A case of placental polyp treated with an intraoperative injection of prostaglandin F2α followed by hysteroscopic resection.

A 27-year-old woman had massive genital bleeding after an artificial abortion. Color Doppler ultrasonography showed a hypervascular mass. Hysteroscopy revealed a placental polyp. Serum hemoglobin level was decreased to 7.7 g/dl. Although uterine artery embolization (UAE) followed by hysteroscopic resection has been used for treatment of a placental polyp, UAE may not be an ideal option for patients with intent for future pregnancy because of the risk of ovarian function failure. This report presents a case of a placental polyp managed successfully with intracervical injection of prostaglandin F2α, as an alternative UAE, followed by hysteroscopic resection.

The role of blood in early endometrial-peritoneal interactions in a syngeneic mouse model of endometriosis.

PURPOSE: The aim of this study was to clarify the role of blood in the early stage of development of endometriotic lesions by developing a syngeneic transplantation model using immunocompetent mice. METHODS: Endometriotic lesions were induced in C57BL/6 mice by an intraperitoneal injection of endometrial fragments plus saline or endometrial fragments plus blood. Some endometrial fragments plus blood were injected with heparin, hirudin or tissue plasminogen activator (tPA). Endometriotic lesions on days 1, 3 and 5 were evaluated by gross and microscopic findings. RESULTS: The areas of endometriotic lesions in the blood group (6.4 ± 1.7 mm2) were significantly larger than those in the saline group (0.5 ± 0.3 mm2). The areas of endometriotic lesions were significantly reduced by the addition of heparin, hirudin or tPA. On day 1, endometriotic lesions in the blood group were observed on the peritoneum in five of the six mice. Endometriotic lesions on days 3 and 5 were significantly larger than those on day 1. On day 5, endometriotic lesions appeared cystic in all the mice. CONCLUSIONS: Blood accelerates the early stage of development of endometriotic lesions when endometrial fragments plus blood are injected. Blood property might be involved in early endometrial-peritoneal interactions.

Lipopolysaccharide promotes early endometrial-peritoneal interactions in a mouse model of endometriosis.

PURPOSE: The aims of this study were to clarify the effects of lipopolysaccharide (LPS) on the early development of endometriosis and on the production of cytokines and chemokines in the murine peritoneal cavity. METHODS: Endometriotic lesions were induced in C57BL/6J adult female mice by intraperitoneal injection of endometrial fragments plus blood or endometrial fragments plus blood with LPS. On day 7, endometriotic lesions were assessed by gross and microscopic evaluations. Time-dependent changes in the secretion of TNF-α,IL-6,and CXCL2/MIP-2 in peritoneal lavage fluid after the intraperitoneal injection of LPS (50 µg/body) were measured by their respective enzyme-linked immunosorbent assays. RESULTS: The areas of endometriotic lesions in the LPS group (10.8 8.6 mm2) were significantly larger than those in the control group (3.1 3.7 mm2).The levels of TNF-α and IL-6 peaked within 2 hours and the level of MIP-2 reached a maximum on day 1 after the injection of LPS. CONCLUSIONS: LPS promotes development of the early stages of murine endometriotic lesions. J. Med. Invest. 66 : 70-74, February, 2019.

Association of serum cytokine concentrations with psychological symptoms in midlife women.

OBJECTIVE: The purpose of the present study was to clarify the association of serum cytokine concentrations, determined using a multiplexed cytokine assay, with psychological symptoms in midlife women. METHODS: Fifty-three peri- and post-menopausal women with and without psychological symptoms in Greene's climacteric scale were enrolled in this study. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. RESULTS: Serum interleukin (IL)-6 concentration in women with psychological symptoms (2.71+/-047 pg/ml) was significantly (p=0.009) higher than that in women without psychological symptoms (0.98+/-0.18 pg/ml). Serum IL-8 concentration in women with psychological symptoms (33.4+/-8.17 pg/ml) was also significantly (p=0.022) higher than that in women without psychological symptoms (7.87+/-1.64 pg/ml). In addition, serum IL-10 concentration in women with psychological symptoms (0.74+/-0.26 pg/ml) was significantly (p=0.048) higher than that in women without psychological symptoms (0.07+/-0.04 pg/ml). Tumor necrosis factor (TNF)-alpha in serum was detected only in women with psychological symptoms. Serum IL-2 concentration in women with psychological symptoms tended (p=0.066) to be higher than that in women without psychological symptoms. No significant differences were found between levels of other cytokines in women with and without psychological symptoms. CONCLUSION: Psychological stress manifested as climacteric symptoms in midlife women may be associated with increases in serum concentrations of IL-6, IL-8, IL-10, and TNF-alpha.

