Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium selenite was found to be toxic to chicks, with an LD50 of 8.5 micrograms/g, which was increased to 16.3 micrograms/g by NaCN. The major symptoms of chicks, treated with selenite, were sedation and then dyspnea and paralysis. The cause of death by selenite was apparently due to the respiratory failure. The possible mechanism of toxicity was explored in the isolated chick biventer cervicis nerve-muscle preparation. Selenite initially increased the amplitude of the twitch, reversed the suppression of the twitch caused by d-tubocurarine, Mg2+, Cd2+ or Mn2+ and significantly increased the quantal content and amplitude of endplate potentials. Subsequently, selenite depressed the amplitude of the twitch, blocked the axonal conduction and inhibited excitatory postsynaptic potentials. Both NH4+ and K+ enhanced the action of selenite in depressing the twitches. In addition, selenite induced a sustained contracture of the muscle, which was partially inhibited by removal of external Ca2+ and markedly blocked by EGTA. Entry of Ca2+ and release of the internal Ca2+ were considered to be responsible for inducing contracture by selenite. Pretreatment with trypsin, glutathione (GSH) and cyanide profoundly inhibited the effects of selenite, indicating that the site of action of selenite was on the outer membrane and the binding of selenite to the sulfhydryl groups of membrane proteins was proposed to be an essential step for selenite-induced contracture and neuromuscular action. These findings suggest that neuromuscular blockade and tetanic spasm, produced by selenite in chicks, may play a role in causing respiratory failure in vivo.
 ...
PMID:Neuromuscular actions of sodium selenite on chick biventer cervicis nerve-muscle preparation. 169 19

The fibrinolytic enzyme plasmin at 0.25 units/ml produced a contraction of isolated canine basilar arteries that developed slowly and was sustained for at least 2 hours. Plasmin and thrombin (1 unit/ml) acted synergistically to enhance the contractile response. In contrast to plasmin, the marked contraction elicited by thrombin ended within 1 hour, and afterward the artery was completely tachyphylactic to thrombin. Fibrin clot, fibrinopeptides, and fibrin degradation products did not prolong significantly the effect of thrombin or prevent the tachyphylaxis. Plasmin and thrombin may occupy a common membrane receptor because exposing the artery briefly to trypsin (24 micrograms/ml) thereafter abolished the contractile effect of plasmin and thrombin without affecting the action of other agonists. Antithrombin III (1.0 unit/ml) relaxed basilar arteries that were precontracted with plasmin (0.5 unit/ml), thrombin (1.0 unit/ml), serotonin (10(-5) M), uridine triphosphate (10(-4) M), or KCl (8 X 10(-2) M). The results suggest that the vasoconstrictor effect of thrombin might contribute to hemostasis after subarachnoid hemorrhage (SAH) but, because of tachyphylaxis, not to delayed vasospasm. On the other hand, the constrictor action of plasmin might appear late in the course of SAH in association with clot lysis and tissue repair. Last, the level of the vasorelaxant antithrombin III in cerebrospinal fluid could control the appearance and severity of cerebral arterial spasm in SAH.
 ...
PMID:Role of plasmin, thrombin, and antithrombin III as etiological factors in delayed cerebral vasospasm. 257 47

Activated mast cells are present in human coronary atheromas, as well as in the adventitia of patients with variant angina, and may play an important role in plaque rupture and coronary vasomotion. To assess whether or not activation of mast cells is a primary event, we measured serum levels of tryptase, a specific marker of mast cell activation, in 8 patients with unstable angina during a spontaneous ischemic episode (Group 1) and in 5 patients with variant angina (Group 2) during ergonovine-induced coronary spasm. Blood samples were collected as soon as possible after the onset of pain and ECG changes (0 min), and after 5, 15 and 60 min. Tryptase levels in Group 1 were 0.13 U/l (range 0.017-0.44) at the onset of pain and significantly raised to 0.75 U/l (range 0.05-2.49) at 5 min, decreasing to 0.076 U/l (range 0.018-0.16) at 15 min and to 0.085 U/l (range 0.01-0.25) at 60 min (p = 0.035). Conversely, tryptase levels in Group 2 were 0.09 U/l (range 0.07-0.13) at 0 min, 0.11 U/l (range 0.07-0.22) at 5 min, 0.10 U/l (range 0.07-0.18) at 15 min, 0.11 U/l (range 0.07-0.17) at 60 min (NS). In conclusion, tryptase levels raise during spontaneous ischemic episodes in unstable angina, but not after ergonovine-provoked ischemia in variant angina, suggesting that a primary, yet unknown stimulus, may activate mast cells during some ischemic episodes in unstable angina.
 ...
PMID:[Tryptase levels are elevated during spontaneous ischemic episodes in unstable angina but not after the ergonovine test in variant angina]. 955 75

