Study IDs Saliva MicroRNA
Differences in Those with Oral
Science Proves The Danger Of
Bleeding Gums- Milwaukee Journal September/6/ 1921
Integrating the "General Dentist's" studies with a university or
research center should be a primary goal of the times. The general
dentist who normally "sees and does" maximum of the
cases in many a times in his own "originally-researched" ways on the
particular "Ethinic patients" , could result as a major investigator
thereby decreasing the time
As we look for more ideas and support for this ideology from our
esteemed readers, we bring you this edition of Dental Follicle.
Adam And Eve had many advantages. The princial one was that they
HEMOGLOBINOPATHIES A Review - Part II
By Dr.Ghazala Danish MDS
Oral Diagnostitian & Radiologist
Genetic councelling in cases where parents have sickle cell
triat. There are obvious economic implications especially as
the disease is more prevalent in the areas of the world
where money for high technology is limited.
Gene replacement therapy
Bone marrow transplantation
General management for alleviation of symptoms
Regular foilc acid supplements 5mg/day to support increased
Prevention and prompt treatment of infections.
Patient should avoid becoming chilled, dehydrated or exposed
to hypoxia like at high altitudes.
Patient should be adequately hydrated.
Transfusion should be done when Hb level falls below 5gm%.
Acute pain crisis- powerful potentially addictive analgesics
may be necessary. After 24-48 hrs they should be replaced
with milder, non-addictive analgesics. Exchange transfusion
may be required to alleviate bouts of severe intractable
Immunization with pneumococcal vaccine.
Ulcers- rest, elevation, dry dressings with antimicrobials.
Healing takes weeks to months.
Patient support groups to be made for patient's psychiatric
Hydroxyurea- it inhibits ribonucleotide reductase blocking
DNA synthesis and cell division. The drug also enhances
fetal hemoglobin by the developing erythrocytes (HbF blocks
Erythropoietin- a hormone produced by the kidneys that
stimulates red cell production. This hormone is produced in
response to hypoxemia. It increases fetal hemoglobin in
Butyrate (Arginine butyrate)- babies born to diabetic
mothers with poor glucose control sustain production of HbF
after birth relative to babies born to normal women.
Butyrate is a byproduct of hyperglycemia.
Clotrimazole (anti-fungal / anti-mycotic belonging to
imidazole group)- red cell dehydration contributes to
polymerization of sickle Hb in patients with sickle cell
anemia. Clotrimazole inhibits dehydration, thus is being
Nitric oxide- it is an inhaled gas. It primarily relaxes the
smooth muscles. However it also forms a covalent link with
Hb affecting polymerization.
In Africa a few shildren with sickle cell anemia survive to
adult life without medical attention. With standard medical
care 15% will die by the age of 20yrs and 50% by the age of
Thalassemia is an inherited impairment of hemoglobin
production, where there is partial or complete failure to
synthesize a specific type of globin. This causes formation
of abnormal hemoglobin thus causing anemia. It is
quantitative disorder of hemoglobin.
It is autosomal recessive blood disease.
Thalassemia is prevalent among Mediterranean people.
Thalassa in Greek means sea, Haema in Greek means
blood, hence the name thalassemia.
It is prevalent in populations living in humid climates.
Malaria is endemic in these areas. Thalassemia protected
these people from malaria as the blood cells in these
patients are degraded easily.
Based on which globin chain of hemoglobin is affected
thalassemia can be classified as follows:
1.Alpha thalassemia- production of alpha globin chain
2.Beta thalassemia- production of beta globin chain is
3.Delta thalassemia- production of delta globin chain
There is decrease in the alpha globin production due to
concerned gene deletion, resulting in excess of beta globin
chains in adults and excess gamma chains in new borns. The
excess beta globin chains form unstable tetramers (Hb called
HbH). They involve HBA1 and HBA2 genes
inherited in a Mendelian recessive fashion.
When all genes are deleted it can present as hydrops fetalis.
