.

Introduction: Acrylamide (ACR) is a known industrial neurotoxic and carcinogenic
chemical in rodents. The recent discovery of acrylamide in wide variety of commonly consumed
foods has energized research efforts worldwide to define toxic mechanisms.
Objective: The present study is carried out to investigate the effect of acrylamide
administration on in vivo malondialdehyde (MDA, a product of lipid peroxidation), reduced
glutathione (GSH) as well as copper and zinc superoxide dismutase enzyme activity (Cu/Zn
SOD) of rats.
Material and Methods: Fourteen adult male Sprague Dawley rats were divided into two
groups each containing "7" rats. Group 1 served as negative control fed on basal diet and group
2 (positive control) received basal diet and acrylamide (0.34g/ kg diet) for 11 days. Levels of
MDA, GSH and activity of SOD were determined in liver, kidneys, brain, heart, testes, spleen
and lungs of rats.
Results: ACR treatment significantly increased MDA in all organs; the highest increase
was detected in testis (87.9%) and heart (71.5%) while the lowest one was found in kidneys
(28.2%). On the other hand, GSH levels and SOD activities were significantly reduced in ACR
treated rats. However, the reduction of GSH level ranged from 10.2% to 36.5 %.The inhibition
of SOD activities were higher in testis (57.3%) and lungs (38.5%).
Conclusion: The present study showed that ACR exerts deteriorated effects on oxidative
status of rats.
Keywords: Acrylamide ­In vivo- Rats- Tissues ­ Lipid peroxidation ­ Reduced
glutathione- Superoxide dismutase.


Acrylamide (NH2-C=O-CH-CH2), a
flocculation of ores, friction reduction, soil
highly reactive vinyl, water soluble mon-
stabilizers, oil-in-water deemulsifiers, gel
omer. It does not occur naturally, but is
photography, dyeing and ceramics, and
acrylonitrile (Macwilliam, 1978). Scientists
food processing (Bergmark et al., 1991).
in several countries have reported high
Human exposure to acrylamide
concentration of ACR in stach-rich
primarily comes from dermal contact with
foodstuffs. It was also found in various
solid monomer and inhalation of dust and
fried, deep-fried and oven- (e.g. chips,
vapor in the occupation setting. The public
crisps and bread, crackers and breakfast
may be exposed to acrylamide through the
cereals) (Tareke et al., 2002), formed by
ingestion of drinking water that is
Maillard reaction from reducing sugars (e.g.
contaminated with acrylamide or the intake
glucose) and amino acids (e.g. asparagines)
of acrylamide from foods (Jerry, 2005). It
(Mottram et al., 2002, Taubert et al., 2004).
has been also reported that acrylamide was
formed in the heating of rodent feed,
manufacture of polyacrylamide used in
suggesting that human exposure to
acrylamide could occur during the cooking
treatment (Blumenthal et al., 1995), as well
of rodent food (Tareke et al., 2002).
as in paper pulp industry (Dearfield et al.,
Acrylamide has been observed to
1988). Polyacrylamides are also used in
produce neurotoxic effects in industrial
drilling muds, textile and laminating resins,
workers and several species of experimental

Full Paper (vol.28 paper# 11)


Hypoglycemic Effet Of Some Fluoroquinolones On Normal And Diabetic
Experimental Animals

*Amr Heshmat Rostom & ** Ali Ibrahim Al-Sultan
* Department Pharmacology, ** Department Internal Medicine.
College of Medicine, Al Hasa, King Faisal University.


