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Biomedical subjects

V Glover

Publications and source records attributed to V Glover.

At least 19 recordsLinked to original sources

The HPA axis and perinatal depression: a hypothesis.

Episodes of depression and anxiety are as common during pregnancy as postpartum. Some start in pregnancy and resolve postpartum, others are triggered by parturition and some are maintained throughout. In order to determine any biological basis it is important to delineate these different subtypes. During pregnancy, as well as the rise in plasma oestrogen and progesterone there is a very large increase in plasma corticotropin releasing hormone (CRH), and an increase in cortisol. The latter reaches levels found in Cushing's syndrome and major melancholic depression. Levels of all these hormones drop rapidly on parturition.We here suggest that the symptoms of antenatal and postnatal depression may be different, and linked in part with differences in the function of the hypothalamic pituitary adrenal (HPA) axis. There are two subtypes of major depression, melancholic and atypical, with some differences in symptom profile, and these subtypes are associated with opposite changes in the HPA axis. Antenatal depression may be more melancholic and associated with the raised cortisol of pregnancy, whereas postnatal depression may be more atypical, triggered by cortisol withdrawal and associated with reduced cortisol levels. There is evidence that after delivery some women experience mild bipolar II depression, and others experience post traumatic stress disorder. Both of these are associated with atypical depression. It may also be that some women are genetically predisposed to depression of the melancholic type and some to depression of the atypical type. These women may be more or less vulnerable to depression at the different stages of the perinatal period.

Corticotropin-Releasing Hormone↗

Maternal anxiety at amniocentesis and plasma cortisol.

OBJECTIVES: To assess whether anticipation of amniocentesis is linked with maternal anxiety, and whether this anxiety is associated with increased maternal plasma cortisol. METHODS: Two hundred and fifty-four women awaiting a morning amniocentesis for karyotyping (gestation range 15-37 weeks, median 17 weeks) completed Spielberger state and trait anxiety inventory (STAI) questionnaires, and provided blood samples immediately before the procedure for cortisol assay. Six hundred and five women at mean gestation of 20 weeks, attending the same hospital for routine ultrasound but not for amniocentesis, also completed Spielberger STAI questionnaires and served as a comparison group for the anxiety ratings. RESULTS: Mean state and trait anxiety scores (+/- SD) in the comparison group of 605 women at mean gestation of 20 weeks were 36.1 +/- 10.2 (range 20-70) and 35.6 +/- 8.9 (range 20-73), respectively. The mean state anxiety score (+/-SD) of 49.8 +/- 14.0 (range 20-77) of the amniocentesis group was considerably higher than the comparison group (p < 0.001), although the mean trait anxiety score in the amniocentesis group was similar at 36.4 +/- 8.6 (range 21-60). The state, but not trait, anxiety correlated with plasma cortisol (r = 0.176, p = 0.005). Maternal cortisol in the amniocentesis group increased with gestational age (r = 0.310, p < 0.001), whereas state anxiety scores showed no significant change with increase in gestational age (r = - 0.042, ns). Multivariate analysis demonstrated that maternal state anxiety was positively correlated with plasma cortisol independent of gestation and time of collection. CONCLUSION: Women awaiting amniocentesis experience a high state anxiety associated with modestly increased plasma cortisol.

Adult↗

A new Mother-to-Infant Bonding Scale: links with early maternal mood.

Some mothers find it hard to relate to their new baby, and such failure may have long-term effects on the infant. This has been a neglected area of research. A new simple 8 item self-rating mother-to-infant bonding questionnaire has been designed to assess the feelings of a mother towards her new baby. A principal components and reliability analysis demonstrated an alpha score of 0.71. One hundred and sixty two women filled in the Kennerley Blues Scale, the Edinburgh Postnatal Depression Scale (EPDS) the Highs Scale and the new Mother to Infant Bonding Scale on day 3 postpartum. Twelve weeks later they were sent the EPDS and the Bonding scales again. One hundred and forty four returned all questionnaires. There was a strong correlation between the Bonding scores at 3 days and at 12 weeks (r(s)=0.54 p<0.001). Multiple regression analysis showed that those with raised Blues scores had worse, and those with raised Highs scores had better bonding at 3 days. Those with raised EPDS scores at 3 days (13 and over) had worse bonding scores in the "first few weeks" (median 4 versus 1, p = 0.028), as recalled at 12 weeks. This simple questionnaire is acceptable for use with mothers and gives significant correlations with their early mood.

