Glukokortikoid vid behandling av k - PowerPoint PPT Presentation

1 / 37
About This Presentation
Title:

Glukokortikoid vid behandling av k

Description:

... term effects of intra-articular sodium hyaluronate, glucocorticoid, and saline ... fluid and blood levels of 5-HT on the effects by intra-articular injections of ... – PowerPoint PPT presentation

Number of Views:72
Avg rating:3.0/5.0
Slides: 38
Provided by: larsfred1
Category:

less

Transcript and Presenter's Notes

Title: Glukokortikoid vid behandling av k


1
Glukokortikoid vid behandling av käkledssjukdomar
- Finns koppling till serotonin?
Lars Fredriksson
2
  1. Anti-inflammatory actions of glucocorticoids
    Barnes PJ. 1998
  2. Short-term effects of intra-articular sodium
    hyaluronate, glucocorticoid, and saline
    injections on rheumatoid arthritis of the
    temporomandibular joint Kopp S, Akerman S,
    Nilner M. 1991
  3. Pain and synovial fluid concentration of
    serotonin in arthritic temporomandibular joints.
    Alstergren P, Kopp S. 1997
  4. Immediate effects of the serotonin antagonist
    granisetron on temporomandibular joint pain in
    patients with systemic inflammatory disorders.
    Voog O, Alstergren P, Leibur E, Kallikorm R, Kopp
    S. 2000

3
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC are widely used for the suppression of
    inflammation in chronic inflammatory diseases
    such as asthma, RA, inflammatory bowel disease
    and autoimmune diseases, all with increased
    expression of inflammatory genes.

4
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC bind to GC-receptors in the cytoplasm which
    then dimerize and translocate to the nucleus,
    where they bind to GC response elements (GRE) on
    GC-responsive genes, resulting in increased
    transcription for genes coding for
    anti-inflammatory proteins

5
GC-receptor (GR)
6
  • GCS bind to GR in the cytoplasm which then
    dimerize and translocate to the nucleus, where
    they bind to GC response elements (GRE) on
    GC-responsive genes, resulting in increased
    transcription for genes coding for
    anti-inflammatory proteins

7
560-561
8
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC inhibit the expression of multiple
    inflammatory genes

9
(No Transcript)
10
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC appear to inhibit cytokine gene expression by
    inhibiting transcription factors that regulate
    their expression, rather than by binding to their
    promotor regions.

11
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC decrease the transcription of genes coding for
    certain receptors that are involved in the
    inflammatory process.

12
GC increase the syntesis of lipocortin-1, that
has inhibitory effect on phospholipas A2 and
therefore inhibit the production of lipid
mediators as well as inhbit genes coding for
COX-2.
13
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC reduce the survival of eosinophils and
    T-lymfocytes, since eosinophils are dependent of
    IL-5 and GM-CSF which are blocked by GC which
    leads to apoptosis of eosinophils and
    T-lymfocytes.

14
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • Adhesion molecules play a key role in trafficking
    of inflammatory cells to the sites of
    inflammation. The expression of many adhesion
    molecules on endothelial cells is induced by
    cytokines and GC may indirectly to a reduced
    expression via their inhibitory effects on
    cytokines such as IL-1beta and TNF-alfa.

15
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • Inhaled GC reduce the secretion of chemokines and
    pro-inflammatory cytokines from alveolar
    macrophages in patients with asthma. Oral
    prednisolone inhibits the increased gene
    expression of IL-Ibeta.

16
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • Systemic GC increase pheripheral neutrophil
    counts, which may reflect the increased survival
    time due to an inhibitory action of neutrofil
    apoptosis.

17
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC inhibit the increased transcription of the
    IL-8 gene induced by TNF-alfa in cultured human
    airway epithelial cells in vitro.
  • GC decrease the transcription of inflammatory
    proteins including iNOS, COX-2, cPLA2 and
    endothelin-1.

18
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC do not appear to have a direct inhibitory
    effect on mediator release from mastcells.

19
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • GC may inhibit several aspects of neurogenic
    inflammation including the synthesis of
    tachykinins by repression of the
    preprotachykinin-A gene, reduced expression of
    tachykinin receptors and by increasing expression
    of neural endopeptidase which degrades
    tachykinins.

20
1
Anti-inflammatory actions of glucocorticoids
Barnes PJ. 1998
  • Rarely patients with chronic inflammatory
    diseases fail to respond to GC but there are
    however patients with GC resistance.