Changes in serum cytokine concentrations during the menopausal transition.

OBJECTIVE: The purpose of the present study was to clarify the changes in serum concentrations of 17 cytokines in healthy women during the menopausal transition by using a multiplexed cytokine assay and to clarify the associations of these cytokines with serum estradiol concentration. METHODS: Sixteen premenopausal, 54 perimenopausal and 52 postmenopausal women were enrolled in this study. Seventeen cytokines in serum samples were measured simultaneously using a Bio-Plex human cytokine 17-Plex assay. RESULTS: Serum IL-6 concentration showed a weak positive correlation with age (r=0.196, p<0.05). Postmenopausal women for whom less than 5 years had passed since menopause showed significant (p<0.05) increase in serum concentrations of IL-2, GM-CSF and G-CSF, while serum IL-4 concentration was significantly (p<0.05) increased in postmenopausal women for whom more than 5 years had passed since menopause. Serum estradiol concentration showed a significant negative correlation with serum IL-6 concentration and weak negative correlations with serum concentrations of IL-2, IL-8 and GM-CSF. CONCLUSION: We were able to simultaneously measure the levels of 17 cytokines using a highly sensitive cytokine assay, and we found that the changes in serum cytokine concentrations during the menopausal transition differed. We also found that serum IL-6 concentration during the menopausal transition was negatively correlated with serum estradiol concentration.

Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women.

OBJECTIVE: We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period. METHODS: The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured. RESULTS: Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p<0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p<0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different. CONCLUSION: The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.

Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women.

OBJECTIVE: The purpose of this study was to identify serum cytokine concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes. METHODS: Serum concentrations of 17 cytokines were simultaneously measured using a multiplexed human cytokine assay in 129 premenopausal, perimenopausal, and postmenopausal women and 50 bilateral oophorectomized women. RESULTS: Serum IL-8 concentrations in midlife women and bilateral oophorectomized women with severe hot flashes were significantly higher than the concentrations in women without hot flashes and women with mild and moderate hot flashes. Serum macrophage inflammatory protein-1beta concentration in women with severe hot flashes was significantly higher than those in women without hot flashes and women with mild and moderate hot flashes. CONCLUSION: Serum IL-8 concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes were significantly higher than those in women without hot flashes. IL-8 may be associated with peripheral vasodilation in women with hot flashes.

Undercarboxylated osteocalcin concentration in postmenopausal women receiving hormone therapy daily and on alternate days.

OBJECTIVE: Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K status. The authors examined the difference in serum ucOC concentrations in postmenopausal women receiving hormone therapy (HT) daily and on alternate days, and assessed the association between ucOC and triglyceride concentrations, which are related to the transport of vitamin K. DESIGN: Seventy-three postmenopausal women were recruited for this study. Thirty-seven women received 0.625 mg of conjugated equine estrogens (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) daily, and 36 women received 0.625 mg of CEE and 2.5 mg of MPA on alternate days. The concentrations of serum ucOC, bone turnover markers, lipid profiles, and hormones were measured before and after 12 months of HT. RESULTS: The ucOC concentration in women taking HT daily was significantly (P < 0.01) lower than that in women taking HT on alternate days. Serum ucOC concentrations during HT showed a significant (P < 0.01) inverse correlation with estradiol concentrations during HT. Serum estradiol concentrations during HT showed a significant (P < 0.01) positive correlation with triglyceride concentrations during HT. Furthermore, ucOC concentrations during HT showed a significant (P < 0.05) inverse correlation with triglyceride concentrations in women receiving HT. CONCLUSIONS: The effect of HT on alternate days on ucOC concentration was weaker than the effect of HT daily. In addition, ucOC concentration after 12 months of HT daily might be decreased due to the conversion of ucOC to carboxylated OC by the effect of vitamin K through increased triglyceride levels induced by oral CEE.

