Evaluation of placental bed uterine in L-NAME-induced early-onset preeclampsia (EO-PE) like the rat model.

Objective: Preeclampsia (PE) is the leading cause of maternal death worldwide and is associated with long-term morbidity in both mothers and newborns. Animal modeling is considered a functional source for understanding PE pathogenesis, diagnostic standards, and therapeutic approaches. Materials and Methods: This study aimed to demonstrate and evaluate the use of N-nitro-L-arginine methyl ester (L-NAME) in a Wistar rat model under conditions similar to PE. A total of 12 rats were divided into 4 groups, each consisting of 3 members, including the pregnant control group and treatment groups administered low-dose (PE 25 mg/kg L-NAME/day), medium-dose (PE 50 mg/kg L-NAME/day), and high-dose L-NAME (PE 75 mg/kg L-NAME/day) L-NAME from gestational day 4 to 19. Measurements included blood pressure, creatinine, and proteinuria levels, placental histological changes, and placental tissue hypoxia-inducible factor 1-alpha, and plasma endothelial nitric oxide synthase levels. Results: The results showed that intervention with L-NAME at 75 mg/kg body weight/day (PE3) induced PE earlier than that with 50 mg/kg body weight/day L-NAME. Conclusion: The model conditions also support further research into PE pathogenesis.

Mesenchymal stem cell secretome ameliorates over-expression of soluble fms-like tyrosine kinase-1 (sFlt-1) and fetal growth restriction (FGR) in animal SLE model.

INTRODUCTION: In the near future, stem cell research may lead to several major therapeutic innovations in medical practice. Secretome, a "by-product" of stem cell line cultures, has many advantages. Its easiness of storage, usage, and fast direct effect are some of those to consider. Fetal growth restriction (FGR) remains one of the significant challenges in maternal-fetal and neonatal medicine. Placentation failure is one of the most profound causal and is often related to increasing sFlt-1 in early pregnancy. This study aimed to investigate hUC-MSC secretome in ameliorating sFlt-1 and how to improve outcomes in preventing FGR in an animal model. MATERIALS AND METHODS: Pristane-induced systemic lupus erythematosus (SLE) in a mouse model was used to represent placentation failure and its consequences. Twenty-one mice were randomized into three groups: (I) normal pregnancy, (II) SLE, and (III) SLE with secretome treatment. Pristane was administered in all Groups four weeks prior mating period. Secretome was derived from human umbilical cord mesenchymal stem cells (hUC-MSC) conditioned medium on the 3rd and 4th passage, around day-21 until day-28 from the start of culturing process. Mesenchymal stem cell was characterized using flow cytometry for CD105+, CD90+, and CD73+ surface antigen markers. Immunohistochemistry anlysis by using Remmele's Immunoreactive Score (IRS) was used to quantify the placental sFlt-1 expression in each group. Birth weight and length were analyzed as the secondary outcome. The number of fetuses obtained was also calculated for pregnancy loss comparison between Groups. RESULTS: The administration of secretome of hUC-MSC was found to lower the expression of the placental sFlt-1 significantly in the pristane SLE animal model (10.30 ± 1.40 vs. 4.98 ± 2.57; p < 0.001) to a level seen in normal mouse pregnancies in Group I (3.88 ± 0.49; p = 0.159). Secretome also had a significant effect on preventing fetal growth restriction in the pristane SLE mouse model (birth weight: 354.29 ± 80.76 mg vs. 550 ± 64.03 mg; p < 0.001 and birth length: 14.43 ± 1.27 mm vs. 19.00 ± 1.41 mm), comparable to the birth weight and length of the normal pregnancy in Group I (540.29 ± 75.47 mg and 18.14 ± 1.34 mm, p = 0.808 and = 0.719). Secretome administration also showed a potential action to prevent high number of pregnancy loss as the number of fetuses obtained could be similar to those of mice in the normal pregnant Group (7.71 ± 1.11 vs. 7.86 ± 1.06; p = 0.794). CONCLUSIONS: Administration of secretome lowers sFlt-1 expression in placenta, improves fetal growth, and prevents pregnancy loss in a mouse SLE model.

