Myometrial Responses to Beta-Adrenoceptor Antagonists in Gynecological Malignancies.

OBJECTIVE: The aim of the study was to determine the influence of beta-adrenoceptor (ADRB) antagonists on contractile activity of the nonpregnant human uterus in patients affected by gynecological malignancies. DESIGN: This was a controlled and prospective ex vivo study. SETTING: The work was conducted as a collaboration between 4 academic departments. MATERIALS AND METHODS: Myometrial specimens were obtained from women undergoing hysterectomy for benign gynecological disorders (reference group; N = 15), and ovarian (N = 15), endometrial (N = 15), synchronous ovarian-endometrial (N = 3), and cervical cancer (N = 10). Contractions of myometrial strips in an organ bath before and after applications of ADRB antagonists (propranolol, bupranolol, SR 59230A, and butoxamine) were studied under isometric conditions. RESULTS: Propranolol and bupranolol attenuated contractions in the endometrial and cervical cancer groups similar to that in the reference group (all p < 0.05), whereas opposite effects were observed in the ovarian and synchronous ovarian-endometrial cancer groups. SR 59230A and butoxamine significantly increased contractions in the ovarian cancer group (both p < 0.001). LIMITATIONS: These results require now to be placed into a firm clinical context. CONCLUSIONS: Our study indicates that ovarian cancer considerably alters contractile activity of the nonpregnant human uterus in response to ADRB antagonists. This suggests a pathogenetic role of beta-adrenergic pathways in this malignancy. Furthermore, propranolol and bupranolol substantially influence spontaneous uterine contractility.

Cancer Prevention by Natural Products Introduced into the Diet-Selected Cyclitols.

Cancer is now the second leading cause of death worldwide. It is estimated that every year, approximately 9.6 million people die of oncologic diseases. The most common origins of malignancy are the lungs, breasts, and colorectum. Even though in recent years, many new drugs and therapeutic options have been introduced, there are still no safe, effective chemopreventive agents. Cyclitols seem poised to improve this situation. There is a body of evidence that suggests that their supplementation can decrease the incidence of colorectal cancer, lower the risk of metastasis occurrence, lower the proliferation index, induce apoptosis in malignant cells, enhance natural killer (NK) cell activity, protect cells from free radical damage, and induce positive molecular changes, as well as reduce the side effects of anticancer treatments such as chemotherapy or surgery. Cyclitol supplementation appears to be both safe and well-tolerated. This review focuses on presenting, in a comprehensive way, the currently available knowledge regarding the use of cyclitols in the treatment of different malignancies, particularly in lung, breast, colorectal, and prostate cancers.

Inositols' Importance in the Improvement of the Endocrine-Metabolic Profile in PCOS.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and metabolic problems among women of reproductive age. The mechanism of PCOS is associated with concurrent alterations at the hormonal level. The diagnosis assumes the occurrence of three interrelated symptoms of varying severity, namely ovulation disorders, androgen excess, or polycystic ovarian morphology (PCOM), which all require a proper therapeutic approach. The main symptom seems to be an increased androgen concentration, which in turn may contribute to different metabolic disorders. A number of papers have demonstrated the significant role of inositol therapy in PCOS. However, there is a lack of detailed discussion about the importance of myo-inositol (MI) and d-chiro-inositol (DCI) in reference to particular symptoms. Thus, the aim of this review is to present the effectiveness of MI and DCI treatment for PCOS symptoms. Moreover, the review is focused on analyzing the use of inositols, taking into account their physiological properties, together with the mechanism of individual PCOS symptom formation.

Placenta Transcriptome Profiling in Intrauterine Growth Restriction (IUGR).