Different effects of oral conjugated equine estrogens and transdermal estrogen on undercarboxylated osteocalcin concentration in postmenopausal women.

OBJECTIVE: Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K status, and triglyceride (TG) has been shown to be the main transporter of vitamin K. In the present study, we examined the difference between ucOC concentrations in postmenopausal women receiving hormone therapy (HT) with oral conjugated equine estrogens (CEE) and transdermal estradiol (TE2). We also examined the associations of ucOC concentration with estradiol concentration and TG. DESIGN: Ninety-two postmenopausal women were recruited for this study. Serum concentrations of ucOC, intact osteocalcin, estradiol, and TG were measured before and after 12 months of HT. Forty-six women received oral administration of 0.625 mg of CEE and 2.5 mg of medroxyprogesterone acetate daily, and 46 women received transdermal administration of 50 mug of 17beta-estradiol twice weekly and 2.5 mg of medroxyprogesterone acetate daily. RESULTS: The ucOC concentration in women during HT with oral CEE was significantly (P < 0.01) lower than that in women during HT with TE2. Serum estradiol concentrations during HT with CEE showed a significant inverse correlation with ucOC concentrations and the ratio of ucOC/OC during HT (P < 0.05 and P < 0.01, respectively). In addition, the serum ucOC concentration in women with an increased percentage of change in TG was significantly (P < 0.01) lower than that in women with a decreased percentage of change in TG during HT with oral CEE. CONCLUSION: The effect of HT with TE2 on ucOC concentration in women is weaker than the effect of HT with oral CEE. Suppression of ucOC concentration in postmenopausal women during HT with oral CEE might be associated with the effect of vitamin K through increased TG induced by oral CEE.

Myeloid-related protein-8/14 is associated with proinflammatory cytokines in cervical mucus.

Myeloid-related protein-8 (MRP-8), MRP-14, and MRP-8/14 are found in a variety of inflammatory conditions and are involved in the host defense system. The objective of this study was to determine the concentrations of MRP-8, MRP-14, and MRP-8/14 in human cervical mucus and the associations between MRP-8/14 and proinflammatory cytokines. Samples of cervical mucus were obtained using a syringe from sexually active women (n=97) during the preovulatory phase. Samples from seven women were obtained using a swab placed in the cervical canal during the proliferative, preovulatory, and luteal phases. Concentrations of MRP-8, MRP-14, MRP-8/14, IL-1alpha, IL-6, IL-8, and granulocyte elastase were measured using an ELISA. The mean levels of MRP-8, MRP-14, and MRP-8/14 in cervical mucus were 1.87, 0.46, and 23.90microg/ml, respectively. The concentration of MRP-8/14 showed positive correlations with concentrations of IL-1alpha (p<0.0001), IL-8 (p<0.0001), and granulocyte elastase (p<0.0001). However, there were no significant differences in MRP-8/14 levels in the cervical mucus of each patient during the menstrual cycle. MRP-8/14 was mainly detected in human cervical mucus and showed a positive correlation with proinflammatory cytokines. The MRP-8/14 level in cervical mucus may be useful as a marker of inflammation of the uterine cervix.

Sperm-zona pellucida interaction and immunological infertility.

Immune reactions against gametes appear to be physiologically important for the maintenance of homeostasis in reproduction. In contrast, aberration of the immune homeostasis might give rise to 'immunological infertility'. Antisperm antibodies cause infertility by blocking fertilization. The mechanism can be explained as inhibiting the acrosome reaction of sperm by their blocking effect on capacitation through inhibiting an increase of fluidity of the sperm membrane. Autoantibodies against zona pellucida also cause infertility by blocking sperm-zona pellucida interaction, though the definitive mechanism has not been elucidated. Pretreatment of spermatozoa with D-mannnose completely inhibited sperm penetration through, but not binding to, the zona pellucida. Furthermore, very rapid kinetics between sperm extracts and D-mannnose by a BIAcore apparatus suggest that a D-mannose ligand of the sperm surface is easy to bind to and dissociate from a D-mannose residue in the sperm receptor site on the zona pellucida. Thus, D-mannnose on the human zona pellucida might be an essential molecule acting as a second sperm receptor, through which sperm penetrate into the zona pellucida. Because these antibodies appear to not cause any deleterious clinical symptoms, sperm and zona pellucida antigens are promising candidates in the development of an immunocontraceptive. (Reprod Med Biol 2006; 5: 95-104).

