Impact of stress reduction instructions on stress and cortisol levels during pregnancy

This pilot study examined whether giving stress reduction (SR) instructions to pregnant women would be effective in regulating stress, mood, and cortisol levels during pregnancy. Forty-one predominantly low-income Latina women, receiving prenatal services at a public county hospital, completed measures of stress and mood (depressive symptoms, positive and negative affect) and provided morning and evening saliva samples to measure cortisol prior to and after receiving SR instructions. We hypothesized that adherence to these SR instructions would result in lower levels of stress, negative mood states, and cortisol levels when compared to baseline values. Repeated measures ANOVA analyses demonstrated significantly lower levels of stress (P < 0.001), lower symptoms of depression and negative affect (P < 0.001), and lower levels of morning cortisol (P = 0.01) under the SR condition, compared to baseline. Health behaviors that were engaged in during the SR condition and implications for prenatal health interventions are discussed.     

Pharmacological blood pressure lowering in the older hypertensive patients may lead to cognitive impairment by altering neurovascular coupling

The link between both high and low blood pressure (BP) levels and cognitive impairment in later life has been reported in several studies. The mechanisms for this link are unclear but may be related to abnormalities in brain blood flow control. Our previous work has shown that cerebral autoregulation (CA) is unimpaired in both young and older people with hypertension at rest and that ageing does not appear to impact on the increase in the cerebral blood flow response to increased metabolic demand of neurones and other cells of the nervous system due to heightened activity (Neurovascular Coupling, NVC). Nonetheless, it is plausible that NVC efficiency becomes compromised during mental activity in older people with hypertension and that certain classes of anti-hypertensive agents may exacerbate the situation by reducing both NVC and CA contributing to cognitive decline. Such a link would have a major impact on prescribing patterns for anti-hypertensive medication.     

Correlation of plasma hormone levels and peripheral circulating lymphocyte subpopulations during human pregnancy

Using monoclonal antibodies (OKT3, OKT4, OKT8) peripheral blood lymphocyte subsets were determined in 40 normal primiparous pregnant women and compared with those of 31 nonpregnant controls. In pregnant women plasma concentrations of estradiol, progesterone, human placental lactogen (HPL), beta subunit of human chorionic gonadotropin (beta HCG), and alpha-fetoprotein were measured by means of radioimmunoassay. We studied if correlations between peripheral lymphocyte subsets and plasma hormone levels might exist. We observed in pregnant women from 10 to 40 wk of amenorrhea a decrease in the percentage of OKT3 and OKT8 cells, and during the course of pregnancy an increase in the percentage of OKT4 cells. This increase inversely correlated with plasma beta HCG levels and directly correlated with plasma HPL levels.     

Changes in systemic type 1 and type 2 immunity in normal pregnancy and pre-eclampsia may be mediated by natural killer cells

A bias of T cell immunity towards type 2 (Th2) is thought to be critical for normal pregnancy. Pathological pregnancies, such as pre-eclampsia, are characterised by cell-mediated (Th1) immune dominance. The Th1/Th2 paradigm, however, is too simplistic. Normal pregnancy is associated with a systemic inflammatory response which increases throughout gestation. This inflammatory response is exaggerated in pre-eclampsia, a syndrome of the third trimester. T helper (Th) cells are considered the primary mediators of these altered immune responses, and other T cells, i.e. T cytotoxic (Tc) cells, and lymphocytes of the innate immune system, i.e. natural killer (NK) and NKT cells, have been largely disregarded. In this study, we have used novel pan type 1 (IL-18 receptor) and pan type 2 (ST2L) lymphocyte function markers in four-colour flow cytometry to broadly characterise peripheral blood lymphocyte populations from non-pregnant, normal pregnant and pre-eclamptic women. There were no changes in the Th1/Th2 or Tc1/Tc2 cell ratios between the three groups; however, the NK1/NK2 and NKT1/NKT2 cell ratios were significantly decreased in normal pregnancy compared with non-pregnant (p <0.001 and p <0.01, respectively) and pre-eclamptic women (p <0.05). These results confirm that immunoregulation occurs in pregnancy, but suggest a dominant role of the innate rather than the adaptive immune system.     