Intrauterine growth restriction (IUGR) is a serious pathological complication associated with compromised fetal development during pregnancy. The aim of the study was to broaden knowledge about the transcriptomic complexity of the human placenta by identifying genes potentially involved in IUGR pathophysiology. RNA-Seq data were used to profile protein-coding genes, detect alternative splicing events (AS), single nucleotide variant (SNV) calling, and RNA editing sites prediction in IUGR-affected placental transcriptome. The applied methodology enabled detection of 37,501 transcriptionally active regions and the selection of 28 differentially-expressed genes (DEGs), among them 10 were upregulated and 18 downregulated in IUGR-affected placentas. Functional enrichment annotation indicated that most of the DEGs were implicated in the processes of inflammation and immune disorders related to IUGR and preeclampsia. Additionally, we revealed that some genes (S100A13, GPR126, CTRP1, and TFPI) involved in the alternation of splicing events were mainly implicated in angiogenic-related processes. Significant SNVs were overlapped with 6533 transcripts and assigned to 2386 coding sequence (CDS), 1528 introns, 345 5' untranslated region (UTR), 1260 3'UTR, 918 non-coding RNA (ncRNA), and 10 intergenic regions. Within CDS regions, 543 missense substitutions with functional effects were recognized. Two known mutations (rs4575, synonymous; rs3817, on the downstream region) were detected within the range of AS and DEG candidates: PA28ß and PINLYP, respectively. Novel genes that are dysregulated in IUGR were detected in the current research. Investigating genes underlying the IUGR is crucial for identification of mechanisms regulating placental development during a complicated pregnancy.

Anti-Müllerian Hormone Expression in Endometrial Cancer Tissue.

Anti-Müllerian hormone (AMH) is a commonly known factor secreted by Sertoli cells, responsible for regression of the Müllerian ducts in male fetuses. AMH has also other functions in humans. In vivo and in vitro studies have shown that AMH inhibits cell cycle and induces apoptosis in cancers with AMH receptors. The aim of the study was to assess whether the tissue of pre-cancerous states of endometrium (PCS) and various histopathologic types of endometrial cancer (EC) exhibit the presence of AMH. We aimed to investigate whether the potential presence of the protein concerns menopausal women or those regularly menstruating, and whether is related to cancers with a good or a bad prognosis, as well as what other factors may influence AMH expression. The undertaken analysis was carried out on tissues retrieved from 232 women who underwent surgical treatment for PCS and EC. Tissues were prepared for immunohistochemical assessment with the use of a tissue microarrays method. AMH expression was confirmed in 23 patients with well differentiated endometrioid adenocarcinoma (G1), moderately differentiated endometrioid adenocarcinoma (G2), clear cell carcinoma (CCA) and nonatypical hyperplasia. AMH was not found in EC tissues in regularly menstruating women. An appropriately long mean period of breastfeeding in line with a prolonged period of hormonal activity had a positive effect on AMH expression. Our results may suggest that AMH is a factor which protects the organism against cancer, and should be further investigated as a potential prognosis marker and a therapeutic agent.

Congenital vesicouterine fistulas-A PRISMA-compliant systematic review.

AIMS: Vesicouterine fistulas (VUFs) are infrequent abnormal connections between the bladder and the uterine cavity or cervical canal, being mainly sequelae of repeat Cesarean sections. Exceedingly rare are congenital VUFs. This is a systematic review of available world data aimed to characterize congenital VUFs and better understand the mechanism(s) of their formation. METHODS: The PubMed® database via MEDLINE® search engine was explored from its inception to March 2018. Relevant studies were identified using selected Medical Subject Heading-based terms. This was further supplemented by cross-referencing and handsearching. Retrieved literature was evaluated in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, guidelines. RESULTS: A total of 6561 articles were identified of which 10 were analyzed. Three VUFs accompanied broader syndromes of congenital defects. A lack of patency at the level of the vagina was present in all assessed cases. Unilateral renal agenesis was confirmed in four of eight (50%) verified patients. Hence, unilateral kidney agenesis was related to a lesser degree (P = 0.0186) than vaginal atresia to VUF. The principal features of these fistulas were as follows: partial or complete vaginal atresia resulting in primary amenorrhea, menouria present since menarche, and urinary continence. CONCLUSIONS: This review provides the first systematic evidence that congenital VUFs are chiefly associated with concomitant vaginal atresia. The symptomatology of such VUFs is consistent with that of type I acquired fistulas.

