BIOLOGIE ORALĂ / ORAL BIOLOGY
MARKERII INFLAMATORI SISTEMICI ÎN BOALA
PARODONTALĂ
INFLAMATORY SYSTEMIC MARKERS IN PERIODONTAL
DISEASE
Silvia Mârţu, Sonia Elena Nănescu, Liliana Constantin
Disciplina de Parodontologie, Facultatea de Medicină Dentară, U.M.F. Iaşi
REZUMAT
Pacienţii cu parodontite marginale severe au nivele
serice crescute ale PRC, hiperfibrinogenemie, leucocitoză
moderată, ca şi nivele serice crescute de IL-1 şi IL-6, TNF-
alfa în comparaţie cu persoanele neafectate. Alte modificări
sistemice se reflectă în numărul total al leucocitelor,
numărul celulelor roşii şi nivelul de hemoglobină. Este
probabil că nivelul mediatorilor inflamatorii produşi de
monocitele unui individ ca răspuns la doze crescute de
stimulare bacteriană (lipopolizaharid) să fie o caracteristică
a răspunsului gazdă al individului. Influenţa generală
asupra bolii parodontale se manifestă şi prin modificarea
receptorilor de suprafaţă şi a altor molecule exprimate de
monocitele izolate din sângele periferic.
INTRODUCERE
Răspunsul de fază acută este iniţiat prin
activarea macrofagelor locale şi a altor celule
(inclusiv fibroblastele si celulele endoteliale, ducând
la eliberarea mediatorilor. Aceştia la rândul lor
determină modificări sistemice inclusiv eliberare
hepatică a unei game de proteine plasmatice
(inclusiv PCR), activarea proteinelor complemen-
tului şi diferite modificări metabolice.
FORMULA LEUCOCITARĂ A PACIEN-
ŢILOR CU PARODONTITĂ MARGINALĂ
Din literatura disponibilă, se pare că numărul
total al leucocitelor, numărul celulelor roşii şi
nivelul de hemoglobină sunt mai scăzute în
parodontită şi există o tendinţă de anemie în boala
cronică. S-a emis ipoteza că episoade zilnice ale
bacteriemiei pornind de la leziunile parodontale ar
putea fi cauza modificărilor în markerii sistemici ai
parodontitelor marginale.
MEDIATORI INFLAMATORI ÎN
SÂNGELE PERIFERIC LA PACIENŢII CU
BOALĂ PARODONTALĂ
Studii recente au indicat că pacienţii cu
parodontite marginale severe au nivele serice
crescute ale CRP, hiperfibrinogenemia, leucocitoză
moderată, ca şi nivele serice crescute de IL-1 şi IL-
6 în comparaţie cu persoanele neafectate (Ebersole
et al., 1997; Loos et al., 2000; Slade et al., 2000).
Modele similare ale nivelelor IL-6 uşor crescute în
plasmă au fost găsite şi la parodontita agresivă.
Culturile nestimulate au demonstrat de asemeni
12
ABSTRACT
Patients with severe periodontitis have increased
serum levels of CRP, hyper-fibrinonegemia, moderate
leukocytosis, as well as increased serum levels of IL-1 and
IL-6, TNF-alpha compared with unaffected individuals.
Other systemic changes reflect in the total number of
leukocytes, the number of red cells and the level of
hemoglobin. It is probably that the level of inflammatory
mediators produced by the monocytes of an individual as a
response to increased doses of bacterial challenge (lipopo-
lysaccharide) to be o characteristic of the host response of
the individual. The overall influence on the periodontal
disease also manifests through alterations of the surface
receptors and other molecules expressed by monocytes
isolated from the peripheral blood.
INTRODUCTION
The acute-phase response initiated by the
activation of local macrophages and other cells
(including fibroblasts and endothelial cells), leading
to the release of mediators These in turn cause
systemic changes including hepatic release of a range
of plasma proteins (including CRP), activation of
complement proteins and various metabolic changes
(Koj 1996, Ebersole & Capelli 2000).
THE LEUCOCITARY FORMULA OF
PATIENTS WITH PERIODONTITIS
From the available literature it appears that the
total numbers of leukocytes, the numbers of red
blood cells and levels of hemoglobin are lower in
periodontitis and there is a trend towards anemia of
chronic disease. It is hypothesized that possibly
daily episodes of a bacteremia originating from
periodontal lesions are the cause for the changes in
systemic markers in periodontitis.
