Awareness of Pregnant Patients about Congenital Cytomegalovirus Infection-A Semi-Systematic Review.

Background: Cytomegalovirus (CMV) infection represents a major issue worldwide, since it constitutes the most common viral congenital infection, with a prevalence of 0.58% and 1-5% in developed and developing countries, respectively. According to recent studies, prenatal treatment significantly decreases the risk of vertical CMV transmission, and early intervention may even prevent the termination of pregnancy. This study aimed to investigate the level of awareness of CMV among pregnant patients through a semi-systematic review. Methods: We included all of the original articles investigating knowledge and awareness about CMV infection among pregnant women. Our research included the PubMed database. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, the Covidence system automatically guided us to screen the titles and/or abstracts, and then full-texts, followed by data extraction from the eligible studies. Results: We screened 764 studies altogether, with 13 studies included in this analysis. Knowledge about the existence of CMV infection risk varied between the articles, ranging from 11.4% in a study performed in Ireland to 60% reported in a study on the French population. Studies analyzing the impact of educational interventions on patients' knowledge about preventive measures reported significant improvement compared to their level of awareness before the intervention. Conclusions: Patients' awareness and knowledge about CMV seemed to be generally low or very low during the last decade before the development of effective secondary prevention methods. Educational interventions seem to be effective, and therefore their wide use could be of potential benefit. In the era of available secondary prevention of vertical transmission, it is crucial to concentrate the efforts of different stakeholders to increase the awareness of cCMV among pregnant women.

The effect of two anti-inflammatory dietary components, omega-3 and resveratrol, on endometriosis.

Endometriosis is an inflammatory condition defined by the presence of endometrial glands and stroma outside the uterine cavity. Given the substantial body of evidence supporting the role of inflammation in the pathophysiology of various chronic illnesses, the concept of an anti-inflammatory diet has garnered significant attention in recent research. Some nutrients, such as omega-3 fatty acids and resveratrol (RES), have demonstrated distinct anti-inflammatory properties. Therefore, the objective of this systematic review was to search the Embase, Medline, and PubMed databases for literature from August 2008 to August 2023 regarding the effects of two anti-inflammatory dietary components, omega-3 and RES, on endometriosis. A total of 215 records were identified, out of which 58 were screened, 23 met the eligibility criteria, and 19 were included in this review. The results of this systematic review indicate that EPA is suggested to have anti-inflammatory properties and may serve as a potential marker for illness severity. RES offers a range of advantages, including inflammation reduction, angiogenesis suppression, proliferation inhibition, and apoptosis induction. To validate these findings and assess their clinical relevance, future research and clinical trials are warranted.

Relationship between the gut microbiome and endometriosis and its role in pathogenesis, diagnosis, and treatment: a systematic review.

Endometriosis is a chronic inflammatory disease affecting approximately 10% of women. It is defined as endometrial tissue outside of the uterus and produces a variety of symptoms including pelvic pain, dysmenorrhea, dyspareunia, and intermenstrual bleeding. Although several theories have been postulated regarding the pathogenesis of endometriosis, no theory has provided a complete explanation, therefore limiting our progress in diagnostic tools and management of endometriosis. Recently, much attention has been paid to the importance and role of the gut microbiome in endometriosis. As defined by Joshua Lederberg - microbiome is a set of the genome of microorganisms inhabiting a human body, including commensal, symbiotic and pathogenic microorganisms. The aim of this systematic review was to conduct a search in the Embase, Medline, and PubMed databases for literature from July 2013 to July 2023 regarding the relationship between the gut microbiome and endometriosis. 147 records were screened, of which 26 met the eligibility criteria, and 16 were included in this review. Our review concludes that patients with endometriosis show an altered gut microbiome, and that this has the potential to provide insight for pathogenesis, markers for diagnosis, as well as therapeutic options for treatment of endometriosis. Future research is necessary to confirm this and further investigate the relationship between the gut microbiome and endometriosis.

