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

Muscle biopsies for histochemical and ultrastructural analysis were obtained from seven critically ill patients admitted to the Intensive Care Unit of the "Domingo Luciani" Hospital, Caracas, Venezuela. The sample included two patients with sepsis of abdominal origin, and five that presented sepsis/MOFS, with renal, hepatic, and respiratory disturbances and muscular weakness. Sections were examined for myosin adenosine triphosphatase (ATPase) after pre-incubation with both acid buffer (pH 4.37 and 4.6) and alkaline buffer (pH 10.3), for reduced nicotinamide dinucleotide diaphorase (NADHd), and for alpha-glycerophosphate dehydrogenase (alpha-GPDH). Sections were stained with hematoxilin and eosin to look for pathological changes and examined with a transmission electron microscope. Skeletal muscle of patients in early stage of sepsis showed a normal aspect with light microscopy, but at the ultrastructural level some of the fibres showed atrophy and some capillaries looked altered. Patients with sepsis/MOFS exhibited an evident muscle disorder with oedema, infiltrate, atrophy and segmental necrosis. All fibre types showed decrease in diameter; specially fibre types IIA and IIB. Intramuscular capillaries were thickened and occluded, indexes of capillarity were slightly reduced, and fibre oxidative activity was decreased. At ultrastructural level fibres showed severe atrophy, contractile system disorganization and segmental necrosis. Capillaries were also altered and the mononuclear cell infiltrate was abundant and represented by macrophages, lymphocytes and mastocytes.
 ...
PMID:Histochemical and ultrastructural study of skeletal muscle in patients with sepsis and multiple organ failure syndrome (MOFS). 947 42

In the present study, we have characterized the dihydrolipoamide dehydrogenase (DLDH) of Strepto-coccus pneumoniae and its role during pneumococcal infection. We have also demonstrated that a lack of DLDH results in a deficiency in alpha-galactoside metabolism and galactose transport. DLDH is an enzyme that is classically involved in the three-step conversion of 2-oxo acids to their respective acyl-CoA derivatives, but DLDH has also been shown to have other functions. The dldh gene was virtually identical in three pneumococcal strains examined. Besides the functional domains and motifs associated with this enzyme, analysis of the pneumococcal dldh gene sequence revealed the presence of an N-terminal lipoyl domain. DLDH-negative bacteria totally lacked DLDH activity, indicating that this gene encodes the only DLDH in S. pneumoniae. These DLDH-negative bacteria grew normally in vitro but were avirulent in sepsis and lung infection models in mice, indicating that DLDH activity is necessary for the survival of pneumococci within the host. The lack of virulence was not associated with a loss of 2-oxo acid dehydrogenase activity, as the wild-type pneumococcal strains did not contain activity of any of the known 2-oxo acid enzyme complexes. Instead, studies of carbohydrate utilization demonstrated that the DLDH-negative bacteria were impaired for alpha-galactoside and galactose metabolism. The DLDH mutants lost their ability to oxidize or grow with galactose or melibiose as sole carbon source and showed reduced oxidation and growth on raffinose or stachyose. The bacteria had an 85% reduction in alpha-galactosidase activity and showed virtually no transport of galactose into the cells, which can explain these phenotypic changes. The DLDH-negative bacteria produced only 50% of normal capsular polysaccharide, a phenotype that may be associated with impaired carbohydrate metabolism.
 ...
PMID:Characterization of the dihydrolipoamide dehydrogenase from Streptococcus pneumoniae and its role in pneumococcal infection. 1197 81

Although 4-hydroxy-2-nonenal (HNE, a product of lipid peroxidation) is a major cause of oxidative damage inside skeletal muscles, the exact proteins modified by HNE are unknown. We used two-dimensional electrophoresis, immunoblotting, and mass spectrometry to identify selective proteins targeted by HNE inside the diaphragm of rats under two conditions: severe sepsis [induced by E. coli lipopolysaccharides (LPS)] and during strenuous muscle contractions elicited by severe inspiratory resistive loading (IRL). Diaphragm HNE-protein adduct formation (detected with a polyclonal antibody) increased significantly after 1 and 3 h of LPS injection with a return to baseline values thereafter. Similarly, HNE-protein adduct formation inside the diaphragm rose significantly after 6 but not 3 h of IRL. Mass spectrometry analysis of HNE-modified proteins revealed enolase 3b, aldolase and triosephosphate isomerase 1, creatine kinase, carbonic anyhdrase III, aconitase 2, dihydrolipoamide dehydrogenase, and electron transfer flavoprotein-beta. Measurements of in vitro enolase activity in the presence of pure HNE revealed that HNE significantly attenuated enolase activity in a dose-dependent fashion, suggesting that HNE-derived modifications have inhibitory effects on enzyme activity. We conclude that lipid peroxidation products may inhibit muscle contractile performance through selective targeting of enzymes involved in glycolysis, energy production as well as CO(2) hydration.
 ...
PMID:Modifications of proteins by 4-hydroxy-2-nonenal in the ventilatory muscles of rats. 1660 97