INOVASIA Study: A Multicenter Randomized Clinical Trial of Pravastatin to Prevent Preeclampsia in High-Risk Patients.

OBJECTIVE: Our objective was to determine if treatment with pravastatin prevents preeclampsia in pregnant patients at risk of preeclampsia. MATERIAL AND METHODS: The study was performed in four major tertiary hospitals in Surabaya, Bandung, and Makassar between 2017 and 2021. Pregnant women at high risk of developing preeclampsia were recruited and randomized into an intervention group and control group. The control group received low-dose aspirin (80 mg) and calcium (1 g) daily, while the intervention group received additional pravastatin (20 mg twice daily) starting from 14 to 20 weeks' gestation until delivery. The pregnancy was followed until delivery, and the clinical data were collected. The primary outcome was the occurrence of preeclampsia. RESULT: A total of 173 people participated in this study, including 86 in the control group and 87 in the pravastatin group. The pravastatin group had a significantly lower rate of preterm preeclampsia (13.8 vs. 26.7%; p = 0.034; odds ratio [OR] = 0.034, 95% confidence interval [CI] = 0.202-0.905) and preterm birth (16.1 vs. 36%; p = 0.003; OR = 0.340, 95% CI = 0.165-0.7), mostly indicated preterm birth. Preeclampsia occurred later in the pravastatin group than in the control group (36.39 + 2.32 vs. 34.89 + 3.38 weeks, p = 0.048). Overall, the pravastatin group showed better perinatal outcomes. Neonates with low Apgar scores (<7) at 1 minute (5.7 vs. 25.6%, p = 0.000) and 5 minutes (2.3 vs. 25.6%, p = 0.028) were significantly less common in the pravastatin group. Additionally, the rate of low birthweight babies (<2,500 g) was lower in the pravastatin group (27.6 vs. 40.7%; p = 0.069). CONCLUSION: Pravastatin (20 mg bid) significantly reduces the risk of preterm preeclampsia and preterm birth in women at a high risk of developing preeclampsia. KEY POINTS: · This is an open-label multicenter RCT to evaluate pravastatin effect to prevent preeclampsia.. · Pravastatin significantly reduces the risk of preterm preeclampsia (PE) and preterm birth in high risk PE women.. · Pravastatin had a beneficial effect on perinatal outcomes, including Apgar scores and birth weight..

Electroacupuncture to Improve Endometrial Receptivity and Folliculogenesis in Polycystic Ovary Syndrome.