妊娠早期母体细胞免疫功能的变化与雌二醇和皮质醇水平之间的关系

胎儿作为同种半异体移植物如何在母亲体内生长发育而不被排斥,使妊娠得以维持下去,其机制十分复杂。近年来的研究发现,T淋巴细胞及其亚群对胚胎在母体内免遭排斥及正常发育起着重要的免疫调节作用。最近研究表明,妊娠期间激素水平的变化是母体免疫反应发生转化的重要因素之一[1~2],但妊娠早期母体的激素变化与免疫功能变化之间的确切关系目前尚不十分清楚。为此,本研究检测妊娠早期母体中T细胞亚群CD4 和CD8 细胞的数量、细胞因子干扰素-γ(interferon-,γIFN-γ)和白介素-4(interleukin-4,IL-4)的浓度以及它们与雌二醇和皮质醇激素之…     

Variations in anxiety levels during pregnancy and psychosocial factors in relation to obstetric complications

Patterns of variation of state and trait anxiety during pregnancy and after delivery were studied prospectively in relation to some obstetrical and neonatal disturbances. Specific pregnancy anxiety, social support, and coping style were also evaluated. State anxiety in the 3rd month was significantly higher among women with obstetric complications and oscillated during the course of pregnancy, with significantly higher levels in the 3rd and 9th months. No such variations were found in the women with uncomplicated pregnancies. None of the other psychosocial variables examined were related to complications.     

A longitudinal study of maternal plasma insulin-like growth factor binding protein-1 concentrations during normal pregnancy and pregnancies complicated by pre-eclampsia

Insulin-like growth factor binding protein-1 (IGFBP-1) is synthesized by the decidual stroma, and is thought to act locally to inhibit IGF activity and so limit trophoblast invasion. Cross-sectional studies have reported conflicting data on maternal circulating concentrations of IGFBP-1 in early pregnancy before the development of pre-eclampsia. A longitudinal study was performed in 10 women who went on to develop pre-eclampsia and a group of 12 normal pregnant controls, chosen to be similar for maternal age, booking body mass index (BMI) and gestational age. Maternal IGFBP-1 concentrations were measured in plasma obtained at 16, 20, 24, 28, 32 and 36 weeks. Plasma IGFBP-1 concentrations were unchanged over this period in normal pregnancy. In contrast, the concentrations in women who developed pre-eclampsia increased progressively. At 16, 20, and 24 weeks the concentrations were significantly lower compared to normal pregnancy, at 28 and 32 weeks, similar, but by 36 weeks the concentrations were significantly greater than the normal controls. The data show that circulating IGFBP-1 concentrations are lower in early pregnancy before the development of pre-eclampsia. Thus, it is suggested that IGFBP-1-induced inhibition of IGF activity is unlikely to be responsible for the impaired trophoblast invasion observed in pre-eclampsia.     

Age-related refractoriness of PHA-induced lymphocyte transformation. I. Comparable sensitivity of spleen cells from young and old mice to culture conditions.

The decline in phytohemagglutinin (PHA) responsiveness of spleen cells from aged mice was studied in an effort to determine the nature of the depressed PHA reactivity. The reduced response of DNA synthesis (thymidine incorporation) to PHA stimulation could not be attributed to a decreased viability of spleen lymphocytes from old mice in in vitro culture conditions, to different PHA dose requirements, or to longer periods of culture time for old mouse spleen cells to reach maximal activity. Culture of cells for 24-48 h prior to addition of PHA gave patterns of thymidine incorporation similar to those of freshly prepared spleen cells. The elimination of red blood cells by a brief hypotonic shock significantly increased thymidine incorporation in spleen lymphocytes from both yound and old mice.     

B lymphocyte sensitivity to IgM receptor ligation is independent of maturation stage and locally determined by macrophage-derived IFN-beta

Compartmentation of B lymphocyte populations is associated with differences in both development stage and sensitivity to Ig (sIg)- dependent triggering. In order to characterize the factors that contribute in setting the level of sensitivity of a B cell, we quantified sIgM-dependent regulation of Ig secretion in purified mature and immature B cells after ex vivo and in vivo modification of their environment. These analyses formally demonstrate that the bone marrow (BM) microenvironment locally induces high B cell sensitivity to sIgM ligation irrespective of differentiation stage. We further provide evidence that BM macrophages create a dominant environment that enhances B cell sensitivity to B cell receptor triggering. Finally, using ex vivo assays as well as type I IFN receptor-deficient mice we show that IFN-beta produced by resident BM macrophages is necessary and sufficient to define B cell sensitivity. Implications of these findings for the understanding of B cell selection processes are discussed.      