THE INFLAMATORY MEDIATORS IN
PERYPHERAL BLOOD IN PATIENTS
WITH PERIODONTITIS
Recent studies have indicated that patients with
severe periodontitis have increased serum levels of
CRP, hyper-fibrinogenemia, moderate leukocytosis,
as well as increased serum levels of IL-1 and IL-6
when compared with unaffected control
populations (Ebersole et al., 1997; Loos et al., 2000;
Slade et al., 2000). Similar patterns of slightly higher
IL-10 levels in plasma were found for aggressive
periodontitis. Uunstimulated cultures also

tipare similare crescute de TNF-alfa (Havemose-
Poulsen A, & coll, 2005)
Merită menţionat faptul că la pacienţii cu boală
parodontală, nivele crescute de PCR serică sunt
asociate cu nivele crescute de infectare cu patogeni
parodontali (Noack et al., 2001). In studiile pe
culturi celulare, Porphyromonas gingivalis, unul dintre
cei mai importanţi patogeni parodontali, a
demonstrat o capacitate de invadare a celulelor
endoteliale (Dorn şi col, 2000). Patogenii
parodontali au fost identificaţi în placa
ateromatoasă carotidiană la pacienţii la care s-a
realizat endarterectomia Haraszthy et al., 2000).
Acidul sialic este prezent în cateva proteine de
fază acută (Sillanaukee et al. 1999). A fost raportată
o asociere semnificativă între parodontita marginală
şi colesterol (Katz et al., 2002).
De asemeni, monocitele izolate la pacienţii cu
boală parodontală produc nivele mai crescute de
prostaglandină E2 în comparaţie cu pacienţii
sănătoşi şi monocitele izolate de la pacienţii care
suferă de forme severe ale bolii parodontale produc
cantităţi chiar mai mari de prostaglandină E2 decât
monocitele pacienţilor care suferă de forme mai
uşoare ale bolii. Nivele de prostaglandină E2
eliberate de monocitele izolate din sângele periferic
sunt intens corelate cu nivelele de prostaglandină
E2 măsurate în fluidul crevicular.
PROFILURI INTERINDIVIDUALE ALE
MEDIATORIULOR INFLAMATORI SISTE-
MICI
Este probabil ca nivelul mediatorilor
inflamatorii produşi de monocitele unui individ (fie
local in fluidul crevicular, fie izolate din monocitele
sângelui periferic) ca răspuns la doze crescute de
stimulare bacteriană (lipopolizaharid) să fie o
caracteristică a răspunsului gazdă al individului.
Există variaţii pe termen lung în concentraţia
acestor molecule (Danesh et al. 1998, Ridker et al.
1999), nivelele serice fiind asociate cu o varietate de
factori, printre care fumatul, indexul de masă
corporală, vârsta subiectului. In termeni ai
citokinelor inflamatorii, homozigoţii pentru alelele
2 pentru IL-1A şi IL-6 sunt asociaţi cu concentraţii
semnificativ crescute ale PCR serice. Există
posibilitatea ca funcţia endotelială să se
îmbunătăţească în paralel cu reducerea spontană a
proteinei C reactive în timp. Este totuşi neclar dacă
rolul său predictiv are implicaţii etiologice, sau dacă
concetraţiile crescute ale PRC reprezintă doar un
marker al aterosclerozei şi/sau afectare vasculară.
ANALIZA MOLECULARĂ A MONOCI-
TELOR IZOLATE DIN SÂNGELE PERIFE-
RIC ÎN PARODONTITA MARGINALĂ
MEDICINA STOMATOLOGICĂ, vol. 9, nr. 6, 2005
BIOLOGIE ORALĂ / ORAL BIOLOGY
demonstrated similar patterns of higher TNF-alpha
levels (Havemose-Poulsen A, & coll, 2005)
It is worthy to mention that in periodontitis
patients, elevated serum CRP is associated with
high levels of infection with periodontal pathogens
(Noack et al., 2001). In cell culture studies,
Porphyromonas gingivalis, one of the most important
periodontal pathogens, has shown the ability to
invade endothelial cells (Dorn et al., 2000).
Periodontal pathogens have been identified in
carotid atheromatous plaques of patients
undergoing endarterectomy (Haraszthy et al., 2000)
Sialic acid is present in several acute-phase
proteins, and so one may expect changes in
circulating levels of sialic acid to mirror changes in
acute-phase proteins (Sillanaukee et al. 1999). A
significant association between periodontitis and
cholesterol has been reported (Katz et al., 2002).