Adult↗

Isatin, an endogenous monoamine oxidase inhibitor, triggers a dose- and time-dependent switch from apoptosis to necrosis in human neuroblastoma cells.

Isatin is an endogenous indole that is increased in stress, inhibits monoamine oxidase (MAO) B and improves bradykinesia and striatal dopamine levels in rat models of Parkinson's disease. Consequently, it has been suggested that isatin might be a possible treatment for Parkinson's disease although little is known about its effects on neural cell growth and survival. The aim of this study was to investigate the survival of dopaminergic human neuroblastoma (SH-SY5Y) cells following treatment with increasing concentrations of isatin. SH-SY5Y cells were exposed to isatin for defined time points, after which cell survival was determined by MTT assay. A combination of Annexin V binding and propidium iodide (PI) exclusion was used to distinguish apoptosis from necrosis in flow cytometry experiments and FACS profiles of permeabilised PI-labelled cells were employed for the assessment of cell cycle distribution. Isatin treatment (1-400 microM) for 24h induced a significant dose-dependent increase in MTT metabolism by SH-SY5Y cells in culture, but this was not due to an increase in cell division. At the higher concentrations (200-400 microm) isatin triggered cell death, although MTT metabolism was still increased in the culture, suggesting that surviving cells were hypermetabolic. Following a longer (48 h) exposure, isatin was found to cause cell death in a dose-dependent manner; at lower concentrations (50 microM), the predominant mode of cell death was apoptosis while at the highest concentration (400 microm) increasing numbers of necrotic cells were also evident. Thus, in dopaminergic SH-SY5Y cells isatin induces cell death in dose- and time-dependent manner. This death occurred as a continuum of survival, apoptosis and necrosis. Our results re-emphasise that caution should be exercised when considering high doses of isatin as a putative anti-Parkinson's disease therapeutic.

Annexin A5↗

The effects of acute relaxation on indices of anxiety during pregnancy.

OBJECTIVES: Antenatal maternal anxiety has adverse effects on the fetus and the child. In this study we determined whether a short period of directed or of passive relaxation reduced maternal self-rated anxiety, heart rate, plasma catecholamines, cortisol and uterine artery resistance index, in pregnant women. METHODS: Fifty-eight women (28-32 wks gestation) were assigned randomly to a session of directed active or passive (sitting quietly) relaxation. Spielberger self-rating anxiety questionnaires were completed, and a venous blood sample taken, before and after a Doppler scan. RESULTS: Both active and passive relaxation significantly reduced State Anxiety and maternal heart rate, but the effect was significantly greater with the active relaxation. In contrast, the passive relaxation significantly reduced noradrenaline levels whereas active did not. Adrenaline levels were not changed significantly with either type of relaxation. Both methods significantly reduced cortisol, with a trend for the passive to have a greater effect. The active relaxation had no effect on uterine artery blood flow, whereas there was a statistically significant, but clinically negligible, increase in mean resistance index after passive relaxation. CONCLUSION: Both methods reduced maternal State Anxiety and heart rate, the active method more so. However there was a striking lack of correlation with the other biological indices studied. In order to reduce specific biological effects of anxiety during pregnancy, different methods may be needed from those which are most effective at reducing subjective anxiety.

Adult↗

Stress responses at birth: determinants of cord arterial cortisol and links with cortisol response in infancy.

OBJECTIVE: To investigate (A) the determinants of infant stress response at delivery and (B) test the hypothesis that stress at birth, as reflected by cord arterial cortisol, influences cortisol response to vaccination at two months. DESIGN: Prospective observational study. SETTING: Tertiary referral maternity hospital. POPULATION: One hundred and seventy-two primiparous women with uncomplicated singleton pregnancies. METHODS: Women were recruited antenatally. At birth, cord arterial blood and obstetric data were collected. Saliva was collected from infants immediately before and after vaccination at two months. Cortisol was analysed from cord blood and saliva by radio-immunoassay. MAIN OUTCOME MEASURES: Stress response at birth, as demonstrated by cord arterial cortisol; association with saliva cortisol response to vaccination at two months. RESULTS: Cord arterial cortisol varied with mode of delivery, combined spinal/epidural use and pH. Salivary cortisol response at two months correlated with cord arterial cortisol (r= 0.24, P < 0.05). Infants with the highest and lowest cord arterial cortisol had markedly different cortisol responses at two months (P= 0.017). These groups had different modes of delivery with caesarean rates of <8% in the high cortisol response group and 83% in the low cortisol response group (P < 0.0001). CONCLUSION: Babies born vaginally mount greater cortisol responses at birth than those delivered by caesarean section. Stress at delivery may influence the infant HPA axis response for up to two months.

