Cell adhesion molecules and endometriosis

The pathogenesis of endometriosis remains poorly defined. The interaction of endometrium with peritoneum is an important aspect of the disease process. Cell adhesion molecules (CAMs) are transmembrane receptors that facilitate intercellular binding and cellular interaction with the extracellular matrix (ECM). CAMs and components of the ECM are divided into large families based on sequence homology and similarity of tertiary structures. The function of eutopic and ectopic endometrial CAMs has been a focus of recent studies concerning the pathogenesis of endometriosis. Specific alterations in endometrial and peritoneal CAMs could facilitate binding of reflux menstruated endometrium at ectopic sites. In addition, the expression of CAMs by endometriotic lesions has been investigated to help understand mechanisms involved in the maintenance of endometrial tissue in ectopic locations. An understanding of the mechanisms involved in the interaction of endometrium with peritoneal tissues may provide new strategies to prevent endometriotic implants from forming and help treat existing lesions.     

Increased levels of intercellular adhesion molecules and vascular cell adhesion molecules in pre-eclampsia

Objective To investigate the correlation between soluble forms of the intercellular adhesion molecule (SICAM-1) and vascular cell adhesion molecule (sVCAM-1) and the severity of pre-eclampsia or its possible consequences for fetal growth.
Design Prospective observational study.
Setting Institute of Medical Genetics, University of Oslo, Department of Medical Genetics and Haematological Research Laboratory, Ullevål University Hospital; and the Department of Obstetrics and Gynaecology, The National Hospital, Oslo, Norway.
Participants Seventy-six women with normotensive pregnancies and 157 women with pre-eclampsia divided into three subgroups: mild, severe and pre-eclampsia with fetal growth retardation.
Methods ELISA-measurements of plasma SICAM-1 and sVCAM-1 were performed in a group of healthy pregnant normotensive women and three groups of women with varying degrees of pre-eclampsia.
Results SICAM-1 concentrations were higher in the pre-eclampsia group compared with the control group, but this difference was not statistically significant. Plasma concentrations of sVCAM-1 were significantly greater ( P < 0.0001) in all pre-eclampsia subgroups (835.34, 855.25 and 964.05 ng/mL) compared with the control group (667.62 ng/mL). Within the pre-eclampsia group, plasma concentration of sVCAM-1 was significantly higher in the subgroup exhibiting fetal growth retardation ( P = 0.03) compared with mild pre-eclampsia.
Conclusion The observed increases in plasma concentrations of sVCAM-1 suggest that measurements of this adhesion molecule may be useful in monitoring pregnancies with respect to the development of pre-eclampsia or fetal growth retardation.     

Pathogenesis of Intra-abdominal and pelvic adhesion development

Abdominal and pelvic adhesions are a frequent occurrence and are responsible for significant morbidity resulting in abdominal and pelvic pain, infertility, and small bowel obstruction. The process of adhesion development begins when damage to peritoneal surfaces from any source (operative trauma, infection, foreign bodies, desiccation, irradiation, allergic reaction, or chemical injury) induces a series of biochemical/molecular biologic cascades involving different elements. These elements include peritoneal fluid, neutrophils, leukocytes, macrophages, cytokines, mesothelial cells, and tissue and coagulation factors, which teleologically have the intention of peritoneal repair; however, these processes also result in adhesion development. Major pathways that play significant roles in the healing process of peritoneal damage leading to adhesion development are the fibrinolytic system, extracellular matrix deposition, growth factor and cytokines, cell adhesion molecules, angiogenesis, apoptosis and proliferation, and remesothelialization. Greater understanding of the regulation and interaction of these processes provides the potential for reduction of postoperative adhesion development.     

Laparoscopy and adhesion formation, adhesions and laparoscopy

Laparoscopic peritoneal adhesion formation follows a pathway similar to laparotomy, both of which are only partially understood. Laparoscopic adhesion formation is complicated and influenced by pressure, dry gas desiccation, and hypoxia caused and superimposed by the pneumoperitoneum. It may further be affected by products of tissue combustion and inappropriate irrigation. Adjuvants are a poor substitute for attention to surgical detail and offer little help for the problem. The best defenses to reduce adhesion formation are maintenance of a normal physiologic peritoneal state that is wet and warm, gentle tissue handling, low intra-abdominal pressure, appropriate irrigation, and evacuation of smoke. Continued research into peritoneal cell response to the provocative circumstances of laparoscopic surgery will hopefully offer assistance to diminish the potential for laparoscopic adhesion formation.     

