Effects of androgenic properties of progestin combined with ethinyl estradiol on vascular endothelial reactivity, plasma lipids and free radical production in women with endometriosis.

AIM: Endothelial reactivity is inhibited and oxidative stress is enhanced in women with endometriosis. Testosterone may adversely affect lipids and endothelium. We investigated the effects of androgenic properties of progestins combined with ethinyl estradiol (EE) on endothelial function, lipids and free radical production in such women. METHODS: Women with endometriosis were treated with 20 µg EE + 3 mg drospirenone (DRSP) or 35 µg EE + 1 mg norethisterone (NET) for 3 months. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, copper (Cu), derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), nitrite/nitrate, endothelin-1 and asymmetrical dimethylarginine (ADMA) were measured before and after treatment. Flow-mediated vasodilation (FMD) of the brachial artery was measured by ultrasonography. RESULTS: DRSP group, but not NET group, significantly increased FMD and concentrations of nitrite/nitrate and small dense LDL cholesterol, while decreased endothelin-1 concentrations. In both groups, ADMA and LDL cholesterol concentrations were significantly decreased, but triglyceride, SHBG, d-ROMs, Cu and ceruloplasmin concentrations increased, and BAP concentrations did not change. DRSP group significantly increased HDL cholesterol concentrations, whereas NET group decreased its concentrations. Changes in triglyceride correlated positively either with changes in SHBG (r = 0.57, P < 0.001) or with small dense LDL cholesterol (r = 0.45, P = 0.005). Changes in Cu correlated positively with changes in d-ROMs (r = 0.87, P < 0.001). CONCLUSION: Androgenic properties of progestin may counteract EE's favorable effects on endothelial function and HDL cholesterol, while eliminating its adverse effects on increased triglyceride-induced small dense LDL cholesterol in women with endometriosis.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2017 edition.

Six years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the third revised edition was published in 2017. The 2017 Guidelines includes 10 additional clinical questions (CQ), which brings the total to 95 CQ (12 on infectious disease, 28 on oncology and benign tumors, 27 on endocrinology and infertility and 28 on healthcare for women). Currently a consensus has been reached on the Guidelines and therefore the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding recommendation level (A, B, C) is indicated.

Hepatic Effects of Estrogen on Plasma Distribution of Small Dense Low-Density Lipoprotein and Free Radical Production in Postmenopausal Women.

AIM: Hepatic effects of estrogen therapy on low-density lipoprotein (LDL) subfraction or oxidative stress have not been previously evaluated. The purpose of the present study was to investigate whether the differential hepatic effects of estrogen affect plasma distribution of small dense LDL and free radical production in postmenopausal women. METHODS: In all, 45 postmenopausal women were given 0.625 mg/day of oral conjugated equine estrogen (CEE) (n=15), 1.0 mg/day of oral 17ß estradiol (E2) (n=15), or 50 µg/day of transdermal 17ßE2 (n=15) for 3 months. Subjects received either estrogen alone or with dydrogesterone at 5 mg/day. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, metallic ions, and derivatives of reactive oxygen metabolites (d-ROMs) were measured. RESULTS: CEE, but not oral 17ßE2, increased the plasma concentrations of triglyceride, copper (Cu), and d-ROMs and the ratio of small dense LDL/total LDL cholesterol, a marker for plasma distribution of small dense LDL. Transdermal 17ßE2 decreased d-ROMs concentrations but did not significantly change other parameters. Plasma concentrations of SHBG increased in the 3 groups. Estrogen-induced changes in triglyceride correlated positively either with changes in SHBG (R=0.52, P=0.0002) or the ratio of small dense LDL/total LDL cholesterol (R=0.65, P＜0.0001). Changes in Cu also correlated positively either with changes in SHBG (R=0.85, P＜0.0001) or d-ROMs (R=0.86, P＜0.0001). CONCLUSION: The hepatic effects of different routes or types of estrogen therapy may be associated with plasma distribution of small dense LDL and free radical production in postmenopausal women.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan.

Hyaluronan synthase expression in ovarian cancer.

To determine if the immunohistochemical expression of hyaluronan synthase (HAS) correlates with the clinicopathological manifestations or clinical outcomes of ovarian carcinoma, sections of tumor tissue from 33 ovarian cancer patients were immunostained by the avidin-biotin-peroxidase complex method using anti-HAS1, anti-HAS2, anti-HAS3 and anti-CD44 antibody. A section was defined as having positive expression when >50% of the tumor cells were intensely stained. The microvessel density, which was defined as the mean number of new vessels, was determined under light microscopy. In the 33 ovarian cancer cases, 12 cases had positive expression of HAS1, 21 cases had positive expression of HAS2 and 11 cases had positive expression of HAS3. The expression of HAS1, HAS2 and HAS3 was unrelated to the stage of disease. CD44 expression occurred more frequently in the HAS1-positive group than in the HAS1-negative group, but the expression of HAS2 and HAS3 was unrelated to CD44 expression. The microvessel density was higher in the HAS1-positive group than in the HAS1-negative group. But the microvessel density did not differ in relation to the expression of HAS2 and HAS3. In the 23 patients that received chemotherapy, the expression of HAS1, HAS2 and HAS3 was unrelated to the chemotherapy response. The overall survival time was longer in the HAS1-negative group than in the HAS1-positive group. However, the expression of HAS2 and HAS3 was unrelated to the overall survival time. These results suggest that HAS1 expression in ovarian cancer may be associated with disease progression through angiogenesis and is an independent predictor of patient survival.