21
2
Short-term effects of intra-articular sodium
hyaluronate, glucocorticoid, and saline
injections on rheumatoid arthritis of the
temporomandibular joint Kopp S, Akerman S,
Nilner M. 1991
AIM To investigate the short-term subjective and
clinical effects of sodium hyaluronate on TMJ
arthritis in individuals with RA and to compare
these effects with those of glucocorticoid and
saline. M and M Forty-one patients with RA.
Three groups HA gruop n14, CO group n14, SA
group n13. RESULTS After treatment Fig 1. 75
of the patients in the CO group were much
improved or symptom free. Subjective symptoms
(VAS) decreased with 34 mm in the CO group. Pain
at rest was significantly lower in the CO
group. Tenderness to digital palpation of the
lateral and posterior aspect were significantly
eliminated or reduced in the CO group. The
maximum voluntary moth opening was increased by 6
mm in the CO group.
22
2
Short-term effects of intra-articular sodium
hyaluronate, glucocorticoid, and saline
injections on rheumatoid arthritis of the
temporomandibular joint Kopp S, Akerman S,
Nilner M. 1991
Conclusion Sodium hyaluronate has a benefical
effect on subjective symptoms as well as clinical
signs of TMJ arthritis in patients with chronic
RA, although not as good as that of
glucocorticoids.
23
3
Pain and synovial fluid concentration of
serotonin in arthritic temporomandibular joints.
Alstergren P, Kopp S. 1997
AIM To investigate the relation between 5-HT in
the synovial fluid and pain of arthritic TM
joints. M and M Eleven patients with chronic
inflammatory joint disease. One male and 10
females (22 joints). RESULTS After treatment PM
was positively correlated to SF-5-HT on the
corresponding side (r 0.51, P 0.014, n 22)
Fig 1. The maximum voluntary mouth opening
capacity was negatively correlated to the
SF-5-HTSum when the influence of S-5-HT was
acconted for (rP -0.73, P 0.012, n 11) .
24
3
Pain and synovial fluid concentration of
serotonin in arthritic temporomandibular joints.
Alstergren P, Kopp S. 1997
Conclusion 5-HT in the TMJ synovial fluid is
associated with pain perceived upon movement of
the joint and to decreased mandibular mobility
25
4
Immediate effects of the serotonin antagonist
granisetron on temporomandibular joint pain in
patients with systemic inflammatory disorders.
Voog O, Alstergren P, Leibur E, Kallikorm R, Kopp
S. 2000
AIM To investigate if the 5-HT3 receptor
antagonist granisetron reduces TMJ pain in
patients with systemic inflammatory joint
disease. M and M Sixteen patients with chronic
inflammatory joint disease. Four males and 12
females. Table 1. RESULTS After treatment with
granisetron Granisetron group VASRest was
decreased 10 minutes after i.a. injection of
granisetron (p 0.028) but not after 20 minutes
(Fig. 1). VASMVM was decreased after 20 minutes
(p 0.002), but not after the first 10 minutes
(Fig.2). PPT was increased after 20 minutes (p
0.036). Difference between groups VASRest before
injection was similar in both groups. The
patients in the granisetron group had
signoficantly lower VASRest than the patients in
the saline group 10 minutes after injection (p
0.033 Fig. 1).
26
4
Immediate effects of the serotonin antagonist
granisetron on temporomandibular joint pain in
patients with systemic inflammatory disorders.
Voog O, Alstergren P, Leibur E, Kallikorm R, Kopp
S. 2000
Conclusion Granisetron has an immediate,
shortlasting and specific pain reducing effect in
TMJ inflammatory arthritis. The 5-HT3 receptor
may therefore be involved in the mediation of TMJ
pain in systemic inflammatory joint disorders.
27
Serotonergic mechanisms influence the response to
glucocorticoid treatment in TMJ arthritis Lars
Fredriksson, DDS, PhD Student, Per Alstergren
DDS, PhD, Associate Professor, Sigvard Kopp, DDS,
PhD, Professor and Chairman
28
AIM
  • To investigate the influence of synovial fluid
    and blood levels of 5-HT on the effects by
    intra-articular injections of glucocorticoid on
    pain and allodynia of the TMJ in patients with
    chronic and systemic inflammatory disorders of
    the TMJ.

29
Materials and Methods
  • One male and nineteen female patients with
    inflammatory TMJ disorders participated (Table
    1).

30
(No Transcript)
31
Results
  • Treatment effect
  • Table 2 shows the pretreatment and follow-up
    values of the clinical variables and synovial
    fluid levels of 5-HT.

32
Table 2
33
1A
Change in temporomandibular joint (TMJ) resting
pain intensity (A) after intra-articular
glucocorticoid treatment in 9 patients with
undetectable and 11 patients with detectable
pretreatment levels of serotonin (5-HT) in the
TMJ synovial fluid and chronic inflammatory joint
disease. There was a negative correlation between
5-HT and change in resting pain after treatment
(rs -0.52, n 20, p 0.018).
34
1B
Change in TMJ pain intensity on mouth opening (B)
in 8 patients with undetectable and 5 patients
with detectable pretreatment levels of 5-HT in
TMJ synovial fluid and chronic inflammatory joint
disease. There was a negative correlation between
5-HT and change in pain intensity on mouth
opening after treatment (rs -0.57, n 13, p
0.041).
35
2A
Pretreatment plasma levels of serotonin (5-HT) in
patients with chronic inflammatory joint disease,
7 with a decrease and 3 with an increase of
temporomandibular joint (TMJ) resting pain
intensity (A) after intra-articular
glucocorticoid treatment. There was a positive
correlation between 5-HT and change in resting
pain intensity after treatment (rs 0.66, n
10, p 0.040).
36
2B
Pretreatment plasma level of 5-HT in 5 patients
with a decrease and 5 patients with an increase
of TMJ pressure-pain threshold (B) after this
treatment. There was a positive correlation
between 5-HT and change in pressure-pain
threshold after treatment (rs 0.83, n 10, p
0.003).
37
Conclusions
  • This study shows that local and systemic
    serotonergic mechanisms partly determine the
    effect of intra-articular glucocorticoid
    treatment on TMJ pain in patients with chronic
    TMJ arthritis of systemic nature, while change in
    pressure pain threshold over the TMJ are
    influenced by systemic serotonergic mechanisms.
Write a Comment
User Comments (0)
About PowerShow.com