Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of the kallikrein-kinin system, as indicated by increased plasma kallikrein and depleted plasma kininogen, prekallikrein, and kallikrein inhibitor, was observed in five patients with Rocky Mountain spotted fever. Four of the patients had petechial rashes characteristic of vasculitis. Three patients had alterations in coagulation consistent with disseminated intravascular coagulation, although no hemorrhagic syndrome was found. Our data, along with the known physiologic actions of kinins, suggest a possible role for the kallikrein-kinin system in the pathophysiology of vasculitis, disseminated intravascular coagulation, circulatory shock, and other complications of infection with Rickettsia rickettsii.
 ...
PMID:Activation of the kallikrein-kinin system in Rocky Mountain spotted fever. 30 54

Total esterase activity of blood plasma from healthy persons was equal to 27.4 +/- 4.96 micrometer/ml/hr, activity of kallikrein--74.4 +/- 8.65 micrometer of hydrolysed substrate/hr/ml of blood plasma, inhibitory capacity of blood plasma towards kallikrein was 0.9 +/- 0.1 app. un. Total esterase activity of blood plasma, reflecting the activity of trypsin-like enzymes and kallikrein, was distinctly increased in patients with hemorrhagic vasculitis as compared with control group; content of prekallikrein and the inhibitory capacity of blood plasma towards kallikrein were decreased. In patients with severe forms of hemorrhagic vasculitis the most pronounced activation of blood kinine system was observed due to decrease in content of kallikrein and in the inhibitory capacity of blood plasma towards kallikrein.
 ...
PMID:[Role of the blood kinin system in the pathogenesis of the hemorrhagic syndrome in hemorrhagic vasculitis]. 73 77

Altogether 300 patients suffering from bronchial asthma were examined for serotonin metabolism, the kallikrein-kinin system and histamine. A study was also made of the information relations of the indicated parameters to diverse groups of the signs using Shannon's technique. It has been revealed that serotonin and the kallikrein-kinin system are of importance in the pathogenesis of changes in the efficacy of the diffusion lung capacity in severe bronchial asthma. The authors discuss the significance of excessive accumulation of serotonin and bradykinin as a marker of the impairment of endothelial function of pulmonary vessels, specified by the damaging action of free radicals and immune complex allergic vasculitis as well. Histamine along with macrophages act as delimiters of allergic inflammation, with their action being mediated by negative feedback.
 ...
PMID:[The role of serotonin, histamine and the kallikrein-kinin system in the pathogenesis of asphyxic attacks in bronchial asthma]. 138 48

The purpose of the study was to explore hemostasis in children suffering from hemorrhagic vasculitis (HV) by means of the new amidolytic methods using chromogenic substrates. The patient's plasma was studied for the content of thrombin, trypsin, factor Xa, AT-III, kallikrein, plasmin, free heparin, urokinase, factor 3 of platelets, prothrombin and Willebrand's factor. 69 children with HV were entered into the study. All of them were examined during crises. In cutaneous HV, the content of trypsin decreased 3-fold, the content of factor Xa increased 5-fold; there was a negligible increase in the plasmin and AT-III levels; the content of kallikrein rose 2-fold, that of urokinase 60-fold; the release of platelet factor 3 was intensified 1.5-fold, the activity of prothrombin 3-fold. These data indicate that in cutaneous HV, blood coagulation increased. However, the signs of disseminated intravascular coagulation were lacking because of the high blood anticoagulant activity. In mixed HV, the phase of hypercoagulation was not made for by the blood anticoagulant activity, since the latter one was depleted. The capillary toxic nephritis may give rise to disseminated intravascular coagulation associated with the depletion of the anticoagulant component. The gravity of HV and its complications can be predicted according to the characteristics of the anticoagulant component of hemostasis, especially according to the levels of urokinase and AT-III.
 ...
PMID:[State of hemostasis in hemorrhagic vasculitis in children]. 151 26

It has been shown that irrespective of the primary focus of affliction, M. hominis-induced infection should be regarded as a systemic disease characterized by an immune-mediated inflammation which is contributed to by blood kallikrein-kinin system activation resulting in changes in the coagulative system and fibrinolysis until disseminated intravascular coagulation develops. This allows one to interpret in a new fashion the etiology of some diseases proceeding with signs of vasculitis.
 ...
PMID:[Problem of pathogenesis of Mycoplasma infection]. 192 34

Camostat mesilate, a developed derivative of gabexate mesilate for oral use, was administered in a daily dose of 600 mg for 4 weeks to 17 patients with heavy proteinuria due to various nephropathies. Five patients had glomerulonephritis (3 patients with IgA nephropathy, one each with membranoproliferative GN and membranous nephropathy) and 3 had systemic vasculitis. These patients had been treated with glucocorticoid, cyclophosphamide, anticoagulants, and dipyridamole. Five patients had diabetic nephropathy and had been treated with conventional therapy including angiotensin converting enzyme inhibitors. Two cases with benign nephrosclerosis, one with Alport syndrome, and the rest with end-stage renal failure of undetermined cause were also included in this study. Urinary protein decreased promptly within 2 weeks (from 5.2 +/- 0.7 to 3.5 +/- 0.5, mean +/- SE, p less than 0.005), and serum total protein and albumin levels increased significantly. Serum creatinine levels did not change. Decreases in urinary protein excretion of more than 50% were observed in five out of eight patients with glomerulonephritis or systemic vasculitis, two out of five with diabetic nephropathy, and one with chronic renal failure. However, urinary protein excretion values remained at the same level in two patients with benign nephrosclerosis and a patient with Alport syndrome. We suggest that camostat mesilate caused a change in glomerular capillary permeability for macromolecules through its inhibitory effects on the kallikrein-kinin system, complement system, coagulation system, and platelet function, which contributed to the treatment of the various nephropathies.
 ...
PMID:Effect of camostat mesilate on heavy proteinuria in various nephropathies. 279 62

