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Penicillin causes non-allergic anaphylaxis by activating the contact system.

Immediate hypersensitivity reaction (IHR) can be divided into allergic- and non-allergic-mediated, while "anaphylaxis" is reserved for severe IHR. Clinically, true penicillin allergy is rare and most reported penicillin allergy is "spurious". Penicillin-initiated anaphylaxis is possible to occur in skin test- and specific IgE-negative patients. The contact system is a plasma protease cascade initiated by activation of factor XII (FXII). Many agents with negative ion surface can activate FXII to drive contact system. Our data showed that penicillin significantly induced hypothermia in propranol

Candesartan Cilexetil is not Associated with Cough in Patients with Enalapril-induced Cough.

Treatment with angiotensin-converting enzyme (ACE) inhibitors is frequently associated with persistent dry cough. This side effect is thought to be due to the non-specific action of ACE inhibitors, which, in addition to suppressing the renin-angiotensin system (RAS), leads to the accumulation of kinins, encephalins and other biologically active peptides. Candesartan cilexetil is a new, long-acting angiotensin II type 1 (AT 1 ) receptor blocker, which offers a more specific means of suppressing the RAS than can be achieved with ACE inhibitors. In this study, we compared the incidence and severi…

Liver disease and the renin-angiotensin system: recent discoveries and clinical implications.

The renin-angiotensin system (RAS) is a key regulator of vascular resistance, sodium and water homeostasis and the response to tissue injury. Historically, angiotensin II (Ang II) was thought to be the primary effector peptide of this system. Ang II is produced predominantly by the effect of angiotensin converting enzyme (ACE) on angiotensin I (Ang I). Ang II acts mainly through the angiotensin II type-1 receptor (AT(1)) and, together with ACE, these components represent the 'classical' axis of the RAS. Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding

Effect of prolonged administration of a urinary kinase inhibitor, ebelactone B on the development of deoxycorticosterone acetate-salt hypertension in rats.

The effect of prolonged administration of a carboxypeptidase Y-like kininase inhibitor, ebelactone B (EB) (2-ethyl-3, 11-dihydroxy-4, 6, 8, 10, 12-pentamethyl-9-oxo-6-tetradecenoic 1, 3-lactone), on the development of deoxycorticosterone acetate (DOCA)-salt hypertension was tested. The systolic blood pressure (SBP) of non-treated 6-week-old Sprague-Dawley strain rats was gradually increased by DOCA-salt treatment from 137+/-2 mmHg (n=11) to 195+/-7 mmHg at 10 weeks of age. With daily oral administration of lisinopril (5 mg kg(-1), twice a day), which is an inhibitor of angiotensin converting e

Воспаление и воспаление болезней, маркеры и посредники: роль КПИ в некоторых воспламенительных заболеваниях

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Mediation by bradykinin of rat paw oedema induced by collagenase from Clostridium histolyticum.

1. Collagenases are thought to play a major role in the pathology of gas gangrene caused by Clostridium histolyticum, because they can destr … f nociceptive afferent neurones following injection of collagenase is due to the action of released kinins.7. In conclusion, bradykinin appears to be the main mediator of inflammation induced by a collagenase from Clostridium histolyticum. As well as having direct relevance to a known pathological condition,collagenase-induced paw oedema could prove to b …

Unveiling the Complexities of Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder, constituting approximately 2% of all clinical cases of angioedema, with a global prevalence estimated between 1 in 50,000 and 1 in 150,000 individuals. The condition affects individuals of all genders and ethnic backgrounds without significant variation. HAE is classified into three types. Type I HAE, which accounts for 85% of cases, is characterized by a deficiency of the C1 esterase inhibitor (C1-INH) gene. Type II HAE, making up 15% of cases, involves a dysfunctional C1-INH. Type III HAE, which represen

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… These mutations affect the kallikrein–kinin and fibrinolytic system pathways, leading to increased bradykinin production and consequent vascular permeability, resulting in angioedema [ 1 , 29 , 30 ]. … The degradation and accumulation of kinins, including bradykinin, can influence the clinical presentation of HAE [ 10 , 74 ]. Major enzymes involved in kinin catabolism include carboxypeptidase N (CPN), ACE, and aminopeptidase P (APP) [ 10 , 74 ]. …

Characterizing the inflammatory response to cardiopulmonary bypass in children.

