Comparative analysis of the immunomodulatory potential of caprine fetal adnexa derived mesenchymal stem cells.

The caprine mesenchymal stem cells (MSCs) derived from fetal adnexa are highly proliferative. These cells possess tri-lineage differentiation potential and express MSC surface antigens and pluripotency markers with a wound-healing potential. This present study was conducted to compare the immunomodulatory potential of caprine MSCs derived from the fetal adnexa. Mid-gestation caprine uteri (2-3 months) were collected from the abattoir to isolate MSCs from amniotic fluid (cAF), amniotic sac (cAS), Wharton's jelly (cWJ) and cord blood (cCB), which were expanded and characterized at the 3rd passage. These MSCs were then stimulated with inflammatory cytokines (IFN-γ and TNF-α) to assess the percentage of inhibition produced on peripheral blood mononuclear cells (PBMCs) proliferation. The percentage of inhibition on activated PBMCs proliferation produced by cWJ MSCs and cAS MSCs was significantly higher than cCB and cAF MSCs. The relative mRNA expression profile and immunofluorescent localization of different immunomodulatory cytokines and growth factors were conducted upon stimulation. The mRNA expression profile of a set of different cytokines and growth factors in each caprine fetal adnexa MSCs were modulated. Indoleamine 2, 3 dioxygenase appeared to be the major immunomodulator in cWJ, cAF, and cCB MSCs whereas inducible nitric oxide synthase in cAS MSCs. This study suggests that caprine MSCs derived from fetal adnexa display variable immunomodulatory potential, which appears to be modulated by different molecules among sources.

A positive urine pregnancy test (UPT) with adnexal mass; ectopic pregnancy is not the ultimate diagnosis.

A positive urine pregnancy test (UPT) with adnexal mass in ectopic pregnancy is not the ultimate diagnosis. The incidence of ectopic pregnancy is about 27 per 1000 pregnancies [1]. On average, about 6-16% will present to an emergency department with first-trimester bleeding and abdominal pain [2]. On presenting with these symptoms with the simultaneous presence of an adnexal mass and an empty uterus, a UPT is of paramount importance to determine whether the symptoms are pregnancy related or not. When the UPT is positive, an ectopic pregnancy is not the only diagnosis as the rare entity of non-gestational ovarian choriocarcinoma (NGOC) should be considered. Here we present two case reports of NGOC, which were initially diagnosed as ectopic pregnancy. The first case is a 16-year-old girl, with vaginal bleeding and an adnexal mass due to an ovarian choriocarcinoma, She underwent unilateral oophorectomy and received multiple courses of chemotherapy. She is disease free without evidence of recurrence or metastasis after 12 months of follow-up. The second patient is also 16 years old and presented with an acute abdomen. She was diagnosed as a ruptured luteal cyst and underwent partial oophorectomy. When the pathologist diagnosed a choriocarcinoma she received multiple courses of chemotherapy, but thereafter an advanced disease was diagnosed with evidence of distant metastasis.

Clinical performance of two multi-marker blood tests for predicting malignancy in women with an adnexal mass.

BACKGROUND: Reliable methods that allow appropriate triage of women with an adnexal mass to a gynecologic oncologist are needed. We evaluated the clinical performance of OVA1 and ROMA for the prediction of malignancy in women with an adnexal mass. METHODS: One hundred forty-six prospectively collected serum samples were collected from women with an adnexal mass, 31 of whom had surgically confirmed malignancies. OVA1 and ROMA tests were performed on all samples. Receiver operating characteristic curve analysis was used to determine interpretive cutoffs for ROMA. Performance characteristics of both tests were determined and compared. RESULTS: The sensitivity of OVA1 and ROMA was 97% and 87%, respectively (p=0.25). ROMA was more specific than OVA1 (83% vs. 55%, respectively; p<0.0001). The negative predictive values of both tests were similar (98.4% and 96.0%, respectively). ROMA performed on all patients identified as high risk by OVA1 (a sequential strategy) produced a positive predictive value of 69%. CONCLUSIONS: OVA1 and ROMA have similar performance characteristics, with OVA1 having non-significant greater diagnostic sensitivity and ROMA having greater diagnostic specificity. The use of these tests to appropriately triage women with an adnexal mass should be gauged within the context of their respective limitations. A sequential testing strategy may improve overall performance.

Serous carcinoma of the ovary with squamous differentiation: a case report and a literature review.

