Lysine Acetylsalicylate Research Articles

Different Patterns of Response in Hypersensitivity Reactions to Arylpropionic Acid Derivatives

Ibuprofen and other arylpropionic acid derivatives (APs) are among the most consumed nonsteroidal anti-inflammatory drugs worldwide at all age ranges; however, little is known about drug hypersensitivity reactions (DHRs) they induce. To characterize in detail patients reporting DHRs to APs. We prospectively evaluated patients with symptoms suggestive of AP-DHRs and analyzed their clinical characteristics, reported reactions, and diagnostic approaches. Six hundred sixty-two patients confirmed as hypersensitive to APs were included: 489 with cross-reactive reactions (CRs) (73.86%) and 173 with selective reactions (SRs) (26.13%). The percentage of subjects reporting reactions to ibuprofen and dexketoprofen was higher in CRs (P= .005 and P= .01, respectively), whereas naproxen and ketoprofen were more frequently involved in SRs (P= .0002 and P= .00001, respectively). The most frequent symptoms induced by ibuprofen, dexketoprofen, and naproxen were isolated angioedema and urticaria, combined or not with angioedema in both CRs and SRs. The result of nasal provocation test with lysine acetylsalicylate was positive in 156 cases (77.14% in patients showing exclusively respiratory symptoms, and in 68.18% of those with both cutaneous and respiratory involvement). To confirm diagnosis, drug provocation test with acetylsalicylic acid was required in 246 CR patients (50.3%), whereas in 28 SR patients (16.18%) drug provocation test with the culprit AP was required. Skin is the organ most commonly involved in AP-DHRs, with ibuprofen and dexketoprofen inducing most frequently CRs, and naproxen and ketoprofen SRs. More studies are necessary to clarify the underlying mechanism in DHRs induced by APs.

Antipyretic Activity of Aqueous Extract of Daniellia oliveri Leaves (Rolfe, Hutch Et Dalz) (Fabaceae)

The pharmacological study of the aqueous extract of Daniellia oliveri (Fabaceae) leaves revealed antipyretic properties .This dose-dependent reduction in brewer's yeast-induced hyperthermia in rats is similar to that of lysine acetylsalicylate. Qualitative phytochemical screening shows that the aqueous leaf extract of Daniellia oliveri contains polyphenols, flavonoids, saponosides, quinone substances, alkaloids, catechic and gallic tannins, sterols, polyterpenes and cardiodic heterosides. The oral LD50 of the aqueous extract of Daniellia oliveri leaves conducted according to OECD guideline 423 [1], is greater than 5000 mg/kg B.W, making this plant a substance of low toxicity, thus justifying its traditional use in painful ailments.

Effects of intravenous lysine acetylsalicylate versus oral aspirin on platelet responsiveness in patients with ST-segment elevation myocardial infarction

Abstract Background Prasugrel and ticagrelor, new P2Y12-ADP receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events in patients with an acute coronary syndrome. However, evidence is lacked about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared to oral aspirin on prasugrel inhibited platelets in patients with an ST-segment elevation myocardial infarction (STEMI). Methods This is a prospective, randomized, multicenter, open platelet function study conducted. STEMI patients were randomly assigned to receive a loading dose (LD) of intravenous LA 450mg plus oral ticagrelor 180mg, or LD of aspirin 300mg plus ticagrelor 180mg orally. Platelet function was evaluated at baseline, 30 min, 1h, and 24h using multiple electrode aggregometry and vasodilator-stimulated phosphoprotein phosphorylation (VASP). The primary endpoint of the study is the inhibition of platelet aggregation after arachidonic acid (AA) 1.5mM at 30 min. Secondary endopoints are the inhibition of platelet aggregation after AA baseline and at 1h, and 24h, and measurement of aggregation with other platelet test (ADP, collagen and VASP). Results A total of 32 STEMI patients were randomized (16 LA, 16 aspirin). The inhibition of platelet aggregation after AA 1.5 mM at 30 min was greater in subjects treated with LA compared with aspirin: 166 vs. 412 respectively, p=0.001. This differential effect was observed at 1 hour (p=0.01), but not at 24 hours. Subjects treated with LA presented less variability and faster and greater inhibition of platelet aggregation with AA compared with aspirin (Figure 1). Conclusions The administration of intravenous LA resulted in a significantly reduction of platelet reactivity compared to oral aspirin on ticagrelor inhibited platelets in patients with STEMI. Loading dose of LA achieves an earlier platelet inhibition, and with less variability than aspirin. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the CTU-SCReN (Clinical Trial Unit – Spanish Clinical Research Network) from San Carlos University Hospital (Madrid, Spain), financed by the ISCII (Project PI16/00191)

