Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenal insufficiency is believed to occur frequently in severe sepsis and septic shock. The aim of the present study was to determine whether adrenal function is also related to the severity of community-acquired pneumonia (CAP). In total, 64 Japanese patients with CAP were consecutively enrolled in the present study, which was carried out during 2005-2006. Serum adrenocorticotropic hormone (ACTH) and cortisol were measured in each subject, as was the response of cortisol secretion when 250 mug of cosyntropin was administered. Analyses were performed comparing these values with the score calculated according to the Pneumonia Patient Outcomes Research Team (PORT) cohort study, the number of in-hospital deaths and the length of hospital stay. As the PORT score increased, serum ACTH and cortisol also increased, while the response of cortisol secretion to the administration of cosyntropin decreased. In the analysis by receiver operating characteristic curves, adrenal dysfunction was related significantly to both the number of in-hospital deaths and the length of hospital stay. Adrenal dysfunction was shown to correlate with the Pneumonia Patient Outcomes Research Team score and the clinical outcomes, while adrenal insufficiency defined by the cosyntropin stimulation test was rare in the present study.
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PMID:Adrenal function in patients with community-acquired pneumonia. 1851 53

Ectopic adrenocorticotropin (ACTH) secretion accounts for less than 10% of all causes of endogenous Cushing's syndrome (CS) and is usually associated with neuroendocrine tumors and small cell carcinoma of the lung. We report the case of a 62-year-old man with CS due to ectopic ACTH production by small cell carcinoma of the prostate. He presented with severe hypercortisolism and associated symptoms. Plasma neuron specific enolase (NSE) was grossly elevated. Despite performing a laparoscopic bilateral adrenalectomy, the patient died as a result of sepsis with multi-organ failure. Post-mortem immunohistochemical staining of prostate tumor tissue showed ACTH expression. ACTH staining was also performed in four additional patients with small cell carcinoma of the urinary tract without CS. None of these additional cases showed a positive staining for ACTH. Although a rare cause of ectopic ACTH production, neuroendocrine prostate carcinoma should be considered in male patients with Cushing's syndrome, in particular in those with an occult source of ACTH overproduction.
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PMID:Cushing's syndrome due to ectopic ACTH production by (neuroendocrine) prostate carcinoma. 1832 2

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. alpha-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new alpha-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 h after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-alpha and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-kappaB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis.
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PMID:AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality. 1835 76

This is a review of the management of septic shock that suggests an approach to treatment (ABCDEF: Airway, Breathing, Circulation, Drugs, Evaluate the source of sepsis, Fix the source of sepsis) for clinicians. The incidence of septic shock is increasing and mortality ranges from 30% to 70%. The commonest sources of infection are lung (25%), abdomen (25%), and other sources. Septic shock occurs because of highly complex interactions between the infecting microorganism(s) and the responses of the human host. The innate immune response is rapidly followed by the more specific adaptive immune response. Septic shock is characterized by alterations in the coagulant/anticoagulant balance such that there is a more pro-coagulant phenotype. Lung protective ventilation (which means the use of relatively low tidal volumes of 4 -6 mL/kg ideal body weight) is recommended for treatment of patients who have septic shock. Rivers early goal-directed therapy is recommended because it showed a significant increase in survival. Surviving Sepsis guidelines recommend resuscitation of septic shock with either crystalloid or colloid. Patients who have septic shock should be treated with intravenous broad-spectrum antibiotics as rapidly as possible and certainly within one hour. Activated protein C (APC) is a vitamin K dependent serine protease that is an anticoagulant and is also cytoprotective and anti-inflammatory. APC (24 mg/kg/hour infusion for 96 hours) decreased mortality (APC 25% vs placebo 31%, relative risk 0.81P=0.005) and improved organ dysfunction in patients at high risk of death (e.g. APACHE II >25 [APC 31% vs placebo 44%]). APC is not recommended to treat surgical patients who have one organ system dysfunction. In 2006, the European regulatory authority indicated that there must be another randomized placebo-controlled trial of APC to further establish efficacy as assessed by mortality reduction. Vasopressin is a key stress hormone in response to hypotension. The VASST study was a randomized trial of vasopressin versus norepinephrine in septic shock. There was no difference in mortality between vasopressin versus norepinephrine-treated patients (35% versus 39% respectively). In patients who had less severe septic shock, patients treated with vasopressin may have lowered mortality compared with norepinephrine (26% vs 36%). Annane et al. found that hydrocortisone plus fludrocortisone (compared to placebo) was associated with lower mortality in patients who had an inadequate response to corticotropin stimulation test (mortality 53% vs 63% respectively). Sprung et al. did a randomized controlled trial of hydrocortisone (50 mg intravenously every 6 hours) compared to placebo (CORTICUS) to address lingering questions regarding the Annane trial. There was no difference in mortality (39.2% hydrocortisone vs 36.1%) or organ dysfunction. Several randomized controlled trials of intensive insulin versus conventional insulin in the critically ill have yielded conflicting results and do not support the routine use of intensive insulin in the ancillary management of septic shock. A recent randomized controlled trial of intensive versus less intensive renal support in patients who had acute kidney injury found no difference in mortality (53.6% vs 51.5% respectively), duration of renal support, or rates of recovery of renal and non-renal organ dysfunction.
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PMID:The current management of septic shock. 1897 11

