Anaesthetic aspects of simultaneous aortocaval occlusion

Major elective surgery is known to contribute to intensive care occupancy, with a significant mortality rate. Routine preoperative optimisation of patients undergoing major elective surgery is found to give a significant and cost effective improvement in perioperative care. Criteria that were used to select patients for routine preoperative optimisation for a large randomised controlled trial are shown at Table 1. When performing major surgery, the extent of necessary perioperative monitoring is usually dependent on the view of the anaesthetist, while the site of postoperative care is dependent on the anticipated development of complications and the availability of intensive care or high dependency beds

Local Control of Steroid Hormone Biosynthesis

Steroids are essential for vertebrate physiology during pre- and postnatal life. Whereas the skeleton structure of cyclopenta[α]phenanthrene rings is common to all steroid molecules, differences occur in methyl- of ethylgroups attached to the four rings or the oxidation state of the carbon atoms in the rings (Figure 1).1 Endogenous production of steroids is realized in steroidogenic tissues. From these tissues, steroid molecules can be secreted into the circulation to act in an endocrine fashion. By binding to receptors in target tissues they manipulate gene transcription, influencing a wide variety of cellular functions. Steroids can also exert local effects in the steroidogenic tissues after secretion into the extracellular space (paracrine or autocrine) or directly within the cell in which they are produced (intracrine)

Epigenetic Mechanisms Modulated by Glucocorticoids With a Focus on Cushing Syndrome

In Cushing syndrome (CS), prolonged exposure to high cortisol levels results in a wide range of devastating effects causing multisystem morbidity. Despite the efficacy of treatment leading to disease remission and clinical improvement, hypercortisolism-induced complications may persist. Since glucocorticoids use the epigenetic machinery as a mechanism of action to modulate gene expression, the persistence of some comorbidities may be mediated by hypercortisolism-induced long-lasting epigenetic changes. Additionally, glucocorticoids influence microRNA expression, which is an important epigenetic regulator as it modulates gene expression without changing the DNA sequence. Evidence suggests that chronically elevated glucocorticoid levels may induce aberrant microRNA expression which may impact several cellular processes resulting in cardiometabolic disorders. The present article reviews the evidence on epigenetic changes induced by (long-term) glucocorticoid exposure. Key aspects of some glucocorticoid-target genes and their implications in the context of CS are described. Lastly, the effects of epigenetic drugs influencing glucocorticoid effects are discussed for their ability to be potentially used as adjunctive therapy in CS.</p

Epigenetic Mechanisms Modulated by Glucocorticoids With a Focus on Cushing Syndrome

In Cushing syndrome (CS), prolonged exposure to high cortisol levels results in a wide range of devastating effects causing multisystem morbidity. Despite the efficacy of treatment leading to disease remission and clinical improvement, hypercortisolism-induced complications may persist. Since glucocorticoids use the epigenetic machinery as a mechanism of action to modulate gene expression, the persistence of some comorbidities may be mediated by hypercortisolism-induced long-lasting epigenetic changes. Additionally, glucocorticoids influence microRNA expression, which is an important epigenetic regulator as it modulates gene expression without changing the DNA sequence. Evidence suggests that chronically elevated glucocorticoid levels may induce aberrant microRNA expression which may impact several cellular processes resulting in cardiometabolic disorders. The present article reviews the evidence on epigenetic changes induced by (long-term) glucocorticoid exposure. Key aspects of some glucocorticoid-target genes and their implications in the context of CS are described. Lastly, the effects of epigenetic drugs influencing glucocorticoid effects are discussed for their ability to be potentially used as adjunctive therapy in CS.</p