The Impact of Prenatal Stress on the Mother-Infant Behavior at six Months after Birth: The Role of different Dimensions of Stress.

Early life stress is known to influence mothers and consequently also the infant pre-, peri-, and postnatally. Both stress sensitization and inoculation theories have speculated about the conflicting previous findings of beneficial as well as impairing influences of early life stress. Findings of an impact on infant development, behavior and later vulnerability for cognitive and emotional problems, physical diseases and mental disorders, suggested the need to identify possible pathways between early life stress and infant outcome. Suggested underlying processes, such as fetal programming, were discussed. The present thesis focused on the possible impact of prenatal maternal stress on mother-infant dyadic behavior in a standardized observation paradigm, i.e. the still-face paradigm. Study I aimed to illuminate the prospective influence of psychological and physiological stress during pregnancy on mother-infant dyadic behavior in the first play episode of the still-face paradigm. In Study II, both the first play episode and the reunion episode were investigated. In Study I, the first play episode of the still-face paradigm was investigated. The findings provided evidence of an impact of psychosocial prenatal stress on mother-infant dyadic behavior during the normal mother-infant play, as it was expected for the first play episode. Mother-infant dyads with more psychosocial PS in pregnancy showed significantly more positive dyadic behavior then the less stressed dyads. The same was found for perceived maternal prenatal stress, although the effect vanished when analyses were conducted including all covariates. Hence, the findings were considered as providing only restricted evidence. No other stress index (i.e., psychopathological PS, cortisol decline and cortisol AuCg) reached significance in predicting mother-infant dyadic play behavior. In Study II, the impact of prenatal stress on mother-infant dyadic behavior in both play situations of the still-face paradigm was investigated. The dyadic behavior in the first play episode was compared with that in the reunion episode. The results provided evidence for the “still-face” and “carry-over” effect, with mother-infant dyads in both the high- and low-stress groups showing decreasing positive and increasing negative dyadic behavior in the reunion episode. Here too, mother-infant dyads with higher psychosocial prenatal stress showed significantly more positive dyadic behavior in the first play episode, but not in the reunion episode. In the latter episode, the positive behavior of the dyads with high prenatal stress decreased to approximately the same level as that of the dyads with low stress. In Study II, significant results emerged for physiological stress dimensions, with mother-infant dyads with a prenatally flat diurnal cortisol decline and low diurnal cortisol AUCg levels showing a distinctive, significant increase in negative dyadic behavior in the reunion episode. Mediation analyses run in both studies showed that maternal behavior was not a significant mediator between prenatal stress and infant behavior. The present findings contribute to inoculation theories on the impact of stress. Nevertheless, both studies provide merely a glimpse into the complex relationship of early life stress factors, maternal and environmental factors, and the infant’s development. Taken together, given the vast amount of studies reporting an impairing impact of prenatal stress on the infant, the present results should be interpreted with caution. The results add further support to the idea of individual resilience factors, suggesting that some individuals are not influenced by stressors or even benefit from them. Future research should focus on the underlying mechanisms, such as early programming, sensitive time periods in infant development, as well as possible influencing factors, in order to contribute to the explaining the mixed results, and to inform the creation of preventive programs for mothers and infants

Heme Oxygenase-1 and Its Role in Colorectal Cancer

Heme oxygenase-1 (HO-1) is an enzyme located at the endoplasmic reticulum, which is responsible for the degradation of cellular heme into ferrous iron, carbon monoxide and biliverdin-IXa. In addition to this main function, the enzyme is involved in many other homeostatic, toxic and cancer-related mechanisms. In this review, we first summarize the importance of HO-1 in physiology and pathophysiology with a focus on the digestive system. We then detail its structure and function, followed by a section on the regulatory mechanisms that control HO-1 expression and activity. Moreover, HO-2 as important further HO isoform is discussed, highlighting the similarities and differences with regard to HO-1. Subsequently, we describe the direct and indirect cytoprotective functions of HO-1 and its breakdown products carbon monoxide and biliverdin-IXa, but also highlight possible pro-inflammatory effects. Finally, we address the role of HO-1 in cancer with a particular focus on colorectal cancer. Here, relevant pathways and mechanisms are presented, through which HO-1 impacts tumor induction and tumor progression. These include oxidative stress and DNA damage, ferroptosis, cell cycle progression and apoptosis as well as migration, proliferation, and epithelial-mesenchymal transition