Objective: Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting folliculogenesis and endometrial receptivity. PCOS causes low fertility due to failures in folliculogenesis and ovulation. Electroacupuncture (EA) may help improve folliculogenesis and endometrial receptivity. EA can decrease tonic activity in the sympathetic vasoconstrictor pathway to the uterus. This study was conducted to determine the effect of the addition of EA therapy on folliculogenesis and endometrial receptivity in women with PCOS. Materials and Methods: This case-control study was conducted at the Dr. Moewardi General Hospital, in Jawa Tengah, Indonesia. The subjects were women with PCOS, ages 20-45, who were infertile. They were divided into a control group (17 women) and an experimental group (17 women). The control group received letrozole therapy, and the experimental group received EA + letrozole therapy. Folliculogenesis is determined by measuring the growth of follicle diameter on days 2, 6, 8, 10, and 12 of the menstrual cycle. Endometrial receptivity is determined by resistance index (RI) and pulsatility index (PI) examinations on days 19 and 21; endometrial thickness is measured on day 12. Results: There was a significant difference in folliculogenesis on days 2, 6, 8, 10, and 12. Folliculogenesis with letrozole versus EA + letrozole, respectively, were: day 2 = 5.59 ± 1.06 versus 7.01 ± 1.53, P = 0.004; day 6 = 6.71 ± 1.59 versus 9.11 ± 1.23, P < 0.001; day 8 = 9.51 ± 2.68 versus 12.44 ± 1.49, P < 0.001; day 10 = 11.30 ± 3.08 versus 15.53 ± 2.34, P < 0.001; and day 12 = 13.92 ± 3.61 versus 19.86 ± 0.75, P < 0.001. RI value with letrozole versus EA + letrozole were, respectively, day 19 = 0.91 ± 0.07 versus 0.88 ± 0.07, P = 0.150; day 21 = 0.88 ± 0.07 versus 0.79 ± 0.09, P < 0.001. PI value with letrozole versus EA + letrozole were respectively, day 19 = 3.00 ± 0.89 versus 2.30 ± 0.65, P = 0.009; and day 21 = 2.72 ± 0.88 versus 2.02 ± 0.55, P = 0.009. Endometrial thickness with letrozole versus EA + letrozole were, respectively, day 12 = 6.95 ± 1.82 versus 8.22 ± 1.76, P = 0.005. Conclusions: The addition of EA to letrozole therapy improved folliculogenesis, RI, PI, and endometrial thickness in patients with PCOS. Further studies are needed to gain a better understanding of the dosage and timing of this therapy and its potential synergy with other current treatments.

Electroacupuncture Effect on Polycystic Ovary Syndrome to Improve Oocytes' Growth.

Objective: Polycystic ovary syndrome (PCOS) is a condition of anovulation causing infertility. Many kinds of therapy have been used to treat PCOS. However, the results have not been satisfactory. Acupuncture is a trusted way to repair the reproductive system. Yet, there is not enough evidence of the effectiveness of acupuncture to induce ovulation or to treat infertility in patients who have PCOS. The objectives of this study were to find out how successfully electroacupuncture (EA) could complete conventional therapy for patients with PCOS-related infertility, to analyze the effect of EA on these patients, and if EA could repair folliculogenesis to create quality oocytes so that these patients could become pregnant. Materials and Methods: A case controlled study was conducted in Sekar Dr. Moewardi General Hospital, Surakarta, Central Java, Indonesia. There were 44 patients with PCOS who were included according to Rotterdam criteria and exclusion criteria. The patients' characteristics studied were age, height, weight, and duration of infertility. Subjects were divided randomly into 2 groups (22 subjects in a PCOS+Lifestyle Management as a control group and 22 subjects in a PCOS Lifestyle Management+EA case group. EA was performed for 15 minutes twice per week for a total of 12 sessions. The main outcome measure was transvaginal ultrasonographic detection of follicle size in ovulation on days 2, 6, 8, 10 and 12, starting from the first day of each patient's last menstruation. Results: There were significant differences in follicle growth on days 2, 6, 8, 10, and 12. Follicle growth in the PCOS+Lifestyle Management group versus the PCOS Lifestyle Management+EA group was, respectively, on day 2: 5.59 ± 0.73 versus 6.45 ± 1.22, p = 0.012; on day 6: 7.40 ± 1.14 versus 9.45 ± 1.94, p = 0.012; on day 8: 9.50 ± 1.40, versus 11.63 ± 2.25, p = 0.002; on day 10: 11.59 ± 1.36, versus 13.77 ± 2.22, p = 0.001, and on day 12: 13.72 ± 1.20; versus 16.13 ± 2.43; p = 0.001. Conclusions: EA improves oocytes' growth in patients with PCOS.

COMPARISON OF MULTIPLEX SINGLE ROUND PCR AND MICROSCOPY IN DIAGNOSIS OF AMOEBIASIS.

