Peroxisome proliferator-activated receptor-(gamma) receptor ligand partially prevents the development of endometrial explants in baboons: a prospective, randomized, placebo-controlled study.
ABSTRACT A prospective, randomized, placebo-controlled study was conducted in a baboon model to determine if a thiazolidinedione agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone, can impede the development of endometriosis. Endometriosis was induced using laparoscopic, intrapelvic injection of eutopic menstrual endometrium, previously incubated with placebo or pioglitazone for 30 min, in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. At this point, the 12 baboons were randomized into two groups and treated from the day of induction. They received either PBS tablets (n = 6, placebo control, placebo tablets once a day by mouth) or pioglitazone (n = 6, test drug, 7.5 mg by mouth each day). A second and final laparoscopy was performed in the baboons to record the extent of endometriotic lesions between 24 and 42 d after induction (no difference in length of treatment between the two groups, P = 0.38). A videolaparoscopy was performed to document the number and surface area of endometriotic lesions. The surface area and volume of endometriotic lesions were significantly lower in pioglitazone treated baboons than the placebo group (surface area, 48.6 vs. 159.0 mm(2), respectively, P = 0.049; vol, 23.7 vs. 131.8 mm(3), respectively, P = 0.041). The surface area (3.5 vs. 17.8 mm(2), P = 0.017, pioglizatone vs. placebo) and overall number (1.5 vs. 9.5, P = 0.007, pioglizatone vs. placebo) of red lesions were lower in the pioglitazone group. A peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, effectively reduced the initiation of endometriotic disease in the baboon endometriosis model. Using this animal model, we have shown that thiazolidinedione is a promising drug for preventive treatment of endometriosis.
- SourceAvailable from: Brett Mckinnon[show abstract] [hide abstract]
ABSTRACT: To assess the effect of thiazolidinediones on the regulation of inflammatory cytokines related to endometriosis in endometrial tissue and determine whether these effects occur via activation of the peroxisome proliferating activating receptor gamma (PPAR)-γ. In vitro study using eutopic endometrial tissue. University hospital. Premenopausal women undergoing laparoscopy for infertility or abdominal pain. Isolation of endometrial stromal cells and the culture of these cells in the presence of thiazolidinediones, ciglitazone and pioglitazone, both with and without a pretreatment of the specific, irreversible PPAR-γ antagonist GW9662. Quantitation of interleukin (IL)-6 and IL-8 released into the cell culture medium by ELISA. Real-time polymerase chain reaction to quantitate PPAR-γ gene expression in the primary cell preparations and the expression of IL-6 and IL-8 after thiazolidinedione treatment. Treatment of stromal cells with thiazolidinediones attenuated IL-6 and IL-8 release in a dose-dependent manner. This effect was not inhibited by GW9662 pretreatment. Ciglitazone induced IL-6 messenger RNA expression, an effect that was suppressed by GW9662 pretreatment. Thiazolidinediones decrease the proinflammatory cytokines IL-6 and IL-8 in endometrial stromal cells via a PPAR-γ-independent mechanism. A better understanding of the anti-inflammatory action of this class of drugs may improve their safety and efficacy for endometriosis treatment.Fertility and sterility 12/2011; 97(3):657-64. · 3.97 Impact Factor
Conference Proceeding: Nitridized InAs/GaAs self-assembled quantum dots for optical communication wavelength[show abstract] [hide abstract]
ABSTRACT: A technique to grow InAs quantum dot (QD) to extend the emission wavelength into optical communication range has been developed. We performed nitridation after growing InAs QDs by molecular-beam epitaxy. The nitridized InAs QDs show a remarkable red shift of the photoluminescence peak. We have confirmed a 1.3μm emission peak at room temperature.Indium Phosphide and Related Materials, 2004. 16th IPRM. 2004 International Conference on; 07/2004