Hydrops fetalis is a condition in the fetus characterized by
accumulation of fluid or edema in at least two fetal
compartments, including the subcutaneous tissue, pleura,
pericardium or in the abdomen. Edema is usually seen in the
fetal subcutaneous tissues sometimes leading to spontaneous
abortion. It is a prenatal form of heart failure, in which
heart is unable to satisfy its demand for a high amount of
blood flow. It is usually due to fetal anemia when the heart
needs to pump a much greater volume of blood to deliver the
same amount of oxygen.
It is due to mutations in the HBB gene inherited in a
Mendelian recessive fashion. There is no formation or
reduced formation of beta chains depending upon the type of
mutations. Relatively there is excess formation of alpha
globin chains. They donot form tetramers, but bind to the
cell membrane damaging it.
3% adult hemoglobin has two alpha and two delta chains. Just
as with beta chains, mutations can occur in genes
responsible for delta chain production.
Thalassemia can co-exist with other hemoglobinopathies
Hemoglobin E / Thalassemia
Hemoglobin S / Thalassemia
Hemoglobin C / Thalassemia
Beta thalassemia is of two types:
Thalassemia minor- has one affected beta thalassemia
gene and one normal beta chain gene.
Thalassemia major- has both affected beta thalassemia
An individual with thalassemia minor has only one affected
beta thalassemia gene (together with one perfectly normal
beta chain gene). The person is said to be heterozygous for
Affected individuals have mild anemia resembling iron
deficiency anemia with little or no clinical disability.
They have normal blood iron levels. Usually detected when
iron therapy for mild microcytic anemia fails. No treatment
is usually required.
Thalassemia major (Cooley's anemia)
The clinical picture associated with thalassemia major was
first described in 1925 by the American pediatrician Thomas
Cooley, hence the name Cooley's anemia.
An individual with thalassemia major has two affected beta
thalassemia genes and no normal beta chain gene. The
individual is said to be homozygous for beta thalassemia.
This is a serious condition as there is a striking
deficiency in beta chain production of HbA.
At birth an infant with thalassemia major appears normal.
This is because of predominant fetal hemoglobin (HbF). It
has two alpha and two gamma chains. Since HbF has no beta
chains, the infant does not manifest the affects of
thalassemia major. As the HbF levels start decling anemia
begins to develop from the first months after birth. Anemia
progressively increases in severity. Infant fails to grow
normally, has feeding problems due to easy fatigue from lack
of oxygen. There are bouts of fever due to infections
predisposed by anemia. Dairrhoea and other intestinal
problems are also encountered.
Splenmomegaly is common is thalassemia due to high rate of
hemolysis. Spleen identifies the RBCs in thalassemia as
defective and removes them from circulation. In case of
transfused red cells the spleen identifies them as invaders
foreign to the body and removes them also from the
circulation. Therefore transfused red blood cells survive
only for a few weeks, whereas normal RBCs have a life span
of about 120 days.hyperactivity and increase in the number
of cells filtered in the spleen leads to splenomegaly.
Iron toxicity- Iron deposits due to chronic blood
transfusion exceed the storage capacity of ferritin (iron
storage protein of the body). Consequently free / loosely
bound iron begins to accumulate in tissues and blood. Theis
free iron catalyses the formation of hydroxyl radicals (OH)
from hydrogen peroxide which are normal metabolic
byproducts. Hydroxyl radicals are highly reactive. They
attack lipids, proteins and DNA to form peroxides (Eg: lipid
peroxide). The peroxides interact with other molecules to
form cross links. These cross linked molecules perform their
normal function poorly or not at all. DNA cross links impair
cell replication, leading to cell death.
Liver- hepatocytes are the major storage site for body iron.
With iron overload, these cells are affected and eventually
die. They are replaced by fibroblasts causing liver fibrosis
and cirrhosis. Similarly cardiac cells are damaged by iron
overload. Damaged, poorly functioning cells often fail.
Clinical manifestations include congestive heart failure
(due to injury to myocytes) and arrhythmias (due to damage
to the cells of the cardiac conducting system).
Enlargement of maxilla due to eryhtroid mass leading to
chipmunk facies. Spacing of teeth, forward drift of
maxillary incisors. Therefore orthodontic treatment is
Expansion of diploe of skull giving rise to hair on end
appearance conspicuous on lateral skull radiographs.