Fluoroquinolones are among the anti-microbial that have widespread use for
treatment of community- and hospital-acquired infections. Although uncommon, hypoglycemia has
been reported with some fluoroquinolones and appears to occur most frequently in elderly patients
with type 2 diabetes mellitus who were receiving therapy with oral hypoglycemics. The clinical data
emerged suggest that the fluoroquinolones can affect glucose homeostasis through an unknown
mechanism. The present work aimed to explore the potential effects of some fluoroquinolones on
glucose metabolism and blood glucose level in experimental animals. Two fluoroquinolones
(gatifloxacin, moxifloxacin) were used in the present study using different rabbit groups; normal
and experimentally diabetic. Dug interaction with anti-diabetic drugs was also investigated. Safety
considerations were our goal.
Materials And Method: In the present work, alloxan (100 mg / kg body weight 3
successive doses, intraperitonially) was used to induce diabetes in experimental animals. The
blood glucose level after alloxan was measured. Oral anti-diabetics glimepiride, rosiglitazone, and
metformin produced significant lowering effect on blood glucose level in normal and diabetic
animals. Gatifloxacin and moxifloxacin were similar in producing lowering of blood glucose level
in non diabetic and diabetic animals and significantly potentiated the hypoglycemic action of
oral anti-diabetics in the alloxan diabetic rabbits.
: Oral anti-diabetics Glimepiride, Rosiglitazone, Metformin, Fluoroquinolones
(Gatifloxacin and Moxifloxacin) Alloxan and diabetes mellitus.


A variety of medications has been
Many drugs produce a hypoglycemic state
associated with hypoglycemia, and the list of
in normal and diabetic persons by different
these medications is expanding. Fluoroqu-
mechanisms of action. Some of them are used
inolones are generally regarded as safe
mainly for this therapeutic effect like
antimicrobial agents with relatively few
sulfonylureas, metformin and rosiglitazone
adverse effects or drug interaction (Basaria et
(Harrower, 1996 , Buse, 2000, and Harrigan
al., 2002).
et al., 2001). Other agents intensify the
The World Health Organization (WHO)
hypoglycemic action of oral hypoglycemics
recognized type 2 diabetes and obesity as a
such as chloramphenicol (Brunova et al.,
global health problem that has reached
1977), tetracycline (Basaria et al, 2002),
epidemic proportion (WHO, 1997). Diabetes
erythromycin (Petrakis et al., 1999),
mellitus is one of the most common
clarithromycin (Bussing and Gende, 2002),
diseases in the world; it was estimated
isoniazid (Ovali et al., 2004), and rifampicin
that 150 million patients suffered from
(Niemi et al., 2001b).
diabetes mellitus in the year 2000 (Buse,
Alloxan hyperglycemic effect is due
2000), and that number may reach 300
to partial or total necrosis of beta cells
millions in the year 2025 (Zimmet, 2003).
which is presented histopathologically by

Full Paper (vol.28 paper# 12)

Expression of C-erbB-2 in endometrial hyperplasia and endometroid adenocarcinoma and its clinicopathological significance The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 418 ­ 428

Expression of Her-2/neu in endometrial carcinoma
and its relation with clinicopathological variables

*Hanaa O Badr Eldin and **Wafaa H A Helmy
*Departments of Obstetrics and **Gynecology and Pathology
Faculty of medicine, Al Azhar University.


Objective and background
: Her-2/neu tyrosine kinase has been implicated in the
development and progression of several human cancers and is target for therapeutic
intervention. Smaller studies suggest that Her-2/neu may be involved in the tumerogenesis of
endometrial adenocarcinoma. The aim of this study was to evaluate Her-2/neu expression in
endometrial carcinoma (EC) and its correlation with clinicopathological features in order to
define the potential prognostic value of Her-2/neu overexpression in EC.
Patients and methods:
Nineteen patients with stage I-IV EC were included in this study.
Demographic, clinical and pathologic information was obtained and recorded. Her-2/neu
expression was evaluated by immunohistochemistry (IHC) on paraffin embedded tissue sections
with Her-2/neu antibody. Overexpression was defined as complete membrane staining in greater
than 10% of cells.
Results: The positive rate of Her-2/neu in EC was 42.1%. Her-2/neu was associated with
surgical stage (p<0.01), lymph node involvement (p<0.05), lymph vascular space invasion (p
<0.05) and depth of myometrial invasion (p <0.01) but not associated with histological grade or
the age of the patients (p >0.05).
Conclusion: Our study provides evidence of Her-2/neu overexpression in a considerable
proportion of the patients with uterine adenocarcinoma, thus suggesting the opportunity for the
possible use of anti-Her-2/neu therapy in this malignancy by selective inhibition of Her-2/neu.
The use of Herceptin, a monoclonal antibody directed against Her-2/neu, for therapy of patients
harboring Her-2/neu positive EC may be beneficial. Her-2/neu overexpression is related to
most of the prognostic variables of EC and may be incorporated into the criteria for
determination of tumor aggressiveness as a prognostic marker.