Serous carcinoma of the ovary showing squamous differentiation is a rarely reported neoplasm. We present 1 case of such a tumor extensively involving the adnexa and the pelvis, which shows these 2 intimately entwined, yet with morphologically and immunohistochemically distinct patterns of differentiation. We also report immunohistochemical evidence of protein expression changes in areas of this carcinoma that provide evidence for differentiation from a serous to a squamous phenotype.

Does HE4 have a role as biomarker in the recurrence of ovarian cancer?

Human epididymis protein 4 (HE4) was recently approved by the Food and Drug Administration to monitor recurrence or progressive disease in epithelial ovarian cancer in conjunction with CA125. This is the first prospective controlled study in literature evaluating the sensitivity and specificity of HE4 and CA125 in detecting recurrent ovarian cancer. Serum samples were obtained 24 h before surgery from 34 patients with suspicious recurrent ovarian cancer and from 34 patients with benign adnexal pathology, operated from November 2010 to November 2011 at University Campus Bio-Medico of Rome. The CA125 normal value is considered less than 35 U/mL. Two HE4 cut-off are considered: less than 70 pmol/L and less than 150 pmol/L. The specificity analysis was performed using the parametric t test to compare the CA125 series and the Mann-Whitney test for the HE4 series. The level of statistical significance is set at p < 0.05. The CA125 sensitivity and specificity in detecting recurrent ovarian cancer is 35.29 and 58.82 %, respectively. The HE4 sensitivity is 73.53 and 26.47 %, for 70 pmol/L and 150 pmol/L cut-off, respectively. The HE4 specificity is 100 %. Combining CA125 and HE4 at cut-off of 70 pmol/L, the sensitivity to detect recurrent ovarian cancer is 76.47 % with a specificity of 100 %. The combination of CA125 and HE4 at cut-off of 70 pmol/L improves the overall sensitivity and specificity of CA125 alone, suggesting a useful application of HE4 in strategies for surveillance of ovarian cancer recurrence.

Expression of aquaporin water channels in canine fetal adnexa in respect to the regulation of amniotic fluid production and absorption.

Amniotic fluid (AF) is created by the flow of fluid from the fetal lung and bladder and reabsorbed in part by fetal swallowing and partly by the transfer across the amnion to the fetal circulation. Placental water flux is an important factor in determining AF volume and fetal hydration. In addition the fetal membranes might be involved in the regulation of fluid composition. To understand the mechanisms responsible for maintaining a correct balance of AF volume we evaluated the expression of aquaporins (AQPs) in canine fetal adnexa. AQPs are a family of integral membrane proteins permitting passive but physiologically rapid transcellular water movement. The presence of AQP1, 3, 5, 8 and -9 was immunohistochemically assessed in canine fetal adnexa, collected in early, middle and late-gestation during ovario-hysterectomies performed with fully informed owners' consent. Changes in AF volume and biochemical composition were also evaluated throughout pregnancy. Our results show distinct aquaporin expression patterns in maternal and extraembryonic tissues in relation to pregnancy period. AQP1 was localized in placental endothelia, allantochorion, amnion, allantois and yolk sac. AQP3 was present in the placental labyrinth, amnion, allantois and yolk sac. AQP8 was especially evident on the epithelia lining the glandular chambers, the amniotic and allantois sacs. AQP9, a channel highly permeable to water and urea, was observed in epithelia of amnion, allantois and yolk sac. In summary, AQP1, 3, 5, 8 and -9 have distinct expression patterns in canine fetal membranes and placenta in relation to pregnancy period, suggesting an involvement in mediating the AF changes during gestation.

Isolation, proliferation, cytogenetic, and molecular characterization and in vitro differentiation potency of canine stem cells from foetal adnexa: a comparative study of amniotic fluid, amnion, and umbilical cord matrix.