Lysis by RNK-16 cytotoxic lymphocyte granules. Rate assays and conditions to study control of cytolysis

Dense subcellular granules of cytolytic lymphocytes can mediate rapid lysis of erythrocytes or nucleated cells. The granules contain several different proteases and proteoglycans that regulate cytolysis. We describe a rate assay that we have already used to demonstrate the requirement for serine proteases in granule-mediated lysis. In this assay, 51Cr-labeled erythrocytes are lysed by limiting concentrations of granules from RNK-16 tumor cells. Cytolysis is initiated by the addition of calcium (1 mM final concentration) and stopped at 0.5-1 min intervals by acidification to pH 6.0. The effects of the granule protein concentration, temperature, the concentration of erythrocytes, pH, and the concentration of calcium on the rate of lysis are reported. A preliminary mathematical approach is described and suggested as a means to differentiate 'lag' or activation times from the initial burst of lysis. With this rate assay, we have found four classes of protease inhibitors that block granule-mediated lysis (Hudig et al. (1987) Biochem. Biophys. Res. Commun. 149, 882). The utility of the rate assays is underscored by the observation that reversible protease inhibitors only showed rates of cytolysis whereas irreversible protease inhibitors stopped cytolysis completely. Rate assays are essential for future analyses of the complex physiological regulation of granule-mediated cytotoxicity by proteases, endogenous protease inhibitors and proteoglycans.     

Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating TFH/B cell axis

Circulating T_FH (cT_FH) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cT_FH1, cT_FH2, cT_FH17, and cT_FR cells, respectively. This CD4⁺T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cT_FH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-β-estradiol (E2) directly increased the percentage of different cT_FH subsets. While E2 and progesterone (P4) increased the proportion of differentiated T_FH cells derived from naïve CD4⁺T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/T_FH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10⁺T_FR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT_FH and B cell subsets.     

Human resistance to Plasmodium falciparum increases during puberty and is predicted by dehydroepiandrosterone sulfate levels

Immunity to Plasmodium falciparum develops slowly in areas of endemicity, and this is often ascribed to poorly immunogenic or highly variant parasite antigens. However, among populations newly exposed to malaria, adults acquire immunity more rapidly than children. We examined the relationship between pubertal development and resistance to P. falciparum. During two transmission seasons in western Kenya, we treated the same cohort of young males to eradicate P. falciparum and then obtained blood smears each week for 4 months. We determined pubertal development by Tanner staging and by levels of dehydroepiandrosterone sulfate (DHEAS) and testosterone in plasma. In multivariate and age-stratified analyses, we examined the effect of pubertal development on resistance to malaria. In both seasons (n = 248 and 144 volunteers, respectively), older males were less susceptible than younger males. Age-related decreases in the frequency and density of parasitemia were greatest during puberty (15- to 20-year-olds). DHEAS and testosterone were significant independent predictors of resistance to P. falciparum parasitemia, even after accounting for the effect of age. Fifteen- to 20-year-old males with high DHEAS levels had a 72% lower mean parasite density (P<0.01) than individuals with low DHEAS levels. Similarly, 21- to 35-year-old males with high DHEAS levels had a 92% lower mean parasite density (P<0.001) and 48% lower frequency of parasitemia (P<0.05) than individuals with low DHEAS levels. These data suggest that the long period needed to attain full immunity could be explained as a consequence of host development rather than as the requirement to recognize variant or poorly immunogenic parasite antigens.     

Screening of school children for blood lead levels and attempts to reduce them by nonpharmacological means in a coastal city of India

Context : Lead is a major health hazard, especially in children. Impact of lead poisoning on our society is not known. Effectiveness of environmental interventions in reducing blood lead levels is not exactly known, though the Center for Disease Control and Prevention strongly advocates use of such means. Aims: We aimed at screening school children for blood lead levels (BLLs) and reducing the BLLs of children with preliminary BLL> 20 microg/dL by environmental intervention and intensive education. Materials and Methods: To assess the extent of lead poisoning, a screening of 106 children was done, which showed that children belonging to a particular government primary school had higher BLLs. A second screening program of 87 children conducted in that school showed that only 19% had BLL < 10 microg/dL; whereas 44% had BLL between 10 and 20 microg/dL, and 37% had BLL> 20 microg/dL. Thirty-eight children having BLL> 20 microg/dL were selected from the two screening programs. After removing all potential sources of lead from their environment and educating them about the ways to prevent exposure to lead, follow-up of their BLLs was carried out at an interval of 6 months for a period of 1 year. Statistical Analysis: Values of the different follow-up studies were compared using repeated-measure ANOVA. Results : Our results showed that there was a significant (P < 0.0001) reduction in the BLLs in the first and second follow-up studies. Conclusions: The study is a proof of the concept that a decline in the BLLs can be achieved by intense education and avoiding the potential environmental sources of lead.     