Also, monocytes isolated from periodontitis
patients produced higher levels of prostaglandin E2
than healthy individuals, and monocytes isolated from
patients suffering from severe forms of periodontal
diseases produced even higher levels of prostaglandin
E2 than monocytes isolated from patients suffering
from milder forms of the disease. Levels of
prostaglandin E2 released by isolated peripheral blood
monocytes were highly correlated to the levels of
prostaglandin E2 measured in the GCF.
INTERINDIVIDUAL PROHPILES OF
SYSTEMIC INFLAMMATORY MEDIA-
TORS
It is likely then that the amount of inflammatory
mediator produced by an individual’s monocytes
(whether locally in the GCF or from isolated
peripheral blood monocytes) in response to
increasing doses of bacterial challenge
(lipopolysaccharide) is a characteristic of that
individual’s host response.
There are long-term interindividual variations in
concentrations of these molecules (Danesh et al.
1998, Ridker et al. 1999), the serum levels being
associated with a variety of factors, such as cigarette
smoking, body mass index, age of the subject. In
terms of inflammatory cytokines, being
homozygous for allele 2 for IL-1A or IL-6 was
associated with significantly higher serum CRP
concentrations. There is the possibility that
endothelial function may improve in parallel with
spontaneous reduction in C-reactive protein over
time. It is still unclear, however, whether its
predictive role has etiologic implications, or
whether elevated CRP concentrations are only a
marker of atherosclerosis and/or vascular damage.
MOLECULAR ANALISYS MONOCYTES
13

O altă metodă de investigare a influenţei
generale asupra bolii parodontale este de a
determina receptorii de suprafaţă şi alte molecule
ale monocitelor izolate din sângele periferic.
Subseturile de monocite care exprimă CD16 cu
nivele scăzute de CD14 (receptorul pentru
lopopolizaharid) cresc în diferite boli inflamatorii,
inclusiv şocul septic, sugerând că bacteriemia
produsă de parodontita marginală poate afecta
expresia CD16 şi CD14 la pacientul parodontopat.
De asemeni, examinarea CD45RA pe monocite
ar putea ajuta la detectarea activării monocitelor
circulante.
INFLUENŢA STATUSULUI GENERAL
ASUPRA PROFILELOR MEDIATORILOR
INFLAMATORI
Champagne Catherine M. E (2003), analizând
influenţa statusului general, a observat că diabeticii
au nivele ale prostaglandinei E2 şi interleukinei 1 în
fluidul crevicular semnificativ crescute în
comparaţie cu pacienţii nondiabetici cu status
parodontal similar şi că atunci când sunt stimulate
cu diferite doze de lipopolizaharid, monocitele
isolate de la pacienţii diabetici eliberau cantitaţi mai
mari de postaglandină E2, interleukină 1 si factor
de necroză tumorală decât monocitele isolate de la
pacientul nediabetic. Aceste constatări pot fi
explicate printr-un tipar hiperresponsiv monocitic
general al individului, care se manifestă prin nivele
crescute ale mediatorilor inflamatori eliberaţi de
monocite ca răspuns la stimularea bacteriană, iar
nivelul de control al plăcii sistemic şi local în
ţesuturile gingivale (igiena orală) nu este asociată cu
severitatea sau extinderea bolii unui individ,
prezenţa unui anumit nivel al patogenilor
parodontali constituind o contribuţie semnificativă
statistic dar redusă la modelele multivariate ale bolii
(Wilton JM, 1992).
CONCLUZII
Există mai mult decât o relaţie întâmplătoare
între nivelele lipidelor serice şi sănătatea sistemică
(în special boala cardiovasculară, diabet, capacitatea
de reparaţie tisulară şi funcţia celulelor imune),
susceptibilitatea pentru boala parodontală şi
nivelele serice ale citokinelor pro-inflamatorii.
În termenii relaţiei potenţiale dintre boala
parodontală şi boala sistemică, este posibil ca
modificările induse de parodontită în funcţia
celulelor imune să determine un dezechilibru în
metabolismul lipidelor prin mecanisme implicând
citokinele pro-inflamatorii.
Nivele susţinute ale lipidelor serice şi/sau
citokinelor pro-inflamatorii pot avea un impact
negativ serios.
14
BIOLOGIE ORALĂ / ORAL BIOLOGY
FROM PERYPHERAL BLOOD IN PERIO-
DONTITIS
Another way to investigate the general influence
of the periodontal disease is to determine the
surface receptors and other molecules of
monocytes isolated from peripheral blood.