Usefulness of collagen gel droplet embedded culture drug sensitivity testing in ovarian cancer.

Due to the emergence of new anticancer agents for the treatment of ovarian cancer, methods to determine which agents will be most effective in individual patients are required. In order to investigate the potential for tailor-made chemotherapy, the drug sensitivities of various ovarian cancers were examined using collagen gel droplet embedded culture drug sensitivity testing (CD-DST), and the results were correlated with clinical outcomes. Sensitivities to paclitaxel, cisplatin, doxorubicin, etoposide, and SN-38, which is an active metabolite of irinotecan, were examined. Eight out of 22 samples failed to grow colonies and thus, their cell sensitivities could not be determined. Out of the 14 cases from which CD-DST results were obtained, seven patients then received chemotherapy aimed at inducing remission, while four received adjuvant, and three did not receive any chemotherapy. Three of the four tumors subsequently treated with adjuvant chemotherapy showed sensitivity to TXL and CDDP on CD-DST analysis, while one did not. None of these patients experienced recurrent disease from 24 to 36 months. Five of the seven tumors subsequently treated with chemotherapy aimed at inducing remission showed sensitivity to the relevant anticancer agents upon CD-DST analysis, while two did not. Among the five cases that showed tumor cell sensitivity, three experienced complete responses, one achieved a partial response and one had progressive disease. For the remaining two cases that demonstrated tumor cell resistance, one had stable disease and one had progressive disease following chemotherapy. Thus, six out of the seven cases (85.7%) that received chemotherapy aimed at inducing remission had clinical outcomes in keeping with the results of CD-DST. In conclusion, CD-DST results reflect clinical outcomes and may be a useful means by which to select drugs to which ovarian cancer cells are chemosensitive.

Serum antibody response to the heat shock protein 60 of Chlamydia trachomatis in women with developing cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether serum antibody response to the three versions of chlamydial heat shock protein 60 is associated with an increased risk for cervical cancer. STUDY DESIGN: Women with cervical carcinoma were identified by linking the data files of three Nordic serum banks with cancer registries. Overall, 178 women with invasive cervical carcinoma were identified. For each case, the earliest prediagnostic serum sample was chosen, and three matched control subjects who were free of cancer at the time of the case diagnosis were selected randomly. Serum antibodies to the chlamydial heat shock protein 60 were measured by enzyme-linked immunosorbent assay and correlated with the risk of the subsequent development of cervical cancer. RESULTS: Antibodies to chlamydial heat shock protein 60-1 were associated with cervical squamous cell carcinoma among cases with long lag time (>3.5 years; odds ratio, 2.4; 95% CI, 1.1-5.1). Antibodies to chlamydial heat shock protein 60-2 or chlamydial heat shock protein 60-3 were not associated with cervical cancer risk. CONCLUSIONS: The finding that chlamydial heat shock protein 60-1 antibodies are associated with an increased cervical cancer risk suggests that persistent Chlamydia trachomatis infection may contribute to cervical neoplasia.

Angiostatin expression in ovarian cancer.

Angiostatin is a potent inhibitor of neovascularization, tumor growth and metastasis. We examined the expression of angiostatin and vascular endothelial growth factor (VEGF) through immunohistochemical analysis, along with microvessel density, in primary tumors obtained from 55 ovarian carcinoma patients. Angiostatin expression was not related to either stage of disease or histology. However, VEGF expression and microvessel density were related to stage of disease. Angiostatin expression did not correlate with VEGF expression. Microvessel density correlated with VEGF, but not angiostatin expression. Univariate analysis revealed that lack of angiostatin expression, VEGF expression, microvessel density and advanced stage of disease were significant risk factors for reduced survival. Multivariate analysis revealed that lack of angiostatin expression and advanced stage of disease were significant risk factors for reduced survival. Survival time was longer in patients with angiostatin-positive and VEGF-negative tumors than in patients with angiostatin-negative and VEGF-positive tumors. The presence of angiostatin expression and absence of VEGF expression are favorable prognostic factors with regard to survival in ovarian carcinoma patients.

Molecular analysis of the multiple GroEL proteins of Chlamydiae.

Genome sequencing revealed that all six chlamydiae genomes contain three groEL-like genes (groEL1, groEL2, and groEL3). Phylogenetic analysis of groEL1, groEL2, and groEL3 indicates that these genes are likely to have been present in chlamydiae since the beginning of the lineage. Comparison of deduced amino acid sequences of the three groEL genes with those of other organisms showed high homology only for groEL1, although comparison of critical amino acid residues that are required for polypeptide binding of the Escherichia coli chaperonin GroEL revealed substantial conservation in all three chlamydial GroELs. This was further supported by three-dimensional structural predictions. All three genes are expressed constitutively throughout the developmental cycle of Chlamydia trachomatis, although groEL1 is expressed at much higher levels than are groEL2 and groEL3. Transcription of groEL1, but not groEL2 and groEL3, was elevated when HeLa cells infected with C. trachomatis were subjected to heat shock. Western blot analysis with polyclonal antibodies raised against recombinant GroEL1, GroEL2, and GroEL3 demonstrated the presence of the three proteins in C. trachomatis elementary bodies, with GroEL1 being present in the largest amount. Only C. trachomatis groEL1 and groES together complemented a temperature-sensitive E. coli groEL mutant. Complementation did not occur with groEL2 or groEL3 alone or together with groES. The role for each of the three GroELs in the chlamydial developmental cycle and in disease pathogenesis requires further study.