Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase.

Background: Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors.

Objective: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT.

Methods: In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT.

Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase-a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity.

Background: Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined.

Objective: Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting.

Methods: In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting.

Experimental asthma in rats.

Animal models of asthma have been used for over 100 years. The accuracy of extrapolations from animal models to human asthmatics is highly dependent on the species of animal selected. The rat, in comparison with other animals, demonstrates many features of airway allergy and allergic asthma that are similar to the human conditions.

[GERD and respiratory tract diseases].

Gastroesophageal reflux disease (GERD) depends on acid reflux into the distal oesophagus. The typical symptoms of GERD are heartburn, dysphagia, chest discomfort and acid regurgitation. Besides typical symptoms GERD could by manifested by extraesophageal signs.

Plasmin system regulation in an ovalbumin-induced rat model of asthma.

Background: So far studies showing the role of the plasmin system in airway remodelling have been conducted using in vitro models. The aim of the present study was to determine plasmin system regulation in an in vivo rat model of asthma.

Methods: Asthma in Wistar rats was induced by ovalbumin (OVA) sensitization followed by an OVA challenge (OVA/OVA, n = 6).

The concentration of kynurenine in rat model of asthma.

Asthma is a chronic inflammatory disease that involves the immune system activation. Evidence is accumulating about the role of kynurenine pathway in the immune system regulation. The kynurenine pathway includes several metabolites of tryptophan, among others kynurenine (KYN).

[Thrombin activatable fibrinolysis inhibitor (TAFI) in allergic asthma patients].

Increased thrombin generation occurs in the airways of asthmatic patients. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme which after activation by a thrombin-thrombomodulin complex inhibits fibrinolysis. The aim of this study was to evaluate TAFI concentration and activity in plasma of bronchial asthma patients challenged with Dermatophagoides pteronyssinus (Dp) extracts.

Basal serum tryptase level correlates with severity of hymenoptera sting and age.

Background: Increased serum tryptase has been linked to the severity of the reaction after Hymenoptera stings. The aim of the study was to measure basal tryptase levels in patients with Hymenoptera venom allergy and investigate the possible correlation between these levels and the severity of sting reaction.

Methods: One hundred nine patients were included in the study.

[Tissue factor and tissue factor pathway inhibitor during specific bronchial challenge in allergic asthma patients].

Allergic asthma is characterized by bronchial inflammation and repair processes at the same time, that cause increased airway obstruction. Recent evidences suggest that monocytes and macrophages may play important role in allergic inflammation. Activated by proinflammatory factors they can express tissue factor (TF) and tissue factor pathway inhibitor (TFPI).

The influence of inhaled corticosteroids on exhaled nitric oxide in stable chronic obstructive pulmonary disease.

The aim of the study was to evaluate the exhaled nitric oxide (F(ENO)) in clinically stable chronic obstructive pulmonary disease (COPD), its relationship to the severity of the disease, pulmonary function, smoking status, reversibility of airflow limitation, and ICS therapy. The study was conducted in 47 patients with COPD and 40 healthy controls. Flow/volume spirometry and F(ENO) measurement were performed before and after 2 months of ICS therapy.

Antithrombotic effect of captopril and enalapril in young rats.

Angiotensin converting enzyme inhibitors (ACE-Is) are the main drugs used in the treatment of essential hypertension and congestive heart failure in adults. Recently, we have demonstrated the antithrombotic effect of captopril (CAP) and enalapril (ENA) in venous thrombosis model in adult rats. One might also suggest the beneficial effect of those drugs on hemostasis in young individuals.

The plasmin system in airway remodeling.

Recent studies suggest that the plasmin system plays an active role in tissue remodeling. Plasmin degrades the extracellular matrix (ECM), either directly removing glycoproteins from ECM or by activating matrix metalloproteinases (MMPs). PAI-1 blocking MMPs may prevent ECM degradation, but inhibiting fibrinolysis leads to fibrin accumulation and fibrosis.

Nitric oxide-dependent antiplatelet action of AT1-receptor antagonists in a pulmonary thromboembolism in mice.

The aim of this study was to determine whether AT1-receptor antagonists could inhibit platelet activation-dependent pulmonary thromboembolism in mice and to investigate the involvement of nitric oxide in this action. Losartan, its active metabolite EXP3174, and valsartan given intraperitoneally 1 hour before the thrombotic challenge (in doses of 3, 10, or 30 mg/kg) protected mice from death or hind-limb paralysis in response to intravenous injection of a mixture of collagen and epinephrine; losartan was effective in all doses used, whereas EXP3174 and valsartan reduced mortality only in the two higher doses. The protective action of EXP3174 and valsartan was abolished when nitric oxide synthase was inhibited with l-NAME, whereas that of losartan was only partially reduced.