Amniotic Fluid↗

Fetal plasma testosterone correlates positively with cortisol.

BACKGROUND: Fetal exposure to testosterone has been implicated in programming childhood behaviour, but little is known about the determinants of fetal testosterone concentrations. AIMS: To investigate the relation between fetal testosterone and maternal and fetal cortisol. METHODS: Clinically indicated blood samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15-38), together with paired maternal samples, were analysed for testosterone and cortisol concentrations. RESULTS: Male fetuses had significantly higher concentrations of testosterone than females. Female but not male fetal concentrations rose significantly with gestational age. Fetal testosterone correlated positively with both fetal cortisol and maternal testosterone concentrations. Multiple regression showed that maternal testosterone and fetal cortisol were independently correlated with fetal plasma testosterone in both sexes. CONCLUSION: Unlike the norm in the adult, where testosterone production is often inhibited by cortisol, in the fetus there is a positive link between the two.

Adult↗

Prenatal stress alters cardiovascular responses in adult rats.

Environmental factors in early life are clearly established risk factors for cardiovascular disease in later life. Most studies have focused on nutritional programming and analysed basal cardiovascular parameters rather than responses. In the present study we have investigated whether prenatal stress has long-term effects on cardiovascular responses in adult offspring. Female pregnant Sprague-Dawley rats were subjected to stress three times daily from day 15 to day 21 of gestation. Litters from stressed and control females were cross-fostered at birth to control for mothering effects. When the offspring were 6 months old, blood pressure was measured in the conscious rats through implanted catheters at rest, during restraint stress and during recovery. Basal haemodynamic parameters were similar in the different groups but the pattern of cardiovascular responses during stress and recovery differed markedly between prenatally stressed (PS) and control animals. PS rats had higher and longer-lasting systolic arterial pressure elevations to restraint stress than control animals. They also showed elevated systolic and diastolic blood pressure values during the recovery phase. PS rats demonstrated a greater increase in blood pressure variability compared with control animals during exposure to restraint stress, and showed more prolonged heart rate responses to acute stress and delayed recovery than controls. There was no effect of prenatal stress on baroreflex regulation of heart rate. PS females showed a greater increase in systolic arterial pressure and blood pressure variability and delayed heart rate recovery following return to the home cage then did PS males. These findings demonstrate for the first time that prenatal stress can induce long-term, sex-related changes in the sensitivity of the cardiovascular system to subsequent stress.

Adrenergic alpha-Agonists↗

Infant cortisol response after prolonged antenatal prednisolone treatment.

Prednisolone is widely used to treat medical conditions in pregnancy, despite the lack of long-term safety studies on infants. Animal studies have shown that antenatal glucocorticoid treatment can cause in utero growth restriction and up-regulation of the offsprings' hypathalamic-pituitary-adrenal axis. We recruited women treated antenatally with prednisolone, and followed 12 of the infants up to four months, using routine infant vaccinations as a stressor. Birthweights were similar to controls (n = 289, uncomplicated, singleton term pregnancies), as were infants' baseline and stress-induced cortisol levels. Mothers rated their infants as less difficult and more adaptable than controls. This study provides initial reassurance about the safety of prednisolone in pregnancy.

Adult↗

Human fetal and maternal corticotrophin releasing hormone responses to acute stress.

OBJECTIVES: To study the effect of acute stress, caused by intrauterine needling at the intrahepatic vein (IHV), on fetal plasma concentrations of corticotrophin releasing hormone (CRH), and to compare paired fetal and maternal samples for CRH concentration to determine the extent of their joint control. DESIGN: Venous blood samples were obtained from fetuses (gestational age 17-38 weeks) undergoing fetal blood sampling (n = 29) or intrauterine transfusion (n = 17) through either the IHV or the placental cord insertion (PCI). SETTING: The Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London, UK. PATIENTS: Pregnant women undergoing clinically indicated fetal blood sampling or intrauterine blood/platelet transfusion. RESULTS: Fetal plasma cortisol increased with intrahepatic vein transfusion (mean (SD) cortisol response Delta64.7 (54.5) nmol/l; p < 0.0001, n = 11), and fetal corticotrophin concentrations were higher after IHV (n = 7) than PCI needling (n = 6). Neither fetal nor maternal plasma CRH increased after IHV transfusion. Fetal CRH levels did not rise with gestation, whereas maternal CRH levels did (r = 0.58; n = 36; p < 0.0001). There was a modest correlation between paired maternal and fetal values (r = 0.36; n = 36; p = 0.03). CONCLUSIONS: Acute fetal stress, caused by IHV needling of the fetal abdomen, resulted in hypothalamic-pituitary-adrenal axis activation, as shown by a rise in fetal cortisol and corticotrophin. However, it did not result in measurable CRH release into fetal plasma. This suggests that fetal plasma CRH is not derived from the hypophyseal-portal circulation, but from another source, presumably the placenta.