The Influence of Time of Day of Vaccination with BNT162b2 on the Adverse Drug Reactions and Efficacy of Humoral Response against SARS-CoV-2 in an Observational Study of Young Adults.

An increasing body of evidence from both academic and clinical studies shows that time-of-day exposure to antigens might significantly alter and modulate the development of adaptive immune responses. Considering the immense impact of the COVID-19 pandemic on global health and the diminished efficacy of vaccination in selected populations, such as older and immunocompromised patients, it is critical to search for the most optimal conditions for mounting immune responses against SARS-CoV-2. Hence, we conducted an observational study on 435 healthy young adults vaccinated with two doses of BNT162b2 (Pfizer-BioNTech) vaccine to determine whether time-of-day of vaccination influences either the magnitude of humoral response or number of adverse drug reactions (ADR) being reported. We found no significant differences between morning and afternoon vaccination in terms of both titers of anti-Spike antibodies and frequency of ADR in the studied population. In addition, our analysis of data on the occurrence of ADR in 1324 subjects demonstrated that the second administration of vaccine in those with previous SARS-CoV-2 infection was associated with lower incidence of ADR. In aggregate, vaccination against COVID-19 with two doses of BNT162b2 mRNA vaccine is presumed to generate an equally efficient anti-Spike humoral response.

The Potential of Asiatic Acid in the Reversion of Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats.

The purpose of this study was to determine if asiatic acid may act efficiently in the model of cyclophosphamide (CYP)-induced cystitis in rats. We performed experiments after administration of CYP (single dose 200 mg/kg, intraperitoneally), asiatic acid (30 mg/kg/day for 14 consecutive days, by oral gavage), or CYP plus asiatic acid, during which conscious cystometry, measurements of urothelium thickness and bladder edema, as well as selected biomarkers analyses were conducted. In rats that received asiatic acid together with CYP, a drop in bladder basal pressure, detrusor overactivity index, non-voiding contraction amplitude, non-voiding contraction frequency, and the area under the pressure curve were observed, when compared to the CYP group. Furthermore, a significant increase in threshold pressure, voided volume, intercontraction interval, bladder compliance, and volume threshold to elicit NVC were found in that group accordingly. Administration of the asiatic acid successfully restored concentrations of biomarkers both in bladder urothelium (BDNF, CGRP, OCT-3, IL-1ß, IL-6, NGF, nitrotyrosine, malondialdehyde, TNF-α, SV2A, SNAP23, SNAP25, PAC-1, ORM1, occludin, IGFBP-3, HB-EGF, T-H protein, Z01, and HPX) and detrusor muscle (Rho kinase and VAChT) in CYP-treated rats. Finally, asiatic acid significantly decreased urothelium thickness and bladder oedema. Asiatic acid proved to be a potent and effective drug in the rat model of CYP-induced cystitis.

Peroxiredoxin-1 as a prognostic factor in patients with ovarian cancer.

INTRODUCTION AND OBJECTIVE: Peroxiredoxin-1 (PRDX-1) belongs to a family of antioxidant enzymes and has proved to be a versatile molecule regulating cell growth, differentiation and apoptosis. PRDX1-regulated signaling pathways play an important role in the progression and metastasis of human tumours, especially in breast, esophageal and lung cancers. The aim of the study was to evaluate the expression of PRDX-1 in ovarian cancer tissues, and to test the clinical value of PRDX-1 as a prognostic factor in this malignancy. MATERIAL AND METHODS: PRDX-1 expression was assessed by automated immunohistochemistry in tumours taken from 55 patients with ovarian cancer during primary surgery. Specimen were formalin-fixed and preserved in paraffin-embedded blocks. The results were correlated with clinicopathological data. RESULTS: A high expression of PRDX-1 was observed in 20% of cases, and was associated with worse compliance to chemotherapy protocol (P<0.002), worse response to chemotherapy (P<0.04), and higher levels of CA 125 after the 1st line treatment (P<0.004). PRDX-1 positive subjects had a significantly lower 5-year disease-free survival (9.1% vs. 42.6%, P<0.01) and a lower 5-year overall survival (9.1% vs. 56.7%; P<0.002). Multivariate analysis showed that a high expression of PRDX-1 is an independent prognostic factor of poor, overall survival (P<0.002) and a disease-free survival (P<0.01). CONCLUSIONS: Results of the study show that PRDX-1 expression in tumour tissues can be another biomarker of prognosis in patients with ovarian cancer.