Structural arrangement of vesicouterine fistula revisited: An immunohistochemical study documenting the presence of the endometrium.

Previous research has described a woman of reproductive age who presented with a vesicouterine fistula (VUF) of 20 months' duration. The VUF was lined with a metaplastic glandular epithelium containing both estrogen receptors (ER) and progesterone receptors (PR) in abundance. The aim of the present investigation was to evaluate the histology of the VUF canal when exposure to urine of the cellular elements within the fistula was of much shorter duration. A 41-year-old woman who developed a VUF during her third cesarean section was treated with transvesical fistula excision, electrocoagulation, and subsequent attempted hormonal treatment. Later, the patient underwent open surgery fistula repair. Postoperative specimens were subjected to anatomopathological examination together with immunohistochemical staining for ER and PR using monoclonal anti-human antibodies. Herein, we present for the first time detailed microscopic evidence that, at two separate timepoints, the fistulous tract was lined with the endometrium, which covered approximately 80% of the length of the VUF canal. In its intermediate segment, the urothelium formed an additional layer on the surface of the endometrium. At both timepoints, in the columnar epithelial and stromal endometrial cells lining the fistula, both ER and PR were present in abundance. In conclusion, VUF in subjects of reproductive age fulfill criteria for endometriosis. This study provides a rationale for the conservative treatment of VUF consistent with the hormonal treatment of endometriosis.

Preliminary RNA-Seq Analysis of Long Non-Coding RNAs Expressed in Human Term Placenta.

Development of particular structures and proper functioning of the placenta are under the influence of sophisticated pathways, controlled by the expression of substantial genes that are additionally regulated by long non-coding RNAs (lncRNAs). To date, the expression profile of lncRNA in human term placenta has not been fully established. This study was conducted to characterize the lncRNA expression profile in human term placenta and to verify whether there are differences in the transcriptomic profile between the sex of the fetus and pregnancy multiplicity. RNA-Seq data were used to profile, quantify, and classify lncRNAs in human term placenta. The applied methodology enabled detection of the expression of 4463 isoforms from 2899 annotated lncRNA loci, plus 990 putative lncRNA transcripts from 607 intergenic regions. Those placentally expressed lncRNAs displayed features such as shorter transcript length, longer exon length, fewer exons, and lower expression levels compared to messenger RNAs (mRNAs). Among all placental transcripts, 175,268 were classified as mRNAs and 15,819 as lncRNAs, and 56,727 variants were discovered within unannotated regions. Five differentially expressed lncRNAs (HAND2-AS1, XIST, RP1-97J1.2, AC010084.1, TTTY15) were identified by a sex-bias comparison. Splicing events were detected within 37 genes and 4 lncRNA loci. Functional analysis of cis-related potential targets for lncRNAs identified 2021 enriched genes. It is presumed that the obtained data will expand the current knowledge of lncRNAs in placenta and human non-coding catalogs, making them more contemporary and specific.

Transcriptome profile of the human placenta.

The human placenta is a particular organ that inseparably binds the mother and the fetus. The proper development and survival of the conceptus relies on the essential interplay between maternal and fetal factors involved in cooperation within the placenta. In our study, high-throughput sequencing (RNA-seq) was applied to analyze the global transcriptome of the human placenta during uncomplicated pregnancies. The RNA-seq was utilized to identify the global pattern of the gene expression in placentas (N = 4) from women in single and twin pregnancies. During analyses, we obtained 228,044 transcripts. More than 91% of them were multi-exon, and among them 134 were potentially unknown protein coding genes. Expression levels (FPKM) were estimated for 38,948 transcriptional active regions, and more than 3000 of genes were expressed with FPKM >20 in each sample. Additionally, all unannotated transcripts with estimated FPKM values were localized on the human genome. Highly covered splice junctions unannotated in the human genome (6497) were identified, and among them 30 were novel. To gain a better understanding of the biological implications, the assembled transcripts were annotated with gene ontology (GO) terms. Single nucleotide variants were predicted for the transcripts assigned to each analyzed GO category. Our results may be useful for establishing a general pattern of the gene expression in the human placenta. Characterizing placental transcriptome, which is crucial for a pregnancy's outcome, can serve as a basis for identifying the mechanisms underlying physiological pregnancy, as well as may be useful for an early detection of the genomic defects.