Acute Disease↗

High EPDS scores in women from ethnic minorities living in London.

BACKGROUND: The aim of this study was to determine whether women from ethnic minorities and/or birth in a non-English speaking country were at increased risk for postnatal depression. METHOD: The Edinburgh Postnatal Depression Scale (EPDS) was used to screen a sample of 830 primiparous women 4 weeks after delivery. Ethnicity data was available on 743, and from these, 530 responses were received (71.3%). RESULTS: Two independent variables were found to be significantly associated with high EPDS scores. These were being non White (especially Asian; adjusted Odds Ratio 2.7, 95% CI 1.3-5.8) and being born in a non-English speaking country (Odds Ratio 1.9; 95% CI 1.0-3.5). LIMITATIONS: The study was conducted using self rating questionnaires. There was only a 71% response overall, and a 50% response rate among the ethnic minority group. CONCLUSIONS: Women from ethnic minorities or from a non-English speaking background should be regarded at high risk group for postnatal depression.

Adolescent↗

Effects of isatin on atrial natriuretic peptide-mediated accumulation of cGMP and guanylyl cyclase activity of PC12 cells.

We have previously demonstrated that isatin (indole-2,3 dione), an endogenous compound widely distributed in mammalian tissues and body fluids, effectively inhibits atrial natriuretic peptide (ANP) receptor binding and ANP-stimulated guanylyl cyclase activity of rat membrane preparations. In the present study the effects of isatin on ANP-mediated accumulation of cGMP and guanylyl cyclase (GC) activity of PC12 cells were studied. Isatin (0.1 mM) effectively inhibited ANP-stimulated GC-activity of broken cells but was nearly inactive in attenuating ANP-dependent accumulation of cGMP in intact PC12 cells. The ATP-analogue adenylylimidodiphosphate (AMP-PNP) slightly potentiated the ANP effect on GC activity in broken cell preparations and significantly reduced GC sensitivity to isatin. Isatin caused a more pronounced reduction of ANP-dependent cGMP accumulation in cells grown in the presence of 10% embryonal calf serum (ECS) than in 0.5% ECS. The data obtained suggest that, in intact cells, the manifestation of the isatin effect on ANP-mediated signal transduction may depend on intracellular factor(s), possibly interacting at the kinase domain.

Adenylyl Imidodiphosphate↗

Cyclic GMP excretion blocked by isatin administration under conditions of fluid overload.

Isatin is a potent inhibitor of atrial natriuretic peptide (ANP) receptors and ANP-induced generation of cGMP in vitro. This study was designed to determine whether it had a similar effect in vivo, using a model of fluid overload known to induce ANP. We confirmed that this model increased urinary output of cGMP 3 hr after volume loading, and showed that this effect was blocked by i.p. injection of isatin (50 mg/kg). Isatin had no effect on urine volume or sodium output. However, isatin did have an effect on plasma protein concentration, both compared with control values, compatible with shifting fluid to the vascular compartment, and after volume overload, in which it normalised such a shift. Isatin thus affected both the generation of cGMP and fluid balance in vivo.

Analysis of Variance↗

Infant massage improves mother-infant interaction for mothers with postnatal depression.

BACKGROUND: Postnatal depression can have long term adverse consequences for the mother-infant relationship and the infant's development. Improving a mother's depression per se has been found to have little impact on mother-infant interaction. The aims of this study were to determine whether attending regular massage classes could reduce maternal depression and also improve the quality of mother-infant interaction. METHOD: Thirty-four primiparous depressed mothers, median 9 weeks postpartum, identified as being depressed following completion of the Edinburgh Postnatal Depression Scale (EPDS) at 4 weeks postpartum, were randomly allocated either to an infant massage class and a support group (massage group) or to a support group (control group). Each group attended for five weekly sessions. Changes in maternal depression and mother-infant interaction were assessed at the beginning and the end of the study by comparing EPDS scores and ratings of videotaped mother-infant interaction. RESULTS: The EPDS scores fell in both groups. Significant improvement of mother-infant interaction was seen only in the massage group. LIMITATION: The sample size was small and had relatively high dropout. It was not possible to distinguish which aspects of the infant massage class contributed to the benefit. CONCLUSION: This study suggests that learning the practice of infant massage by mothers is an effective treatment for facilitating mother-infant interaction in mothers with postnatal depression.