Cardiopulmonary bypass is known to trigger a global inflammatory response. Age-dependent differences in the inflammatory response, the increased susceptibility to injury of immature organ systems, and the larger extracorporeal circuit to patient size ratio results in greater susceptibility of younger and smaller patients to the damaging effects of cardiopulmonary bypass. In this review the components of the inflammatory response to cardiopulmonary bypass are reviewed with special reference to the pediatric age group, including the age-specific impact on organ systems. In addition the current a

Urinary kallikrein excretion in essential and mineralocorticoid hypertension.

Urinary kallikrein excretion has been reported to be decreased in patients with essential hypertension and elevated in patients with primary aldosteronism as a reflection of mineralocorticoid activity. Low renin essential hypertension (LREH) has been postulated to result from excess production of an unknown mineralocorticoid(s). Urinary kallikrein excretion was compared in outpatients with essential hypertension, mineralocorticoid hypertension (primary aldosteronism and 17alpha-hydroxylase deficiency), and in normal subjects of the same race. No significant difference in urinary kallikrein exc

Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Hereditary angioedema is a rare and potentially life-threatening genetic disease that is associated with kallikrein-kinin system dysregulation. Garadacimab (CSL312), a novel, fully-human monoclonal antibody that inhibits activated factor XII (FXIIa), is being studied for the prevention of hereditary angioedema attacks. The aim of this study was to evaluate the efficacy and safety of once-monthly subcutaneous administrations of garadacimab as prophylaxis for hereditary angioedema. METHODS: VANGUARD was a pivotal, multicentre, randomised, double-blind, placebo-controlled, phase 3 tr

Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway.

Binding of negatively charged macromolecules to factor XII induces a conformational change such that it becomes a substrate for trace amounts of activated factor present in plasma (less than 0.01%). As activated factor XII (factor XIIa or factor XIIf) forms, it converts prekallikrein (PK) to kallikrein and kallikrein cleaves high molecular weight kininogen (HK) to release bradykinin. A far more rapid activation of the remaining unactivated factor XII occurs by enzymatic cleavage by kallikrein (kallikrein-feedback) and sequential cleavage yields two forms of activated factor XII; namely, factor

Polyethyleneimine-treated polyacrylonitrile membrane hemofilter for critically ill patients receiving anticoagulant-free prolonged intermittent renal replacement therapy: a single-center, prospective, self-controlled pilot study.

BackgroundCritically ill patients requiring renal replacement therapy (RRT) are at risk of disease-related bleeding. Systemic heparinization should be avoided. AN69ST, a polyethyleneimine-treated polyacrylonitrile (AN69) membrane hemofilter, can be primed with heparin, improving its local anticoagulative activity. Prolonged intermittent RRT (PI-RRT) is of shorter duration and cheaper, considered as an alternative to continuous RRT. This study was performed to compare the success rate of anticoagulant-free PI-RRT using AN69ST versus AN69 membrane hemofilter. We also evaluated risk factors for f

A guide to immunotherapy for COVID-19.

Immune dysregulation is an important component of the pathophysiology of COVID-19. A large body of literature has reported the effect of immune-based therapies in patients with COVID-19, with some remarkable successes such as the use of steroids or anti-cytokine therapies. However, challenges in clinical decision-making arise from the complexity of the disease phenotypes and patient heterogeneity, as well as the variable quality of evidence from immunotherapy studies. This Review aims to support clinical decision-making by providing an overview of the evidence generated by major clinical trial

Etodolac improves collagen induced rheumatoid arthritis in rats by inhibiting synovial inflammation, fibrosis and hyperplasia.