The diagnosis of Weber-Christian disease was made by clinical and histopathologic findings in a 25-year-old woman who had recurrent nodules on the legs and arms. The patient's history also disclosed multiple episodes of swelling trauma. Histopathologic examination of the lesions showed a prominent vasculitis. Studies of serum complement and kallikrein levels and of the fibrinolysis-clotting system showed a decrease in the levels of C3, C4, and total hemolytic complement activity and deficiencies (less than 20% of the normal values) of alpha 1-antitrypsin (alpha 1-AT) and antichymotrypsin activity. Chemical analyses of the patient's alpha 1-AT indicated a PiZZ genotype. Intermediate values of both inhibitor levels were detected in six family members. It is assumed that protease-inhibitor deficiencies predispose the development of panniculitis and vasculitis on trauma.
 ...
PMID:Protease-inhibitor deficiencies in a patient with Weber-Christian panniculitis. 620 90

FUT-175, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamstat mesilate), a novel synthetic protease-inhibiting agent, was studied to determine its in vitro effects against various proteases and other enzymes, as well as to determine its in vivo protease inhibitory effects. FUT-175 was found to inhibit, in an intense, specific and reversible way, the enzyme activities of trypsin, C1r, C1s, thrombin, kallikrein and plasmin with IC50 values of the order of 10(-6)-10(-8) M. FUT-175 also inhibited complement-mediated hemolysis, including both classical and alternative pathways, sites of inhibition being on C1r and C1s as evidenced by the intermediate-cell technique. In animal model reactions in which the complement system is known to be involved as pathogenetic factors, e.g., Forssman shock, Forssman cutaneous vasculitis, zymosan-induced paw edema, endotoxin shock and local Shwartzman reaction, FUT-175 was highly effective in that, for example, intravenous dosing at 3 mg/kg could completely protect guinea pigs from the lethal Forssman shock. FUT-175 was also found to be effective in trypsin-induced shock in mice, in lethality due to thrombin-thrombosis in mice and in kinin formation in the inflammatory process in rats.
 ...
PMID:Pharmacological studies of FUT-175, nafamstat mesilate. I. Inhibition of protease activity in in vitro and in vivo experiments. 648 87

Previous studies have suggested an association between systemic lupus erythematosus (SLE) and an insertion/deletion polymorphism in the angiotensin-converting enzyme gene (ACE). This polymorphism consists of a 250-bp insertion/deletion of an alu repeat in the 16th intron of the ACE gene. Individuals homozygous for the deletion have a higher level of circulating enzyme. Due to the important role of this enzyme in regulating the renin--angiotensin and kallikrein--kininogen systems, it is possible that the ACE insertion/deletion may play a role in SLE, which can include vasculitis and vascular changes. Using primers flanking the insertion/deletion site, we have examined the ACE gene in lupus patients and family members using genomic DNA obtained from the Lupus Multiplex Registry and Repository (LMRR). We were unable to detect significant linkage or genetic association between the ACE gene and SLE.
 ...
PMID:Linkage analysis of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and systemic lupus erythematosus. 1137 23

The receptor for the globular heads of C1q, gC1qR/p33, is a ubiquitously expressed protein, which is distributed both intracellularly and on the cell-surface protein. In addition to C1q, this molecule also is able to bind several other biologically important plasma ligands, including high-molecular-weight kininogen (HK), factor XII (FXII), and multimeric vitronectin. Previous studies have shown that incubation of FXII, prekallikrein, and HK with gC1qR leads to a zinc-dependent and FXII-dependent conversion of prekallikrein to kallikrein, a requisite for kinin generation. In addition, these studies showed that normal plasma, but not plasma deficient in FXII, PK, or HK, activate upon binding to endothelial cells (EC), and that this activation could be inhibited by antibody to gClqR. In these studies, we show that incubation of serum with microtiter plate bound gC1qR results in complement activation, as evidenced by the binding and activation of C1 and generation of C4d. However, neither Clq-deficient serum nor a truncated form of gC1qR (gC1qRA74-96), supported complement activation. Taken together, the data strongly suggest that at sites of inflammation, such as vasculitis and atherosclerosis, where gC1qR as well as its two important plasma ligands, C1q and HK, have been shown to be simultaneously present, soluble or cell-surface-expressed gC1qR may contribute to the inflammatory process by modulating complement activation, kinin generation, and perhaps even initiation of clotting via the contact system. Based on these and other published data, we propose a model of inflammation in which atherogenic factors (e.g., immune complexes, virus, or bacteria) are perceived not only to convert the endothelium into a procoagulant and proinflammatory surface, but also to induce enhanced expression of cell surface molecules such as gC1qR. Enhanced expression of gC1qR in turn leads to: (i) high-affinity C1q binding and cell production of proinflammatory factors, and (ii) high-affinity HK binding and facilitation of the assembly of contact activation proteins leading to generation of bradykinin and possibly coagulation through activation of FXI.
 ...
PMID:gC1qR/p33 serves as a molecular bridge between the complement and contact activation systems and is an important catalyst in inflammation. 1689 67


1 2 Next >>