Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine and glutamate with proline, histidine, arginine and ornithine, comprise 25% of the dietary amino acid intake and constitute the "glutamate family" of amino acids, which are disposed of through conversion to glutamate. Although glutamine has been classified as a nonessential amino acid, in major trauma, major surgery, sepsis, bone marrow transplantation, intense chemotherapy and radiotherapy, when its consumption exceeds its synthesis, it becomes a conditionally essential amino acid. In mammals the physiological levels of glutamine is 650 micromol/l and it is one of the most important substrate for ammoniagenesis in the gut and in the kidney due to its important role in the regulation of acid-base homeostasis. In cells, glutamine is a key link between carbon metabolism of carbohydrates and proteins and plays an important role in the growth of fibroblasts, lymphocytes and enterocytes. It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle. Deamidation of glutamine via glutaminase produces glutamate a precursor of gamma-amino butyric acid, a neurotransmission inhibitor. L-Glutamic acid is a ubiquitous amino acid present in many foods either in free form or in peptides and proteins. Animal protein may contain from 11 to 22% and plants protein as much as 40% glutamate by weight. The sodium salt of glutamic acid is added to several foods to enhance flavor. L-Glutamate is the most abundant free amino acid in brain and it is the major excitatory neurotransmitter of the vertebrate central nervous system. Most free L-glutamic acid in brain is derived from local synthesis from L-glutamine and Kreb's cycle intermediates. It clearly plays an important role in neuronal differentiation, migration and survival in the developing brain via facilitated Ca++ transport. Glutamate also plays a critical role in synaptic maintenance and plasticity. It contributes to learning and memory through use-dependent changes in synaptic efficacy and plays a role in the formation and function of the cytoskeleton. Glutamine via glutamate is converted to alpha-ketoglutarate, an integral component of the citric acid cycle. It is a component of the antioxidant glutathione and of the polyglutamated folic acid. The cyclization of glutamate produces proline, an amino acid important for synthesis of collagen and connective tissue. Our aim here is to review on some amino acids with high functional priority such as glutamine and to define their effective activity in human health and pathologies.
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PMID:II. Glutamine and glutamate. 1248 81

Auto transplantation of the spleen can be performed in the patients with traumatic rupture of the spleen, in whom spleen could not be conserved in the other way. The right indication for this method is isolated rupture of the spleen (concvasation or complete devascularisation). This method is not recommended in the endangered patients, patients with previous disease of the spleen as well as in the patients with the perforation of the other abdominal organs at the same time. Auto transplantation was performed in 12 patients with isolated splenic rupture and hematoperitoneum, 11 men and one woman. The majority of patients are younger. In 8 patients, autotransplant was placed into big omentum, in three into lipomatous tissue surrounding left kidney, and in one into anterior abdominal wall. In all the patients from this group, following analysis were taken: MCV (middle volume of erythrocytes), HTC, Hb, Le, Glucose, urea, creatinin, sodium, potassium, alkali phosphatasis, target cells, Howell Jolly's bodies, Heinz's bodies, IgG, IgA, IgM, C3, C4, T3, T4, T8, B, segmentated, eosinophiles, lymphocytes, reticulocytes, thrombocytes, fibrinogen, PT, APTT, aggregation of thrombocytes and aggregation of thrombocytes on collagen. The same parameters were taken in 12 patients with surgery similar to splenectomy and in 12 after splenectomy. After splenectomy, there was decrease of the immunologic defending abilities of the organism because of the loss of the childrens function of the spleen, decreased level of the opsonines and tutsin, which leads to the impaired phagocytosis, decreased concentration of IgM and T and B lymphocytes, while in patients after auto transplantation the results were physiological. The most important thing in the assessment of the function of the autotransplanted spleen is scintigraphic investigation using 99mTc-denaturated red blood cells. In our study, auto transplant function was assessed in 10/12 patients by scintigraphy. Five years after surgery, no one patient was proved to have postsplenectomic sepsis.
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PMID:[Autotransplantation of the spleen]. 1258 57