Evaluation of recombinant tissue-type plasminogen activator in adhesion prevention and neoangiogenesis in a rat experimental adhesion model

This study was designed to test the effect of recombinant tissue-type plasminogen activator (rt-PA) in reducing adhesion formation and to observe its influence on peritoneal neoangiogenesis. In 20 Wistar rats, a 4-cm midline incision was made, and a square piece of Silastic, 0.5×0.5 cm and 0.2 mm thick, was fixed on the right side of the peritoneum with two separate angular stitches of nylon 9/O. The rats were randomized into two groups of 10 animals each. In the first group we injected 0.2 mg of rt-PA intraperitoneally three times a day. The second group of 10 rats was used as a control group. Each rat was reoperated on day 12. Intraperitoneal injection of rt-PA seemed not to affect adhesion formation, as a 100% adhesion rate was reported in the treated group compared with 90% of the control group. The results showed that rt-PA acts on the neoangiogenesis involved in postsurgical adhesion formation by reducing the size and length of the vessels. This action seems to slow down peritoneal healing with a negative effect on postsurgical adhesion prevention.     

Evaluation of the SprayGel adhesion barrier in the rat cecum abrasion and rabbit uterine horn adhesion models

OBJECTIVE: To evaluate the efficacy of a new adhesion barrier in the prevention of postoperative adhesion formation. DESIGN: A double-blind controlled study of the efficacy of SprayGel in reducing postoperative adhesion formation in two animal models. SETTING: Animal care facility of a contract testing laboratory. ANIMAL(S): Sixteen Sprague-Dawley male rats were randomly allocated into two groups in the cecum abrasion model. Twenty New Zealand white female rabbits were randomly allocated into two groups in the uterine horn abrasion model. INTERVENTION(S): In the rat model, the cecum was abraded with gauze and the abdominal wall was abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. In the rabbit model, uterine horns were abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. MAIN OUTCOME MEASURE(S): Postoperative adhesion formation. RESULT(S): In the rat model, SprayGel was found to significantly reduce the incidence of adhesions, which formed in 7 of 8 control rats compared with 1 of 8 treated rats. In the rabbit model, SprayGel was found to significantly reduce both the extent and severity of adhesions. CONCLUSION(S): Application of SprayGel in two animal models reduced formation of postoperative adhesions. Further investigation in large animal and clinical settings is warranted.     

Postoperative adhesion prevention with an oxidized regenerated cellulose adhesion barrier in infertile women

OBJECTIVE: To evaluate the efficacy of an oxidized regenerated cellulose adhesion barrier as an adjuvant in preventing postoperative adhesions in infertile women undergoing reconstructive surgery. STUDY DESIGN: Thirty-eight cases of reconstructive surgery that could be followed up for more than two years (myomectomy 19, cystectomy 5, tuboplasty 10, uteroplasty 4) at the Fujita Health University Hospital were evaluated retrospectively. The barrier (Intercede, Johnson & Johnson) was used to cover the surgical site in 23 of these cases (Intercede group); no adjuvant was used in 15 cases, which represent the surgical control group (Intercede - group), including 23 second-look operation cases (16 in the Intercede and 7 in the control group). Postoperative adhesion prevention and pregnancy rates were estimated. RESULTS: At the second-look operation, six cases (37.5%) in the Intercede + group and six (85.7%) in the Intercede - group had postoperative adhesions. No significant difference was found in either intensity or area covered with adhesions between the two groups. Eighteen cases (78.3%) in the Intercede and seven (46.7%) in the Intercede - group conceived during the follow-up period. CONCLUSION: The use of Intercede significantly reduced the rate of postoperative adhesion formation, with a statistically significant increase in the pregnancy rate as compared to the surgical controls.     