Identification of Novel Placentally Expressed Aspartic Proteinase in Humans.

This study presents pioneering data concerning the human pregnancy-associated glycoprotein-Like family, identified in the genome, of the term placental transcriptome and proteome. RNA-seq allowed the identification of 1364 bp hPAG-L/pep cDNA with at least 56.5% homology with other aspartic proteinases (APs). In silico analyses revealed 388 amino acids (aa) of full-length hPAG-L polypeptide precursor, with 15 aa-signal peptide, 47 aa-blocking peptide and 326 aa-mature protein, and two Asp residues (D), specific for a catalytic cleft of the APs (VVFDTGSSNLWV91-102 and AIVDTGTSLLTG274-285). Capillary sequencing identified 9330 bp of the hPAG-L gene (Gen Bank Acc. No. KX533473), composed of nine exons and eight introns. Heterologous Western blotting revealed the presence of one dominant 60 kDa isoform of the hPAG-L amongst cellular placental proteins. Detection with anti-pPAG-P and anti-Rec pPAG2 polyclonals allowed identification of the hPAG-L proteins located within regions of chorionic villi, especially within the syncytiotrophoblast of term singleton placentas. Our novel data extend the present knowledge about the human genome, as well as placental transcriptome and proteome during term pregnancy. Presumably, this may contribute to establishing a new diagnostic tool for examination of some disturbances during human pregnancy, as well as growing interest from both scientific and clinical perspectives.

Urinary tract infections during pregnancy - an updated overview.

Urinary tract infections (UTIs) are the most common type of infection during pregnancy, affecting up to 10% of pregnant women. They are also recognized as the second most common ailment of pregnancy, after anemia. Three clinical types of pregnancy-related UTI are distinguished: asymptomatic bacteriuria (ASB), cystitis, and pyelonephritis. A particular form of ASB is the presence of Group B streptococci in the urinary tract of the pregnant woman. All clinical types of UTI may lead to serious maternal and fetal complications. Therefore, unlike in the nonpregnant female patient, all UTIs during pregnancy, including the asymptomatic infection, require treatment. In some patients, antibiotic prophylaxis should also be introduced. In the present work, we collectively summarize current practical recommendations from a number of international bodies and organizations.

Surface antigen expression on peripheral blood monocytes in women with gynecologic malignancies.

BACKGROUND: Of many specialized blood cells, monocytes are gaining increasing attention for their role in neoplastic disorders. The purpose of the present investigation was to determine the expression of selected peripheral blood monocyte surface antigens in cases of cervical, endometrial, and ovarian cancers. In addition, our aim was to validate the diagnostic value of two artificial coefficients recently proposed for the diagnosis of gynecologic malignancies: Neutrophil to Lymphocyte Ratio (NLR), and Multiplication of Neutrophil and Monocyte Counts (MNM). METHODS: We studied 69 white Caucasian women with histopathologic confirmation of endometrial (N = 42), cervical (N = 13), and ovarian (N = 14) cancers. Reference Group I were women suspected of cancer but histologically nullified (N = 20), and Group II were healthy blood donors (N = 23). Expression of CD11a, CD11b, CD11c, CD16, CD54 (ICAM-1), CD62 L (L-selectin), CD64, and HLA-DR was measured with immunofluorescence in a flow cytometer. RESULTS: CD54 expression increased by ≥35.6% (p < 0.001) whilst HLA-DR decreased by ≥10.8% (p < 0.001) in all cancer subgroups and Group I as compared to blood donors. A correlation (p < 0.05) between CD54 and CD62 L was stronger in all cancers studied than in healthy subjects. There was no difference in the NLR values between any of these subgroups. Moreover, we observed an increase in MNM parameter in cases of cervical and endometrial cancer and in the Reference Group I. CONCLUSIONS: In the studied gynecologic malignancies, CD54 expression on peripheral blood monocytes is enhanced, indicating a higher transmigrational potential present in such patients, and HLA-DR expression diminished, indicating a decreased readiness of the immune system to recognize foreign antigens. The more pronounced correlation for the expression of CD54 and CD62 L in cancer suggests that monocytes uptake from the bloodstream and their local adhesion increase the pool of tumor-associated macrophages. This study challenged the suggested credibility and usefulness of the artificial parameters of MNM and NLR for the differential diagnosis of gynecologic malignancies.