Heme Oxygenase-1 and Its Role in Colorectal Cancer

Heme oxygenase-1 (HO-1) is an enzyme located at the endoplasmic reticulum, which is responsible for the degradation of cellular heme into ferrous iron, carbon monoxide and biliverdin-IXa. In addition to this main function, the enzyme is involved in many other homeostatic, toxic and cancer-related mechanisms. In this review, we first summarize the importance of HO-1 in physiology and pathophysiology with a focus on the digestive system. We then detail its structure and function, followed by a section on the regulatory mechanisms that control HO-1 expression and activity. Moreover, HO-2 as important further HO isoform is discussed, highlighting the similarities and differences with regard to HO-1. Subsequently, we describe the direct and indirect cytoprotective functions of HO-1 and its breakdown products carbon monoxide and biliverdin-IXa, but also highlight possible pro-inflammatory effects. Finally, we address the role of HO-1 in cancer with a particular focus on colorectal cancer. Here, relevant pathways and mechanisms are presented, through which HO-1 impacts tumor induction and tumor progression. These include oxidative stress and DNA damage, ferroptosis, cell cycle progression and apoptosis as well as migration, proliferation, and epithelial-mesenchymal transition

Impact of prenatal stress on mother-infant dyadic behavior during the still-face paradigm

Abstract Background Mother-infant interaction provides important training for the infant’s ability to cope with stress and the development of resilience. Prenatal stress (PS) and its impact on the offspring’s development have long been a focus of stress research, with studies highlighting both harmful and beneficial effects. The aim of the current study was to examine the possible influence of both psychological stress and hypothalamic-pituitary-adrenal (HPA) axis activity during pregnancy with mother-child dyadic behavior following stress exposure. Methods The behavior of 164 mother-infant dyads during the still-face situation was filmed at six months postpartum and coded into three dyadic patterns: 1) both positive, 2) infant protesting-mother positive, and 3) infant protesting-mother negative. PS exposure was assessed prenatally according to psychological measures (i.e., psychopathological, perceived and psychosocial PS; n = 164) and HPA axis activity measures (maternal salivary cortisol, i.e., cortisol decline and area under the curve with respect to ground (AUCg); n = 134). Results Mother-infant dyads in both the high- and low-stress groups showed decreasing positive and increasing negative dyadic behavior in the reunion episode, which is associated with the well-known “still-face” and “carry-over” effect. Furthermore, mother-infant dyads with higher psychosocial PS exhibited significantly more positive dyadic behavior than the low psychosocial PS group in the first play episode, but not in the reunion episode. Similarly, mother-infant dyads with high HPA axis activity (i.e. high AUCg) but steeper diurnal cortisol decline (i.e. cortisol decline) displayed significantly less negative behavior in the reunion episode than dyads with low HPA axis activity. No significant results were found for psychopathological stress and perceived stress. Conclusions The results suggest a beneficial effect of higher psychosocial PS and higher prenatal maternal HPA axis activity in late gestation, which is in line with “stress inoculation” theories

Combination chemotherapy in advanced adrenocortical carcinoma

BACKGROUND: Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment. METHODS: We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival. RESULTS: For first-line therapy, patients in the EDP–mitotane group had a significantly higher response rate than those in the streptozocin–mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP–mitotane group and 2.2 months in the streptozocin–mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments. CONCLUSIONS: Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival. (Funded by the Swedish Research Council and others; FIRM-ACT ClinicalTrials.gov number, NCT00094497.)Martin Fassnacht... David J. Torpy... et al