Effects of postmenopausal hormone therapy every day and every other day on lipid levels according to difference in body mass index.

OBJECTIVE: The objective of this study was to determine the effects of postmenopausal estrogen and progestogen therapy (EPT) every day and every other day on lipid levels, particularly triglyceride (TG) levels, according to difference in body mass index (BMI). DESIGN: Ninety-nine postmenopausal women (mean age, 53.9 +/- 5.6 years; mean BMI, 22.8 +/- 2.8 kg/m) were randomly treated with EPT every other day or every day for 1 year. Fifty women received oral administration of 0.625 mg of conjugated equine estrogen (CEE) and 2.5 mg of medroxyprogesterone acetate (MPA) every other day, and 49 women received oral administration of 0.625 mg of CEE and 2.5 mg of MPA every day. Blood samples were collected at baseline and after 1 year of therapy for measurement of fasting TG, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), and apolipoproteins. Data from 88 of the 99 postmenopausal women were used for analysis. RESULTS: In women whose BMI was 25 kg/m or higher, TG levels during EPT every day increased by 26.8%, while TG levels during EPT every other day decreased by 12.3%. There was a significant (P < 0.05) difference between percentage changes in TG during EPT every day and every other day. In women whose BMI was less than 25 kg/m, TG levels during EPT every day increased by 21.7%, while during EPT every other day TG levels did not change. The mean levels of estradiol during EPT every day in women whose BMI was less than 25 kg/m and in women whose BMI was 25 kg/m or higher were 28.5 and 38.7 pg/mL, respectively, the difference between these levels was significant (P < 0.01). On the other hand, there was no significant difference between levels of estradiol during EPT every other day in these two BMI groups. CONCLUSIONS: Triglyceride levels during EPT every day with conventional doses of CEE and MPA increased more in overweight and obese postmenopausal women in association with increased estrogen levels.

Serum estrogen level after hormone replacement therapy and body mass index in postmenopausal and bilaterally ovariectomized women.

OBJECTIVE: The objective of this study was to determine the relationships of serum estrogen levels after hormone replacement therapy (HRT) every other day and every day with body mass index (BMI) in postmenopausal and bilaterally ovariectomized women. METHODS: Eighty-six postmenopausal and 51 bilaterally ovariectomized women who had been suffering from vasomotor symptoms such as hot flush or atrophy of the vagina were randomly treated with HRT every other day or every day. Seventy-four patients received oral administration of 0.625 mg conjugated equine estrogen (CEE) and 2.5 mg medroxyprogesterone acetate (MPA) every other day, and 63 patients received oral administration of 0.625 mg CEE and 2.5 mg MPA every day as conventional HRT. RESULTS: Eighty-four postmenopausal and 50 bilaterally ovariectomized women completed this study. Serum estradiol levels after HRT every day in postmenopausal and bilaterally ovariectomized women were significantly (P <0.05 and <0.01, respectively) correlated with BMI, while those after HRT every other day were not correlated with BMI. The differences between estradiol levels after 12 months of treatment and initial estradiol levels were also significantly (P <0.01) correlated with BMI in both postmenopausal and bilaterally ovariectomized women who received HRT every day but not in women who received HRT every other day. Serum estrone level after HRT every day and the difference between estrone level after 12 months of treatment and initial estrone level were significantly (P <0.05 and <0.01, respectively) correlated with BMI only in bilaterally ovariectomized women. CONCLUSION: Serum estradiol levels after HRT every day increase more in overweight women than in non-overweight postmenopausal and bilaterally ovariectomized women. The results of the present study regarding the relationship between serum estradiol levels after HRT and BMI should be useful for selecting dosages of drugs to be used in HRT.

Involvement of carbohydrate molecules on zona pellucida in human fertilization.

