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)

There were 52 patients with sepsis, 61.6% were over 60 years of age (63.3% of patients had septicemia, 36.7% had septicopyemia). The disease was caused by ++pyo-inflammatory diseases of the vessels in 34.6% and the urinary system in 17.3% of cases. Microbial causative agents were isolated from the blood in 83.3% of patients (monoculture in 46.6%, associations of microorganisms in 36.6%; staphylococcus in 59.7%, gram-negative microflora in 46.7%). The most frequently encountered disorders of the immunological status were reduction of the number of lymphocytes and their T- (85%) and B-population (62.9%), increase of the level of immunoglobulins M (81.5%) and A (55.6%), decrease of the number of accessory T-cells (73.6%) and the ratio of accessory and suppressant T-cells (52.6%). Along with the application of antibacterial therapy, which relieved the microcirculatory blockage, and detoxication measures in the treatment of the purulent foci, much attention was paid to immunologic correction for the removal of primary and secondary insufficiency (endobulin, ++T-activin, isoprinosin). Blocking of the immunological reaction was relieved in 65.5% of patients by discrete plasmapheresis with compensation for the deficiency with endobulin, quick-frozen plasma, and rheopreparations. In the group of 52 patients 12 died (mortality 23.1%).
 ...
PMID:[Diagnosis and treatment of septicemia]. 146 67

Blocking the effects of cytokines is a potential new therapeutic avenue for the treatment of Gram-negative sepsis. Three classes of agents are currently being evaluated: antibodies, circulating inhibitors, and receptor antagonists. Data in the current literature support the consideration of these agents as potential therapeutic agents in Gram-negative sepsis. The clinical utility of these agents is contingent on the results of well-designed, prospective, randomized, placebo-controlled clinical trials in well-defined clinical populations. These trials will require the cooperation of clinical and basic scientists. At this time, preliminary and early clinical trials are in progress utilizing IL-1 and TNF-alpha circulating inhibitors, IL-1 receptor antagonists, and monoclonal antibodies to TNF-alpha and the TNF-alpha receptor.
 ...
PMID:Potential treatment of sepsis syndrome with cytokine-specific agents. 164 55

In vitro and in vivo experiments with Balb/c mice and Pseudomonas aeruginosa ATCC 27853 supported our hypothesis that bacterial lectins play an important role in the organotropy of infectious diseases. In vitro and in vivo adhesion of P. aeruginosa was mediated by N-acetylneuraminic acid (NANA) receptors. Blocking of the binding sites (lectins) on the bacterial surfaces with competitive specific carbohydrates (NANA) completely prevented the bacterial adhesion process in vitro. In vivo the number of adherent organisms in various organs decreased dramatically in the presence of NANA, whereas non-related carbohydrates (e.g. D-galactose) just showed negligible effects. Additionally, the application of NANA-treated organisms protected the animals from septicemia and death. Therefore, blocking of bacterial lectin receptors with specific carbohydrates might be of clinical relevance to prevent bacterial attachment to organ cells.
 ...
PMID:In vitro and in vivo inhibition of lectin mediated adhesion of Pseudomonas aeruginosa by receptor blocking carbohydrates. 311 98

Sepsis is associated with net breakdown of skeletal muscle protein, mediated partly by reduced rates of muscle protein synthesis. This study investigated the role of altered gene expression for specific muscle proteins in mediating reduced protein synthesis in a rat model of acute severe sepsis. Adult rats were given a single sublethal intraperitoneal dose of endotoxin (bacterial lipopolysaccharide). Protein, RNA and DNA contents of muscle were measured and changes in expression of mRNA in tibialis anterior and extensor digitorum longus muscles were detected by quantification of Northern blots at 6, 24, 48 and 72 hr after endotoxin and in animals starved for 24 hr. Results showed that at 24 hr after endotoxin there was a loss of about 14% of muscle protein content. No reduction in mRNA was found at any time point for beta-myosin heavy chain (MHC), fast-MHC, alpha-actin, skeletal muscle troponin or carbonic anhydrase III (CA III); rather, at 48 hr there was increased expression of beta-MHC (224 +/- 123% control) and CA III (202 +/- 56%). Blocking TNF-alpha by pre-treatment with a monoclonal antibody did not appear to influence this. Total RNA content of muscle was reduced to 67% of the control values 24 hr after LPS, although this was no different to pair-fed animals starved for 24 hr. It is concluded that reduced protein synthesis in skeletal muscle in early acute sepsis is not primarily associated with reduced muscle protein gene expression.
 ...
PMID:The effect of endotoxin on skeletal muscle protein gene expression in the rat. 869 96

Blocking the primary stages of infection, namely bacterial attachment to host cell receptors and colonization of the mucosal surface, may be the most effective strategy to prevent bacterial infections. Bacterial attachment usually involves an interaction between a bacterial surface protein called an adhesin and the host cell receptor. Recent preclinical vaccine studies with the FimH adhesin (derived from uropathogenic Escherichia coli) have confirmed that antibodies elicited against an adhesin can impede colonization, block infection, and prevent disease. The studies indicate that prophylactic vaccination with adhesins can block bacterial infections. With recent advances in the identification, characterization, and isolation of other adhesins, similar approaches are being explored to prevent infections, from otitis media and dental caries to pneumonia and sepsis.
 ...
PMID:Adhesins as targets for vaccine development. 1034 Nov 76

