Patterns of salivary cortisol secretion in pregnancy and implications for assessment protocols

Cortisol is used in research as a biomarker of psychological stress. Logistical considerations argue for collecting as few samples as possible, balanced against diurnal rhythms and intra-individual variations. 100 pregnant women gave five saliva samples a day for 3 days, at waking, 30 min after waking, and 11:00 a.m., 5:00 p.m., and 9:00 p.m. Timing of collection was confirmed by monitors. Another sample was taken during a clinic visit. Using the 15 measures as the gold standard, correlations and mean area under the curve (AUC) were compared with subsets and the single clinic sample to evaluate alternate collection protocols. Five samples in 1 day, or protocols involving morning and night samples, had the highest correlations with mean AUC (correlation coefficient ranging from 0.82 to 0.88). Standardizing the clinic measurement to a single time of day did not substantially improve correlations with mean AUC. Correlations with measures of reported stress were also not strong.     

Relationship between salivary cortisol and progesterone levels in humans

In four studies, each with multiple hormone assessments before and after positive emotion-arousing laboratory manipulations, salivary progesterone positively correlated with salivary cortisol in men and women taking hormonal contraceptives but not in freely cycling women. This is consistent with the idea that progesterone in men is largely adrenal in origin, whereas in women its sources are both ovarian and adrenal. In addition, bi-partial correlations revealed that change in cortisol was positively related to change in progesterone levels; this effect was stronger in men than in women. These findings suggest that progesterone is released from the adrenal along with cortisol in humans, due to general adrenal activation and/or possibly as an additional negative feedback mechanism to down-regulate the stress response.     

Psoriatic arthritis: lessons from imaging studies and implications for therapy

Introduction: Modern imaging may aid in the diagnosis, prognosis and monitoring of therapeutic response in psoriatic arthritis (PsA). Detection of osteitis and technical advances like whole body magnetic resonance imaging (MRI) exemplify the value of this technology.

Areas covered: Ultrasound (US) provides a clinic-based tool for evaluating both joint pathologies and extra-articular structures (especially enthesitis) including skin and nail disease. Recent studies have demonstrated subclinical disease in psoriasis without arthritis, as well as in PsA, with implications for diagnosis and treatment classification. Modern imaging can also facilitate decisions on tapering of expensive biologics, though real-world clinical studies are still lacking.

Expert commentary: The increase in novel PsA therapies should increase the utilization of modern imaging, providing both increased validation of imaging biomarkers as well as responsive outcome measures.     

Oxytocin, cortisol, and triadic family interactions

The neuropeptide oxytocin (OT) supports the development of parenting in mammals primarily through its impact on parent-infant proximity and touch behaviors; however, much less is known about the links between OT and parental touch and contact in humans. In this study, we examined the relations between maternal and paternal OT and patterns of touch and contact in the family unit during triadic interactions. Thirty-seven parents and their firstborn child were seen twice: during the 2nd and 6th postpartum month. Plasma OT and salivary cortisol (CT) were assessed with ELISA methods. At six months, triadic mother-father-infant interactions were videotaped and micro-coded for patterns of proximity, touch, and gaze behavior. Triadic synchrony, defined as moments of coordination between physical proximity and affectionate touch between the parents as well as between parent and infant while both parent and child are synchronizing their social gaze, was predicted by both maternal and paternal OT. Among mothers, triadic synchrony was also independently related to lower levels of CT. Results highlight the role of OT in the early formation of the family unit at the transition to parenthood.     

Sponge-microbial interactions: Ecological implications and bioprospecting avenues

Sponges are closely associated with microorganisms that occur either intracellularly and extracellularly. Sponges are soft-bodied sessile organisms appear to be defenseless in facing predation. Microbial symbionts supposed to have a functional role in the host defense against pathogens, predation and microfouling processes. Recently, the ubiquitous defense enzyme, phospholipase A2 (PLA2) detected in the sponge associated bacterium envisaged the possible functional role in the ecological succession of host sponge against predatory / fouling pressure in the habitat. In present review, we highlighted the possible functional interactions between associated microbes and host sponges and its potentials in bioprospecting approaches.     

Effects of estrogen versus estrogen and progesterone on cortisol and interleukin-6

Objectives

The purpose of this study was to compare the effects of 3 months of estrogen replacement therapy, estrogen plus progesterone replacement therapy and a placebo, on the resting cortisol and interleukin-6 (IL-6) levels in post-menopausal women.

Methods

Forty-three women were randomised to one of three treatment arms: estradiol 2 mg/day (ERT), estradiol 2 mg/day plus medroxyprogesterone acetate 5 mg/day (HRT), or a placebo that was administered orally for 3 months.

Results

Cortisol levels showed a significant condition by intervention interaction. Post hoc tests showed that ERT significantly increased cortisol levels after treatment compared to baseline, while in the HRT group a trend toward increased cortisol was found. No changes were observed in IL-6 levels.