Influence of Glycemic Control on Coagulation and Lipid Metabolism in Pregnancies Complicated by Pregestational and Gestational Diabetes Mellitus.

Hypercoagulability and altered lipid metabolism, which are observed in normal pregnancy, can be enhanced in diabetes mellitus. The aim of the study was to evaluate the influence of glycemic control on coagulation and lipid metabolism in women with pregestational (PGDM) and gestational (GDM) diabetes treated with insulin. There were 50 patients with PGDM and 101 patients with GDM enrolled into the study. Serum lipid and coagulation parameters were assessed at 18-22, 25-28, and 31-34 weeks of pregnancy and were compared within the diabetic groups with reference to the effectiveness of glycemia control. We found that poor glycemic control was associated with shortened activated partial thromboplastin time (APTT) and increased activity of antithrombin III (ATIII) in both diabetic groups and with a higher plasminogen activator inhibitor (PAI-1) content level in the GDM group. Poorly controlled PGDM was associated with higher levels of total cholesterol and high-density cholesterol (HDL) in the second trimester and triglycerides in the third trimester. In patients with poorly controlled GDM, a higher concentration of HDL was observed in third trimester, whereas a higher triglyceride level was found in both second and third trimesters. Positive correlations between total cholesterol and APTT and between triglyceride and APTT and ATIII were found in the poorly controlled PGDM group. We conclude that poor glycemic control of diabetic pregnancy impacts both lipid metabolism and the blood coagulation system.

Prognostic value of tissue plasminogen activator (tPA) in patients with epithelial ovarian cancer undergoing chemotherapy.

OBJECTIVES: Tissue plasminogen activator (tPA) is a key enzyme for fibrin degradation and the proteolytic defense against formation of the thrombotic endothelial deposits. tPA is involved in carcinogenesis but its exact role in tumor biology is not very well understood and a prognostic value of tPA remains ambiguous in different cancers. The aim of the study was to assess the prognostic value of plasma tPA in patients with epithelial ovarian cancer (EOC) in the course of the first line chemotherapy. MATERIAL AND METHODS: the study covered 60 patients with EOC who underwent the 1st line chemotherapy. Plasma tPA was assessed at onset, after 3 and 6 cycles of chemotherapy. The groups were stratified according to tPA level at onset of chemotherapy (low tPA group < 6.5 mg/L, N = 37 and high tPA group > 6.5 mg/L, N = 23). Survival analysis was repeated for the cut-off of tPA level at 6.5 mg/L and 5.1 mg/L after 3 and 6 cycles. RESULTS: Only subjects with tPA > 6.5 mg/L at onset of chemotherapy had a significantly lower probability of a 5-year survival (34.8% vs. 72.7%, P < 0.006) and lower chance for disease free survival within 5 years (39.3% vs. 72.7%, P < 0.014). tPA < 6.5 mg/L plasma level evaluated at onset of chemotherapy was an independent marker of better overall survival (RR = 0.44, 95%CI = 0.19-0.98) but not disease-free survival. CONCLUSIONS: Plasma tPA may serve as a marker of survival if assessed at onset of the first line chemotherapy in patients with ovarian cancer.

Plasminogen Activator Inhibitor Type 1 in Blood at Onset of Chemotherapy Unfavorably Affects Survival in Primary Ovarian Cancer.

