In-vitro study of the effect of anti-hypertensive drugs on placental hormones and angiogenic proteins synthesis in pre-eclampsia

Antihypertensive drugs lower the maternal blood pressure in pre-eclampsia (PE) by direct or central vasodilatory mechanisms but little is known about the direct effects of these drugs on placental functions

The Imperative for Justiciability of Economic, Social, and Cultural Rights in Post-Civil War Sri Lanka

Between 2015 and 2019 Sri Lanka has been in the process of drafting a new Constitution in the aftermath of the civil war that lasted from 1983 to 2009. In spite of the very high human development in Sri Lanka, public expenditures on education and health as a proportion of the GDP have declined since the 1960s. Besides, it is argued that democracy in Sri Lanka is patronage cum greed based, and hence a case is made for inculcating a merit cum need based democracy for which justiciability of Economic, Social, and Cultural Rights (ESCR) is a sine qua non. Moreover, we argue a case for incorporating ESCR as justiciable rights in the proposed new Constitution not only on its own right but also as a means of durable peacebuilding in the aftermath of a savage civil war

Inflammatory Cytokines in Maternal Circulation and Placenta of Chromosomally Abnormal First Trimester Miscarriages

The impact of abnormal placental karyotype on the inflammatory response within the villous tissue and peripheral circulation of women with miscarriage was evaluated. Villous (n = 38) and venous blood samples (n = 26) were obtained from women with missed miscarriage. Tissue chromosome analysis indicated 23 abnormal and 15 normal karyotypes. Concentration of tumour necrosis factor alpha (TNFα), TNF-R1 and TNF-R2, and interleukin (IL)-10 were measured using flowcytometric bead array in fresh villous homogenate, cultured villous extracts, culture medium, maternal whole blood, and plasma. Plasma TNFα/IL-10 ratios were significantly (P < 0.05) lower in miscarriages with abnormal karyotype. In the abnormal karyotype group, there were significantly higher levels of TNFα (P < 0.01), IL-10 (P < 0.01), TNF-R1 (P < 0.001), and TNF-R2 (P < 0.001) in the villous extracts and culture-conditioned medium compared to normal karyotype group. In miscarriage with abnormal karyotype, there is an exacerbated placental inflammatory response, in contrast to miscarriage of normal karyotype where maternal systemic response is increased

Relationships between TGFβ Proteins and Oxygen Concentrations Inside the First Trimester Human Gestational Sac

In early pregnancy, the O2 gradient between the maternal circulation and the gestational sac tissues modulates trophoblast biological functions. The aim was to evaluate if placental partial pressure of oxygen (PaO2) modulates in vivo synthesis of specific placental proteins inside the first trimester gestational sac. Matched samples of peripheral venous blood, blood from the placental bed (PB), coelomic fluid (CF) and placental tissue were obtained in 37 normal pregnancies at 6–12 weeks gestation. PaO2 was measured in PB and CF using an IRMA blood gas monitor. Inhibin A, activin A, sEng, PlGF, sFlt-1 and free VEGF concentrations were measured in all samples. HSP 70 was measured in placental extracts. ANOVA showed ∼60% increase in PB PaO2 (P = 0.02) between after 10 weeks gestation. Unpaired Student's T-test between two groups (6–9 weeks vs 9–12 weeks) shows a significant increase in MS Activin A (P = 0.001), CF activin A (P<0.001), MS P1GF (P = 0.001), CF PlGF (P<0.001), MS sFLT-1 (P = 0.03), CF sFLT-1 (P = 0.01), HSP 70 in placental extracts (P = 0.04) and a significant decrease in PB inhibin A levels (P<0.001) and PB sFLT-1 (P = 0.02) . Multiple correlation analysis showed a significant negative correlation between PB inhibin A levels and gestation (r = −0.45, P<0.05) and PB PaO2 (r = −0.5, P = 0.008) and also between sFLT-1 and PB PaO2 (P = 0.03). There was a positive correlation (P<0.01) between PlGF, sEng and VEGF levels in the placental extracts. Our results indicate a direct relationship in the early intrauterine PaO2 in vivo and inhibin A and sFLT-1 concentrations confirming our hypothesis that specific placental proteins are regulated by intrauterine O2 tension