[Levonorgestrel-releasing intrauterine system Mirena® (Bayer) for the prevention and treatment of endometrial adenocarcinoma and the incidence of other malignancies in women]. / Wplyw systemu wewnatrzmacicznego uwalniajacego lewonorgestrel Mirena® (Bayer) na prewencje i leczenie raka gruczlowego blony sluzowej macicy oraz na inne nowotwory zlosliwe u kobiet.

The use of hormone-releasing intrauterine devices has been on the increase for the last three decades. To date, evidence of their long-term efficiency is available. The aim of the present paper was to briefly review beneficial prophylactic effects of the levonorgestrel-releasing intrauterine system on the incidence of a variety of malignancies in women. Such an influence is of a particular importance in the light of the currently observed increased prevalence of endometrial and cervical adenocarcinomas. Low-dose releasing intrauterine systems are also available, but the hard evidence-based medical data have been derived primarily for Mirena® (Bayer) device, which topically releases from 20 to 14 pg of levonorgestrel daily. Consequently the risk of developing endometrial carcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk To a lesser extent, the intrauterine system decreases the risk for cervical adenocarcinoma and squamous cell carcinoma, as well as ovarian, pancreas, and lung carcinomas. In one population-based study Mirena® increased the risk for breast carcinoma by approximately 20%, whereas a number of other studies failed to demonstrate such a hazard. In the recent decades of the increased predominance of insulin resistance and obesity and an occurrence of hormone-dependent carcinomas at earlier age, a broad application of levonorgestrel-releasing intrauterine systems may become a particularly important component of primary prevention of malignancies in women. Both obese and overweight patients seem perfect candidates for such a hormonal intervention.

Dermatofibrosarcoma Protuberans: An Updated Review of the Literature.

Dermatofibrosarcoma protuberans (DFSP) is a rare proliferative condition representing skin sarcomas which is known to locally recur yet very rarely metastasizes. Its genetic background is a reciprocal translocation t(17;22)(q22;q13) that produces COL1A1-PDGFB gene fusion. Complete resection is the primary treatment. The aim of this review is to outline the pathogenesis, diagnosis, and management of DFSP. A clear-cut distinction between low-to-moderate-grade DFSP with excellent prognosis and high-grade fibrosarcomatous DFSP with a much worse prognosis is underlined. Malignant transformation within DFSP (or high histologic grade), older age, being female, large primary tumor size (≥10 cm), narrow surgical margins of excision (<3 cm), surgical margin positivity for tumor cells, short time to recurrence, numerous recurrences, tumor that was recently rapidly enlarging, and presence of pain in the tumor have all been proposed as clinicopathological risk factors for recurrence and metastasis. A tendency for local growth and local relapses of well- and moderately differentiated DFSPs is an argument for their surgical excision, possibly combined with reconstructive surgery, even in patients of advanced age. Another main point of this review is that cases of DFSP with fibrosarcomatous transformation are a challenge and require careful medical attention. Both anatomopathological evaluation of the presence of lymphovascular space invasion and sentinel lymph node biopsy at DFSP surgery merit further study.

Role of Receptor for Advanced Glycation End-Products in Endometrial Cancer: A Review.