Synovial hyperplasia is the main cause of chronic rheumatoid arthritis (RA), but the mechanism of synovial hyperplasia is still unclear. Etodolac (ETD) is a selective COX-2 inhibitor for relieving pain and stiffness in RA, but the disease modifying effect is still lack of evidence. Proteomics method was used to study the differential proteome of synovial tissue in collagen induced arthritis (CIA) in rats. With the help of STRING analysis, the upregulated proteins enriched in the cluster of complement and coagulation cascades and platelet degranulation were highlighted, these proteins with fibr

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… What is noteworthy is that the kallikrein-kinin system might also be involve in RA and may be the target of ETD. As reported, beside the control of prostaglandins by inhibiting COX2, ETD might also inhibit active oxygen generation and bradykinins formation [ 20 ]. … Here, the expression of Klkb1 was significantly upregulated in the synovium tissue of CIA rats, and ETD treatment significantly downregulated it, which indicated that ETD alleviated CIA might also by inhibiting kallikrein-kinin system. …

Daratumumab-based treatment of monoclonal gammopathy-associated angioedema due to acquired C1-inhibitor deficiency.

Daratumumab-based treatment could control severe, treatment-refractory, life-threatening angioedema due to acquired C1-inhibitor deficiency associated with monoclonal gammopathy.

Фактор XII-А Новая терапевтическая цель? Систематический обзор.

Фактор XII — это молекула нечеткой физиологической функции, которая привлекает все больший интерес к исследованиям в различных медицинских дисциплинах. В последние годы был накоплен значительный объем данных о вкладе фактора XII в патогенез подстрекательских и протромботических заболеваний. Было продемонстрировано, что FXII играет защитную роль в коагуляции на основе FXII во время хостинговой защиты от инфекций и защищает от многоорганических неудач в моделях сепсиса животных. В случае синдрома острой дыхательной недостаточности (АРДС) деятельность FXII способствует высвобождению провоспалител

Recombinant human C1 esterase inhibitor (conestat alfa) in the prevention of severe SARS-CoV-2 infection in hospitalized patients with COVID-19: A structured summary of a study protocol for a randomized, parallel-group, open-label, multi-center pilot trial (PROTECT-COVID-19).

OBJECTIVES: Conestat alfa, a recombinant human C1 esterase inhibitor, is a multi-target inhibitor of inflammatory cascades including the complement, the kinin-kallikrein and the contact activation system. The study objective is to investigate the efficacy and safety of conestat alfa in improving disease severity and short-term outcome in COVID-19 patients with pulmonary disease. TRIAL DESIGN: This study is an investigator-initiated, randomized (2:1 ratio), open-label, parallel-group, controlled, multi-center, phase 2a clinical trial. PARTICIPANTS: This trial is conducted in 3 hospitals in Sw

[Pharmacology of non-steroidal anti-inflammatory drugs and ENT pathology].

UNLABELLED: 1. BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAID) belong to a variety of chemical classes with no common features ex … re explained by sensitization of nociceptive nerve endings to the stimulating effect (algogenic) of kinins (bradykinin), serotonin and histamine. In addition, production of prostanoids in the brain has a thermoregulatory effect. 3. MODE OF ACTION: NSAID have a common effect, inhibiting the production of prostanoids via reduced activity of two cyclo-oxyg …

Acute Abdominal Pain as the Initial Presentation of an Acquired C1 Inhibitor Deficiency.

INTRODUCTION: Acquired angioedema (AAE), a rare cause of adult-onset non-urticarial mucocutaneous angioedema, can present as acute abdomen, a frequent complaint in the emergency room (ER), often leading to unnecessary and potentially harmful procedures. CASE PRESENTATION: We report a 47-year-old hypertense male, controlled with an angiotensin converting enzyme inhibitor (ACEI), who presented in the ER with progressively worsening abdominal pain, nausea, and vomiting, and a radiologic workup revealing small intestine thickening, initially diagnosed with ACEI-induced angioedema. However, furthe