BACKGROUND: Amoebiasis, the cause of dysentery and extra-intestinal abscesses, now becomes second fatal parasitic disease in the world. As routine microscopic diagnosis cannot differentiate causative Entamoeba histolytica from non-pathogenic E. dispar and E. moshkovskii, better diagnosis has to be searched. MATERIALS AND METHODS: Multiplex single round PCR was tested and compared with results of microscopy of wet preparation on 30 samples of diarrheic stools and extra intestinal lesions from amoebiasis suspected patients. RESULTS: Microscopy examination showed that 21 (70%) of the samples were positive for E. histolytica/E. dispar/E. moshkovskii complex and 18 (86%) of them contained hematophagous trophozoites. Multiplex single round PCR showed 12 positive results, from which seven were positive for E. histolytica, two were positive for E. moshkovskii, and three showed mixed of E. histolytica and E. moshkovskii. No samples were positive for E. dispar. High positive rate of microscopy might be related with highly suspected amoebiasis cases, while lower positive PCR might be caused by low parasite density and time-related trophozoite disintegration. CONCLUSION: The study showed that multiplex single-round PCR is a valuable diagnostic tool for species differentiation, but cannot replace microscopy in the diagnosis of amoebiasis because of its low sensitivity and impossibility to discriminate the form of E. histolytica and whether it is in the disease-causing stage, while microscopic examination is capable to demonstrate the presence of hematophagous trophozoites that indicates it is invasive and at the disease-causing stage of E. histolytica.

The effect of logotherapy on the expressions of cortisol, HSP70, Beck Depression Inventory (BDI), and pain scales in advanced cervical cancer patients.

This study aims to analyze the effect of logotherapy on the expression of cortisol, HSP70, and the Beck Depression Inventory (BDI) and to conduct pain assessments in advanced cervical cancer patients. We carried out this research through pretest-posttest control-group design on the expression of cortisol, HSP70, the BDI, and pain scales after a patient receives logotherapy treatment. Based on a comparative test conducted with the two groups before the treatment, there is no significant difference (p > .05). There is a significant difference (p < .05) after the treatment, however, except for on HSP70. This study suggests that logotherapy affects the expression of cortisol, BDI, and pain scales in advanced cervical cancer patients, and that it does not affect the expression of HSP70.

Recombinant vascular endothelial growth factor 121 injection for the prevention of fetal growth restriction in a preeclampsia mouse model.

AIM: To discover the potential role of recombinant VEGF121 (rVEGF121) injection for the prevention of fetal growth restriction in a preeclampsia (PE) mouse model (Mus musculus). SUBJECTS AND METHODS: This is an experimental study of 30 pregnant mice that were randomly divided into three groups: normal, PE, and PE with rVEGF121 injection. The PE mouse model was created by injecting anti Qa-2 10 ng iv, which is deleterious to Qa-2 expression (homologous to HLA-G), from the first to the fourth day of gestation. PE was validated by measuring serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor(PIGF) and also by kidney histopathology. Recombinant VEGF121 was given on the ninth day until the 11th day of pregnancy; mice were terminated on the 16th day. Fetal weights were acquired with a Denver analytical balance. Serum levels of sFlt-1 and PlGF were measured using enzyme-linked immunosorbent assay (ELISA). The data were statistically analyzed via analysis of variance (ANOVA). RESULTS: On average, fetal birth weight was 0.7150 g in the normal group, 0.4936 g in the PE group, and 0.6768 g in the PE with rVEGF121 injection group. ANOVA showed significant growth restriction in the PE group (P=0.006), confirming the use of anti Qa-2 as a suitable PE model. Kidney histopathology results, sFlt-1 levels, and PlGF levels also demonstrated that anti Qa-2 consistently conferred hallmarks of PE in mice. Vascular endothelial growth factor (VEGF) injection prevented fetal growth restriction; comparable fetal weights were observed between the PE model with VEGF treatment and the normal group (P=0.610) but differed from the untreated PE group (P=0.021). CONCLUSIONS: Injection of rVEGF121 has the potential to prevent fetal growth restriction in a newly proposed PE mouse model.