Conclusions

Estrogen administration elevated cortisol levels, but this effect may be moderated by progestins. IL-6 was not altered by ERT or HRT, future studies should consider the interaction of cortisol increases on change in IL-6 expression.     

Cancer in pregnancy: maternal and fetal implications

Cancer is the second leading cause of death in women during their reproductive years, and complicates approximately 0.1% of all pregnancies. When cancer occurs during gestation it poses immense pressure on the pregnant patient, her relatives and her physicians. As cancer is diagnosed during gestation, it raises conflicts between optimal maternal therapy and fetal well-being. In this review, the available data are analysed regarding the impact of pregnancy on the course of the disease, and the effects of the malignant process and its treatment on both the mother and her fetus. Here, attention is focused on the most common malignancies associated with pregnancy; cervical and breast cancer, malignant melanoma and lymphoma. In addition, attention is focused on the available data regarding the impact of cytotoxic and radiation treatments on the mother and fetus.     

Serum inflammatory responses of transcortin binding activities and of total and free corticosterone and progesterone levels in developing rats: a kinetic approach

The kinetics of the inflammatory responses of 5 serum parameters involved in specific protein-hormone interactions were studied, namely: transcortin (CBG) binding activities; total corticosterone (B), main ligand of CBG; unbound corticosterone (free B); total progesterone (P4), main competitor of B for binding on CBG; and the free P4. The studies were performed in developing animals, i.e. on rats given a single turpentine injection at 1, 10, 21 or 90 days of post-natal age. The responses showed similar trends at all ages, but age-dependent differences in kinetics and reactivities. Common characteristics were 3-5-fold increases of the hormone parameters as soon as 4-8 h after the injection, and 2-3-fold decreases in CBG activities. A remarkable age-dependent difference was the contrast of early CBG decrease in adults (4 h after turpentine) to the delayed occurrence of this reaction in immatures (8-24 h after turpentine). On the other hand, the increase of free B lasted for 72 h in neonates, but only 40 h in rats treated at 21 or 90 days. Age-dependent characteristics were seen also in reactivities: the peak increases in the hormone levels were highest in the young, while the peak decreases of CBG were most marked in the mature animals. The results suggest that the regulatory mechanisms governing the mutual effects of hormonal activities and CBG synthesis might depend on the stage of development.     

Complement-endothelial cell interactions: pathophysiological implications.

The function of the endothelial cells can be modulated by humoral factors present in the circulation and in the extravascular fluid, including proteins of the complement system. This review examines the multiple interactions between the complement system and the endothelial cells and their functional consequences on inflammation, coagulation and regulation of vascular tone. The implications of these interactions in the induction and progression of the vascular lesions occurring in atherosclerosis, ischemia/reperfusion and xenotransplantation and the possible therapeutic approaches in terms of complement regulation are also discussed.     

Response to LPS in female offspring from sows treated with cortisol during pregnancy

Prenatal stress has been shown to program responsiveness of the hypothalamus-pituitary-adrenal axis (HPA-axis) and behavior in offspring. In pig husbandry, sows are exposed to stressful conditions during gestation. Previously, cortisol treatment of pregnant sows has been shown to alter stress responsiveness and immunological parameters in their piglets. In the present study, we explored whether cortisol treatment of pregnant sows affects the offspring's response to an inflammatory stimulus. Sows were treated orally with cortisol either during the first, second, or third period of gestation, or received a placebo during this period. At 8 weeks of age, female offspring were injected intravenously with lipopolysaccharide (LPS). Offspring of sows that received cortisol during the first and third period of gestation showed a higher fever response to LPS. Cortisol treatment of sows during gestation did not affect offspring's response to LPS with regard to their cortisol response. LPS-induced sickness behavior, which was measured as the latency time in a human approach test, appeared to recover more quickly in offspring from sows that received cortisol during the second period of gestation. These results suggest that prenatal cortisol exposure programs responsiveness to inflammatory stimuli in female piglets.     

Suicidal ideation in pregnancy: assessment and clinical implications

Summary The objectives of this study were 1) to determine the prevalence of suicidal ideation (SI) in pregnant women with a history of neuropsychiatric illness, 2) to assess the relative sensitivity of commonly used depression rating scales for detecting SI, and 3) to examine the sociodemographic and clinical predictors of SI in pregnant women. Demographic data, Beck Depression Inventory [BDI] and Hamilton Rating Scale for Depression [HRSD] questionnaires, and SCID interviews were obtained from 383 pregnant women presenting to the Emory Women’s Mental Health Program or the Emory Women’s Epilepsy Program. Among those who completed both scales, 29.2% endorsed SI on the BDI and 16.9% on the HRSD, with 33.0% endorsing SI on at least one of the rating scales and 13.1% on both rating scales. The rate of SI endorsement on the BDI was 73.3% higher than the HRSD. Multivariate logistic regression demonstrated that SI in pregnant women was associated with unplanned pregnancy (OR = 2.97), current major depression (OR = 4.12), and comorbid anxiety disorder (OR = 4.17). Further studies are warranted to identify additional predictors of perinatal suicidality and to clarify the nature of the association between such factors and the presence of SI in pregnant women.     

Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: comparison to salivary cortisol

Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair cortisol provides a simple way to monitor total cortisol release over an extended period of time. Hair cortisol levels were determined from each trimester (15, 26 and 36 weeks gestation) and 3 months postpartum. Hair cortisol levels were compared to diurnal salivary cortisol collected over 3 days (3 times/day) at 14, 18, 23, 29, and 34 weeks gestational age and 6 weeks postpartum from 21 pregnant women. Both salivary and hair cortisol levels rose during pregnancy as expected. Hair cortisol and diurnal salivary cortisol area under the curve with respect to ground (AUCg) were also correlated throughout pregnancy. Levels of cortisol in hair are a valid and useful tool to measure long-term cortisol activity. Hair cortisol avoids methodological problems associated with collection other cortisol measures such as plasma, urine, or saliva and is a reliable metric of HPA activity throughout pregnancy reflecting total cortisol release over an extended period.     

Molecular interactions between dendritic cells and Salmonella: escape from adaptive immunity and implications on pathogenesis

Dendritic cells (DCs) constitute the link between innate and adaptive immunity by directly recognizing pathogen-associated molecular patterns (PAMPs) on bacteria and by processing and presenting bacterial antigens to T cells. Recognition of PAMPs renders DCs as professional antigen-presenting cells with the ability to prime naive T cells and to initiate the adaptive immune response against pathogen-derived antigens. For this reason, any interference with DC function might be advantageous for bacterial survival and dissemination. Identification of the molecular interactions occurring between DCs and bacterial pathogens is necessary to understand the mechanisms that virulent bacteria have evolved to prevent recognition by the adaptive immune system. This could be helpful in the identification of possible new targets that might lead to the design of effective therapies aimed at preventing or treating serious infections by these pathogens. In this article, we focus on Salmonella enterica serovar Typhimurium, the causative agent of typhoid-like disease in the mouse, and how it is able to escape from DC-mediated antigen presentation by avoiding lysosomal degradation. This feature of virulent Salmonella requires the functional expression of the Type Three Secretion System (TTSS) and effector proteins encoded within the Salmonella pathogenicity island 2 (SPI-2). Recent studies have demonstrated that impairment of DC function by the activity of SPI-2 gene products is crucial for Salmonella pathogenesis.     

Molecular interactions during pregnancy: Identification of cyclophilin A from human decidual and placental tissue in the first trimester of pregnancy

The protein patterns of tissue homogenates from human deciduaand placenta of first trimester pregnancies were investigated.Particular attention was paid to the low molecular weight componentsof these tissues, since substantial evidence has accumulatedthat some of these smaller proteins show a characteristic cyclicand pregnancy expression. Two specific bands were purified fromhomogenates of first trimester decidua and placenta using gelfiltration and anion exchange chromatography. These bands wereseparated by gel electrophoresis and blotting onto polyvinylidendifluoridemembrane. Partial amino acid sequencing of both proteins revealedsequences identical to human cyclophilin A. One protein wassequenced V-N-P-T-V-F-F-D-l-A-V-D-G-E-P-L-G-R-(X)-S-F-E-L-F-A-D-K-V-Pand identified as the 17 kDa isoform of cyclophilin A. The otherprotein was sequenced V-N-P-T-V-F-F-D-I-A and identified asthe 18 kDa isoform of cyclophilin A.     

Interpopulation, interindividual, intercycle, and intracycle natural variation in progesterone levels: a quantitative assessment and implications for population studies.

Methodological challenges in studying sex steroid hormones in premenopausal women result from the existence of variation at three levels: among women from the same population, among menstrual cycles recorded for women at different times of the year, and among days of the same cycle. We partitioned, for a Polish rural population, the natural, nonpathological, variation in salivary progesterone concentrations (measured during 14 days of the luteal phase) into the intracycle component (which accounts for 65% of the total variation) and the among-cycle component (the remaining 35% of the total variation). Out of the among-cycle variation in salivary progesterone, as much as 46% is expressed as differences among individual women (interindividual component); the remaining 54% of variation is due to differences among cycles of individual women (intercycle, within-women component). Such intercycle variation is probably caused by a seasonality of agricultural workload and is much higher than in nonseasonal, industrial populations. We also used bootstrap analyses to generate heuristic recommendations for choosing sample sizes of the number of subjects, number of cycles per woman, and number of days per cycle. Studies in populations with seasonal lifestyles should rely on measurements of at least three cycles per woman. Given the substantial intracycle amplitude in hormone levels to reliably assess biologically and medically relevant variation in ovarian function, at least 7-8 days/cycle should be measured.