The possibility to isolate canine mesenchymal stem cells (MSCs) from foetal adnexa is interesting since several canine genetic disorders are reported to resemble similar dysfunctions in humans. In this study, we successfully isolated, cytogenetically and molecularly characterized, and followed the differentiation potency of canine MSCs from foetal adnexa, such as amniotic fluid (AF), amniotic membrane (AM), and umbilical cord matrix (UCM). In the three types of cell lines, the morphology of proliferating cells typically appeared fibroblast-like, and the population doubling time (DT) significantly increased with passage number. For AF- and AM-MSCs, cell viability did not change with passages. In UCM-MSCs, cell viability remained at approximately constant levels up to P6 and significantly decreased from P7 (P < 0.05). Amnion and UCM-MSCs expressed embryonic and MSC markers, such as Oct-4 CD44, CD184, and CD29, whereas AF-MSCs expressed Oct-4, CD44. Expression of the hematopoietic markers CD34 and CD45 was not found. Dog leucocyte antigens (DLA-DRA1 and DLA-79) were expressed only in AF-MSCs at P1. Isolated cells of the three cell lines at P3 showed multipotent capacity, and differentiated in vitro into neurocyte, adipocyte, osteocyte, and chondrocyte, as demonstrated by specific stains and expression of molecular markers. Cells at P4 showed normal chromosomal number, structure, and telomerase activity. These results demonstrate that, in dog, MSCs can be successfully isolated from foetal adnexa and grown in vitro. Their proven stemness and chromosomal stability indicated that MSCs could be used as a model to study stem cell biology and have an application in therapeutic programs.

[Clinical application of azithromycin extended-release (ER) formulation to treat female sexually transmitted infection].

The prevalence of female sexually transmitted infection (STI) in Japan is in the decreasing tendency after 2002, however it still actualizes as a social problem. Azithromycin, which is 15-member macrolide antimicrobial agent, has indication to treat the chlamydia STI in a single dose of 1 g. In April 2009, a single dose of 2 g of azithromycin extended release (ER) formulation, which is improved formulation by the viewpoint of pharmacokinetics-pharmacodynamics, was approved and has indications to treat not only chlamydial STI but also gonococcal STI. We considered the clinical application of azithromycin ER to treat female STI, including our new our own experiences because the clinical studies of azithromycin ER for STI had not been conducted. In conclusion, azithromycin ER was suggested theoretically becoming one of the choices of new treatment STI caused by not only chlamydia but also gonococcus, more clinical consideration to treat STI will be necessary in the future.

Differential expression of smooth muscle regulatory proteins in the uterosacral ligaments of women with uterine prolapse.

OBJECTIVE: To compare smooth muscle regulatory protein expression in the uterosacral ligament (USL) of women with and without uterine prolapse. STUDY DESIGN: USLs ligament were sampled in women with (n = 9) or without (n = 9) uterine prolapse. Caldesmon, smooth muscle actin (SMA), myosin heavy chain, and zinc finger protein messenger RNA expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry and digital image analysis were used to determine protein expression. RESULTS: Caldesmon messenger RNA expression and the ratio of caldesmon-SMA messenger RNA expression was significantly increased in the USL from women with uterine prolapse compared with women without prolapse (caldesmon mean +/- standard deviation messenger RNA, 0.81 +/- 0.46 vs 0.39 +/- 0.16; P = .01 and caldesmon-SMA messenger RNA ratio, mean +/- standard deviation, 0.11 +/- 0.04 vs 0.07 +/- 0.02; P = .01). In addition, the ratio of caldesmon-SMA staining was significantly increased in women with uterine prolapse compared with women without prolapse (mean +/- standard deviation, 0.44 +/- 0.28 vs 0.28 +/- 0.16; P = .03). CONCLUSION: Uterine prolapse is associated with an increased ratio of caldesmon-SMA actin expression.

The amount and activity of active matrix metalloproteinase 13 is suppressed by estradiol and progesterone in human pelvic floor fibroblasts.

As a key degrader of fibrillar collagens, matrix metalloproteinase 13 (MMP13), may contribute to the progression of pelvic organ prolapse. Here we aimed to define the regulation of MMP13 by estradiol and progesterone in the vaginal supportive tissues. Fibroblasts cultured from the arcus tendineous fasciae pelvis of three pre- and three postmenopausal women with prolapse were treated with 17-beta-estradiol (E2), progesterone (P4), E2 + P4, or E2 + ICI 182,780 (ICI). Collagenase inhibitor I (CI) and MG-132 were employed to investigate the mechanism of MMP13 degradation into inactive fragments (fragmentation) by hormones. The regulation of MMP13 in vivo was assessed by comparing tissues of ovariectomized (ovx) vs. sham-operated rats. Expression of MMP13 (proenzyme and active and fragment forms) was quantitated by Western immunoblotting, and MMP13 enzymatic activity was measured using a substrate degradation assay. The amount of cellular active MMP13 and MMP13 proteolytic activity decreased in the presence of hormones. The decrease was paralleled by increased proenzyme and fragment forms. MG-132, not CI, suppressed cellular MMP13 fragmentation. Active MMP13 increased in rats following ovx and was suppressed by E2 + P4 supplementation. Active MMP13 is suppressed in vivo and in vitro by estradiol and progesterone, suggesting a protective effect against vaginal supportive tissue deterioration.