Plasminogen activator inhibitor type 1 (PAI-1) belongs to the family of the plasminogen activator system. PAI-1 stimulates fibrinolysis and also promotes tumor progression. The aim of this study was to evaluate the prognostic value of blood plasma PAI-1 content in patients with epithelial ovarian cancer who start the first-line chemotherapy. PAI-1 content was measured in the blood of 61 patients with epithelial ovarian cancer at onset of first-line chemotherapy. The patients were further stratified into the low PAI-1 group (≤20 ng/mL; 33 patients) and the high PAI-1 group (>20 ng/mL; 28 patients). We found that the greater plasma PAI-1 content was associated with a significantly lower probability of a 5-year-long survival compared to that when PAI-I content was lower (45.5% vs. 69.5%, respectively; p = 0.04). However, the risk of cancer recurrence within 5 years failed to differ appreciably. A multivariate analysis revealed that the lower PAI-1 plasma content was an independent factor of longer overall survival (death risk ratio of 0.36, 95%CI = 0.16-0.79; p < 0.01). We conclude that PAI-1 is yet another biomarker of survival in patients with ovarian cancer.

Peroxiredoxin-5 is a negative survival predictor in ovarian cancer.

OBJECTIVES: Peroxiredoxins (PRDXs) constitute a family of antioxidant enzymes which are also involved in the process of carcinogenesis. They are composed of six identified isoforms (PRDX-1-6) and are supposed to play different roles in tumor progression, depending on type of cancer and member of the PRDX family. The aim of the study was to assess the prog- nostic value of PRDXs in ovarian cancer. MATERIAL AND METHODS: a dataset of patients with ovarian cancer from The Cancer Genome Atlas was analyzed. Expression of PRDX-1 to 6 mRNA was evaluated in 260 samples. The prognostic value of PRDXs was assessed using the Cox regression model which included the following clinical and pathological data: age, clinical stage, tumor grade, and residual disease. RESULTS: Within the PRDXs family, only higher expression of PRDX-5 was associated with worse overall survival both, in unselected patients and > 50-year-olds. PRDX-5 expression and residual disease were independent negative prognostic factors of patient survival. CONCLUSIONS: PRDX-5 is a negative predictor of survival in ovarian cancer.

Magnetic resonance diffusion-weighted imaging in diagnostics of primary fallopian tube carcinoma - is it useful?

PURPOSE: Primary fallopian tube carcinoma (PFTC) is the rarest form of female genital malignancy. The imaging applied for suspected adnexal masses includes transvaginal ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI), but the vast majority of PFTC is recognised intraoperatively. MATERIAL AND METHODS: The study group consisted of seven women with postoperatively histopathological diagnosis of PFTC. To recognise characteristic findings for PFTC, retrospective analysis of preoperative MRI was performed. All patients underwent MRI of the pelvis and abdomen using a 1.5T MR system. Based on the results of the above imaging, suspected adnexal masses were recognised. MRI protocol contained T2-weighted images, fat-suppressed T2-weighted, T2-TIRM, DW EPI, pre- and postcontrast dynamic 3D T1 GRE in transverse orientation, with diffusion weightings of 0, 50, 100, 150, 200, 400, 800, and 1200 s/mm2. Regions of interest were outlined by a radiologist, who documented the character of adnexal masses on diffusion-weighted (DW) images and apparent diffusion coefficient (ADC) maps. RESULTS: In all seven patients with PFTC unilateral tumour was found. On all DW images (with ß values of 0, 50, 100, 150, 200, 400, 800, and 1200 s/mm2) the mean signal intensities of solid parts of tumour were significantly higher than the mean signal intensities of normal ovarian tissue (p = 0.0001). There were no statistically significant differences between eight ß values applied for ADC calculations. CONCLUSIONS: Preoperative diagnostics of PFTC is difficult and mainly based on morphological features. Previous research did not show characteristics of PFTC in post-contrast dynamic imaging. In our material a clear increasing of signal intensity in DW imaging occurred independently of the ß value.

Potentialization of N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) cytotoxic activity by 2-(1-adamantylamino)-6-methylpyridine (AdAMP) in human ovarian cancer cells.

