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PB.1 Prostaglandin-like lipid oxidation products in the peritoneal fluid of women with endometriosis
European Journal o f Obstetrics & Gynecology and Reproductive Biology 123 (2005) S 1 ~ 6 6
S14
(ERB), cyclooxygenase-2 (Cox-2), cytochrome P450 (CYP1A1) and progesterone receptor (PR) by real-time NAT. Samples were examined from menstrual blood samples as well as from peripheral blood. Endometriosis was verified laparoscopically and distributed to the endometriosis stages according the rAFSguidelines. Results: Patients with endometriosis showed significant increased levels of estrogene receptor beta and progesterone receptor in menstrual blood samples whereas no differences were recognized between women with endometriosis and control group in peripheral blood samples (p=0.03 for ER beta; p=0.01 for PR). Conclusion: These data suggest that endometriosis resuks from the dislocation of basal endometrium. The real-time PCR screening for estrogen receptor beta and progesterone receptor in patients with strong suspicion for endometriosis provides the opportunity to verify the diagnosis without invasive laparoscopic examinations. This study demonstrates the principle of proof, examinations in a larger population are eagerly awaited.
References [1] Leyendecker G., Herbertz M., Kunz G., Mall G.(2002): Endomerriosis results from the dislocation of basal endometrium. Hum Reprod, 17; 2725-36.
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•
l
t
is possible to evaluate deeply infiltrating endometriosis with transvaginal ultrasound
M.S. Abrao 1 , M.O. Gonqalves 2, M. Gonzales 3, J.A. Dias Jr. 3, S. Podgaec 3.
S~o Paulo, Brazil," 2Fleury, S~o Paulo, Brazil," 3Sgto Paulo University, S~o Paulo, Brazil Study objective: Evaluation of transvaginal ultrasound (TVUS) in deeply infiltaring endometriosis. Design: Prospective study of 110 consecutive patients with clinical signs of deeply infiltrating endometriosis submitted to TVUS and laparoscopic procedures. Setting: Mukidisciplinary group practice and teaching hospital at S~o Paulo Brazil. Patients: One hundred and ten patients (ages 18 52 years) with clinical signs of rectosigmoid endometriosis studied between October 2002 and February 2004. Interventions: TVUS with a retrograde bowel preparation performed 1 hour previous to the examination. The examination evaluate the rectosigmoid and the deeply infiltrating retrocervical endometriosis. Measurements and Main Results: The ultrasound images were compared with laparoscopic findings and histological confirmation of endometriosis. TVUS suggested deeply infiltrating retrocervical endometriosis in 39 cases and in 32 patients this evaluation was confirmed during surgery and after histological examination. Statistical analysis revealed sensitivity of 88.9% (95%CI: 0.74 0.97), specificity of 90.5% (95%CI: 0.81 0.96), positive predictive value of 82.0% (95%CI: 0.66 0.92) and negative predictive value of 94.4% (95%CI: 0.86 0.98). TVUS suggested rectosigmoid endometriosis in 44 cases and in 42 patients this evaluation was confirmed during surgery and after histopathological examination. TVUS suggested no involvement of rectosigmoid in 66 cases and in 64 patients this evaluation was confirmed during surgery. Statistical analysis revealed sensitivity of 95.4% (95%CI: 0.84 0.99), specificity of 96.4% (95%CI: 0.89 0.99), positive predictive value of 95.4% (95%CI: 0.84 0.99) and negative predictive value of 96.5% (95%CI: 0.89 0.99). Conclusions: Transvaginal ultrasound is a helpful tool in the management of deeply infiltrating endometriosis since it can predict retrocervical and rectosigmoid involvement by this disease
Parallel session B. Friday, 16 September 2005, 12.00-13.00
inflammatory markers. Prostaglandins such as PGE2 are considered to be pain causing molecules. Our earlier studies show that oxidative stress might play an important role in the etiology of endometriosis and there is an increased presence of oxidative stress markers in the peritoneal fluid (PF) of these women. In particular, we find high levels of mildly oxidatively modified lipoproteins present in the peritoneal fluid of women with endometriosis. In this study, we show that non-enzymatically modified lipoproteins generate prostaglandin-like molecules. For this, low density lipoprotein (LDL) was isolated from normal human volunteers by the ultracentrifugation, which was then subjected to oxidation using the copper method. The oxidation was stopped at different time points which reflect the native LDL (zero time), mm LDL or minimally modified LDL (as soon as the antioxidants are consumed and the oxidation begins lag time), oxidized LDL (as soon as the conjugated dienes are completely formed) and completely oxidized LDL (after 24 hours of oxidation). At the end of the preparation the PGE2 was determined in the above four fractions using the commercially available ELISA kits. We observed an increase in prostaglandinlike molecules as the oxidation of LDL increased. Similarly, the PF of women with endometriosis had higher levels of these molecules compared to control PF and these levels decreased in endometriosis women supplemented with antioxidants for two months. The presence of inflammatory cytokines also decreased in these women. Whether these molecules are responsible for the pain in women with endometriosis needs to be determined. Our finding suggests that the source of these molecules may be oxidation related and can be decreased by antioxidant supplementation.