Endometrial carcinoma (EC) is the
most common malignant neoplasm of the
different biomarkers such as oncogene Her-
genital tract and, despite its relative
2/neu has shown the contribution of these
frequency; the molecular events that
molecules to endometrial carcinogenesis in
contribute to the
development and
a hormone-dependent or independent
progression of the lesion remain poorly
manner as an early or late event. In addition
understood (Iochin, 2005, Jemal et al., 2004
these biomarkers seem to be correlated with
and Jemal et al., 2006). The normal human
different clinicopathologic variables, and
endometrium is characterized by hormone-
therefore could be considered as indicators
dependent variation during the menstrual
of the biological behavior of endometrial
cycle. This tightly controlled system is
carcinomas (Iochin, 2005). However, these
disturbed during endometrial hyperplasia
prognostic markers have been not fully
and carcinomas and a series of changes
identified (Slomovitz et al., 2004). A
initiate and promote progression toward
better understanding of the molecular basis
malignant phenotype. These changes can be
of the biologic behavior of EC and the
subdivided into discrete steps, involving
development of a novel, more specific, and
activation of oncogenes or other proteins
more effective treatment modalities against
involved in tumor invasion and progression.
it remain a high priority (Santin et al.,

Full Paper (vol.28 paper# 13)

OCR Document The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 429 ­ 438

Study on the Oxidant and Antioxidant Status in Vitiligo Patients

Fatma Hassan Shabaka*, Sawsan Khalifa EL- Sayed*,
Gada Abdel- Badea*, Manal Mohsen Mahmoud** and
Rania Mahmoud Hossni***
From Department of Dermatology and Venereology, AI- Azhar University for Girl*, Prof. of
Biochem. Faculty of Medicine Cairo Univ. ** and M.B., B. ch. ***


Backgrounds: The aetiology of vitiligo is still unknown. Several hypotheses have been
proposed to explain vitiligo: genetic neural, immunological, self destructive, convergence
hypothesis and oxidative stress hypothesis
The current study is concerned with the oxidative stress hypothesis and how oxidants and
antioxidants affect the pathogenesis of vitiligo. So, our aim is to determine the role of
malondialdehyde and glutathione in the pathogenesis of vitiligo. The amount of
malondialdehyde (oxidant) and glutathione (antioxidant) were measured in serum and in skin
tissue in 30 vitiligo cases and 20 healthy controls
Results: The study showed significant changes between patients and controls in
glutathione level in blood and tissue samples. Also there were significant changes between
patients and controls in malondialdehyde in blood and in tissue samples favoring that
glutathione and malondialdehyde play a role in the pathogenesis of vitiligo.


Vitiligo is a relatively common, acqu-
Insufficient antioxidant protection or
ired pigmentary disorder characterized by
excess production of reactive oxygen
areas of depigmented skin resulting from
species (ROS) causes oxidative damage.
loss of epidermal melanocytes (Odom et
The balance between oxidative damage and
al., 2000)
antioxidant enzyme systems appears to
It affects between 1 % and 4 % of the
determine the physiological and patholo-
general population, males and females are
gical effects of ROS (Passi et al.,1998).
equally affected and it can develop at any
The aim of this work is to determine
age, but in approximately half of all vitiligo
the role of oxidant (malondialdehyde) and
cases onset is before age of 20 years (Koca
antioxidant (glutathione) In the pathog-
et al., 2004).
enesis of vitiligo. This will be done through
The aetiology of vitiligo is still
estimating their levels in blood and tissue of
unknown. Several hypotheses have been
patients with vitiligo.
proposed to explain vitiligo: genetic, neural,

immunological, self destructive, conver-
Patients and Methods
gence hypothesis and oxidative stress

hypothesis (Odom et al., 2000).
The present study was carried out at
Oxidative stress could act as the initial
out-patient clinic of dermatology depart-
triggering event in melanocytes degener-
ment of El Zahraa Hospital of Al- Azhar
ation. Free radicals (FRS) are atoms or
University. It includes two groups.
molecules [e.g. superoxide, hydrogen
Group I: thirty patients suffering
peroxide & nitricoxide] that occur during
from vitiligo, 20 females and ten males
several physiological and pathological
with mean age of 32.4 ±14.6 years. They
processes (Weller, 1999).
classified further into two subgroups:
Free radicals can damage cell
subgroup A: included 18 patients with
compounds such as protein, carbohydrate,
generalized vitiligo, 14 females and 4 males
DNA and particularly lipid (Knight, 1995).
with mean age of 30.4 ± 13.5 years and