A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations.

BACKGROUND: Early serous carcinomas predominate in the fimbria of women with BRCA mutations (BRCA+). An entity in non-neoplastic mucosa sharing several properties of early serous carcinomas--the "p53 signature"--has been described in the distal fallopian tube and proposed as a precursor to serous carcinomas. This study compared the prevalence of p53 signatures in ovarian cortical inclusion cysts (CICs) and fallopian tubes from BRCA+ women and explored their relationship. DESIGN: All tissues from 75 completely excised ovaries and tubes obtained during prophylactic surgery were studied by conventional microscopy, immunostaining for p53, and in selected cases, gamma-H2AX (DNA damage). P53 signatures were defined as 12 or more consecutive p53-positive secretory cell nuclei. Their prevalence in fallopian tubes and CICs was recorded, compared to an existing database of consecutive women without a suspicion of BRCA+ or ovarian cancer, and correlated with the number of CICs. RESULTS: Tubal p53 signatures were detected in 29 of 75 cases (38%); 20 of 30 (66%) signatures examined were gamma-H2AX-positive. One ovary contained a small gamma-H2AX negative p53 signature on the ovarian surface; no p53 signatures were identified in CICs. The prevalence of BRCA+ p53 tubal signatures was similar to that of women with unknown BRCA status (38 v 33%). Presence of p53 signatures did not correlate with number of CICs. CONCLUSIONS: p53 signatures were common in the fallopian tubes of BRCA+ women, were not identified in CICs, and did not correlate with the latter. The tubal p53 signature merits serious consideration as an important early event in serous carcinogenesis in BRCA+ women.

A case of hydrosalpinx associated with the menstrual cycle.

OBJECTIVE: To describe a case report of hydrosalpinx that changed dramatically in size during the menstrual cycle. DESIGN: Case report. SETTING: University teaching hospital reproductive endocrinology and infertility practice. PATIENT(S): A 32-year-old woman with a history of medical and surgical treatments of endometriosis who sought infertility treatment. INTERVENTION(S): Transvaginal ultrasonography performed sequentially during menstrual cycles. MAIN OUTCOME MEASURE(S): Size of hydrosalpinx-like image. RESULT(S): The size of the hydrosalpinx-like image in the left adnexal region varied; it peaked during the ovulatory period and then remarkably diminished in a cyclic manner. Laparoscopy revealed a dense adhesion between the left tubal fimbriated end and the posterior uterine wall, which led to terminal obstruction of the tube. CONCLUSION(S): Change in the volume of the hydrosalpinx in this case was speculated to reflect the normal tubal fluid production regulated by ovarian hormones.

Ultrastructure and estrogen regulation of the lymphatic stomata of ovarian bursa in mice.

The ovarian bursa is a key player in maintaining adaptive ovarian microenvironment for ovulation. The lymphatic stomata are believed to be a major contributor to execute the function of the ovarian bursa, whereas little is known about their ultrastructure and regulation. Here, we examined the ultrastructure of lymphatic stomata in mouse ovarian bursa by scanning electron microscopy and transmission electron microscopy and investigated its regulation by estrogen. We found that the mesothelium on the visceral layer of mouse ovarian bursa was composed of the cuboidal and flattened cells. The lymphatic stomata with round and oval shapes were mainly among the cuboidal cells. The particles, cells, and fluid passed through the stomata and entered into the lymphatic drainage unit composed of connective tissue and lymphatic endothelial cells beneath the stomata. We also used trypan blue as a tracer and found that the absorption of trypan blue through the lymphatic stomata was increased by estrogen that enlarged the average opening area of lymphatic stomata. Furthermore, we detected that there existed estrogen receptors in the nuclei of the mesothelial cells on the visceral ovarian bursa by using immunoelectron microscopy. Taken together, these data suggest that both the absorption and opening area of the lymphatic stomata in mouse ovarian bursa may be influenced by estrogen.

The impact of size of the adnexal mass on the accuracy of frozen section diagnosis.