Although the involvement of several receptors and ligand molecules in sperm-zona interaction in many species have been proposed, there has been a little analysis of the kinetics between these molecules during the interaction. In the present study, we applied the detection method using surface plasmon resonance (SPR) by a BIAcore apparatus for the analysis of the putative receptor-ligand interaction of sperm-egg binding. Mannose-BSA or [man](5)-[GlcNAc](2)-Asp was immobilized on the surface of a sensor chip. When concanavalin A (Con A) was delivered to each of two different sensor chips to evaluate their usefulness, the resonance signal after sample injection onto a [man](5)-[GlcNAc](2)-Asp-fixed chip decreased rapidly than the mannose-BSA-fixed chip. However, the amount of binding for Con A during the injection onto the [man](5)-[GlcNAc](2)-Asp-fixed chip was high. When acid sperm extracts (acid extracts) and fractions through a CM column, containing protease activity (protease fractions), were delivered to the mannose-BSA-fixed chip, the SPR signal during the injection was not obviously changed compared with that of the control. However, when sperm samples were delivered to the [man](5)-[GlcNAc](2)-Asp-fixed chip, the SPR response during the injection was enormous. These results suggest that the [man](5)-[GlcNAc](2)-Asp-fixed chip is more useful than the mannose-BSA-fixed chip for investigating the interactions with sperm extracts and that the sensitive method using SPR by a BIAcore apparatus is applicable for the analysis of the putative receptor-ligand interaction of sperm-egg binding.

A repertoire of cytokines in human seminal plasma.

The pathophysiological significance of seminal cytokines in sperm function is still controversial. We determined the repertoire of cytokines in seminal plasma obtained from men with or without abnormalities in semen and assessed the pathophysiological significance of seminal cytokines. After conventional analysis of semen samples obtained from 86 men, levels of seminal cytokines (interleukin [IL]-1alpha, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha], interferon-gamma, granulocyte colony-stimulating factor [G-CSF], macrophage CFS [M-CSF]) and granulocyte elastase were measured by an enzyme-linked immunosorbent assay. Leukocytospermia was defined as seminal plasma, which has > or =1000 ng/ml granulocyte elastase. Leukocytospermia was found in nine of 62 of the subjects in the normozoospermic group but in none of the 24 subjects showing abnormal sperm parameters (azoospermia, n=5; oligozoospermia, n=4; asthenozoospermia, n=15). The IL-8 level in the leukocytospermic group was significantly higher than those in the normal and oligozoospermic groups. IL-1alpha and TNF-alpha levels in the leukocytospermic group were significantly higher than those in the normal and asthenozoospermic groups. Although the G-CSF level in the leukocytospermic group was significantly higher than that in the normal group, high levels of M-CSF were detected in all groups. The IL-8 level was strongly correlated with IL-1alpha (r=0.935, P<0.0001) and G-CSF (r=0.916, P<0.0001) levels. Cytokines detected in seminal plasma are associated with the pathogenesis of leukocytospermia but not with the pathogenesis of asthenozoospermia and oligozoospermia.

Sperm-immobilizing antibodies suppress an increase in the plasma membrane fluidity of human spermatozoa.

OBJECTIVE: To clarify the mechanism by which capacitation is blocked by sperm-immobilizing antibodies, changes in the plasma membrane fluidity of human spermatozoa exposed to sperm-immobilizing antibodies were evaluated. DESIGN: In vitro cell culture study using human spermatozoa. SETTING: Department of Obstetrics and Gynecology, School of Medicine, The University of Tokushima. PATIENT(S): Semen samples were obtained from four healthy, fertile volunteers. INTERVENTION(S): The internalization of [3H]lyso-platelet activating factor (lyso-PAF) across the plasma membranes of human spermatozoa, which were exposed to sperm-immobilizing antibodies (antisperm group) or not exposed (control group), was measured at 20 and 60 minutes after the addition of a phospholipid probe using the modified albumin-back extraction method. MAIN OUTCOME MEASURE(S): The percentage of internalization of [3H]lyso-PAF across the plasma membrane of human spermatozoa. RESULT(S): Although the percentages of internalization of [3H]lyso-PAF (mean +/- SE) in the antisperm and control groups 20 minutes after addition of [3H]lyso-PAF were not significantly different (6.6% +/- 1.5% and 9.2% +/- 2.1%, respectively), at 60 minutes after the addition, the percentage in the antisperm group (9.0% +/- 1.3%) was significantly lower than that in the control group (13.4% +/- 1.3%). This inhibitory effect was diminished when spermatozoa exposed to sperm-immobilizing antibodies were incubated in an antibody-free medium. CONCLUSION(S): Sperm-immobilizing antibodies suppress the increase in internalization of an alkyl ester lysophospholipid probe in plasma membranes of human spermatozoa, and this inhibitory effect is reversible. Therefore, sperm-immobilizing antibodies suppress the fluidity of the plasma membranes of human spermatozoa, thus blocking capacitation.