Full Paper (vol.28 paper# 14)

Cytogenetic and biochemical studies of the effect of DDB in albino mice and their embryos The Egyptian Journal of Hospital Medicine (2007) Vol., 28: 439­ 447

Cytogenetic and biochemical studies on the effect of DDB in
albino mice and their embryos.

Adel El Rokeeb and Amira Abd El Raouf
AL. Azhar University Faculty of Medicine
(Boys branch) Egypty
National Research Centre Cell Biology Department Dokki - Egypt


Introduction: DDB (Dimethyl ­ 4,4/ ­ dimethoxy ­ 5,6,5/,6/ ­ dimethlene ­ dioxybi-
phenyl ­ 2,2 ­ dicarboxylate) is important drug of medicine not expensive since large number of
people are using it in virus B and C cases for very large periods extend to many years.
The protective of DDB on chemically induced damage was studied in primary cultures of
mammals hepatocytes.
Results:This work study of cytogenetic and biochemical effect of DDB, in mice using
the chromosomes of bone marrow of male and pregnant female shown some changes with liver
embryos. Also germ cells of testes given non significant aberration when compared with
As well as some biochemical parameters in serum and tissues, shown non significant
changes in nucleic acid, total protein, total cholesterol, total glucose, total triglycerides and
lactate dehydrogenase (LDH). Also, enzyme analysis of liver function and kidney.


Investigation of DDB (Dimethly
activity (Gao et al, 2005). It was frequently
dimethoxy biphenyl Dicarboxylate) is
used in Egypt in the management of chronic
synthetic analogue of schisandrin C which
viral and non-viral hepatitis. It showed
is a traditional Chinese medicine since 1977
reduction of hepatocellular carcinoma
and was tried in treatment of chronic HCV
thought the decrease of alpha-fetoprotein
in china and Egypt with encouraging results
levels (Montaser, 1999).
(Montasser 2000 and 2001).
Treatment options for common liver
DDB with the chemical structure
disease such as cirrhosis, faty liver chronic
given below has been used for the treatment
hepatitis. In china DDB has been tested
of viral hepatitis and drug ­ induced liver
clinically scince Liu (1979) on patients with
injury in china for about ten years.
viral hepatitis B. The results indicate that
Liver represents the largest organ in
DDB markedly improve impaired liver
the mammaline body. DDB had been
function. Similarly Mak and Ko (1997)
shown to be able to protect the liver against
Suggested that DDB had hepatoprotective
hepatotoxins such as CCL2, and thioacet-
effect on CCL4 ­ induced liver toxicity.
amide to induce liver microsomal cytoch-
However Kim and Colleagues (1999)
rome P-450 in mice and rats ( Liu et al
investigated the effect of DDB and
1997, 1982 and Liu and Lesca 1982).
observed that either single or repeated DDB
This drug was also shown to inhibit
pretreatment did not alter hepatotoxicity
the mutagenic action of benzo pyrene (BP)
induced by CCL4.
and aflatoxine (AFB1) in Ames test (Liu
This work aims to study the
and Lesca 1982 & Wang 1984) and to
cytogenetic and biochemical effects of
inhibit (AFB1) ­ induced hepatocarcin-
DDB (Bifendate pilutes) in mice using the
ogenesis in rats (Yan et al, 1986).
chromosomes of bone marrow cells, liver
DDB which is a synthetic analogue to
embryoes and germ cells.
schisandrin C (active ingredient in
Some biochemical parameters like
schisandra chinesis extract) showed the
Nucleic acid protein and enzymes were
powerful hepatoprotective and antiviral

Full Paper (vol.28 paper# 15)