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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine-immune interactions are vital for the individual's survival in certain physiopathological conditions such as sepsis and tissular injury. It is known that several snake venoms (SV) are potent neurotoxic compounds and that their main component is a specific phospholipase type 2 (PLA2). It has been recently described that the venom from crotalus durissus terrificus (SV) possesses a cytotoxic effect in different in vitro and in vivo animal models. In the present study we investigated whether SV is able to stimulate both TNFalpha and neuroendocrine functions in a sexual dimorphic fashion. For this purpose the modulatory role of endogenous sex steroids during neurotoxemia was evaluated. Our results indicate that SV (25 microg/animal) stimulates the hypothalamo-pituitary-adrenal axis and TNFalpha secretion when administered (ip) to adult male mice, such responses were characterized by a time-related enhance in plasma glucose, ACTH, corticosterone and TNFalpha levels. SV-stimulated glycemia, corticosteronemia and adrenal glucocorticoid were sexually dimorphic. Twenty-day gonadectomized mice showed a similar sexual dimorphism to that found in intact animals, however, they additionally showed a sexual dimorphic pattern in cytokine release in plasma 30 min post-SV. Estradiol (E2) treatment, in gonadectomized mice, abolished some characteristics of the sexual dimorphism, such as hyperglycemia, hypercorticosteronemia and hypercytokinemia. Finally, in vitro experiments indicate that: a) gonadectomy increased spontaneous and SV-stimulated cytokine output by incubated peripheral mononuclear cells (PMNC), regardless of the sex; and b) despite E2 treatment, in gonadectomized, did not modify the pattern of basal and SV-elicited TNFalpha secretion induced by orchidectomy, fully reversed the enhance in basal and SV-stimulated cytokine release found after ovariectomy alone. Our results further indicate that neurotoxemia, due to SV challenge, induces several symptoms common to those of inflammatory stress; they also strongly support that both gender and endogenous sex steroids are responsible for neuroendocrine-immunological sexual dimorphism.
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PMID:Sexual dimorphism in the hypothalamo-pituitary-adrenal (HPA) axis and TNFalpha responses to phospholipase A2-related neurotoxin (from crotalus durissus terrifcus) challenge. 1100 68

To get insight in the endocrine and metabolic responses in children with meningococcal sepsis 26 children were studied the first 48 h after admission. On admission there was a significant difference in cortisol/ACTH levels between nonsurvivors (n = 8) and survivors (n = 18). Nonsurvivors showed an inadequate cortisol stress response in combination to very high ACTH levels, whereas survivors showed a normal stress response with significantly higher cortisol levels (0.62 vs. 0.89 micromol/L) in combination with moderately increased ACTH levels (1234 vs. 231 ng/L). Furthermore, there was a significant difference between nonsurvivors and survivors regarding pediatric risk of mortality score (31 vs. 17), TSH (0.97 vs. 0.29 mE/L), T3 (0.53 vs. 0.38 nmol/L), reverse T3 (rT3) (0.75 vs. 1.44 nmol/L), C-reactive protein (34 vs. 78 mg/L), nonesterified fatty acids (0.32 vs. 0.95 mmol/L), and lactate (7.3 vs. 3.2 mmol/L). In those who survived, the most important changes within 48 h were seen in a normalization of cortisol and ACTH levels, but without a circadian rhythm; a decrease of rT3 and an increase in the T3/rT3 ratio; and a decrease in the levels of the nonesterified free fatty acids and an unaltered high urinary nitrogen excretion. At this moment, it is yet unknown whether the hormonal abnormalities are determining factors in the outcome of acute meningococcal sepsis or merely represent secondary effects. Understanding the metabolic and endocrine alterations is required to design possible therapeutic approaches. The striking difference between nonsurvivors and survivors calls for reconsideration of corticosteroid treatment in children with meningococcal sepsis.
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PMID:Endocrine and metabolic responses in children with meningoccocal sepsis: striking differences between survivors and nonsurvivors. 1106 34

Septic shock in animals and humans is associated with thymic atrophy and generalized lymphocyte apoptosis that impairs T cell responses. Injection of animals with E. coli lipopolysaccharide (LPS) mimics bacterial sepsis-induced thymic atrophy. Leukemia inhibitory factor (LIF) induces pituitary ACTH release in vivo, and LIF administration to mice induces acute thymic atrophy. We have investigated the role of LIF in LPS-induced thymic atrophy. LPS significantly elevated serum LIF within 1 h and induced thymic LIF mRNA within 6 h. Moreover, pretreatment of mice with anti-LIF antibody significantly reduced LPS-induced thymic atrophy. Using adrenalectomized mice and 17-day fetal thymic organ cultures treated with the steroidogenic enzyme inhibitor metyrapone, we demonstrated that LIF induced both systemic and intrathymic corticosteroid production. These data demonstrate systemic and intrathymic pathways of E. coli LPS-induced acute thymic atrophy mediated by LIF and corticosteroids.
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PMID:Leukemia inhibitory factor is a mediator of Escherichia coli lipopolysaccharide-induced acute thymic atrophy. 1238 26