Alveolar bone rarefaction produces chicken wire appearance.
Pneumatization of the sinuses is delayed.
Painful swelling of the parotid glands and xerostomia caused
by iron deposition.
Sore or burning tongue due to folate deficiency, as most of
the folic acid is utilized by increased erythropoiesis.
There is increased risk of hepatitis B or C, HIV carriage
due to repeated blood transfusions.
If splenectomy has been done, it results in immune defects.
Prophylactic antibiotics have to be administered
Local anesthesia can be safely given.
General anesthesia is difficult / contraindicated because of
chronic anemia and cardiomyopathy. Even intubation becomes
difficult because of enlarged maxilla.
Carrier detection / prevention
There is a serious concern that thalassemia may become a
very serious problem in the next 50 yrs, burdening world's
blood bank supplies and the health care system in general.
In autosomal recessive forms of the disease, both parents
must be carriers for the child to be affected. If both
parents carry a hemoglobinopathy triat there is 25% chance
with each pregnancy for the child to be affected.
Therefore Genetic counseling and genetic testing is
recommended for families that carry a thalassemia triat.
Premarital screening policy exists in Cyprus and Iran to
reduce the incidence of thalassemia.
·Geographic location of the individual
·Complete blood count- Hemoglobin level in
blood is reduced. Moderate and severe thalassemias are
usually diagnosed in early childhood (severe anemia appears
within 2 yrs of life). Milder forms of thalassemia are
diagnosed after a routine blood test showing anemia. There
is microcytosis, hypochromia.
·Hemoglobin electrophoresis-mild form of
thalassemia shows higher than normal amounts of HbA2
and HbF. Severe form of thalassemia shows low levels of HbA
and high levels of HbF.
·Ferritin blood test (to check iron level in
blood)- normal in thalassemia minor and raised in
Thalassemia minor usually does not require any specific
·Chronic blood transfusion to maintain
hemoglobin level more than 10gm%.
·Iron chelation therapy- to prevent iron
mediated injury to the cells, thus preventing heart, liver
damage caused by iron overload. When metal ion binds to the
chelator, the metal ion becomes chemically inert. Therefore
chelator detoxifies metal ions and prevents poisoning. Iron
chelator desferrioxamine removes excess iron that
accumulates with chronic blood transfusion. It is not
absorbed from thegastrointestinal tract. It has to be given
as continuous subcutaneous infusion or continuous
intravenous infusion. It involves expensive medical
paraphernalia. Given 5-7 days a week.
·Allogenic hematopoietic transplantation
·Administration of folic acid 5mg daily.
·Anti-oxidant indicaxanthine prevents oxidation
of RBCs and prevents hemoglobin degradation.
·Recent reports suggest that 3% of patients
with beta thalassemia produce HbF. Use of hydroxyurea
increases the production of HbF.
General management for alleviation of symptoms
Prevention and prompt treatment of infections.
Patient support groups / psychiatric support
Indonesians Win Dental
The University of Indonesia
claimed first prize in a scientific research
competition held by the Asia Pacific Dental
Students Association in Penang, Malaysia,
last week, beating several prominent
universities, including some from South
Korea and Malaysia.
Devie Rahmawati, the deputy director of
corporate communications at UI, said their
team competed against 14 other teams from
other dental hygiene faculties across the
region, including Malaysia, South Korea and
Cambodia. A team from Greece, from the
European Association of Dental Students,
Devie said that the university won with
innovative research titled: “The Effect of
Xylitol on Candida Albicans Growth and Its
Resistance in Serum (In Vitro Study).”
Malaysia came second and South Korea third.
VIDEO OF THE MONTH
Study IDs Saliva MicroRNA
Differences in Those with Oral Cancer
A team of researchers from California and Serbia, used reverse
transcriptase pre-amplification quantitative PCR to identify nearly 50 miRNAs in
saliva samples from a dozen healthy individuals.Later they assessed a subset of
these in individuals with oral squamous cell carcinoma, the team
found four miRNAs that were differentially expressed, including two that were at
significantly lower levels in oral cancer patients.The study would be published
in Clinicl cancer research September Issue.