Investigation of antiparasitic activity of ten European tree bark extracts on Toxoplasma gondii and bioguided identification of triterpenes in Alnus glutinosa barks

Toxoplasmosis is a worldwide parasitosis that affects one-third of the population. People at risk, such as immunocompromised patients (AIDS, chemotherapy treatment) or fetuses (maternal-fetal transmission) can develop severe forms of the disease. The antiparasitic activity of extracts of different polarities ( n -heptane, MeOH, MeOH/H 2 O) of ten tree species endemics to temperate regions was investigated against Toxoplasma gondii infection in vitro . Our results showed that the n -heptane extract of the black alder ( Alnus glutinosa ) exhibited a significant antiparasitic activity without any cytotoxicity at the tested concentrations, with an IC 50 of up to 25.08 μg/mL and a selectivity index higher than 3.99. The chemical profiling of this extract revealed triterpenes as major constituents. The ability of commercially available triterpene (betulin, betulinic acid, and betulone) to inhibit the growth of T. gondii was evaluated and showed growth inhibition rates of 44%, 49%, and 99% at 10 μM, respectively.

Literature Review: Transplacental Transmission of COVID-19 and Its Teratological Aspect

Coronavirus disease 2019 (Covid-19) pandemic affects all populations, including pregnant women. Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in pregnancy needs to be a concern because of the risk of transplacental transmission to the fetus and the potential to interfere with fetal development. The objective of this study is to review the transplacental transmission of COVID-19 and the teratological aspects of the event. This article is a literature study. Based on the literature obtained, placental infection, vertical transmission, and fetal infection have been identified in some cases. However, there is still no consistent and enough scientific evidence to show that those condition causes fetal damage or causes congenital anomalies. Virus and host characteristics are thought to explain why SARS-Cov-2 infection has not shown a teratological effect. SARS-CoV-2, similar to severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) infection, does not indicate maternal-fetal transmission. The low-level expression of angiotensin-converting enzyme 2 (ACE2) and S protein priming proteases type II transmembrane serine protease (TMPRSS 2) in the placenta is also considered to be the factor that plays a role in inhibiting the vertical transmission of COVID-19. Adverse outcome of fetal death is more due to pathophysiological conditions of maternal health caused by SARS-CoV-2 infection during gestation.

Role of adipokines in embryo implantation

Embryo implantation is a complex process in which multiple molecules acting together under strict regulation. Studies showed the production of various adipokines and their receptors in the embryo and uterus, where they can influence the maternal-fetal transmission of metabolites and embryo implantation. Therefore, these cytokines have opened a novel area of study in the field of embryo-maternal cross-talk during early pregnancy. In this respect, the involvement of adipokines has been widely reported in the regulation of both physiological and pathological aspects of the implantation process. However, the information about the role of some recently identified adipokines is limited. This review aims to highlight the role of various adipokines in embryo-maternal interactions, endometrial receptivity, and embryo implantation, as well as the underlying molecular mechanisms.

Hofbauer cells and coronavirus disease 2019 (COVID-19) in pregnancy: Molecular pathology analysis of villous macrophages, endothelial cells, and placental findings from 22 placentas infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with and without fetal transmission

Context.– Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can undergo maternal-fetal transmission, heightening interest in the placental pathology findings from this infection. Transplacental SARS-CoV-2 transmission is typically accompanied by chronic histiocytic intervillositis together with necrosis and positivity of syncytiotrophoblast for SARSCoV-2. Hofbauer cells are placental macrophages that have been involved in viral diseases including HIV and Zika virus, but their involvement in SARS-CoV-2 in unknown. Objective.– To determine whether SARS-CoV-2 can extend beyond the syncytiotrophoblast to enter Hofbauer cells, endothelium and other villous stromal cells in infected placentas of liveborn and stillborn infants. Design.– Case-based retrospective analysis by 29 perinatal and molecular pathology specialists of placental findings from a preselected cohort of 22 SARS-CoV-2-infected placentas delivered to pregnant women testing positive for SARS-CoV-2 from 7 countries. Molecular pathology methods were used to investigate viral involvement of Hofbauer cells, villous capillary endothelium, syncytiotrophoblast and other fetal-derived cells. Results.– Chronic histiocytic intervillositis and trophoblast necrosis was present in all 22 placentas (100%). SARS-CoV-2 was identified in Hofbauer cells from 4/22 placentas (18%). Villous capillary endothelial staining was positive in 2/22 cases (9%), both of which also had viral positivity in Hofbauer cells. Syncytiotrophoblast staining occurred in 21/22 placentas (95%). Hofbauer cell hyperplasia was present in 3/22 placentas (14%). In the 7 cases having documented transplacental infection of the fetus, 2 occurred in placentas with Hofbauer cell staining positive for SARS-CoV-2. Conclusions.– SARS-CoV-2 can extend beyond the trophoblast into the villous stroma, involving Hofbauer cells and capillary endothelial cells, in a small number of infected placentas. Most cases of SARS-CoV-2 transplacental fetal infection occur without Hofbauer cell involvement.