Monocyte subsets expressing CD16 with low CD14
(lipopolisacharide receptor) increases in various
inflammatory diseases, including septic shock
suggesting that bacteremia caused by periodontitis
might affect the expression of CD14 and CD16 in
periodontitis patient.
Also examination of CD45RA on monocytes
might help to detect the activation of circulating
monocytes.
THE INFLUENCE OF THE OVERALL
STATUS ON PROPHILES OF THE
INFLAMMATORY MEDIATORS
Champagne Catherine M. E (2003), analyzing the
influence of the overall status, noticed that diabetics
had significantly higher levels of prostaglandin E2
and intercleukin-1 in GCF ompared to nondiabetic
patients with similar periodontal status and when
stimulated with various doses of lipopolysaccharide,
the isolated monocytes from diabetic patients relased
higher doses of prostaglandin E2, intercleukin-1 and
tumor necrosis factor than monocytes isolated from
nondiabetic patient. These findings may be
explicated through an overall hyperresponsive trait
of the individual which manifests by increased levels
of inflammatory mediators realeased from monytes
as response to the bacterial challenge and the level of
plaque control (oral hygiene) is not necessarily
associated with an individual’s disease severity or
extent, the presence or a certain level of specific
pathogens (such as Porphyromonas gingivalis) makes a
statistically significant but small contribution in
multivariate models of disease (Wilton JM, 1992)
CONCLUSIONS
There is more than a casual relationship
between serum lipid levels and systemic health
(particularly cardiovascular disease, diabetes, tissue
repair capacity, and immune cell function),
susceptibility to periodontitis, and serum levels of
pro-inflammatory cytokines.
In terms of the potential relationship between
periodontitis and systemic disease, it is possible that
periodontitis-induced changes in immune cell
function cause metabolic dysregulation of lipid
metabolism through mechanisms involving
proinflammatory cytokines.
Sustained elevations of serum lipids and/or pro-
inflammatory cytokines may have a serious negative
impact.
 BIOLOGIE ORALĂ / ORAL BIOLOGY

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ACTUALITĂŢI / NEWS
DENTIN EXPOSURE IN TOOTH PREPARATIONS FOR PORCELAIN VENEERS: A PILOT STUDY
George P. Cherukara BDS, M Clin Dent, Graham R. Davis BSc, PhD, Kevin G. Seymour BDS, MSc,
PhD, Lifong Zou BSc, PhD and Dayananda Y.D. Samarawickrama BDS, PhD
Statement of problem
The various clinical techniques available for even reduction of a tooth surface to receive a porcelain veneer restoration do not produce
a consistently even conservative reduction. In addition, it is not known which technique is most conservative of enamel.
Purpose The purpose of this pilot study was to assess the effectiveness of 3 clinical techniques, namely, dimple, depth groove, and
freehand, in producing an intraenamel preparation. The relation between overpreparation beyond the commonly accepted depth of
preparation of 0.5 mm and dentin exposure was also examined.
Material and methods A single operator prepared 3 groups of 5 extracted maxillary central incisors to a depth of 0.5 mm
using dimple, depth-groove, and freehand methods of tooth preparation. The prepared teeth were scanned using an x-ray
microtomography scanner. The reconstructed images were studied using software that provided a volume-rendering routine so that, by
choosing suitable x-ray linear attenuation coefficient thresholds, enamel (2.78 cm−1 at 40 keV) and dentin (1.63 cm−1 at 40 keV)
surfaces could be viewed. The percentage area of enamel conserved was analyzed from these images. Coordinate metrology was used to
produce color-coded images depicting the depth of preparation. The Kruskal-Wallis test was used to determine the statistical significance
(α=.05) in the difference between the mean percentage area of enamel conserved in the 3 technique groups. The coordinate metrology and
x-ray microtomography images were visually compared to study the correlation between overpreparation and dentin exposure.
Results The Kruskal-Wallis test did not demonstrate significant difference (P=.07) between the 3 techniques in conserving
enamel. However, the dimple technique showed a greater trend to retaining a larger mean percentage area of enamel (77.5% ± 14.2)
compared to depth-groove (50.1% ± 17.5) and freehand (76.8% ± 24.4) techniques. Preparation depth in the range of 0.4 to 0.6
mm was largely seen to be intraenamel, except in the cervical region.
Conclusion Within the limitations of this pilot study, the 3 different techniques tested did not differ significantly in conserving
enamel.
(The Journal of Prosthetic Dentistry Volume 94, Issue 5, November 2005, Pages 414-420)

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MEDICINA STOMATOLOGICĂ, vol. 9, nr. 6, 2005 15