Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms of action of monoamine oxidase inhibitors (MAOIs) suggest that patients taking them may respond with hyper- or hypotension when undergoing coronary artery surgery. We describe a case where MAOIs were present and fentanyl and midazolam were the anaesthetic agents used. The anaesthesia and surgery were performed without incident. Postoperative ICU care was complicated by hypertension, hyperthermia, and severe shivering followed by hypotension resistant to therapy and finally death. Diagnoses of pulmonary embolism and sepsis were unproven and may have played a role. The MAOIs may also have played a role. Reactions in patients while taking both meperidine and MAOIs are unusual and animals react differently from humans to a combination of MAOIs and narcotics. There are only five reported cases where fentanyl was given to patients on MAOIs. We conclude that, until there is more information, MAOIs should be discontinued, if possible, before surgery in which catecholamines may be needed.
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PMID:MAO inhibitors and coronary artery surgery: a patient death. 146 33

Similar neurological disturbances and metabolic alterations have been observed in liver insufficiency and in bacterial sepsis. In both liver failure and sepsis an altered neurotransmitter profile in the central nervous system (CNS) has been implicated in the pathogenesis of encephalopathic symptoms. It has been suggested that equivalent disturbances in brain neurotransmitters, especially serotonin, play a role in the encephalopathy accompanying sepsis and liver failure. The objective of this study was to compare the CNS serotonin metabolism in rats with an end-to-side portacaval shunt (PCS) with that found in rats with 12 or 24 hr of intraabdominal sepsis. The metabolism of CNS serotonin was estimated after inhibition of two enzymes acting in the 5-hydroxyindole synthetic pathway (decarboxylase and monoamine oxidase). The 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in different regions of the CNS, thereby permitting evaluation of the synthetic activity of the serotonin neurotransmitter system. As previously reported, a marked increase in CNS serotonin synthetic rate was noted following PCS. In contrast, and in contradistinction to several recent reports, no major changes in the CNS serotonin synthesis rate were present following 12 or 24 hr of sepsis. CNS levels of the serotonin metabolite 5-HIAA were elevated in both sepsis and PCS rats. These data indicate that sepsis and liver failure have different effects upon serotonin metabolism in the CNS and suggest that differing pathogenetic mechanisms may underlie the encephalopathy clinically associated with these conditions.
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PMID:Serotonin metabolism in the central nervous system following sepsis or portacaval shunt in the rat. 244 49

The induction of inducible nitric oxide synthase (iNOS) serves an important immuno-protective function in inflammatory states, but ungoverned nitric oxide (NO) generation can contribute to a number of pathologic consequences. Delineation of the mechanisms that can downregulate iNOS-generated NO in inflammation could have therapeutic relevance. Here we show that agmatine, a metabolite of arginine, inhibits iNOS mediated nitric oxide generation in cytokine stimulated cell culture preparations. This effect was not cell type specific. Increased diamine oxidase (DAO) and decreased aldehyde dehydrogenase (AldDH) activities are also representative of inflammatory settings. Increasing the conversion of agmatine to an aldehyde form by addition of purified DAO or suppression of aldehyde breakdown by inhibition of AldDH activity increases the inhibitory effects of agmatine in an additive fashion. Inhibitors of DAO, but not monoamine oxidase (MAO), decreased the inhibitory effects of agmatine, as did the addition of AldDH or reacting aldehydes with phenylhydrazine. We examined rats given lipopolysaccharide (LPS) to evaluate the potential effects of agmatine in vivo. Endotoxic rats administered agmatine prevented the decreases in blood pressure and renal function normally associated with sepsis. Agmatine treatment also increased the survival of LPS treated mice. Our data demonstrate the capacity of agmatine aldehyde to suppress iNOS mediated NO generation, and indicate a protective function of agmatine in a model of endotoxic shock. How agmatine may aid in coordinating the early NO phase and the later repair phase responses in models of inflammation is discussed.
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PMID:Suppression of inducible nitric oxide generation by agmatine aldehyde: beneficial effects in sepsis. 1147 57

Linezolid is a synthetic antimicrobial agent of the oxazolidinone class with weak, nonspecific inhibitor of monoamine oxidase enzymes. Concomitant therapy with an adrenergic or serotonergic agent or consuming tyramine (>100 mg/day) may induce serotonin syndrome (SS). We present a case report of near-fatal adverse interaction between linezolid and escitalopram inducing SS in a 65-year-old woman with sepsis, under empirical antibiotic treatment. This report also summarizes the current relevant literature as identified via PubMed, EMBASE, and PsycINFO, supplemented with a manual search of cross references.
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PMID:Linezolid-induced near-fatal serotonin syndrome during escitalopram therapy: case report and review of literature. 2437 9

Acute kidney injury (AKI) refers to an abrupt decrease in kidney function. It affects approximately 7% of all hospitalized patients and almost 35% of intensive care patients. Mortality from acute kidney injury remains high, particularly in critically ill patients, where it can be more than 50%. The primary causes of AKI include ischemia/reperfusion (I/R), sepsis, or nephrotoxicity; however, AKI patients may present with a complicated etiology where many of the aforementioned conditions co-exist. Multiple bio-markers associated with renal damage, as well as metabolic and signal transduction pathways that are involved in the mediation of renal dysfunction have been identified as a result of the examination of models, patient samples, and clinical data of AKI of disparate etiologies. These discoveries have enhanced our ability to diagnose AKIs and to begin to elucidate the mechanisms involved in their pathogenesis. Studies in our laboratory revealed that the expression and activity of spermine/spermidine N1-acetyltransferase (SAT1), the rate-limiting enzyme in polyamine back conversion, were enhanced in kidneys of rats after I/R injury. Additional studies revealed that the expression of spermine oxidase (SMOX), another critical enzyme in polyamine catabolism, is also elevated in the kidney and other organs subjected to I/R, septic, toxic, and traumatic injuries. The maladaptive role of polyamine catabolism in the mediation of AKI and other injuries has been clearly demonstrated. This review will examine the biochemical and mechanistic basis of tissue damage brought about by enhanced polyamine degradation and discuss the potential of therapeutic interventions that target polyamine catabolic enzymes or their byproducts for the treatment of AKI.
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PMID:Polyamine Catabolism in Acute Kidney Injury. 3156 75