A 21-year-old man with signs and symptoms of rapidly progressive shock was admitted to the intensive care unit for treatment of suspected sepsis. Levels of inflammatory markers (including procalcitonin) were highly elevated, but no obvious focus of infection was apparent. Initial sepsis therapy included administration of broad-spectrum antibiotics, vasoconstrictors, and drotrecogin alfa. Cultures of blood, sputum, and urine showed no growth, and no viruses were detected. The random (no stimulation with corticotropin) cortisol level at admission was less than 25 nmol/L. Assays for autoantibodies to the adrenal cortex were strongly positive and confirmed the diagnosis of adrenal failure caused by Addison disease. After initiation of steroid therapy, the patient fully recovered. Although increased procalcitonin levels are considered a reliable and specific indicator of severe generalized infections and bacterial sepsis, elevated procalcitonin levels cannot be relied on when trying to differentiate between addisonian crisis and septic shock.
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PMID:An unusual case of progressive shock and highly elevated procalcitonin level. 1930 64

The inflammatory and immune responses evoked in sepsis may create not only an acute brain dysfunction, which occurs in the majority of septic patients, but also long-term deficits such as memory impairment. In this context, we evaluated depressive-like parameters in sepsis survivor rats. For this purpose, male Wistar rats, weighing 300-350 g, underwent cecal ligation and perforation (CLP) (sepsis group) followed by "basic support", or were sham-operated (control group). After 3 days of the sepsis procedure, the animals were treated with imipramine at 10 mg/kg or saline during 14 days (days 3-17). The consumption of sweet food was measured for 7 days (days 10-17) and the body weight was measured before CLP, 10, and 17 days after CLP. Seventeen days after sepsis (immediately after sweet food consumption measurement), the animals were anesthetized and blood was withdrawn for the analyses of corticosterone and adrenocorticotropic hormone (ACTH) levels, and immediately killed by decapitation. The adrenal gland and hippocampus were immediately isolated and weighed, and the hippocampus was utilized for determining brain-derived neurotrophic factor (BDNF) levels. It was observed that animals subjected to CLP presented decreased sucrose intake. Septic rats did not increase body weight and presented an increase in the weight of adrenal gland. Both corticosterone and ACTH levels were increased, while hippocampus weight and BDNF levels in the hippocampus decreased. The treatment with imipramine reversed all the parameters described above. Our results supported the hypothesis that rats that survive sepsis show depressive-like behavior, alterations in the hypothalamus-pituitary-adrenal axis, and decreased BDNF levels in the hippocampus.
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PMID:Depressive-like parameters in sepsis survivor rats. 1970 13

