Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metformin is an oral antihyperglycemic agent that is approved by the Food and Drug Administration for the treatment of noninsulin-dependent diabetes mellitus. It differs from the sulfonylureas in that it is does not enhance insulin secretion and normally does not produce hypoglycemia. Metformin acts to decrease preprandial and postprandial blood glucose concentrations by increasing skeletal muscle uptake of glucose, decreasing gluconeogenesis, and decreasing absorption of glucose. The addition of metformin to maximum dosages of a sulfonylurea may synergistically improve glucose control. The drug may offer other potential benefits, such as weight loss or minimal weight gain, improved blood flow in patients with peripheral vascular disease, reduction of tissue plasminogen activator inhibitor, and improved lipid profiles. It is relatively safe if taken appropriately. Its most common side effects are gastrointestinal (nausea, diarrhea, anorexia), metallic taste, and vitamin B12 malabsorption. Lactic acidosis may also occur, but it is rare if metformin is avoided in patients with contraindications to its use. With careful monitoring, the agent may be considered for the initial treatment of obese patients who fail dietary measures, and those whose disease is refractory to maximum dosages of sulfonylureas or who do not tolerate them.
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PMID:Metformin in noninsulin-dependent diabetes mellitus. 872 92

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin producing Eschericia coli. We hypothesized that verotoxin binding to glomerular endothelial cells causes localised endothelial cell activation and thus activation of coagulation and reduction of fibrinolytic potential. We also proposed that treatment with fresh frozen plasma or dialysis would not affect these changes. Markers of activation of coagulation and fibrinolysis were measured in 30 children with acute D+ HUS serially, in healthy children and in children on dialysis. In acute D+ HUS, levels of thrombin-antithrombin III complex and prothrombin fragment 1+2 were significantly increased (p <0.001). The source of thrombin generation was unclear. Factor XIIa levels were increased in patients and controls with renal failure. Factor VIIa levels were not significantly raised in children with acute D+ HUS. D-dimers were increased, but fibrinolytic potential as measured by fibrin plate was reduced. Levels of plasminogen activator inhibitor antigen and activity and tissue plasminogen activator antigen were increased. Neither peritoneal dialysis nor administration of blood products, the most common treatments, altered parameters of coagulation or fibrinolysis.
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PMID:Activation of coagulation and fibrinolysis in childhood diarrhoea-associated haemolytic uraemic syndrome. 942 93

A 6-month-old male Quarter Horse was evaluated for chronic respiratory tract disease. Diagnostic investigations revealed pulmonary inflammation; Pneumocystis carinii was detected within macrophages. Lymphocyte subpopulation phenotyping and immunoglobulin concentration analysis were performed and results suggested immune suppression. Trimethoprim-sulfamethoxazole administration was initiated; the colt was discharged but was reexamined 8 days later because of profuse diarrhea and endotoxemia. Bacterial culture of feces recovered Salmonella spp resistant to trimethoprim-sulfamethoxazole, and a diagnosis of antimicrobial-associated colitis was made. Bilateral fibrinous hypopyon developed and was treated with topical medication and intracameral injections of human recombinant tissue plasminogen activator. Dapsone (3 mg/kg [1.4 mg/lb], PO, q 24 h; dose extrapolated from human data) was administered for treatment of P carinii pneumonia (56-day treatment period). The colt recovered from the pneumonia and diarrhea. Dapsone may be a useful adjunct to traditional treatment for P carinii pneumonia in horses or as a sole medication for horses that cannot tolerate other treatments.
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PMID:Use of dapsone in the treatment of Pneumocystis carinii pneumonia in a foal. 1476 1

Enterohemorrhagic Escherichia coli (EHEC) infection causes hemolytic uremic syndrome, a leading cause of acute renal failure in children. Dutch Belted (DB) rabbits are susceptible to EHEC-induced disease. Using real-time quantitative RT-PCR we measured the renal mRNA expression of cytokines and fibrinolytic factors in DB rabbits challenged with intravenous Shiga toxin 2 (Stx2) (1200 ng/kg). Group 1 rabbits received an incremental dose during an 8-day period whereas Group 2 rabbits received a single dose. Group 1 rabbits developed mild disease. In contrast, Group 2 rabbits developed severe diarrhea, higher levels of circulating polymorphonuclear leukocytes, increased mean platelet volume, and increased fibrinogen levels. Group 2 rabbits developed polymorphonuclear leukocyte infiltration in the intestine and kidney as well as glomerular congestion, luminal constriction, and mesangial glomerulonephropathy. These renal lesions were associated with up-regulation of interleukin-8 (P<0.006), plasminogen activator inhibitor-1 (P<0.04), and tissue plasminogen activator (P<0.05). Circulating Stx2 promoted dose-dependent enteritis and renal injury characterized by inflammation and impaired fibrinolysis leading to thrombosis.
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PMID:Intravenous Shiga toxin 2 promotes enteritis and renal injury characterized by polymorphonuclear leukocyte infiltration and thrombosis in Dutch Belted rabbits. 1846 72

