Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031350 (pharyngitis)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Group A streptococci can be classified according to their tendency to cause either impetigo, pharyngitis, or both types of infection. Genotypic markers for tissue site preference lie within emm genes, which encode fibrillar surface proteins that play a key role in virulence. emm gene products (M and M-like proteins) display an extensive array of binding activities for tissue and plasma proteins of the human host. In a previous study, a high-affinity binding site for human plasmin(ogen) was mapped to the emm53 gene product. In this report, a structurally similar plasminogen-binding domain is found to be widely and selectively distributed among group A streptococci harboring the emm gene marker for the skin as the preferred tissue site for infection. The findings are highly suggestive of a central role for bacterial modulation of host plasmin(ogen) during localized infection at the epidermis.
 ...
PMID:Selective distribution of a high-affinity plasminogen-binding site among group A streptococci associated with impetigo. 1041 56

Neutrophil-derived proteinases cause glomerular injury by proteolysis of the glomerular basement membrane and alterations in glomerular metabolism. Recently, a marked elevation of the plasma elastase complex with alpha1-proteinase inhibitor (alpha 1-PI) both in the acute phase and during remission of nephrotic syndrome (NS) compared with age-matched controls was reported. In experimental immune-mediated glomerulonephritis epsilon-aminocaproic acid (EACA) significantly reduced albuminuria, and it was suggested that this may be linked with the antiproteolytic activity of the drug. We studied plasma antithrombin III (AT-III), alpha 1-PI, alpha 2-antiplasmin (alpha 2-A), alpha 2-macroglobulin (alpha 2-M) activity, and some blood coagulation and fibrinolysis tests in children with frequently relapsing prednisone-responsive NS. Also, the effect of prednisone alone (Group I, n = 9) and prednisone plus EACA (Group II, n = 10) treatment regimens on the studied parameters was estimated. All investigations were performed on admission to the hospital and after approximately 13 days of prednisone alone therapy (Group I), as well as before the administration of prednisone plus EACA and 24 hours after the last dose of EACA, ie, after approximately 5 days of treatment (Group II). Prednisone was administered at the usual dose of approximately 2 mg/kg/d and EACA was given orally at the doses of 72 to 230 mg/kg of body weight per day for 3 to 10 days. In the acute phase of disease, NS patients (n = 19) were shown to have a statistically significant decrease of plasma AT-III (16.4 +/- 4.7 vs. 21.9 +/- 2.5 IU/mL) and alpha 1-PI (1.28 +/- 0.6 vs. 1.97 +/- 0.34 IU/mL) activity, as well as a marked increase in plasma alpha 2-M activity (14.96 +/- 5.81 vs. 9.6 +/- 1.6 IU/mL), and fibrinogen concentration (5.51 +/- 1.78 vs. 2.96 +/- 0.34 g/L) compared to the age-matched controls; no significant changes in plasma alpha 2-A activity, plasminogen concentration, euglobulin clot lysis time, activated partial thromboplastin time (APTT), or thromboplastin time were noted. In children treated with prednisone alone, a marked increase in plasma AT-III (by 76%, P < 0.001) and alpha 2-A (36%, P < 0.019) activity, and a significant decrease of the plasma fibrinogen concentration (6.07 +/- 1.66 vs. 3.17 +/- 1.64 g/L, P < 0.001), and APTT (45.1 +/- 7.6 vs. 33.8 +/- 4.4 s, P < 0.001) were found. Prednisone plus EACA therapy resulted in a significant increase in plasma AT-III activity (by 53%, P < 0.003), whereas plasma fibrinogen concentration and APTT remained unchanged. However, statistically significant differences between the pre- and posttreatment plasma AT-III, alpha 1-PI, and alpha 2-A activities in these patients were observed. There was also a relationship between EACA dose and the percentage change in plasma alpha 2-A activity. In a few patients receiving prednisone plus EACA regimen, side effects that included purulent rhinitis, pharyngitis, increases in body temperature, loose stools, and an approximately 20% to 30% decrease in systolic and diastolic arterial blood pressure were observed. Thus, although the prednisone plus EACA treatment regimen seems to offer new therapeutic possibilities in some patients with NS, it should not be used in acute phase of the disease.
 ...
PMID:Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report. 1130 63

Primary infection by group A streptococci (GAS) takes place at either the throat or skin of the human host, often leading to pharyngitis or impetigo, respectively. Many GAS strains differ in their preference for throat and skin tissue sites. Previous epidemiological findings show that many of the strains displaying strong tropism for the skin have a high-affinity binding site for plasminogen, located within M protein (PAM), a prominent surface fibril. Plasminogen bound by PAM interacts with streptokinase, a plasminogen activator secreted by GAS, to yield bacterial-bound plasmin activity. In this study, PAM and streptokinase were tested for their roles in infection using an experimental model that closely mimics human impetigo. Inactivation of genes encoding either PAM or streptokinase led to a partial, but significant, loss of virulence in vivo, as measured by net growth of the bacteria and pathological alterations. The relative loss in virulence in vivo was greater for the streptokinase mutant than for the PAM mutant. However, the PAM mutant, but not the streptokinase mutant, displayed a partial loss in resistance to phagocytosis in vitro. The combined experimental and epidemiological data provide evidence that PAM and streptokinase play a key role in mediating skin-specific infection by GAS. In addition, secreted cysteine proteinase activity due to SpeB leads to degradation of streptokinase in stationary phase broth cultures. Since SpeB is also a determinant of tissue-specific GAS infection at the skin, direct interactions between these two proteolytic pathways may constitute an important pathogenic mechanism. An integrated model for superficial infection at the skin is presented.
 ...
PMID:Roles of the plasminogen activator streptokinase and the plasminogen-associated M protein in an experimental model for streptococcal impetigo. 1248 Aug 97

The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)
 ...
PMID:[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs]. 1457 69