We report a case of a 65-year-old lady who presented with acute confusion and profound hyponatraemia (plasma sodium of 97 mmol/L). Five years earlier she had developed sepsis and was found to have hyponatraemia, thought to be due to syndrome of inappropriate antidiuretic hormone secretion. The patient was lost to follow-up. The patient was covered with steroids and investigations confirmed primary adrenal failure with flat response of cortisol to adrenocorticotropic hormone (ACTH) stimulation and very high level of ACTH. Adrenal auto-antibodies were negative and a computed tomography of the adrenals showed bilateral adrenal calcifications, suggestive of previous haemorrhage or infarction. Bilateral adrenal calcification due to haemorrhage/infarction usually does not present with severe hyponatraemia; however, adrenal insufficiency should be excluded in all cases of severe hyponatraemia. In suspected cases, patients should be treated with steroids, even when symptoms or signs are absent, while results of investigations are awaited.
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PMID:An unusual case of profound hyponatraemia and bilateral adrenal calcifications. 1979 4

The concept of relative adrenal insufficiency in patients with severe sepsis continues to be controversial. This arises in part from the lack of an accepted "gold standard" for the diagnosis of adrenal insufficiency in the critically ill. Historically, assessment of adrenal function in this population has relied on measurement of plasma total cortisol level, in a blood sample taken either at random or as part of a corticotropin stimulation test. However, an alternative is to focus on the site of glucocorticoid activity within the tissues as a potentially more useful index of functional adrenal status. We review the mechanisms known to affect tissue glucocorticoid activity and examine how they may be modified by critical illness. These include both free and interstitial cortisol concentrations, intracellular cortisol generation, and glucocorticoid-receptor activity and density. Changes in these factors are not reflected in plasma total cortisol concentrations, and more sophisticated techniques, including genetic transcriptional surveys, may be required to reveal the role of glucocorticoid insufficiency in critical illness.
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PMID:Assessment of tissue cortisol activity. 2000 69

Sepsis is characterized by a systemic inflammatory response of the immune system against an infection, presenting with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, behavior alterations, and high mortality. In this study, we aimed to evaluate the effects of dexamethasone on mortality, anhedonia, circulating corticosterone and adrenocorticotropin hormone (ACTH) levels, body and adrenal gland weight, and aversive memory in sepsis survivor rats. Male Wistar rats underwent sham operation or cecal ligation and perforation (CLP) procedure. Rats subjected to CLP were treated with "basic support" and dexamethasone (at 0.2 and 2mg/kg daily for 7 days after CLP, intraperitonially) or saline. After 10 days of sepsis procedure, it was evaluated aversive memory, sweet food consumption, and body and adrenal gland weight. Serum and plasma were also obtained. It was observed that low dose dexamethasone reverted anhedonia, normalized adrenal gland and body weight, corticosterone and ACTH levels, and decreased mortality and avoidance memory impairment, demonstrating that low doses of dexamethasone for moderate periods may be beneficial for sepsis treatment and its sequelae-depressive-like parameters and memory impairment.
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PMID:Low dose dexamethasone reverses depressive-like parameters and memory impairment in rats submitted to sepsis. 2018 44

The hypothalamic-pituitary-adrenal (HPA) axis response in sepsis remains to be elucidated. Apart from corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol, many other neuroendocrine factors participate in the regulation of HPA stress response. The HPA response to acute and chronic illness exerts a biphasic profile. Tissue corticosteroid resistance may also play an important role. All of these add to the complexity of the concept of 'relative adrenal insufficiency' and may account for the difficulty of clinical diagnosis and for the conflicting results of corticosteroid replacement therapy in severe sepsis/septic shock. The study by Lesur and colleagues expands our understanding of the mechanism, and further study of HPA stress response is warranted.
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PMID:Sepsis-related stress response: known knowns, known unknowns, and unknown unknowns. 2061 66


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