Severe illness with acute renal failure, leukopenia, thrombocytopenia, and coagulopathy frequently occurs with hemolytic uremic syndrome/thrombotic thrombocytopenic purpura, hematological malignancies, sepsis, and collagen-vascular diseases. We present a 16-year-old male fast-food worker with underlying chronic renal insufficiency who manifested these abnormalities as a result of Ehrlichia chaffeensis sepsis. Doxycycline therapy and aggressive supportive care led to complete recovery.
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PMID:Renal, hepatic, and marrow dysfunction in a patient with chronic renal insufficiency. 1264 28

Between 1985 and 2000, a total of 871 patients underwent surgical treatment for infrarenal abdominal aortic aneurysm (AAA), including 98 (11.2%) presenting with ruptured abdominal aortic aneurysms (RAAA). An optimized operative protocol was used to treat 77 RAAA starting in January 1989. The main features of the optimized protocol are routine use of intraoperative autotransfusion, revascularization by aortoaortic bypass, absence of systemic heparinization, and use of a collagen-impregnated prosthesis. Intraoperative mortality (IOM) was 3.8%. Postoperative mortality at 1 month (POM1) was 25.9% and postoperative mortality at 3 months (POM3) was 33.7%. Heart failure (p <0.001), hemodynamic shock (p <0.001), and hemorrhage (p = 0.04) were the only complications correlated with POM1. Pneumonia (p = 0.01) and sepsis (p = 0.01) were the only complications correlated with POM3. Isolated acute renal insufficiency was not a significant risk factor for postoperative mortality. Using a cutoff of 75 years, there was a significant age-related difference (p = 0.025) for POM1 but not for IOM and POM3. The findings of this study show that optimizing the operative protocol decreases mortality related to RAAA. The main predictor of POM1 was hemodynamic status while the main predictor of POM3 was infection. Isolated acute renal insufficiency was not a risk factor for mortality. Age should not be considered a contraindication for operative treatment.
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PMID:Ruptured aneurysm of the infrarenal abdominal aorta: impact of age and postoperative complications on mortality. 1270 41

In this study we aimed to investigate the findings in patients with adult-onset Still's disease (AOSD) admitted with fever of unknown origin (FUO) during the last 18 years in our unit, in order to discover the ratio of such patients to all patients with FUO during the same period, and to determine the clinical features of AOSD in FUO. The number and the aetiologies of the patients with FUO diagnosed between 1984 and 2001, and the clinical features of those with AOSD, were taken from the patient files. The diagnosis of AOSD was reanalysed according to the diagnostic criteria of Cush et al. [11]. The presumed diagnoses before a diagnosis of AOSD was established were also noted. The chi(2) and Fisher's exact tests were used for statistical analysis. We studied 130 patients with a diagnosis of FUO, 36 (28%) of whom had collagen vascular diseases. Of these 36 patients, 20 (56%, 12 female, 8 male, mean age 34 years, range 16-65) had AOSD. Clinical and laboratory findings were as follows: fever (100%), arthralgia (90%), rash (85%), sore throat (75%), arthritis (65%), myalgia (60%), splenomegaly (40%), hepatomegaly (25%), lymphadenopathy (15%), anaemia (65%), neutrophilic leukocytosis (90%), increased erythrocyte sedimentation rate (100%), elevated transaminase levels (65%), a negative RF (100%), and a negative FANA (80%). Antibiotics had been prescribed in 18 (90%) of cases. The presumed infectious diagnoses were streptococcal tonsillitis/pharyngitis (50%), infective endocarditis (four patients), sepsis (two patients) and acute bacterial meningitis (two patients). The presumed non-infectious diagnoses were acute rheumatic fever (three patients), seronegative rheumatoid arthritis (two patients) and polymyositis (two patients). Sixteen patients were followed for a mean duration of 30 months (range 2-59). A remission was obtained with indomethacin in three cases (19%), and with prednisolone in the remainder. Relapse was detected in three cases (19%). AOSD is one of the most frequent aetiologies of FUO. During the diagnostic course of a patient with FUO, a maculopapular rash and/or arthralgia and/or sore throat should raise the suspicion of AOSD. Because the disease has heterogeneous clinical findings, certain bacterial infections (e.g. streptococcal pharyngitis and sepsis) are generally considered and the prescribing of antibiotics is common.
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PMID:Fever of unknown origin: a review of 20 patients with adult-onset Still's disease. 1274 Jun 70