I-~
32I.J. Janicki. University Hospitals of Cleveland, Cleveland, USA Mechanism of chronic pelvic pain in endometriosis has been debated for nearly a century, so far there is no satisfactory explanation for this phenomenon. Similar stages of endometriosis can be either associated with pain (occasionally debilitating), or exhibit total absence of it. Most of the chronic pain conditions including complex regional pain syndromes, interstitial cystitis, irritable bowel syndrome, chronic prostatitis and neurogenic appendicopathy exhibit elements of neurogenic inflammation. One can also hypothesize that neurogenic inflammation is involved in chronic pelvic pain with or without endometriosis. Common elements of neurogenic inflammation include: presence of autonomic dysfunction, increase number of local nerve fibers, local increase in number of mast cells and aggravation of pain symptoms by psychological stress. The pathophysiologic basis for initiation and maintenance of neurogenic inflammation can be traced to the bi-directional communication between the nervous and the immune systems. Both of the systems carry surveillance of homeostasis and use many of the same neurotransmitters and pro-inflammatory kinases allowing the periphery to notify central nervous system of immune activation via both neural fibers and blood/lymphatic routes. At the periphery the autonomic and the somatic nerve fibers are closely associated with inflammatory cells, including mast cells. Substance P (SP) released from the nerve fibers degranulates mast cells, during degranulation the mast cells release multitude of proinflammatory agents including among the others nerve growth factor (NGF). Degranulation of the mast cells is modulated among the others by presence of local estrogen. In addition the animal experiment proven that psychological stress alone is able to induce degranulation of the bladder mast cells. Recent published and unpublished data concerning patients with pelvic pain and endometriosis indicate evidence of autonomic dysfunction and increased number of nerve fibers at or near the loci or endometriosis/adenomyosis. There are also reports of increased level of NGF in adenomyotic nodules and increase in number of mast cells near endometriotic implants. All of this findings suggests active neuroimmune process in patients with endometriosis.
I-~
I•
Prostaglandin-like lipid oxidation products in the peritoneal fluid of women with endometriosis
N. Santanam 1 , J. Bolnick 2, S. Parthasarathy 1 . ]LSUHealth Sciences Center,
New Orleans, USA," 2 University of New Mexico, New Mexico, USA Endometriosis is an inflammatory disease whose etiology is still unknown. The two major characteristic of this disease is pain and infertility. The peritoneal milieu of women with endometriosis is a rich source of growth promoting and
Local neurogenic inflammation as a mechanism of chronic visceral pain including chronic pelvic pain associated with endometriosis
Endometriosis and immunology: is the dosage of the natural killer cells relevant?