Endometrial cancer (EC) is the most common gynecological malignancy. EC is associated with metabolic disorders that may promote non-enzymatic glycation and activate the receptor for advanced glycation end-products (RAGE) signaling pathways. Thus, we assumed that RAGE and its ligands may contribute to EC. Of particular interest is the interaction between diaphanous-related formin 1 (Diaph1) and RAGE during the progression of human cancers. Diaph1 is engaged in the proper organization of actin cytoskeletal dynamics, which is crucial in cancer invasion, metastasis, angiogenesis, and axonogenesis. However, the detailed molecular role of RAGE in EC remains uncertain. In this review, we discuss epigenetic factors that may play a key role in the RAGE-dependent endometrial pathology. We propose that DNA methylation may regulate the activity of the RAGE pathway in the uterus. The accumulation of negative external factors, such as hyperglycemia, inflammation, and oxidative stress, may interfere with the DNA methylation process. Therefore, further research should take into account the role of epigenetic mechanisms in EC progression.

The Study of Myo-Inositol's Anxiolytic Activity on Zebrafish (Danio rerio).

INTRODUCTION: Myo-inositol (MI) is the most abundant inositol found in nature. To date MI supplementation is reported to be effective in the treatment of polycystic ovary syndrome, it is also suggested to alleviate the symptoms of diabetes and neurodegenerative disorders, but to date no statistically significant effects of inositol on depressive and anxiety symptoms were proven. In the study of anxiolytic effects in zebrafish, we often use the thigmotaxis index measuring the ratio of the amount of time the animal spends near the walls compared to the entire arena. AIM: The objective of this paper was to examine the effect of MI on zebrafish embryos' locomotor activity, as well as its potential anxiolytic activity in zebrafish larvae. MATERIAL AND METHODS: In the first part of the experiment, the embryos were incubated with 5, 10, 20, and 40 mg/mL MI. 1-day post fertilization, embryo mobility was evaluated and burst activity was calculated. In the next part of the study, the behavior of 5-day-old larvae was tested. RESULTS: Tests on embryo movement showed an increase in burst activity in the MI group at concentrations of 40 mg/mL (p < 0.0001) and a slight decrease in the group at concentrations of 10 mg/mL (p < 0.05). MI in the light/dark challenge had no impact on the thigmotaxis index. CONCLUSIONS: MI was shown to not affect stress reduction in zebrafish larvae. Further research on the potential of MI and other stereoisomers is needed.

Human breast milk sugars and polyols over the first 10 puerperium days.

OBJECTIVE: The transition from colostrum to mature breast milk during early puerperium is associated with significant concentration changes of numerous compounds. However, it is not known whether the free sugars, aminohexoses, and polyols are affected. Therefore, in this study, we aimed to determine their concentrations in human colostrum and milk during the first 10 days postpartum. METHODS: This prospective longitudinal study in a sample of normal consecutive obstetric patients was conducted as a collaboration between two academic centers-Polish and American. Participants were 13 women after uncomplicated pregnancy and delivery at term of a singleton, appropriate-for-gestational-age fetus. Lactose, galactose, glucose, mannose, galactosamine, glucosamine, glycerol, and myo-inositol concentrations were measured using high performance liquid chromatography. RESULTS: During the first 3 days postpartum, the concentrations of lactose and glucose increased significantly (P < 0.001), to steady-state values thereafter. In contrast, the concentrations of myo-inositol and glycerol decreased significantly (P < 0.001) over the first 4 days, to reach relatively low stable values. ANOVA analysis indicated that the postpartum day at which early changes ceased to be significantly different from their plateau values was Day 4. myo-Inositol concentrations were significantly higher (P = 0.022) in multiparas than in primiparas. CONCLUSIONS: The colostrum-to-milk transition is associated with significant changes in concentrations of free sugars and polyols, changes which are completed by the fourth postpartum day. Parity influences the concentrations of some compounds in the breast milk.

Identification and subsequent validation of transcriptomic signature associated with metabolic status in endometrial cancer.