An acute septic inflammatory response with access to the portal circulation was created in a rat model using an intra-abdominal abscess composed of a sterile agar pellet, or one contaminated with 102 Escherichia coli (E. coli) and 109 Bacteriodes fragilis (B. fragilis). After 3 days postimplantation, a well-formed intra-abdominal abscess occurred whose wall showed IL-6 DNA by PCR and IL-6 mRNA by in situ hybridization. Portal venous blood draining into the liver from the intra-abdominal abscess had increased levels of TNF-alpha, IL-1beta, and IL-6 in both sterile and septic groups compared with a control normal animal group. Increased levels of these cytokines were also found in suprahepatic inferior vena caval blood, but were correlated with the higher portal vein levels, suggesting a gradient from abscess wall to portal vein into the systemic circulation via the liver. Liver histology demonstrated sinusoidal congestion centering on the central vein, growing worse with progression from normal in control, to sterile, to septic. Similarly, the degree of intrahepatic myeloperoxidase-positive inflammatory cell infiltration and hepatocellular lipid deposition and apoptosis also increased from control, to sterile, to septic. Gene expression by in situ hybridization demonstrated a significant increase in IL-6 and fibrinogen mRNAs in cells surrounding the central vein in sterile and septic animals, being greatest in animals with sepsis, associated with an increased deposition of collagen in the central vein area, most prominent in the septic liver. The pericentral vein cells with IL-6 and fibrinogen mRNA increases paralleled the increases in cells containing IL-6 and fibrinogen mRNAs in the abscess walls of sterile and septic animals, respectively. The data suggest that an intra-abdominal abscess, especially when contaminated with gram-negative bacteria, induces mRNA-generated cytokine responses in the abscess wall that are related to increased portal venous levels of the inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 perfusing the liver. These, in turn, induce localized production of IL-6 and fibrinogen mRNAs in cells at the central vein area with resultant outflow fibrosis and increased inflammatory cell sequestration within the liver lobular sinuses. This is associated with a generalized inflammatory response and intrahepatic portal sinusoid congestion. There is also increased hepatocellular lipid deposition and apoptosis. Thus, the cytokine production of the abscess wall itself appears to be a major mediator of the septic hepatic response.
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PMID:The septic abscess wall: a cytokine-generating organ associated with portal venous cytokinemia, hepatic outflow fibrosis, sinusoidal congestion, inflammatory cell sequestration, hepatocellular lipid deposition, and focal cell death. 1281 73

Matrix metalloproteinases (MMPs) are degradative enzymes, which act to remodel tissue. Their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). An imbalance in the degradation/inhibition activities has been associated with many diseases, including sepsis. We have previously shown that TIMP-3 knockout animals develop spontaneous, progressive air space enlargement. The objectives of this study were to determine the effects of a septic lung stress induced by cecal ligation and perforation (CLP) on lung function, structure, pulmonary surfactant, and inflammation in TIMP-3 null mice. Knockout and wild-type animals were randomized to either sham or CLP surgery, allowed to recover for 6 h, and then euthanized. TIMP-3 null animals exposed to sham surgery had a significant increase in lung compliance when compared with sham wild-type mice. Additionally, the TIMP-3 knockout mice showed a significant increase in compliance following CLP. Rapid compliance changes were accompanied by significantly decreased collagen and fibronectin levels and increased gelatinase (MMP-2 and -9) abundance and activation. Additionally, in situ zymography showed increased airway-associated gelatinase activity in the knockout animals enhanced following CLP. In conclusion, exposing TIMP-3 null animals to sepsis rapidly enhances the phenotypic abnormalities of these mice, due to increased MMP activity induced by CLP.
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PMID:Negative impact of tissue inhibitor of metalloproteinase-3 null mutation on lung structure and function in response to sepsis. 1290 86

