Numerous studies have shown that supplementation of the growth medium of human fibroblasts with dexamethasone at physiologic concentrations extends replicative lifespan up to 30%. While this extension of lifespan has been used to probe various aspects of the senescent phenotype, no mechanism for the increased lifespan of human fibroblasts grown in the presence of dexamethasone has ever been identified.
The human tyrosine hydroxylase (hTH) gene has a 42†bp evolutionarily conserved region designated (CR) II at -7.24†kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7†bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines.
BACKGROUND: A history of early adverse experiences is an important risk factor for adult psychopathology. Changes in stress sensitivity and functioning of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the association between stress and risk for psychiatric disorders. Preclinical work in rodents has linked low levels of maternal care to increased methylation of the promoter region of the glucocorticoid receptor (GR) gene, as well as to exaggerated hormonal and behavioral responses to stress.
BACKGROUND: Enhanced glucocorticoid receptor (GR) sensitivity is present in people with posttraumatic stress disorder (PTSD), but the molecular mechanisms of GR sensitivity are not understood. Epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained PTSD symptoms given that PTSD develops in only a subset of trauma survivors.
OBJECTIVE: Differential effects of maternal and paternal posttraumatic stress disorder (PTSD) have been observed in adult offspring of Holocaust survivors in both glucocorticoid receptor sensitivity and vulnerability to psychiatric disorder. The authors examined the relative influences of maternal and paternal PTSD on DNA methylation of the exon 1F promoter of the glucocorticoid receptor (GR-1F) gene (NR3C1) in peripheral blood mononuclear cells and its relationship to glucocorticoid receptor sensitivity in Holocaust offspring.
The International Journal of Neuropsychopharmacology
BACKGROUND: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. METHODS: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study.
BACKGROUND: Chronic psychological stress is associated with accelerated aging and increased risk for aging-related diseases, but the underlying molecular mechanisms are unclear. RESULTS: We examined the effect of lifetime stressors on a DNA methylation-based age predictor, epigenetic clock. After controlling for blood cell-type composition and lifestyle parameters, cumulative lifetime stress, but not childhood maltreatment or current stress alone, predicted accelerated epigenetic aging in an urban, African American cohort (n?=?392).
Archives Internationales De Pharmacodynamie Et De Thérapie
Interactions of cholinesterase inhibitors or dexamethasone with the hypnotic effect of benzodiazepines appear to be strongly dependent on the dose of the cholinesterase inhibitor used and to a lesser extent on the dose of the hypnotic. The duration of the loss of righting reflex caused by the benzodiazepines, diazepam or chlorodiazepoxide, is markedly prolonged by 500 micrograms/kg, significantly antagonized both diazepam and chlorodiazepoxide. Relatively higher doses of physostigmine have no significant effect on either diazepam or chlorodiazepoxide.
A case of an acute reversible visual loss in a 10-year-old child who was on mefloquine prophylaxis, and was treated with artesunate-amodiaquine for an acute febrile illness diagnosed clinically as uncomplicated malaria, is reported. On admission the patient could not perceive light and had bilateral papilloedema. She was treated with dexamethasone and recovered her sight gradually over a 21-day period.
The aim of this work was to study the influence of the hormonal milieu on the facilitory effects of olfactory stimuli originating from female urine on lordosis behavior in orchidectomized (ORCH) feminized rats. Urine from ovariectomized (OVX) rats was shown to increase the proportion of ORCH rats displaying lordosis behavior, an effect which was enhanced if the OVX rats had been given progesterone. Treatment of OVX rats with estradiol benzoate did not affect the pheromonal activity of their urine.