OBJECTIVES: TNF is one of the key cytokines involved in cancer development. TNF signaling can result in both stimulating and inhibitory signals that can result in opposite biological effects in cancerogenesis. 2-(1-adamantylamino)-6-methylpyridine (AdAMP) enhances TNF secretion whereas N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) is a NF-κB inhibitor potentially stimulating proapoptotic TNF signals. The aim of the study was to assess the effect of TPCK in combination with AdAMP on human ovarian cells. MATERIAL AND METHODS: CAOV-1 human ovarian cell line was incubated with TPCK and AdAMP for 24 hours. The cytotoxic effect was evaluated in a crystal violet assay. A monoclonal antibody against TNF, Infliximab, was added to examine the possible mechanism of interactions. RESULTS: Depending on concentration, AdAMP potentialized cytotoxic activity of TPCK or had a synergistic effect with TPCK. Infliximab did not reverse cytotoxicity of AdAMP and TPCK and in some cytotoxic and non-cytotoxic concentrations even enhanced their cytotoxicity. CONCLUSIONS: AdAMP and TPCK cytotoxicity seems to be dependent on TNF signaling, however, the exact mechanism of interactions remains unclear.

Results of optimal debulking surgery with bowel resection in patients with advanced ovarian cancer.

BACKGROUND: The surgical treatment of patients with advanced-stage ovarian cancer is based on maximal cytoreduction with widening the debulking on the extra-ovarian tissues and infiltrated organs. The purpose of the study was to assess the outcome after optimal cytoreduction with partial bowel resection and to find the risk factors of relapse. Another goal was the quantitative and qualitative assessment of intra- and postoperative complications in the studied group. METHODS: The analysis of debulking procedures with intestinal resection and postoperative period in 33 ovarian cancer patients, The International Federation of Gynecology and Obstetrics (FIGO) stages III and IV, was performed. RESULTS: The optimal cytoreduction defined as less than 1.0 cm residual disease was achieved in all patients including the following: 26 patients (78.8%) with no macroscopic residual disease, 4 patients (12.1%) with the largest residual tumor less than 0.5, and 3 patients (9.1%) with 0.5 cm to less than 1.0 cm residual disease. The rectosigmoid resection was the most common surgical procedure (n = 27). The risk of relapse was significantly higher in subjects who had the macroscopic residual tumor left during the primary operation (57.1 vs. 11.5%, P = 0.035). A primary bowel tumor size was another predictor of relapse. The maximum tumor diameter was significantly larger (14.9 ± 6.7 cm vs. 10.3 ± 4.7 cm, P = 0.047) in patients who developed the relapse. CONCLUSIONS: As presented in the article, our outcomes and other authors' observations indicate that debulking surgery with bowel resection in patients with advanced ovarian cancer brings good results. Complications connected with bowel surgery are to be accepted. The interesting thing is that a primary bowel tumor size was a predictor of relapse.

[Splenectomy as a part of debulking surgery in patients with advanced ovarian cancer]. / Splenektomia jako czesc operacji cytoredukcyjnej u pacjentek z zaawansowanym rakiem jajnika.

OBJECTIVES: The aim of the study was the assessment of perioperative complications in patients with advanced ovarian cancer who underwent splenectomy to achieve optimal debulking. MATERIAL AND METHODS: We analyzed eight debulking procedures with splenectomy and the postoperative period in ovarian cancer patients, FIGO stage III/B-IV. Preoperative diagnostics included multidetector computed tomography (MDCT) or diffusion-weighted echo-planar magnetic resonance (MR-DWI). The following factors were analyzed: size of the removed tumor, size of remains left, blood loss, packed red blood cell transfusion, quantity and reason for reoperations, pancreatic amylase concentrations in the drainage fluid, wound infection, fever over 38 degrees C, and length of hospitalization. RESULTS: Complete debulking was achieved in 8 patients, including 5 cases with no macroscopic residual lesions and 3 patients with lesion diameter of < 10 mm. Median operative time was 175 min. There was one case of reoperation caused by perforation of the stomach wall (histologically confirmed stress ulcer). Median blood loss was 1050 ml and the rate of packed red blood cells transfusion was 75%. Elevated amylase levels in the drainage fluid was noted in 6 patients. Amylase concentration was greater than 5 times the normal serum value during the first postoperative day. After postoperative day 3 it was lower than normal serum range. There were no cases of postoperative fever wound infections, or deaths. The length of hospitalization was 6 days. CONCLUSIONS: Splenectomy as a part of cytoreductive surgery for advanced ovarian cancer may contribute to achieving complete debulking and bring benefits, especially in cases with no macroscopic residual disease. The risk of intra- and postoperative complications related to splenectomy seems to be acceptable.