SARS-CoV-2 and Placenta: New Insights and Perspectives

The study of SARS-CoV-2 positive pregnant women is of some importance for gynecologists, obstetricians, neonatologists and women themselves. In recent months, new works have tried to clarify what happens at the fetal–placental level in women positive for the virus, and different pathogenesis mechanisms have been proposed. Here, we present the results of a large series of placentas of Coronavirus disease (COVID) positive women, in a reference center for COVID-positive pregnancies, on which we conducted histological, immunohistochemical and electron microscopy investigations. A case–control study was conducted in order to highlight any histopathological alterations attributable to SARS-CoV-2. The prevalence of maternal vascular malperfusion was not significantly different between cases and controls (54.3% vs. 43.7% p = 0.19), whereas the differences with regard to fetal vascular malperfusion (21.1% vs. 4.2% p < 0.001) were significant. More frequent in cases with respect to controls were decidual arteriopathy (40.9% vs. 1.4% p < 0.0001), decidual inflammation (32.4% vs. 0.7% p < 0.0001), perivillous fibrin deposition (36.6% vs. 3.5% p < 0.0001) and fetal vessel thrombi (22.5% vs. 0.7% p < 0.0001). No significant differences in the percentage of terminal villous hyperplasia and chorioamnionitis were observed between the two groups. As the pandemic continues, these studies will become more urgent in order to clarify the possible mechanism of maternal–fetal transmission of the virus.

Molecular Pathology Analysis of SARS-CoV-2 in Syncytiotrophoblast and Hofbauer Cells in Placenta from a Pregnant Woman and Fetus with COVID-19

A small number of neonates delivered to women with SARS-CoV-2 infection have been found to become infected through intrauterine transplacental transmission. These cases are associated with a group of unusual placental pathology abnormalities that include chronic histiocytic intervillositis, syncytiotrophoblast necrosis, and positivity of the syncytiotrophoblast for SARS-CoV-2 antigen or RNA. Hofbauer cells constitute a heterogeneous group of immunologically active macrophages that have been involved in transplacental infections that include such viral agents as Zika virus and human immunodeficiency virus. The role of Hofbauer cells in placental infection with SARS-CoV-2 and maternal-fetal transmission is unknown. This study uses molecular pathology techniques to evaluate the placenta from a neonate infected with SARS-CoV-2 via the transplacental route to determine whether Hofbauer cells have evidence of infection. We found that the placenta had chronic histiocytic intervillositis and syncytiotrophoblast necrosis, with the syncytiotrophoblast demonstrating intense positive staining for SARS-CoV-2. Immunohistochemistry using the macrophage marker CD163, SARS-CoV-2 nucleocapsid protein, and double staining for SARS-CoV-2 with RNAscope and anti-CD163 antibody, revealed that no demonstrable virus could be identified within Hofbauer cells, despite these cells closely approaching the basement membrane zone of the infected trophoblast. Unlike some other viruses, there was no evidence from this transmitting placenta for infection of Hofbauer cells with SARS-CoV-2.

Karakteristik Ibu Hamil dengan Covid-19 dan Luaran Persalinannya di Rumah Sakit Kasih Ibu Surakarta

Background: Kasih Ibu Hospital as one of the referral hospitals for COVID-19 in Surakarta City, Central Java, had treated 1333 confirmed cases of COVID-19, including among them obstetric patients with COVID-19. Pregnant women are considered to be more susceptible to COVID-19 infection than those who are not pregnant and it is feared that it will result in unfavorable conditions for both mother and fetus. Until now, research on pregnant women with COVID-19 in Indonesia is still very few and limited.Objective: To provide an overview of the characteristics of maternal and neonatal outcomes at the Kasih Ibu Hospital Surakarta.Method: Data were collected from medical records of pregnant women confirmed with COVID-19 who gave birth at the Kasih Ibu Hospital, Surakarta. Data was presented in the form of a distribution based on maternal age, parity, gestational age, complication of delivery, typical complaints of COVID-19 in mothers, birth weight of infant, infant APGAR score, and infant COVID-19 status.Results and Discussion: A total of 62 pregnant women confirmed with COVID-19 gave birth at the Kasih Ibu Hospital Surakarta by sectio caesarean procedure. Of all pregnant women, most were asymptomatic and had mild symptoms, only 3.2% had moderate symptoms and no severe or critical symptoms were found. Out of 20 out of 62 babies born (32%) confirmed with COVID-19. All babies were born with good APGAR score and 4 babies were found with low birth weight, one of whom also had hypospadias.Conclusions: Further research is needed regarding the maternal-fetal transmission of COVID-19. Keywords: COVID-19; neonates; pregnancy

Management of SARS-CoV-2 infection in pregnancy

The SARS-CoV-2 infection, which originated from a market in Wuhan, China, spread rapidly, so on March 11, 2020, the WHO decreed that the outbreak became a pandemic. Over 90% of people infected with SARS-CoV-2 are either asymptomatic or have mild symptoms. However, there are cases that develop severe forms of the disease, from acute respiratory distress syndrome to septic shock with multiorgan failure and exitus. However, reports of pregnant women diagnosed with Covid-19 are low. Changes in the maternal organism in pregnancy, including immunity, respiratory system and hypercoagulability, but also various comorbidities, could be a risk factor for pregnant women to develop complications associated with COVID-19, with increased morbidity and mortality compared to the general population. The effects of SARS-CoV-2 infection on pregnancy are not sufficiently understood, nor are the effects of pregnancy on disease progression. Although the existence of the virus has been shown in biological samples such as the placenta, umbilical cord, or amniotic fluid, the maternal and fetal effects of the virus are not well known. Recent studies confirm the possibility of intrauterine maternal-fetal transmission of the virus, but also of specific antibodies. The possibility of infection by breastfeeding is not yet sufficiently investigated. We looked for data on the treatment and prophylaxis of SARS-CoV-2 infection during pregnancy, as well as on the choice of the optimal birth pathway in these women. The aim of this paper was to conduct a systematic review of the literature on pregnancy and birth management in patients infected with SARS-CoV-2 that could lead to an improvement in the quality of their medical care.

Spontaneous Abortion and Chikungunya Infection: Pathological Findings

Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40–50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.