Lipopolysaccharide(LPS) is important in the pathogenesis of sepsis infected by gram-negative bacteria in humans, and part or all of this pathophysiology is mediated by a complex secondary inflammatory response. Administration of purified LPS or a variety of LPS-free recombinant mediators can reproduce much of the pathophysiology of gram-negative sepsis. There has been an explosion of new information over the last several years regarding the interactions of LPS with proteins and cells. Blocking sepsis at the bacterial toxin level is appealing because it is upstream, so that the secondary pathologic inflammatory cascade may be limited or prevented. A variety of antiendotoxin strategies have been proposed. Therapies under investigation include agents that bind and neutralize LPS, agents or systems that enhance LPS clearance, and agents that inhibit LPS interaction with serum elements or cellular receptors.
 ...
PMID:[The new antiendotoxin strategies]. 1151 92

Sepsis is a complex clinical syndrome resulting from a harmful host inflammatory response to infection. Chemokines and their receptors play a key role in the pathogenesis of sepsis. BX471 is a potent nonpeptide CC chemokine receptor-1 (CCR1) antagonist in both human and mouse. The aim of the present study was to evaluate the effect of prophylactic and therapeutic treatment with BX471 on cecal ligation and puncture-induced sepsis in the mouse and to investigate the underlying mechanisms. In sepsis induced by cecal ligation and puncture, treatment with BX471 significantly protected mice against lung and liver injury by attenuating MPO activity, an indicator of neutrophil recruitment in lungs and livers and attenuating lung and liver morphological changes in histological sections. Blocking CCR1 by BX471 also downregulated ICAM-1, P-selectin, and E-selectin expression at mRNA and protein levels in lungs and livers compared with placebo-treated groups. These findings suggest that blockage of CCR1 by specific antagonist may represent a promising strategy to prevent disease progression in sepsis.
 ...
PMID:Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic inflammatory response during sepsis. 1723 93

Increased tissue factor (TF)-dependent procoagulant activity in sepsis may be partly due to decreased expression or function of tissue factor pathway inhibitor (TFPI). To test this hypothesis, baboons were infused with live Escherichia coli and sacrificed after 2, 8, or 24 hours. Confocal and electron microscopy revealed increased leukocyte infiltration and fibrin deposition in the intravascular and interstitial compartments. Large amounts of TF were detected by immunostaining in leukocytes and platelet-rich microthrombi. TF induction was documented by quantitative reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and coagulation assays. Lung-associated TFPI antigen and mRNA decreased during sepsis, and TFPI activity diminished abruptly at 2 hours. Blocking antibodies against TFPI increased fibrin deposition in septic baboon lungs, suggesting that TF-dependent coagulation might be aggravated by reduced endothelial TFPI. Decreased TFPI activity coincided with the release of tissue plasminogen activator and the peak of plasmin generation, suggesting that TFPI could undergo proteolytic inactivation by plasmin. Enhanced plasmin produced in septic baboons by infusion of blocking antibodies against plasminogen activator inhibitor-1 led to decreased lung-associated TFPI and unforeseen massive fibrin deposition. We conclude that activation of TF-driven coagulation not adequately countered by TFPI may underlie the widespread thrombotic complications of sepsis.
 ...
PMID:Sepsis-induced coagulation in the baboon lung is associated with decreased tissue factor pathway inhibitor. 1764 Sep 67

Substance P (SP), acting on the neurokinin-1 receptor (NK-1R), is a neuropeptide, involved in the inflammatory processes. It promotes vasodilatation and increases vasopermeability, thus ensuing extravasation and accumulation of leucocytes at sites of injury. The aim of this study was to assess the impact of SP signalling on the responses during staphylococcal infection and the accompanying arthritis. Three experiments were performed where NK-1R-/- mice and controls were intravenously infected with different doses of Staphylococcus aureus. Clinical assessment of arthritis was performed as well as histological analysis of bone and cartilage destruction in the joints. In addition, the impact of NK-1R mutation on bacterial load in the kidneys as well as the phagocytic capacity of blood leucocytes were studied. Mice lacking the NK-1R displayed significantly higher bacterial load in the kidneys and significantly more severe synovitis and cartilage/bone destruction than the controls when inoculated with 1.4 x 10(7) staphylococci. Infection with 3.5 x 10(8) CFU/mouse induced sepsis. Thus, 11 days after bacterial inoculation 15 of 19 mice in the NK-1R-/- group had died versus 8 of 15 in the control group. Phagocytosis test revealed that significantly fewer macrophages from NK-1R-/- mice were able to phagocytose S. aureus when compared with macrophages from congenic control mice. Blocking the biological responses to substance P via its receptor NK-1R results in a less efficient clearance of bacteria leading to more severe arthritic lesions in mice.
 ...
PMID:The impact of substance P signalling on the development of experimental staphylococcal sepsis and arthritis. 1822 12

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. Blocking of TREM-1 can protect against sepsis in mice. To date, the predisposition of TREM-1 gene polymorphisms to sepsis has not been reported. This study was designed to investigate whether TREM-1 genomic variations were associated with the development of severe sepsis. Three common polymorphisms (rs7768162, rs9471535, and rs2234237) within the TREM-1 gene were detected in 175 patients with severe sepsis and in 139 healthy control subjects. Neither allelic frequencies nor genotype distributions of the assayed single nucleotide polymorphisms were found to be significantly different between patients and controls as well as between surviving and nonsurviving patients in different models of inheritance. The distributions of estimated haplotype patterns were also comparable between the defined groups. The present findings suggest that the three studied polymorphisms within the TREM-1 gene may not play a major role in the predisposition to severe sepsis in a Chinese Han cohort. Further replication studies with large sample size to achieve sufficient power (80%) to dismiss these polymorphisms as candidate markers for severe sepsis are warranted.
 ...
PMID:Lack of association between TREM-1 gene polymorphisms and severe sepsis in a Chinese Han population. 1839 15


1 2 3 4 5 Next >>