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Angiogenesis is likely to be involved in the pathogenesis of endometriosis. According to the transplantation theory, when the exfoliated endometrium is attached to the peritoneal layer, the establishment of a new blood supply is essential for the survival of the endometrial implant and development of endometriosis. From the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a pivotally important regulator of normal angiogenesis and pathological neovascularization. The VEGF protein was evaluated immunohistochemically in the eutopic endometrium of 10 women without endometriosis (group I) at laparoscopy and the eutopic endometrium and peritoneal endometriotic lesions of 43 women with endometriosis (group II). VEGF histological scores were 9.7 +/- 4.3 and 4.0 +/- 2.6 respectively in the epithelium and stroma of the eutopic endometrium of group I women, and 10.3 +/- 2.3 and 3.6 +/- 2.3 respectively in women of group II. In red lesions, the VEGF scores were 11.1 +/- 3.0 in the epithelium and 5.1 +/- 3.0 in the stroma, and in black lesions were 8.6 +/- 2.7 and 1.6 +/- 1.6, respectively. Significantly lower values were observed in black lesions as compared with eutopic endometrium and red lesions, the values of which were similar. Scores were also evaluated according to the phase of the cycle. In eutopic as well as ectopic endometrium, no significant cyclic variations were observed throughout the cycle. However, VEGF content was found to be higher in the eutopic glandular epithelium of women with endometriosis during the late secretory phase, possibly suggesting a more likely tendency to implant. In contrast, significantly higher VEGF content was noted in red lesions as compared with black lesions. During all phases of the cycle, the VEGF content in stromal cells of red lesions was higher than in black lesions. Similarities in VEGF content were observed in the glandular epithelium of the eutopic endometrium of women with endometriosis and red lesions, suggesting that endometriosis probably arises from the peritoneal seeding of viable endometrial cells during retrograde menstruation and that red lesions can be considered as the first stage of implantation. After the attachment phase, the high VEGF levels could provoke an increase in the subperitoneal vascular network and facilitate implantation and viability in the retroperitoneal space. Lower VEGF levels in black lesions explain the decrease in both stromal vascularization, followed by fibrosis and inactivation of the implant.

The management of large endometriomas was described in a series of 814 patients. Combined therapy using gonadotrophin-releasing hormone agonist (GnRHa) and carbon dioxide laser laparoscopy was proposed. Drainage and GnRHa for 12 weeks provoked a reduction of the endometrioma size up to 50% of the initial value. After vaporization of the internal wall, a cumulative pregnancy of 51% after 1 year was achieved. A recurrence rate of 8% was observed for a follow-up of 2-11 years. Histological data demonstrated that the epithelium covering the ovary which is the mesothelium can invaginate in the ovarian cortex. Some of the invaginations were seen to be continuous with endometrial tissue, strongly suggesting the metaplasia theory in the pathogenesis of ovarian endometrioma.

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BackgroundThiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine monophosphate (ThMP), thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), present in many organisms, may have still unidentified physiological functions. Diseases linked to thiamine deficiency (polyneuritis, Wernicke-Korsakoff syndrome) remain frequent among alcohol abusers and other risk populations. This is the first comprehensive study on the distribution of thiamine derivatives in human biopsies, body fluids and cell lines.Methodology and Principal FindingsThiamine derivatives were determined by HPLC. In human tissues, the total thiamine content is lower than in other animal species. ThDP is the major thiamine compound and tissue levels decrease at high age. In semen, ThDP content correlates with the concentration of spermatozoa but not with their motility. The proportion of ThTP is higher in humans than in rodents, probably because of a lower 25-kDa ThTPase activity. The expression and activity of this enzyme seems to correlate with the degree of cell differentiation. ThTP was present in nearly all brain and muscle samples and in ∼60% of other tissue samples, in particular fetal tissue and cultured cells. A low ([ThTP]+[ThMP])/([Thiamine]+[ThMP]) ratio was found in cardiovascular tissues of patients with cardiac insufficiency. AThTP was detected only sporadically in adult tissues but was found more consistently in fetal tissues and cell lines.Conclusions and SignificanceThe high sensitivity of humans to thiamine deficiency is probably linked to low circulating thiamine concentrations and low ThDP tissue contents. ThTP levels are relatively high in many human tissues, as a result of low expression of the 25-kDa ThTPase. Another novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation.

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The cell proliferation-associated antigen Ki 67 and the immunohistochemical content of oestrogen receptors (ER), progesterone receptors AB (PRAB) and progesterone receptors B (PRB) were evaluated in leiomyomata and adjacent myometrium during the menstrual cycle and in leiomyomata under gonadotrophin-releasing hormone agonist (GnRHa) therapy. The proliferative status of muscular cells was measured by evaluating the percentage of nuclei staining positive for Ki 67 (proliferation index). Quantitative analysis (QH-score) was carried out using advanced stereographic computer technology to investigate ER, PRAB and PRB. Leiomyoma and myometrial biopsies were taken from 30 patients undergoing hysterectomy or myomectomy because of symptomatic leiomyomata (subgroup I). Leiomyoma biopsies were taken from 10 patients suffering from symptomatic submucosal leiomyomata, after 2 month GnRH therapy (subgroup II). During the secretory phase, the proliferation index (Ki 67) was found to be higher in leiomyomata than in myometrium, but the difference was not significant. Oestrogen receptor content was significantly higher in leiomyomata than in myometrium only during the proliferative phase of the cycle. PRAB and PRB content were found to be higher in leiomyomata than in adjacent myometrium with a statistically significant dominance of PRAB over PRB. Under GnRHa therapy, a dramatic decrease was observed in PRAB and B content as well as Ki 67 but ER content remained comparable with the results obtained during the menstrual cycle. The results suggest that leiomyomata may be under the influence of progesterone which may play a major role in their growth.