Somatic, mood, and vasomotor symptoms at midlife in relation to family structure and household workloads in Sylhet, Bangladesh

The purpose of this study was to test whether the frequencies of vasomotor, somatic, and emotional symptoms at midlife were associated with household composition or workloads. Patrilocal family arrangements are common in Bangladesh and, since mothers-in-law hold a position of power vis-à-vis their daughters-in-law, we hypothesized that living with a mother-in-law would increase the likelihood of symptoms at midlife, while living with a daughter-in-law would decrease likelihood of symptoms. We also hypothesised that women with high levels of household workloads would be more likely to report symptoms associated with midlife. Women aged 35-59 living in Sylhet, Bangladesh, (n=157) participated in interviews and anthropometric measures. Symptom frequencies during the past two weeks were collected. Household workloads were computed as minutes spent in housework, caring for dependents, and cooking. Daily values were multiplied by times per week the activity was carried out. Logistic regression was used to evaluate the association between family composition, workloads, and symptoms. Dizzy spells, nervous tension, lack of energy, aches/stiffness in joints, and trouble sleeping were most frequent. Hot flashes were reported by 46% of participants. Women spent more hours caring for dependents than cooking or doing housework. The likelihood of hot flashes increased with time spent in housework and cooking, with daughters in the household, and with chewing betel nut. Daughters-in-law in the household decreased the likelihood of hot flashes. The likelihood of nervous tension increased with peri-menopausal status, stress, and sons in the household, and decreased with more hours spent caring for dependents. The frequency of somatic symptoms and depressed mood exceeded the frequency of hot flashes. Household composition and workloads were more important than menopausal status in explaining variation in symptom frequencies. After controlling for other variables, the presence of mothers-in-law did not increase the likelihood of reporting symptoms at midlife; however, the presence of a daughter-in-law reduced the likelihood of hot flashes, perhaps because of fewer hours spent on housework and cooking

Religious minority identity associates with stress and psychological health among Muslim and Hindu women in Bangladesh and London

This study examined the association of minority religious identification (Hindu or Muslim) with self-reported stress and psychological symptoms among sedentee and immigrant Bangladeshi women. Women, aged 35-59 (n = 531) were drawn from Sylhet, Bangladesh and London, England. Muslim immigrants in London and Hindu sedentees in Sylhet represented minority religious identities. Muslim sedentees in Sylhet and Londoners of European descent represented majority religious identities. In bivariate analyses, minority religious identity was examined in relation to self-reported measures of stress, nervous tension, and depressed mood. Logistic regression was applied to examine the relationship between these variables while adjusting for marital status, parity, daily walking, and perceived financial comfort. In bivariate analyses, religious minorities reported more stress than religious majorities in all group comparisons (p < .05), and minority Muslims reported more nervous tension and depressed mood than majority Muslims (p < .05). In logistic regression models, minority Muslims had greater odds of high stress than majority Muslims (OR 2.00, 95% CI 1.18-3.39). Minority Muslims had greater odds of stress (OR 3.05, 95% CI 1.51-6.17) and nervous tension (OR 3.37, 95% CI 1.66-6.87) than majority Londoners. Financial comfort reduced odds of stress and symptoms in all models. Socioeconomic situation, immigration history, and minority ethnicity appear to influence the relationship between religious identity and psychosomatic symptoms in Bangladeshi women. Attention to personal and socioeconomic context is important for research examining the association between religion and mental health

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

<div><p>Objective</p><p>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.</p><p>Methods</p><p>Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.</p><p>Results</p><p>Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10^-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10^-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).</p><p>Conclusions</p><p>A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the <i>in vivo</i> pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</p></div