J.A. Dias Jr. 1 , R.M. Oliveira2, S. Podgaec 1 , M. Abrfio 1 . JHCFMUSP, S~o Paulo, Brazil," 2Laboratbrio Salomgto e Zoppi, Sgto Paulo, Brazil Introduction: Immunological aspects of pathogenesis of endometriosis are studied in several publications. The literature shows that patients with endometriosis have a higher incidence of auto-antibodies, an issue that could be associated with T helper 2 (Th2) response. On the other hand, the number and activity of the natural killer cells (which are related to the T helper 1 response Thl) in patients with endometriosis is not well established: some
S14
(ERB), cyclooxygenase-2 (Cox-2), cytochrome P450 (CYP1A1) and progesterone receptor (PR) by real-time NAT. Samples were examined from menstrual blood samples as well as from peripheral blood. Endometriosis was verified laparoscopically and distributed to the endometriosis stages according the rAFSguidelines. Results: Patients with endometriosis showed significant increased levels of estrogene receptor beta and progesterone receptor in menstrual blood samples whereas no differences were recognized between women with endometriosis and control group in peripheral blood samples (p=0.03 for ER beta; p=0.01 for PR). Conclusion: These data suggest that endometriosis resuks from the dislocation of basal endometrium. The real-time PCR screening for estrogen receptor beta and progesterone receptor in patients with strong suspicion for endometriosis provides the opportunity to verify the diagnosis without invasive laparoscopic examinations. This study demonstrates the principle of proof, examinations in a larger population are eagerly awaited.
References [1] Leyendecker G., Herbertz M., Kunz G., Mall G.(2002): Endomerriosis results from the dislocation of basal endometrium. Hum Reprod, 17; 2725-36.
l
•
l
t
is possible to evaluate deeply infiltrating endometriosis with transvaginal ultrasound
M.S. Abrao 1 , M.O. Gonqalves 2, M. Gonzales 3, J.A. Dias Jr. 3, S. Podgaec 3.
S~o Paulo, Brazil," 2Fleury, S~o Paulo, Brazil," 3Sgto Paulo University, S~o Paulo, Brazil Study objective: Evaluation of transvaginal ultrasound (TVUS) in deeply infiltaring endometriosis. Design: Prospective study of 110 consecutive patients with clinical signs of deeply infiltrating endometriosis submitted to TVUS and laparoscopic procedures. Setting: Mukidisciplinary group practice and teaching hospital at S~o Paulo Brazil. Patients: One hundred and ten patients (ages 18 52 years) with clinical signs of rectosigmoid endometriosis studied between October 2002 and February 2004. Interventions: TVUS with a retrograde bowel preparation performed 1 hour previous to the examination. The examination evaluate the rectosigmoid and the deeply infiltrating retrocervical endometriosis. Measurements and Main Results: The ultrasound images were compared with laparoscopic findings and histological confirmation of endometriosis. TVUS suggested deeply infiltrating retrocervical endometriosis in 39 cases and in 32 patients this evaluation was confirmed during surgery and after histological examination. Statistical analysis revealed sensitivity of 88.9% (95%CI: 0.74 0.97), specificity of 90.5% (95%CI: 0.81 0.96), positive predictive value of 82.0% (95%CI: 0.66 0.92) and negative predictive value of 94.4% (95%CI: 0.86 0.98). TVUS suggested rectosigmoid endometriosis in 44 cases and in 42 patients this evaluation was confirmed during surgery and after histopathological examination. TVUS suggested no involvement of rectosigmoid in 66 cases and in 64 patients this evaluation was confirmed during surgery. Statistical analysis revealed sensitivity of 95.4% (95%CI: 0.84 0.99), specificity of 96.4% (95%CI: 0.89 0.99), positive predictive value of 95.4% (95%CI: 0.84 0.99) and negative predictive value of 96.5% (95%CI: 0.89 0.99). Conclusions: Transvaginal ultrasound is a helpful tool in the management of deeply infiltrating endometriosis since it can predict retrocervical and rectosigmoid involvement by this disease
Parallel session B. Friday, 16 September 2005, 12.00-13.00
inflammatory markers. Prostaglandins such as PGE2 are considered to be pain causing molecules. Our earlier studies show that oxidative stress might play an important role in the etiology of endometriosis and there is an increased presence of oxidative stress markers in the peritoneal fluid (PF) of these women. In particular, we find high levels of mildly oxidatively modified lipoproteins present in the peritoneal fluid of women with endometriosis. In this study, we show that non-enzymatically modified lipoproteins generate prostaglandin-like molecules. For this, low density lipoprotein (LDL) was isolated from normal human volunteers by the ultracentrifugation, which was then subjected to oxidation using the copper method. The oxidation was stopped at different time points which reflect the native LDL (zero time), mm LDL or minimally modified LDL (as soon as the antioxidants are consumed and the oxidation begins lag time), oxidized LDL (as soon as the conjugated dienes are completely formed) and completely oxidized LDL (after 24 hours of oxidation). At the end of the preparation the PGE2 was determined in the above four fractions using the commercially available ELISA kits. We observed an increase in prostaglandinlike molecules as the oxidation of LDL increased. Similarly, the PF of women with endometriosis had higher levels of these molecules compared to control PF and these levels decreased in endometriosis women supplemented with antioxidants for two months. The presence of inflammatory cytokines also decreased in these women. Whether these molecules are responsible for the pain in women with endometriosis needs to be determined. Our finding suggests that the source of these molecules may be oxidation related and can be decreased by antioxidant supplementation.