雌激素在宫腔粘连中的应用及机制探讨

宫腔粘连(IUA)对女性的身体及心理造成不同程度的伤害。宫腔镜手术能恢复宫腔正常形态,但不能修复子宫内膜,从而造成再粘连的发生。有研究显示,行宫腔镜宫腔粘连分离的患者术后再粘连的发生率为3.1%~23.5%。雌激素能促进内膜腺体和间质细胞的增殖,促进内膜血管的生成,从而达到尽快修复创面、形成子宫壁的功能性分离,有利于新生内膜的生长。因此,IUA术后多应用雌激素预防再粘连发生,但目前关于雌激素的用法、用量并不十分统一,有待于进一步的深入研究。     

Cell adhesion molecules and the regulation of development

Cell adhesion molecules, in conjunction with the other morphoregulatory molecules, substrate adhesion molecules and cell junctional molecules, are dynamically expressed in coordinate patterns throughout development. Their activities are linked to a variety of cellular processes, and their ability to influence mechanochemical processes allows them to influence a variety of other fundamental developmental events. The clinical significance of these molecules remains to be determined, but they are clearly involved in a number of pathologic conditions and could become the focus of a wide range of diagnostic techniques and eventually even therapeutic designs.     

Rapamycin and a hyaluronic acid-carboxymethylcellulose membrane did not lead to reduced adhesion formations in a rat abdominal adhesion model

Purpose

Rapamycin, an immunosuppressive in transplant surgery, has an additional antiproliferative effect. The aim of this study was to investigate the potential protective effects of rapamycin on postoperative adhesion development.

Methods

Ten rats per group underwent midline incision laparotomy and adhesion induction including bowel sutures. Therapy groups received daily intraperitoneal rapamycin injections (1.5?mg/kg body weight) for 3?weeks postoperatively. Controls were rats without any postoperative treatment, rats receiving the rapamycin solvent or a hyaluronic acid-carboxymethylcellulose membrane (Seprafilm^?).

Results

Postoperative rapamycin application led to enhanced adhesion development and there was a higher rate of wound infections. In addition, Seprafilm^? did not reduce adhesions, in subgroups there were even more.

Conclusions

Rapamycin is not recommendable for perioperative immunosuppression, it enhances adhesion development and leads to a higher rate of wound infections. Surprisingly, the established Seprafilm^? membrane led to more adhesions in our experimental setting.     

Soluble adhesion molecule profile in normal pregnancy and pre-eclampsia

Objective: An exaggerated inflammatory response has been implicated as the cause of endothelial cell dysfunction and the maternal syndrome of pre-eclampsia. Adhesion molecules play a central role in the adherence of leukocytes to endothelial cells and the subsequent migration of white blood cells into perivascular tissue. Cellular forms of adhesion molecules mediate specific steps of leukocyte-endothelial cell interaction, and have been implicated in the pathophysiology of pre-eclampsia. Soluble forms of these molecules can be detected in plasma, and their concentrations are thought to reflect the degree of activation of a particular cell type. Elevations in soluble P-selectin (sP-selectin) reflect platelet activation; changes in soluble L-selectin (sL-selectin) suggest leukocyte activation; and an increase in soluble forms of E-selectin (sE-selectin), vascular cell adhesion molecule 1 (sVCAM-1), intercellular adhesion molecule 1 (sICAM-1) and platelet endothelial cell adhesion molecule (sPECAM-1) indicate endothelial cell activation/dysfunction. The objective of this study was to determine whether normal pregnancy and pre-eclampsia were associated with changes in the concentrations of soluble selectins and members of the immunoglobulin superfamily of adhesion molecules. Study design: A cross-sectional study was conducted to determine the plasma concentrations of sL-selectin, sE-selectin, sP-selectin, sVCAM-1, sICAM-1 and sPECAM-1 in peripheral blood obtained from non-pregnant women (n = 20), normal pregnant women (n = 100) and patients with pre-eclampsia (n = 55). Concentrations of soluble adhesion molecules were determined with enzyme-linked immunoassays. Parametric statistics were used for data analysis. Results: Normal pregnancy was associated with a significant increase in the maternal plasma concentration of sP-selectin, a decrease in sL-selectin, and no change in sE-selectin, sVCAM-1, sICAM-1 and sPECAM-1. In contrast, pre-eclampsia was associated with a significant increase in sP-selectin, sE-selectin and sVCAM-1, a decrease in sL-selectin, but no change in sICAM-1 and sPECAM-1 concentrations. Conclusions: The increased concentration of sP-selectin and decreased sL-selectin, as well as the lack of change in endothelial cell-associated soluble adhesion molecules suggest that pregnancy is associated with platelet and leukocyte activation, but not endothelial cell activation. In contrast, pre-eclampsia appears to be characterized by activation of platelets, leukocytes and endothelial cells.     