The ability of chymotrypsin to reach the limits of the bronchial tree has been studied in cats receiving the enzyme by inhalation as a very fine powder. For this purpose derivatives of chymotrypsin were used which had been labelled with a fluorescent molecule or with [(131)I]. Quantitative measurements of the absorption and distribution of inhaled chymotrypsin- [(131)I] revealed a rapid removal of radioactivity from the lungs over the first 24 hr. and corresponding excretion of labelled inorganic iodide in the urine. High levels of activity were not attained in the blood or thyroid. Subcutaneous administration of labelled enzyme led to more rapid accumulation of radioactivity in the blood and thyroid. Consideration of these and other results leads to the conclusion that, while some enzyme ascends the respiratory tract by ciliary movement of mucus, a substantial part is absorbed into the lungs and the [(131)I] subsequently detached from it.The changes in tidal air accompanying inhalation of labelled trypsin and chymotrypsin were followed in anaesthetized cats. Trypsin brings about a decrease in tidal air in distinctly lower doses than does chymotrypsin. Prior administration of mepyramine had an antagonistic effect, and it is suggested that the change in tidal air is essentially the result of bronchial spasm.
 ...
PMID:The pharmacology of chymotrypsin administered by inhalation. 1385 May 40

The first reported human anaphylactic death is considered to be the Pharaoh Menes death, caused by a wasp sting. Currently, anaphylactic cardiovascular events represent one of most frequent medical emergencies. Rapid diagnosis, prompt and appropriate treatment can be life saving. The main concept beyond anaphylaxis lies to myocardial damage and ventricular dysfunction, thus resulting in cardiovascular collapse. Cardiac output depression due to coronary hypoperfusion from systemic vasodilation, leakage of plasma and volume loss due to increased vascular permeability, as well as reduced venous return, are regarded as the main causes of cardiovascular collapse. Clinical reports and experiments indicate that the human heart, in general, and the coronary arteries, in particular, could be the primary target of the released anaphylactic mediators. Coronary vasoconstriction and thrombosis induced by the released mediators namely histamine, chymase, tryptase, cathepsin D, leukotrienes, thromboxane and platelet activating factor (PAF) can result to further myocardial damage and anaphylaxis associated acute coronary syndrome, the so-called Kounis syndrome. Kounis syndrome with increase of cardiac troponin and other cardiac biomarkers, can progress to heart failure and cardiovascular collapse. In experimental anaphylaxis, cardiac reactions caused by the intracardiac histamine and release of other anaphylactic mediators are followed by secondary cardiovascular reactions, such as cardiac arrhythmias, atrioventricular block, acute myocardial ischemia, decrease in coronary blood flow and cardiac output, cerebral blood flow, left ventricular developed pressure (LVdp/dtmax) as well as increase in portal venous and coronary vascular resistance denoting vascular spasm. Clinically, some patients with anaphylactic myocardial infarction respond satisfactorily to appropriate interventional and medical therapy, while anti-allergic treatment with antihistamines, corticosteroids and fluid replacement might be ineffective. Therefore, differentiating the decrease of cardiac output due to myocardial tissue hypoperfusion from systemic vasodilation and leakage of plasma, from myocardial tissue due to coronary vasoconstriction and thrombosis might be challenging during anaphylactic cardiac collapse. Combined antiallergic, anti-ischemic and antithrombotic treatment seems currently beneficial. Simultaneous measurements of peripheral arterial resistance and coronary blood flow with newer diagnostic techniques including cardiac magnetic resonance imaging (MRI) and myocardial scintigraphy may help elucidating the pathophysiology of anaphylactic cardiovascular collapse, thus rendering treatment more rapid and effective.
 ...
PMID:Anaphylactic cardiovascular collapse and Kounis syndrome: systemic vasodilation or coronary vasoconstriction? 3030 71

Kounis syndrome, while an acute coronary syndrome, occurs in the context of a hypersensitivity reaction, allergies, or anaphylaxis and is subdivided into three types: coronary spasm in normal arteries, instability of plaques in atherosclerotic coronary arteries, and thrombosis of coronary stents. Herein, the case of a 73-year-old patient who, after administration of amoxicillin/clavulanic acid, went into cardiorespiratory arrest with evidence of ST-T segment elevation on electrocardiogram is reported. Coronarography revealed no obstructive lesions, and spontaneous resolution of electrocardiographic abnormalities was observed. A review of anamnesis with the family revealed a previous allergy to penicillin. The tryptase dosage was strongly positive. Kounis syndrome type 2 was diagnosed, and the clinical outcome was good.
 ...
PMID:Kounis syndrome. Apropos of a clinical case. 3240 74