Risk factors of abnormal carbohydrate metabolism after pregnancy complicated by gestational diabetes mellitus.

OBJECTIVE: In gestational diabetes mellitus (GDM) abnormal glucose metabolism normalizes soon after delivery. However, the history of GDM predisposes to carbohydrate intolerance in the future. The aim of the study was to explore risk factors and to evaluate risk of glucose intolerance and diabetes mellitus in women with a history of GDM. METHODS: 155 patients entered this case-control study. Participants fulfilled the inclusion criteria: a history of GDM, perinatal care in the study center. Medical and family history and laboratory findings were analyzed. Oral glucose tolerance test (OGTT) was performed. RESULTS: 18.1% of patients presented impaired fasting glucose during the study, 20% presented impaired glucose tolerance and 23.2% presented diabetes mellitus. Gestational age at diagnosis of GDM, the results of OGTT during pregnancy, serum HbA1c concentration at 2nd and 3rd trimester, serum fructosamine concentration, symptoms of diabetic fetopathy in the neonate, the need for insulin therapy after delivery, maternal age at diagnosis of GDM and maternal body mass index before pregnancy were the significant risk factors of impaired glucose tolerance or diabetes in the future. CONCLUSION: GDM increases the risk of diabetes mellitus. Several risk factors of impaired carbohydrate metabolism can be distinguished in patients with a history of GDM.

Synergistic cytotoxic effect of sulindac and pyrrolidine dithiocarbamate against ovarian cancer cells.

Sulindac, a non-steroidal anti-inflammatory drug, suppresses carcinogenesis and inhibits growth of tumor cells. Pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, has been also identified as a potential anti-neoplastic agent. We hypothesized that combination of sulindac and PDTC could result in augmentation of cytotoxicity against ovarian cancer cells. The effect of sulindac and PDTC was examined on several ovarian cancer lines. Tumor cell viability was assessed using the MTT assay. Annexin-V/PI staining was used to detect apoptosis, cell cycle distribution was analyzed in FACS, and expression of cellular proteins was detected by western blotting. Incubation of OVA-14, OVP-10 and CAOV-1 ovarian cancer cells with sulindac and PDTC resulted in significantly greater inhibition of cell viability compared to either compound alone. In a model of OVA-14 cells it was evident that this effect was not related to the expression of COX enzymes since both active (sulindac sulfide) and inactive (sulindac) in vitro compounds affected the growth of tumor cells to a similar extent and synergized in cytotoxicity with PDTC. Combination of sulindac and PDTC lead to G0 arrest and massive apoptosis in co-treated cultures. Western blotting analysis argued for induction of the mitochondrial apoptotic pathway. These data demonstrate the synergistic cytotoxic effect of sulindac and PDTC on ovarian cancer cells through apoptosis and cell cycle arrest and prompt to test the efficacy of this combination in animal models.

[Antitumor effects of sulindac in ovarian cell cultures]. / Przeciwnowotworowy efekt sulindaku w hodowlach komórek raka jajnika.