Leptin, which plays a key role in regulating energy homeostasis, may also modulate the inflammatory response. An inflammatory challenge with endotoxin has been shown to stimulate leptin release in the rodent. This finding has not been reproduced in humans or in nonhuman primates, although leptin levels have been reported to increase in septic patients. We have therefore examined the effects of endotoxin injection on plasma leptin levels in nine ovariectomized monkeys and four postmenopausal women. In an initial study in five monkeys, mean leptin levels did not increase during the first 5 h after endotoxin treatment, but did increase significantly from 6.4 +/- 2.1 ng/ml at baseline to 12.3 +/- 4.4 ng/ml at 24 h (P = 0.043). In a second study, a significant increase in leptin over time was noted after endotoxin treatment (P < 0.001); leptin release during the 16- to 24-h period after endotoxin injection was 48% higher than during the control period (P = 0.043). A similar stimulatory effect of endotoxin on leptin was observed when monkeys received estradiol replacement. In a third study, repeated injections of endotoxin over a 3-d period stimulated IL-6, ACTH, cortisol, and leptin release (P < 0.001). Leptin increased during the first day of treatment in all animals, but only monkeys with baseline plasma leptin levels greater than 10 ng/ml exhibited a sustained increase in leptin throughout the 3-d period. There was a significant correlation (r = 0.81; P = 0.008) between the mean baseline leptin level and the percent increase in leptin over baseline on the last day of treatment. In the human subjects, plasma leptin concentrations did not change significantly during the 7-h period after endotoxin injection. However, leptin increased in all four women from a mean baseline of 8.34 +/- 3.1 to 13.1 +/- 4.3 ng/ml 24 h after endotoxin (P = 0.038). In summary, endotoxin stimulates the release of leptin into peripheral blood in the human and nonhuman primate, but the time course is different from that reported in the rodent. These results are consistent with previous reports of increased blood leptin levels in patients with sepsis. The significance of these findings and the potential role of leptin in modulating the response to inflammation in the human require further study.
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PMID:Endotoxin stimulates leptin in the human and nonhuman primate. 1262 20

After a period of initial enthusiasm, several trials cast serious doubts on the usefulness of corticosteroids for the treatment of patients with severe sepsis. Short course with high doses of steroides should not be given in patients with severe sepsis. The attention is now addressed to low-dose of corticosteroides. The rational for a replacement therapy with hydrocortisone in patients with cathecolamines-dependent septic shock is based on the concept that this may be complicated by an occult adrenal insufficiency and a glucocorticoid peripheral resistance syndrome. Low doses of hydrocortisone has been shown to reproduce the normal effects of cortisol: anti-inflammatory properties and an increased in the vasoconstrictor response to cathecolamines. There is no concordance in literature about the role of replacement therapy with hydrocortisone on survival in patients with septic shock. Waiting for the results of the European confirmatory phase III trial, and based on the results of the French phase III trial, one may recommended to treat septic shock patients who have a cortisol increment after ACTH of less than 9 micro g/dl with 50 mg of hydrocortisone every 6 hours for seven days combined with 50 micro g of fludrocortisone once a day for seven days.
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PMID:Sepsis clinical knowledge: a role of steroid treatment. 1276 16

An experimental model that produces adrenal cortical hemorrhage with endotoxin has been described. When stimulated by thorotrast, endotoxin, or its tropic hormone (ACTH), the adrenal cortex is susceptible to the development of a hemorrhagic reaction during endotoxemia. The hemorrhagic reaction resembles that described in the Waterhouse-Friderichsen syndrome. A pathophysiologic mechanism for the occurrence of adrenal hemorrhage occurring during acute sepsis is presented. Increased metabolic activity associated with the production of corticosteroids seems to make the adrenal cortex susceptible to endotoxin-induced hemorrhage. Adrenal hemorrhage observed during sepsis, as in the Waterhouse-Friderichsen syndrome, may be attributable to endotoxemia occurring during or shortly after stimulation of the adrenal cortex by infection. Significant differences between adrenal cortical hemorrhage and the Shwartzman phenomenon are described.
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PMID:ENDOTOXEMIA AND ADRENAL HEMORRHAGE. A MECHANISM FOR THE WATERHOUSE-FRIDERICHSEN SYNDROME. 1426 70