Post-traumatic inflammation and sepsis induce changes in the lung microvasculature causing increased permeability. Pericytes, contractile cells positioned abluminally to endothelial cells, play a role in regulating this response. An in vitro model of microvascular lung pericytes (MLP) was used to investigate the effect of inhibiting heme oxygenase-1 (HO-1), a stress-induced enzyme, in the presence of varying levels of lipopolysaccharide (LPS), a mediator in the initiation of inflammation, on pericyte contractility. Rat MLP were cultured on collagen gel matrices. Cells were exposed to three concentrations of LPS in the presence of zinc protoporphyrin IX (ZnPP-9), a known inhibitor of HO-1. After 24 hours, the surface area of the collagen disks was quantified, thereby measuring pericyte contraction. ZnPP-9 caused a significant attenuation of the LPS-induced relaxation of the pericytes (P < or = 0.003). The effects of ZnPP-9, however, depended on the concentration of LPS to which the pericytes were exposed. Greater concentrations of LPS decrease the attenuating power of ZnPP-9. The inhibition of HO-1 diminished MLP relaxation triggered by LPS. The effect of ZnPP-9, however, is dependent on the concentration of LPS to which the MLP are exposed, indicating its saturation. ZnPP-9 may antagonize the microvascular response to trauma.
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PMID:Inhibition of heme oxygenase-1 in microvascular lung pericytes diminishes at high concentrations of an inflammatory mediator. 1501 17

For the second time in recent history, studies directed at the pathogenesis of infectious disease have led to the identification of an endogenous mediator of arthritis. HMGB1, a 30-kD nuclear and cytoplasmic protein widely studied as a DNA-binding protein, is a newly described cytokine and a necessary and sufficient mediator of lethal sepsis. HMGB1 is passively released during cell necrosis, but not apoptosis; it activates an inflammatory response to necrosis,but not apoptosis. Furthermore, HMGB1 can also be actively secreted by stimulated macrophages or monocytes in a process that requires acetylation of the molecule, enabling a translocation from the nucleus to secretory lysosomes. Recent evidence indicates that HMGB1 is a mediator of arthritis because of the following: (1) it is produced at the site of joint inflammation, (2) it causes the development of arthritis when applied to normal joints, and (3) therapies that inhibit HMGB1 prevent the progression of collagen-induced arthritis in rodents. Anti-HMGB1 may be studied in future clinical trials of diseases of excessive production of HMGB1, such as severe sepsis and arthritis.
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PMID:HMGB1 as a mediator of necrosis-induced inflammation and a therapeutic target in arthritis. 1526 45

Acute lung injury is usually a complication of sepsis, and endotoxin treatment of mice is a frequently used experimental model. To define this model and to clarify pathogenesis of the lung injury, we injected with 1 mg/kg endotoxin ip and measured pulmonary function, pulmonary edema, serum concentrations of cytokines and growth factors, and lung histology over 48 h. During the first 6 h, tidal volume and minute volume increased and respiratory frequency decreased. Serum concentrations of cytokines showed three patterns: 10 cytokines peaked at 2 h and declined rapidly, two peaked at 6 h and declined, and two had biphasic peaks at 2 and 24 h. Growth factors increased later and remained elevated longer. Both collagen and fibronectin were deposited in the lungs beginning within hours of endotoxin and resolving over 48 h. Histologically, lungs showed increased cellularity at 6 h with minimal persistent inflammation at 48 h. Lung water peaked at 6 h and gradually decreased over 48 h. We conclude that intraperitoneal administration of endotoxin to mice causes a transient systemic inflammatory response and transient lung injury and dysfunction. The response is characterized by successive waves of cytokine release into the circulation, early evidence of lung fibrogenesis, and prolonged increases in growth factors that may participate in lung repair.
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PMID:Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses. 1547 80


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