OBJECTIVE: The purpose of our study was to assess susceptibility of cells of various ovarian cell lines on different nonsteroidal anti-inflammatory drugs (NSAIDs). MATERIALS AND METHODS: Cytotoxic effect of NSAIDs was tested using MTT colorimetric assay. RESULTS: Amongst 6 NSAIDs tested: sulindac, sulindac sulfide, sulindac sulfone, acetylsalicylic acid, nimesulide, and rofecoxib, viability of ovarian carcinoma cells was compromised most strongly by sulindac and sulindac sulfide and concerned all the cell lines tested: SKOV-3, MDAH 2774, OVCA-1, and OVP-10. Sulindac sulfone and rofecoxib also displayed some cytotoxic effect during prolonged 72-hour incubation. Other NSAIDs tested: nimesulide and acetylsalicylic acid were devoid of cytotoxic effect on ovarian cancer cells. CONCLUSION: Our results are encourage enough to conduct clinical trials that could allow to draw conclusions regarding potential application of sulindac in the adjuvant treatment of a standard chemotherapy of ovarian cancer.

Successful perinatal outcome in an early onset intrahepatic cholestasis of pregnancy with extremely high serum hepatic function tests.

We report a case of a 21-year-old pregnant woman with an early onset of intrahepatic cholestasis of pregnancy with very high aminotransferases activity and bilirubin concentration. Viral and autoimmune hepatitis, and other possible causes of liver function impairment were excluded. Treatment with ursodeoxycholic acid improved biochemical markers. The patient delivered a healthy female neonate by caesarean section. Neonatal and postoperative courses were uneventful.

Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone.

OBJECTIVE: To compare the influence of vaginal micronized progesterone and oral dydrogesterone supplementation on uteroplacental circulation in early pregnancy that is complicated by threatened abortion. DESIGN: Randomized, parallel group, double-blind, double dummy-controlled study. SETTING: Tertiary care university hospital. PATIENT(S): Fifty-three patients with threatened abortion and a living embryo. INTERVENTION(S): Three hundred milligrams of micronized vaginal progesterone or 30 mg of oral dydrogesterone daily supplementation for 6 weeks, serial transvaginal Doppler ultrasound measurement of pulsatility index, resistance index, and systolic/diastolic ratio of the spiral arteries, the uterine arteries, and the intrachorionic area. MAIN OUTCOME MEASURE(S): Uteroplacental blood flow. RESULT(S): The study demonstrated that vaginal progesterone administration, but not oral dydrogesterone treatment, results in the decrease in the spiral artery pulsatility and resistance index and systolic/diastolic ratio. Insignificant decrease in pulsatility index and resistance index of the uterine artery was observed at >9 weeks and was not associated with treatment regimen. Dydrogesterone treatment was only accompanied by the decrease in the uterine artery systolic/diastolic ratio. CONCLUSION(S): Vaginal progesterone and oral dydrogesterone supplementation have a different influence on the uteroplacental circulation in early pregnancy that is complicated by threatened abortion.

TNF-alpha production-enhancing activity of 2-(1-adamantylamino)-6-methylpyridine (AdAMP) in cultures of human normal and neoplastic cells.

The purpose of this study was to determine the TNF-alpha-stimulatory effect of a novel immunomodulator 2-(1-adamantylamino)-6-methylpyridine (AdAMP) on normal and neoplastic human cells. In a panel of several human ovarian cancer cell lines, almost half of them spontaneously secreted significant amounts of TNF-alpha. When incubated with AdAMP, a 3-fold enhancement of TNF-alpha production by cells was observed. Furthermore, the phorbol myristic acetate ester (PMA)-induced release of TNF-alpha in cultures of U937 cells was increased in the presence of AdAMP. Primary monocytes isolated from peripheral blood did not respond to AdAMP. Although cytokine release was not triggered in human peripheral blood monocytes, AdAMP co-stimulated these cells to produce TNF-alpha and IL-8 during incubation with lipopolysaccharide (LPS). No effect of AdAMP was found on IL-1beta and IL-6 production by monocytes. In cultures of peripheral blood T lymphocytes, AdAMP significantly decreased the adhesion of these cells to matrix proteins in an in vitro assay. The results suggest that AdAMP, as a stimulator of cytokine secretion, may have potential application in tumor therapy.