Aberrant metabolism has been identified as a main driver of cancer. Profiling of metabolism-related pathways in cancer furthers the understanding of tumor plasticity and identification of potential metabolic vulnerabilities. In this prospective controlled study, we established transcriptomic profiles of metabolism-related pathways in endometrial cancer (EC) using a novel method, NanoString nCounter Technology. Fifty-seven ECs and 30 normal endometrial specimens were studied using the NanoString Metabolic Panel, further validated by qRT-PCR with a very high similarity. Statistical analyses were by GraphPad PRISM and Weka software. The analysis identified 11 deregulated genes (FDR ≤ 0.05; |FC|≥ 1.5) in EC: SLC7A11; SLC7A5; RUNX1; LAMA4; COL6A3; PDK1; CCNA1; ENO1; PKM; NR2F1; and NAALAD2. Gene ontology showed direct association of these genes with 'central carbon metabolism (CCM) in cancer'. Thus, 'CCM in cancer' appears to create one of the main metabolic axes in EC. Further, transcriptomic data were functionally validated with drug repurposing on three EC cell lines, with several drug candidates suggested. These results lay the foundation for personalized therapeutic strategies in this cancer. Metabolic plasticity represents a promising diagnostic and therapeutic option in EC.

Ammonia and female sex hormones concentrations in human preovulatory follicular fluid are not directly related.

OBJECTIVE: The ammonia gradient from the human preovulatory follicular fluid (FF) to blood has been documented. The purpose of the present study was to substantiate whether following controlled ovarian hyperstimulation, female sex hormones are relATED TO THIS PHENOMENON. MATERIAL AND METHODS: Blood was taken from the antecubital veins of 32 randomly selected patients undergoing an in vitro fertilization program prior to oocyte retrieval and FF collection. Ammonia concentrations in blood and FF were determined by the indophenol method, and 17beta-estradiol (E2) and progesterone (PGS) concentrations in plasma and FF by radioimmunoassay RESULTS: The mean ammonia concentration was 39.15 +/- 3.25 microM for FF and 20.15 +/- 1.20 microM for blood (p < 0.001). In all subjects, the ratios of ammonia concentrations in FF to those in blood were above 1.0, confirming the production of ammonia by the preovulatory follicle. No correlation was found between FF ammonia and E2 concentrations (Spearman's rank correlation coefficient r = 0.2546; p = 0.160), nor between FF ammonia and the difference in E2 concentration in FF and plasma (r = 0.2416; p = 0.183). Similarly there was no correlation between FF ammonia and PGS (r = -0.1089; p = 0.553). In support of this finding, no correlation was observed between FF ammonia and the difference in PGS concentration in FF and plasma (r = -0.1133; p = 0.537). CONCLUSIONS: Ammonia production is not directly related to intrafollicular female sex hormones concentrations. The accumulation of ammonia is likely to account for the alkaline pH of the human preovulatory FF.

Differences in the effects of beta2- and beta3-adrenoceptor agonists on spontaneous contractions of human nonpregnant myometrium.

OBJECTIVE: This study aimed to compare the relaxant properties of BRL 37344 with p2-adrenoceptors agonist ritodrine on the contractility of human nonpregnant myometrium. MATERIAL AND METHODS: The activity of myometrial strips mounted in an organ bath was recorded under isometric conditions using force transducers with digital output. Contractility before and after cumulative additions of both uterorelaxants and with preincubation with beta-adrenoceptor antagonists bupranolol, propranolol, and butoxamine were studied. RESULTS: Both BRL 37344 (10(-10)-10(-4) mol/L) and ritodrine (10(-10)-10(-5) mol/L) decreased the area under curve, or AUC, value (log/C50 -6.45 +/- 0.18 and -8.71 +/- 0.35, respectively), and the degree of inhibition of spontaneous contractile activity was similar (< 30%). However BRL 37344 decreased the mean frequency of contractions, whereas ritodrine decreased the mean amplitude of contractions. The inhibition of contractions by BRL 37,344 was partially antagonized by bupranolol and propranolol, but not with butoxamine. The inhibition by ritodrine was counteracted by all these antagonists. CONCLUSIONS: The effects of BRL37344 and ritodrine on human nonpregnant myometrium are quantitatively similar in respect to the inhibition of spontaneous contractility yet are also distinct due to their substantially different influences on contraction parameters. Our data indicate that beta3-adrenoceptor activation is not the sole effect of BRL 37,344 on this tissue.