OBJECTIVE: We recently showed that frozen section diagnosis has an almost perfect specificity for the diagnosis of malignancy in an adnexal mass, whereas the sensitivity was, though good, not perfect. The aim of the present study was to examine whether the accuracy of frozen section diagnosis is affected by the size of the adnexal masses. METHODS: We included women that underwent frozen section diagnosis for adnexal mass surgery. For each patient we recorded serum CA125 level, menopausal status, tumour size, and histologic classification both at frozen section diagnosis and at definite histological examination. We calculated sensitivity and specificity of frozen section diagnoses, both in tumours below and above 10 cm diameter. RESULTS: We included 257 patients, of whom 142 had a benign tumour, 28 had a borderline tumour and 87 had a malignant tumour at definitive histological assessment. In case frozen section diagnosis showed malignancy, this was always confirmed at final histological assessment. In women with a tumour <10 cm, there was only 1 false negative diagnosis in 50 women with a benign frozen section diagnosis, whereas there were 11 false negative diagnoses in 97 women in women with a tumour > or = 10 cm. The corresponding likelihood ratios of a benign diagnosis for presence of malignancy were .15 for tumours > or = 10 cm and 0.03 for tumours <10 cm, respectively. CONCLUSION: The accuracy of frozen section diagnosis is dependent on tumour size. In adnexal masses > or = 10 cm, a benign result of the frozen section diagnosis is less reliable than in women with a tumour <10 in cm.

Adiponectin mRNA levels in parametrial adipose tissue and serum adiponectin levels are reduced in mice during late pregnancy.

Adiponectin, a fat-derived factor, is downregulated in insulin resistance and obesity; insulin resistance has been demonstrated during late pregnancy in both humans and in rodents. The present study examines the physiological change of adiponectin gene expression as well as the circulating levels of adiponectin during pregnancy. We examined the relative quantity of adiponectin mRNA produced in the adipose tissues of pregnant compared to virgin mice. We also measured serum adiponectin levels and parametrial adipocyte size in mice throughout pregnancy. Adiponectin mRNA was significantly reduced by 74 +/- 8 % and 63 +/- 4 % at days 15 and 18 of pregnancy, respectively, compared to virgin mice. Serum adiponectin concentration decreased on days 15 (30.7 +/- 8.5 microg/ml) and 18 (27.9 +/- 8.7 microg/ml) of pregnancy, and the values were significantly lower than that of virgin mice (56.8 +/- 6.6 microg/ml). Parametrial adipocytes from mice on days 15 and 18 of pregnancy were significantly larger than in virgin mice or during early pregnancy. Fat-cell size was closely correlated to degradation of adiponectin gene expression and serum adiponectin levels. These results suggest that changes of adiponectin expression affect metabolic status in pregnant mice.

Mineral accretion in the fetus and adnexa during late gestation in Holstein cows.

Multiparous Holstein cows (n = 18) were bred artificially to the same Holstein bull and then slaughtered at times ranging from 190 to 270 postmating to assess mineral accretion by the conceptus. Fresh weight, DM, and concentrations of Ca, P, Mg, K, Na, Fe, Zn, Cu, and Mn were obtained for the fetus, fetal fluids, fetal membranes, cotyledons, caruncles, and uterine tissues. Rates of accumulation of individual minerals in different components of the conceptus during late gestation were described by either linear or exponential relationships. Estimated Ca accretion rate in the conceptus increased from 2.3 g/d at 190 d of gestation to 10.3 g/d at 280 d of pregnancy; corresponding P accretions were 1.9 and 5.4 g/d. Rates of accretion of Mg, K, and Na in the conceptus in late pregnancy were about .2, 1.0, and 1.4 g/d, respectively, and Fe, Zn, Cu, and Mn accumulated in the conceptus at rates of 18.0, 11.7, 1.6, and .3 mg/d, respectively. These daily rates represent net mineral requirements for conceptus growth during late pregnancy in mature Holstein cows. In general, our values are consistent with current dietary recommendations for minerals during the dry period.

[Experimental and clinical studies of flomoxef in the field of obstetrics and gynecology. Representative Committee Members of the Research Team for Infections in the Field of Obstetrics and Gynecology].