Orally and parenterally administered ibuprofen for postoperative adhesion prevention

Adhesion formation was examined in 45 rats that were divided into five groups of 9 animals each: control, oral ibuprofen, intramuscular ibuprofen, intraperitoneal 32% dextran 70, and oral ibuprofen plus intraperitoneal 32% dextran 70. Four weeks after receiving a standard injury, all the animals were killed and the adhesions scored blindly. Both the oral and intramuscular ibuprofen groups had significantly less severe adhesion formation (P less than .01) when compared to the control group. Although 32% dextran 70 alone showed no beneficial effect in reducing adhesions, the combination of oral ibuprofen and 32% dextran 70 had the least adhesion formation (P less than .002) when compared to the control group. Oral and intramuscular ibuprofen seem to be equally efficient in reducing postoperative adhesions. Furthermore, the combination of oral ibuprofen and 32% dextran 70 appears to have a synergistic effect.     

Serum intercellular adhesion molecule-1 levels and histologic chorioamnionitis

OBJECTIVE: To compare the diagnostic value of intercellular adhesion molecule (ICAM)-1 with that of C-reactive protein (CRP) and white blood cell (WBC) count for detecting histologic chorioamnionitis in serum of women with preterm labor. METHODS: Maternal blood was collected from 97 consecutive women admitted with preterm delivery before 37 weeks' gestation, and 50 women after normal term delivery (38-41 weeks' gestation). Intercellular adhesion molecule-1, CRP, and WBC count were measured before delivery. RESULTS: Histologic chorioamnionitis was diagnosed in 48 of 97 women (48%) who delivered preterm and in none who delivered at term. Maternal serum levels of ICAM-1 (median 169 ng/mL, range 94-510 ng/mL, P <.001), CRP (median 2.8 ng/mL, range 0.5-13.2 mg/dL, P <.001) and WBC count (12.6 x 10(3)/microL, range 6.4-30.6 x 10(3)/microL, P <.02) were statistically significantly higher in women with histologic chorioamnionitis than those without it (ICAM-1 median 70 ng/mL, range 23-107 ng/mL; CRP median 0.7 mg/dL, range 0.5-6.7 mg/dL; WBC count median 10.9 x 10(3)/microL, range 4.3-22.2 x 10(3)/microL). The sensitivity and specificity of maternal serum ICAM-1 (cutoff 106 ng/mL), CRP (cutoff 1.1 mg/dL), and WBC count (cutoff 11.8 x 10(3)/microL) for diagnosing histologic chorioamnionitis were 98.0% and 93.8%, 75.5% and 71.4%, and 63.3% and 61.2%, respectively. CONCLUSION: In women with preterm labor, ICAM-1 is a more reliable indicator of histologic chorioamnionitis than CRP or WBC count.     

A comparative study of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 in preeclampsia.

OBJECTIVES: Maternal serum soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) were evaluated in preeclampsia to investigate whether these molecules could be helpful with regard to this pregnancy complication. STUDY DESIGN: The study population was composed of 30 preeclamptic patients with a mean gestational age of 35.5 +/- 4.6 weeks and 20 age-matched and gestational age-matched normotensive uncomplicated pregnancies (controls). Blood samples from 7 of the 30 preeclamptic patients and 15 of the 20 controls in the second trimester were also analyzed. Data were analyzed by parametric methods. RESULTS: Significantly higher maternal serum sVCAM-1 levels were found in both groups of preeclamptic patients with and without fetal growth restriction (981 +/- 145 ng/ml; n = 13; p < 0.0005 and 846 +/- 84 ng/ml; p < 0.02, respectively) compared with controls (668 +/- 186 ng/ml). In contrast, no significant difference was found in maternal serum sICAM-1 levels between preeclamptic and normotensive pregnancies, or in both adhesion molecules (1) in the controls between second and third trimester samples and (2) in the second trimester between pregnant women who developed preeclampsia later and gestational age-matched controls. CONCLUSION: These findings show a selective significant elevation of maternal serum sVCAM-1 in preeclampsia, with the highest values in cases complicated with fetal growth restriction, perhaps reflecting its angiogenic function. Hence, sVCAM-1 could be helpful in the diagnosis of this fetal complication in preeclampsia.