Adolescent↗

Umbilical cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery.

OBJECTIVES: While it is well established that delivery by elective caesarean section is less stressful for the fetus than normal vaginal delivery, little attention has been paid to the effect on the baby of an assisted delivery. STUDY DESIGN: We examined cortisol levels in venous cord blood from seven babies born by forceps, 10 by ventouse extraction, 28 by unassisted normal vaginal delivery, and 12 born by elective caesarean. Paired maternal bloods were taken immediately after delivery. RESULTS: Cord blood cortisol values were significantly different in the different groups (one-way ANOVA, P < 0.0001). The forceps group had the highest values and the caesarean group the lowest; both were different from the normal vaginal delivery group (P=0.019 and P=0.046, respectively). There was no effect of length of labour, or method of pain relief on cortisol levels. Maternal values were similar in the different groups, confirming that the differences observed derived from the fetus. CONCLUSIONS: There is increasing evidence that the stress experienced by the fetus or neonate can have long-term effects on the function of the hypothalamic-pituitary-adrenal axis in later life. We speculate that the stress caused by some assisted deliveries may contribute to this.

Cesarean Section↗

Fetal hypothalamic-pituitary-adrenal stress responses to invasive procedures are independent of maternal responses.

Paired fetal and maternal samples were obtained, at fetal blood sampling and intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal stress response to transfusion via the intrahepatic vein, which involves piercing the fetal trunk, but not to transfusion via the placental cord insertion [mean cortisol response via intrahepatic vein delta = 52.6 nmol/L, 95% CI (25.3-79.9), P = 0.001; mean beta-endorphin response delta =106 pg/mL, 95% CI (45.3-167), P = 0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7-15.2)] for cortisol and 0.8 [95% CI (0.5-1.0)] for beta-endorphin. The novel findings were: 1) that the fetal responses were independent of those of the mother, which did not change during transfusion at either site; 2) that there was a correlation between baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but not between baseline fetal and maternal ss-endorphin levels, suggesting cortisol transfer across the placenta, rather than joint control by placental CRH; and 3) that fetal beta-endorphin responses were apparent from 18 weeks gestation and independent of gestational age, whereas fetal cortisol responses were apparent from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x, r = 0.51; n = 16; P = 0.04; CI for slope, 0.16-10.0), consistent with the maturation of the fetal pituitary before the fetal adrenal.

Blood Transfusion↗

Perspectives of low-income African Americans on syphilis and HIV: implications for prevention.

Infectious syphilis disproportionately affects African Americans living in poverty in metropolitan areas in the southeastern United States. In this population, where syphilis persists, the rates of HIV and AIDS are also persistently high. In an effort to facilitate the design of more effective prevention programs, the present investigation employed focus groups to obtain information from low-income African Americans concerning the determinants of high rates of syphilis and HIV/AIDS in their communities. The subjects were 36 African American men and women ages 18 to 56 residing in metropolitan Memphis and surrounding Shelby County, Tennessee. Overall, the authors found significant lack of awareness of the magnitude of HIV/AIDS and syphilis in African American communities and lack of knowledge about the etiology and transmission of syphilis. The investigation points to the important role of women and partnerships of community organizations in preventing the spread of HIV, syphilis, and other sexually transmitted diseases in this population.

AIDS Serodiagnosis↗

CuZn-superoxide dismutase transgenic mice: no effect on longevity, locomotor activity and 3H-mazindol and 3H-spiperone binding over 19 months.

This study was designed to determine whether CuZn-superoxide dismutase (SOD) is neuroprotective against aging in the nigrostriatal tract. Twenty-four male mice transgenic for human CuZnSOD, resulting in overexpression of the cytosolic enzyme, were compared with 11 matched controls over 19 months. There was no difference in longevity, locomotor activity, or 3H-mazindol or 3H-spiperone binding in the nigrostriatal tract in the two groups. Thus there was no evidence that increased CuZnSOD was neuroprotective in this model.

Animals↗