Flomoxef (FMOX) has a broad antibacterial spectrum against Gram-positive and Gram-negative bacteria; especially its potent antibacterial activity against Staphylococcus aureus is a significant advantage that may not be found with other cephem compounds. In our determination of its antibacterial potency against various clinical isolates obtained from clinical materials (amniotic fluid, intrauterine secretions, exudates of the pelvic dead space) of patients with various infections, we obtained results representing specific features of this drug. From the results, the drug may be expected to produce an excellent effect in the treatment of various infections. Our study on drug concentrations in body fluids and genital tissues demonstrated a good transfer of this drug into various tissues; in every tissue examined, the drug administered by the usual method in the usual dose yielded a concentration exceeding MIC for principal pathogens, thus promising a good clinical response. Indeed a high clinical efficacy rate of 90.1% (good to very good responses) was obtained in a clinical trial involving 222 cases. Administration of the drug in 2 g quantity daily produced a high response rate of 92.8%. It was especially noteworthy that a good response was obtained in 30 of 32 cases (93.8%) in which other cephem compounds had failed. In evaluation of the bacteriological effect, furthermore, the drug showed an excellent rate of bacterial elimination. In conclusion, this drug is expected to be greatly useful in the light of its good transfer into genital tissues and its strong antibacterial activities against Gram-positive cocci, Gram-negative bacteria and anaerobes as well as against multiple bacterial infections predominating among women with genital infections.

[Fundamental and clinical study on cefuzonam in the field of obstetrics and gynecology].

Cefuzonam (L-105, CZON), a new beta-lactam antibiotic, was studied for its transfer into intrapelvic tissues and for clinical efficacy in the treatment of obstetrical and gynecological infection. 1. Following an intravenous 1 hour drip infusion of 1 g, the transferred CZON into uterine tissues reached and was maintained at effective concentrations which were defined as levels exceeding MICs against clinical isolates frequently obtained from patients in the field of obstetrics and gynecology. The peak concentration of CZON in the pelvic dead space exudate was estimated to be 20 micrograms/ml at 0.5-1 hour after infusion. 2. Subjects studied were 5 patients with the following infections: pyometra (3 cases), puerperal intrauterine infection (1 case), vaginal cuff infection (1 case). Clinical efficacies were good in 4 cases and poor in 1 case. No notable side effects or abnormal laboratory test results were noted.

[Transfer of cefuzonam into female genital organs].

Cefuzonam (CZON) was given intravenously at a 1 gram dose to 24 patients prior to abdominal total hysterectomy for uterine myoma. Concentrations of CZON in the serum of cubital vein, uterine artery, and in tissues of uterus and adnexa uteri were measured by the bioassay method. Bilateral uterine arteries were clamped at 15 and 30 minutes and 1, 2, 4 and 6 hours after the administrations of the drug. Measurements were done on 4 patients at each sampling. Concentrations of CZON in the serum of cubital vein and uterine artery changed in a similar manner with respective half-lives of 52.0 minutes and 48.2 minutes. Peak concentrations in oviduct, ovary, endometrium, myometrium, cervix uteri and portio vaginalis were reached at 15 minutes after drug administration. The peak concentration in the ovary was as high as 37.5 micrograms/g, and those in other tissues varied between 17.6 and 25.5 micrograms/g. Tissue concentrations decreased gradually after their peaks in similar manners to those in serum, and their half-lives ranged between 37.4 and 53.7 minutes. From these results, it was found that CZON was transferred to female genital organs in high enough concentrations to inhibit growth of bacteria which were often isolated from the pelvic inflammatory diseases, and CZON seemed to be highly effective to clinical pelvic inflammatory diseases.

[Pharmacokinetic, bacteriological and clinical studies of cefuzonam in the field of obstetrics and gynecology].

Cefuzonam (CZON, L-105), an antibiotic injectable of cephalosporin family, was studied pharmacokinetically, clinically and bacteriologically to examine its distribution to female genital tissues and the activity on infections in the field of obstetrics and gynecology. Maximum concentrations in serum and genital tissues achieved 19-46 minutes after intravenous injection of CZON 1 g were 69.6 micrograms/ml for serum, 63.1 micrograms/g for oviduct, 34.2 micrograms/g for ovary, 22.5 micrograms/g for endometrium, 33.4 micrograms/g for myometrium, 30.7 micrograms/g for cervix uteri, and 37.1 micrograms/g for portio vaginalis. Clinical efficacies on 15 cases of intrauterine infection and adnexitis were proved with 4 cases of 'marked improvement' and 11 cases of 'improvement', thus the efficacy rate was 100%. Of 21 strains of aerobes and anaerobes isolated from infectious lesions, 19 strains were eliminated after administration of the drug. No side effects were observed. From these results of fundamental and clinical studies CZON appeared to be a highly useful drug fro the obstetric and gynecological infections.