Effects of raloxifene on the production of cytokines in stimulated whole blood in ex vivo and in vitro studies.

PURPOSE: The aims of this study were to determine the effects of raloxifene therapy on production of cytokines and in vitro effects of raloxifene on production of cytokines by whole blood cultures. METHODS: We obtained samples of peripheral blood from 6 postmenopausal women with osteopenia at baseline and after 3 and 6 months of raloxifene therapy and 10 postmenopausal women who did not receive raloxifene therapy. Whole blood from raloxifene-treated women was stimulated with lipopolysaccharide (LPS) or phytohemeagglutinin (PHA). Whole blood from postmenopausal women who were not treated with raloxifene was preincubated with raloxifene at concentrations of 10(-10)-10(-7) M and then stimulated with LPS or PHA. Concentrations of IL-1ß, IL-4, IL-6, IL-12p40, IL-12p70, TNF-α and IFN-γ in the supernatant were measured by respective ELISAs. RESULTS: In ex vivo cultures, raloxifene therapy inhibited LPS-stimulated production of IL-1ß, IL-6, IL-12p40, IL-12p70 and TNF-α, but not PHA-stimulated production of IL-4 and IFN-γ. In in vitro cultures, raloxifene at a concentration (10(-9) M) inhibited LPS-stimulated production of IL-1ß, IL-6 and IL-12p40 and PHA-stimulated production of IFN-γ. CONCLUSIONS: Raloxifene therapy decreases the production of IL-1ß, IL-6, IL-12 and TNF-α but not that of IL-4 and IFN-γ, suggesting that modulation of cytokines could play a role in the mechanisms of the osteoprotective effect of raloxifene.

Raloxifene reduces circulating levels of interleukin-7 and monocyte chemoattractant protein-1 in postmenopausal women.

OBJECTIVE: The aim of the present study was to determine the effects of raloxifene on changes in circulating levels of cytokines and chemokines in relation to changes in lipid profiles and markers of inflammation in postmenopausal women. METHODS: Fifty-three postmenopausal women aged 45-65 years old were randomly assigned in open, parallel-group fashion to a control group or raloxifene group. Twenty-six women received oral administration of 60 mg raloxifene every day and 27 women did not receive any drugs for 12 months. Serum cytokines levels were simultaneously measured using a multiplexed human cytokine assay. RESULTS: Serum IL-7 concentrations in women who received raloxifene were decreased significantly (p=0.014), and serum monocyte chemoattractant protein (MCP)-1 concentrations in women who received raloxifene were decreased significantly (p=0.0003) at 12 months. In the control group, serum levels of MCP-1 and IL-7 did not show significant changes. There were significant differences (p=0.032 and p=0.0024, respectively) in percentage changes in IL-7 and MCP-1 in the control group and in the raloxifene group. Levels of low-density lipoprotein cholesterol (LDL-C) and E-selectin were decreased significantly in women who received raloxifene, but the percentage changes in LDL-C and E-selectin over a period of 12 months were not significantly correlated with percentage changes in IL-7 and MCP-1 over the same period. CONCLUSION: Circulating levels of IL-7 and MCP-1 decrease in postmenopausal women who received raloxifene.

Evaluation of the potential of synthetic peptides of 80 kDa human sperm antigen (80 kDaHSA) for the development of contraceptive vaccine for male.

80 kDaHSA has been demonstrated to be responsible for inducing immunoinfertility. Synthetic peptides NT, 1, 2 and 4 of 80 kDaHSA are immunogenic and immunobiologically mimic the native protein. Peptides 1 and NT being highly immunogenic their potential for contraceptive vaccine development was evaluated. Active immunization of male rabbits with peptide-1 and -NT induced reversible infertility in 100% and 60% of animals, respectively and subsequently active immunization of non-human primate model, male marmosets with peptide-1 induced reversible infertility in six out of seven high antibody titer animals. The present study suggests the potential of peptide-1 of 80 kDaHSA for the development of contraceptive vaccine.