Recent studies have shown that administration of hydrocortisone may lead to a reduction of catecholamines and to an improved outcome in septic patients. However, there are no data on the use of hydrocortisone in burn patients although in these patients reduction of vasopressors might be even more crucial for outcome due to improvement of skin perfusion. This study presents the first results on the impact of hydrocortisone administration in norepinephrine dependent severely burned patients. In a prospective cohort study fourteen consecutive severely burned patients received, 12h after norepinephrine dependency, a hydrocortisone bolus of 100mg followed by 0.18mg/(kgh) hydrocortisone. The course of the necessary norepinephrine dose, as well as the fluid balance was documented 12h prior and after the first dosage of hydrocortisone. Statistical analysis showed an unexpected increase of the required norepinephrine dosage. A statistical post hoc evaluation of surviving and non-surviving patients revealed a significant increase of norepinephrine in non-survivors whereas in survivors it was possible to reduce norepinephrine significantly. Furthermore, the median fluid requirement of surviving patients could be significantly reduced whereas in the group of non-survivors there was no change of volume needed. Our data suggests that hydrocortisone might be useful in selected patients with severe burn injuries. However, patients not responding to hydrocortisone administrations seem to have a poor prognosis. Our findings are in contrast to previously published data on septic patients, in whom hydrocortisone administration resulted in a reduction of norepinephrine. In burned patients the severity of trauma seems to have more profound influence on the pathophysiological mechanism of sepsis. Due to the high number of non-responders, the potential immune suppression and impaired wound healing caused by the side effects of hydrocortisone, further selection criteria seem to be necessary. A short ACTH-test might be considered prior to hydrocortisone administration to select patients who might benefit from this therapy. In summary, further prospective controlled studies will be necessary to establish hydrocortisone in the routine therapy of severely burned patients.
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PMID:Hydrocortisone improved haemodynamics and fluid requirement in surviving but not non-surviving of severely burned patients. 1455 32

A 69-year-old female having a large left adrenal mass and a nodular lesion in thyroid gland was admitted to the hospital. Endocrinologically she showed high levels of plasma ACTH and cortisol, which were not suppressed by high dose dexamethasone, elevated serum parathyroid hormone and markedly increased daily urinary excretion of catecholamines. She died of sepsis, and postmortem examination was performed. A left adrenal pheochromocytoma, which was immunohistochemically proven to be ACTH producing, a papillary thyroid carcinoma and parathyroid adenomas were found. To our knowledge this is the first report of coexistence of these three endocrine tumors in a single patient.
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PMID:[Multiple endocrine neoplasia]. 1514 27

Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the main adrenal androgens (AAs) produced in humans. Production of these steroids, like that of cortisol, is under the control of hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH. Other factors, however, appear to be involved in AA secretion because there are many instances in which their circulating levels do not change in parallel to those of cortisol. Apart from physiological alterations associated with fetal adrenal regression, adrenarche and aging, the main instances of divergence in AA production compared with those of corticosteroids occur when immune function is activated or is aberrant. Relative reductions in DHEA and DHEAS have been noted in subjects with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV) and autoimmune deficiency syndrome (AIDS), sepsis, and trauma. In some instances, differences in the AA responses have been linked to a clinical course. The mechanisms for impairments in AA production in the absence of suppressed corticoid secretion are unclear but may involve circulating cytokines or locally released mediators from immune system cells in the adrenal gland. There also is evidence that DHEA and DHEAS play a role in immune competence, displaying biological effects opposite to those of corticosteroids.
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PMID:Adrenal androgens and the immune system. 1563 95

We report a newborn girl (36th week of gestation, birth weight 1,054 g) with Cushing's syndrome secondary to nodular adrenocortical hyperplasia with normal plasma ACTH levels. From birth she was hypertensive, hyperglycaemic and slightly hirsuit. Hypercortisolaemia (>1,380 nmol/l) was accompanied by normal plasma ACTH levels (8.64-23.9 pg/ml). A 48-h dexamethasone suppression test decreased plasma cortisol by 35%, indicating some degree of ACTH dependency. However, there was no ACTH rise on CRF test. MRI showed enlarged adrenal glands with a possible cyst on the right; the pituitary gland was normal. At the age of 6 weeks she underwent bilateral adrenalectomy. Histology showed enlarged adrenals with multiple non-pigmented nodules (up to 5 mm) in both glands. However, over the next few weeks she developed liver failure and sepsis. She died at the age of 3 months. Post mortem examination confirmed the diagnosis. Nodular adrenocortical hyperplasia may present at birth with severe Cushing's syndrome and unsuppressed ACTH levels, indicating some degree of ACTH dependency in this condition.
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PMID:Prenatal Cushing's syndrome secondary to nodular adrenocortical hyperplasia with unsuppressed plasma ACTH levels. 1645 60


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