I-~
32I.J. Janicki. University Hospitals of Cleveland, Cleveland, USA Mechanism of chronic pelvic pain in endometriosis has been debated for nearly a century, so far there is no satisfactory explanation for this phenomenon. Similar stages of endometriosis can be either associated with pain (occasionally debilitating), or exhibit total absence of it. Most of the chronic pain conditions including complex regional pain syndromes, interstitial cystitis, irritable bowel syndrome, chronic prostatitis and neurogenic appendicopathy exhibit elements of neurogenic inflammation. One can also hypothesize that neurogenic inflammation is involved in chronic pelvic pain with or without endometriosis. Common elements of neurogenic inflammation include: presence of autonomic dysfunction, increase number of local nerve fibers, local increase in number of mast cells and aggravation of pain symptoms by psychological stress. The pathophysiologic basis for initiation and maintenance of neurogenic inflammation can be traced to the bi-directional communication between the nervous and the immune systems. Both of the systems carry surveillance of homeostasis and use many of the same neurotransmitters and pro-inflammatory kinases allowing the periphery to notify central nervous system of immune activation via both neural fibers and blood/lymphatic routes. At the periphery the autonomic and the somatic nerve fibers are closely associated with inflammatory cells, including mast cells. Substance P (SP) released from the nerve fibers degranulates mast cells, during degranulation the mast cells release multitude of proinflammatory agents including among the others nerve growth factor (NGF). Degranulation of the mast cells is modulated among the others by presence of local estrogen. In addition the animal experiment proven that psychological stress alone is able to induce degranulation of the bladder mast cells. Recent published and unpublished data concerning patients with pelvic pain and endometriosis indicate evidence of autonomic dysfunction and increased number of nerve fibers at or near the loci or endometriosis/adenomyosis. There are also reports of increased level of NGF in adenomyotic nodules and increase in number of mast cells near endometriotic implants. All of this findings suggests active neuroimmune process in patients with endometriosis.
I-~
I•
Prostaglandin-like lipid oxidation products in the peritoneal fluid of women with endometriosis
N. Santanam 1 , J. Bolnick 2, S. Parthasarathy 1 . ]LSUHealth Sciences Center,
New Orleans, USA," 2 University of New Mexico, New Mexico, USA Endometriosis is an inflammatory disease whose etiology is still unknown. The two major characteristic of this disease is pain and infertility. The peritoneal milieu of women with endometriosis is a rich source of growth promoting and
Local neurogenic inflammation as a mechanism of chronic visceral pain including chronic pelvic pain associated with endometriosis
Endometriosis and immunology: is the dosage of the natural killer cells relevant?
J.A. Dias Jr. 1 , R.M. Oliveira2, S. Podgaec 1 , M. Abrfio 1 . JHCFMUSP, S~o Paulo, Brazil," 2Laboratbrio Salomgto e Zoppi, Sgto Paulo, Brazil Introduction: Immunological aspects of pathogenesis of endometriosis are studied in several publications. The literature shows that patients with endometriosis have a higher incidence of auto-antibodies, an issue that could be associated with T helper 2 (Th2) response. On the other hand, the number and activity of the natural killer cells (which are related to the T helper 1 response Thl) in patients with endometriosis is not well established: some