This case report concerns a 40-year-old patient with an unspecific abdominal pain, diarrhoea, a big axillary mass and a previous pulmonary infection. After biopsy of the axillary mass the diagnosis of lymphoma was excluded based on the presence of cells expressing polyclonal antibodies. Abdominal CT scans and angionuclear magnetic resonance showed an extensive intestinal venous thrombosis. The patient also presented positive results for C and S proteins, lupic anticoagulant factor and antiphospholipid antibodies (anticardiolipin antibodies - IgM and IgG). Treatment started with administration of recombinant tissue plasminogen activator and heparin which decreased the degree of thrombosis. Antibiotics were also administrated to treat pulmonary and abdominal infections. After 25 days, he was discharged with no signs of infection, no abdominal pain and reduction of the thrombosis. He was medicated with warfarin, hydroxichloroquine and clopidogrel. Forty-five days after discharge, abdominal CT scan showed a significant regression of thrombosis.
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PMID:A large and massive abdominal venous thrombosis associated with the presence of a big axillary mass, lupus-like syndrome and antiphospholipid antibodies. 2269 98

We report a case of a 56-year-old man who presented initially with a sudden onset of right-sided facial droop and weakness, aphasia, and confusion with no associated fever, chills, syncope, fatigue, weight loss, night sweats, nausea, vomiting, diarrhea, odontalgia, palpitations, cough, or dyspnea. Code stroke was called and the patient received tissue plasminogen activator (tPA) with subsequent resolution of his symptoms. Cranial magnetic resonance imaging showed left frontal punctate cortical restricted diffusion consistent with subacute to acute infarction. Transesophageal echocardiogram showed a severely thickened anterior mitral valve leaflet with a shaggy echodensity consistent with a vegetation. Blood cultures grew Bacillus cereus sensitive to clindamycin, trimethoprim sulfamethoxazole, and vancomycin. He was initially treated with ampicillin, clindamycin, and vancomycin and was eventually maintained solely on vancomycin. He had complete return of his neurological function and was discharged on intravenous antibiotic to complete a 6-week course.
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PMID:A Rare Case of Native Mitral Valve Bacillus Cereus Endocarditis Culminating Into a Cerebrovascular Infarction. 2990 54

Devastating outbreaks of porcine epidemic diarrhea (PED) started in China in late 2010 and rapidly spread to North America and Asia causing severe diarrhea and high mortality in neonatal piglets, indicating that a new generation of vaccine against porcine epidemic diarrhea virus (PEDV) is urgently needed. In the present study, to mimic the native spike (S) glycoprotein, a stable cell line producing the trimeric ectodomain of S glycoprotein of the PEDV Pintung-52 (PEDV-PT) strain was successfully established by incorporating T4 bacteriophage foldon sequence of fibritin trimerization domains at the C-terminal end and replacing the signal peptide of S protein with the tissue plasminogen activator signal peptide sequence at the N terminal end. The trimeric structure, bio-reactivity to PEDV-specific antibodies, and the N-glycosylation level of the recombinant S protein were characterized. To induce systemic and mucosal immunity, conventional 5-week-old piglets were immunized with the trimeric S glycoprotein combined with the B subunit of Escherichia coli heat-labile enterotoxin (LTB) by the intramuscular (IM) route. As compared with the control group, all piglets in the S protein-LTB immunized (IM PEDV S-LTB) group generated systemic PEDV S-specific IgG and neutralizing antibody in blood but a low level of fecal PEDV-specific IgA and limited protection against challenge of PEDV-PT strain. Our results suggest that the recombinant PEDV trimeric S glycoprotein could be a potential subunit vaccine candidate against PEDV, but IM immunization with LTB as the adjuvant provided insufficient protection. The development of a vaccine regimen for inducing mucosal immunity is an important task for generating a successful subunit vaccine against PEDVs.
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PMID:Efficacy of heat-labile enterotoxin B subunit-adjuvanted parenteral porcine epidemic diarrhea virus trimeric spike subunit vaccine in piglets. 2996 Oct 99