Angiotensin-(1-7): an active member of the renin-angiotensin system.

Angiotensin-(1-7) [Ang-(1-7)] is an active member of renin-angiotensin system (RAS). It counterbalances vasoconstriction, mitogenic, arrhythmogenic and prothrombotic actions of Ang II. Inducing natiuresis and diuresis opposes also the water and sodium retention produced by Ang II.

Antithrombotic effect of captopril and losartan is mediated by angiotensin-(1-7).

It is well established that renin-angiotensin system blockers exert NO/prostacyclin-dependent antithrombotic effects. Because some beneficial effects of these drugs are mediated by angiotensin (Ang)-(1-7), in the present study we examined if their antithrombotic action could be mediated by Ang-(1-7). Intravenous infusion of Ang-(1-7) (1, 10, or 100 pmol/kg per minute for 2 hours) into rats developing venous thrombosis caused 50% to 70% reduction of the thrombus weight.

The antithrombotic effect of angiotensin-(1-7) closely resembles that of losartan.

Angiotensin-(1-7) [Ang-(1-7)] is the bioactive peptide which may be responsible for some of the pharmacological effects of losartan. Our previous study has demonstrated the antithrombotic action of losartan in a model of experimental thrombosis. In the present study, we compared the antithrombotic action of losartan and Ang-(1-7).

The involvement of AT(2)-receptor in the antithrombotic effect of losartan in renal hypertensive rats.

In previous studies, we have shown that losartan possesses nitric oxide-dependent antithrombotic properties in various models of hypertension in rats. It was demonstrated that stimulation of AT2-receptors plays an important role in the pharmacological effects of AT1-receptor antagonists. Thus, in this study, we examine the participation of AT2-receptors in the antithrombotic action of losartan in renal hypertensive rats on venous thrombosis induced by a two-hour ligation of the vena cava.

Studies on the antithrombotic action of AT1 receptor antagonists.

Background: In our previous experiments we showed that the prototype member of the AT1 receptor antagonists (AT1-As) family, losartan, prevented the development of arterial and venous thrombosis in rats. Recent studies have demonstrated that apart from blocking AT1 receptor, losartan is also a competitive antagonist to thromboxane A2/prostaglandin H2 receptor (TP receptor). Thus, we decided to assess if this feature could contribute to the antithrombotic action of losartan.

Losartan inhibits the adhesion of rat platelets to fibrillar collagen--a potential role of nitric oxide and prostanoids.

The aim of the study was to evaluate the effect of losartan on rat platelet adhesion to fibrillar collagen. Washed platelets were counted before and after 15 minutes incubation with collagen (50 microg/ml) and the percentage of adhering platelets was calculated as the index of their adhesion. When the platelets were incubated with collagen 40.

Thiol repletion prevents venous thrombosis in rats by nitric oxide/prostacyclin-dependent mechanism: relation to the antithrombotic action of captopril.

Clinical and experimental data have recently accumulated for antithrombotic action of angiotensin-converting enzyme inhibitors (ACE-1s). We have shown previously that captopril (which contains a thiol group in the moiety) exerts more pronounced antithrombotic activity than does an equipotent dose of enalapril (the drug devoid of the thiol group). To clarify the relative importance of the presence of the thiol group in the molecule versus angiotensin-converting enzyme (ACE) inhibitory properties in the antithrombotic action of captopril, rats were treated with captopril (5 mg/kg twice daily; CAP), epicaptopril (stereoisomer of captopril devoid of ACE-inhibitory properties; 5 mg/kg twice daily; EPI), N-acetylcysteine (3.

Angiotensin-(1-7). One step forward?

Angiotensin-(1-7) [Ang-(1-7)] is a paracrine hormone of the renin-angiotensin system (RAS). It counterbalances the negative actions of angiotensin II (Ang II) acting in the cardiovascular system, kidneys and central nervous system, and is responsible for blood pressure regulation and antiproliferative effects. Current data strongly suggest the existence of a specific receptor for this peptide.

Hypotensive effect of angiotensin II after AT1-receptor blockade with losartan.

Recent data suggest that hypotensive effect of losartan may not be attributed solely to AT1-receptor blockade, but also to excessive AT2 or other receptors stimulation by elevated angiotensin II and its derivative peptides. Therefore in the present study we examined the effect of angiotensin II on mean blood pressure after AT -receptor blockade with losartan. Male Wistar rats were anaesthetised and received injection of either losartan (30 mg/kg, 1 ml/kg, i.