High analytical sensitivity and low rates of inhibition may contribute to detection of Chlamydia trachomatis in significantly more women by the APTIMA Combo 2 assay

The clinical sensitivity of nucleic acid amplification tests may be determined by analytical sensitivity and inhibitors in patient samples. We established endpoints for detection of propagated Chlamydia trachomatis L2 434, diluted according to swab and urine protocols for APTIMA Combo 2 (AC2), ProbeTec ET (PT), and Amplicor (AMP) assays. AC2 was 1,000-fold more sensitive than PT and 10-fold more sensitive than AMP on mock swab specimens. For urine, AC2 analytical sensitivity was 100-fold greater than those of the other assays. Spiking an aliquot of each clinical-trial sample from 298 women demonstrated inhibition rates in first-void urine (FVU), cervical swabs (CS), and vaginal swabs (VS) of 12.1%, 12.8%, and 10.4% for AMP; 27.2%, 2%, and 2%, for PT; and 0.3%, 1.7%, and 1.3% for AC2. Inhibition of our C. trachomatis spike and the PT or AMP amplification controls from the manufacturers showed less than 50% correlation. Using an infected-patient reference standard (a specimen positive in at least two tests or a single test positive in two of three samples) in AC2, the VS identified 68/69 (98.6%) infected women compared to CS (89.9%) or FVU (81.2%). Significantly fewer women were identified by PT (65.2%, 63.8%, and 66.7%) or AMP (65.2%, 59.4%, and 56.5%) with the three specimens. By individual specimen type, AC2 confirmed virtually all PT- and AMP-positive specimens, but rates of AC2 confirmation by AMP or PT ranged from 62.9 to 80.3%. The AC2 test identified significantly more women infected with C. trachomatis (P = 0.001). Vaginal swabs appear to be the specimen of choice for screening.     

Antibody levels in mothers colonised with group B streptococci during pregnancy and in their newborn infants,as measured by an enzyme linked immunosorbent assay

An enzyme-linked immunosorbent assay (ELISA) was developed to measure serum antibodies to group B streptococci in 20 healthy pregnant women before delivery and in their newborn infants. The sera from 10 of these women who were colonised with group B streptococci and umbilical cord sera from their infants, had higher levels of type-specific lgG antibody than the 10 non-colonised controls and their neonates. All the babies remained well. The results demonstrate that infants from colonised mothers receive type-specific antibody. The possibility that this antibody may provide some degree of protection at birth against this potentially lethal organism warrants investigation.     

Placental phenotype and resource allocation to fetal growth are modified by the timing and degree of hypoxia during mouse pregnancy

AbstractThe placenta adapts its transport capacity to nutritional cues developmentally, although relatively little is known about placental transport phenotype in response to hypoxia, a major cause of fetal growth restriction. The present study determined the effects of both moderate hypoxia (13% inspired O₂) between days (D)11 and D16 or D14 and D19 of pregnancy and severe hypoxia (10% inspired O₂) from D14 to D19 on placental morphology, transport capacity and fetal growth on D16 and D19 (term∼D20.5), relative to normoxic mice in 21% O₂. Placental morphology adapted beneficially to 13% O₂; fetal capillary volume increased at both ages, exchange area increased at D16 and exchange barrier thickness reduced at D19. Exposure to 13% O₂ had no effect on placental nutrient transport on D16 but increased placental uptake and clearance of ³H‐methyl‐d‐glucose at D19. By contrast, 10% O₂ impaired fetal vascularity, increased barrier thickness and reduced placental ¹⁴C‐methylaminoisobutyric acid clearance at D19. Consequently, fetal growth was only marginally affected in 13% O₂ (unchanged at D16 and −5% at D19) but was severely restricted in 10% O₂ (−21% at D19). The hypoxia‐induced changes in placental phenotype were accompanied by altered placental insulin‐like growth factor (IGF)‐2 expression and insulin/IGF signalling, as well as by maternal hypophagia depending on the timing and severity of the hypoxia. Overall, the present study shows that the mouse placenta can integrate signals of oxygen and nutrient availability, possibly through the insulin‐IGF pathway, to adapt its phenotype and optimize maternal resource allocation to fetal growth during late pregnancy. It also suggests that there is a threshold between 13% and 10% inspired O₂ at which these adaptations no longer occur.