P304 CASE OF MYOCARDITIS AFTER COVID 19 VACCINATION

COVID 19 has so far found the only barrier in the use of mRNA and viral vector vaccines. Among the rare adverse effects related to mRNA vaccines is myocarditis (4.8 cases per million doses) a disease already found in COVID 19 infection but not in the safety studies of the vaccines. Males not older than 30 years (40% of the total), subjected to the second dose inoculation, are most affected. During our recent clinical practice there was a case of a patient with myocarditis, attributable to vaccination for COVID 19. It was a male, twenty–year–old, non–allergic smoker, subjected to second dose of Pfizer–BioNTech vaccine (BNT162b2). On the fifth day after the inoculation, the patient, already asthenic from the previous days, complained of an episode of oppressive chest pain, which lasted about 15 minutes, which returned, more intense the following night, associated with dyspnea, lasted for hours. When the patient went to the emergency room the pain was in regression and there was good hemodynamic compensation. EKG: sinus rhythm, slight diffuse ST segment elevation, more pronounced in the inferior–lateral leads, slight lowering of the P–R segment. Blood tests: troponin, CKMB and PCR increase, negativity of the molecular test for COVID 19. Echocardiography: normal left ventricle, non–dilated right sections, normokinetic right ventricle, normal valves, pericardial hyper–refraction without effusion, normal diastolic relaxation. In the suspicion of myocarditis, the patient was admitted to our intensive cardiological care. With the high–dose anti–inflammatory and beta–blocker therapy the pain gradually disappeared; never fever; EKG showed progressive ST segment improvement and T wave negativization. Never arrhythmic events. Negativity for all infections with common viral pathogens. MRI: hyperintensity (T2 STIR sequences and late enhancement) in the infero–lateral area. Patient discharged in therapy with lysine acetylsalicylate, to be reduced, associated with pantoprazole, and metoprolol and indicated for outpatient checks. In conclusion, the case presented reflects the scientific literature in the type of patient and in the favorable evolution of the disease.

The Utility of Nasal Challenges to Phenotype Asthma Patients.

Asthma is a heterogeneous disease in terms of both phenotype and response to therapy. Therefore, there is a great need for clinically applicable tools allowing for improved patient classification, and selection for specific management approaches. Some interventions are highly helpful in selected patients (e.g., allergen immunotherapy or aspirin desensitization), but they are costly and/or difficult to implement. Currently available biomarkers measurable in peripheral blood or exhaled air display many limitations for asthma phenotyping and cannot identify properly the specific triggers of the disease (e.g., aeroallergens or NSAID). The united airway concept illustrates the relevant epidemiological and pathophysiological links between the upper and lower airways. This concept has been largely applied to patient management and treatment, but its diagnostic implications have been less often explored. Of note, a recent document by the European Academy of Allergy and Clinical Immunology proposes the use of nasal allergen challenge to confirm the diagnosis of allergic asthma. Similarly, the nasal challenge with lysine acetylsalicylate (L-ASA) can be used to identify aspirin-sensitive asthma patients. In this review, we will summarize the main features of allergic asthma and aspirin-exacerbated respiratory disease and will discuss the methodology of nasal allergen and L-ASA challenges with a focus on their capacity to phenotype the inflammatory disease affecting both the upper and lower airways.

Assessment of the hepatorenal and hematological parameters of rats exposed to graded doses of lysine acetylsalicylate

Lysine acetylsalicylate (LAS) is an analgesic used for the prevention of cardiovascular disease with few adverse though its effect on the hepatorenal and hematological parameters remains unclear. 45 mature male Wistar rats were equally divided into three groups. Group I, II, and III received daily intramuscular doses of 0.25 mL saline, 40, and 80 mg/kg b. wt. of LAS respectively for 2-weeks. After 2, 4, and 8 weeks from beginning of drug administration, 5 rats/group were assessed for hepatorenal function, complete blood-count, and histopathological findings of liver and kidney. LAS induced a significant increase (p ≤ 0.05) in serum levels of aspartate aminotransferase, alanine aminotransferase, urea, and creatinine in a dose-dependent manner, but a significant decrease (p ≤ 0.05) observed in the hematological parameters. Histopathological alterations were a dose-dependent manner, and persisted for 8-weeks at the higher dose. In conclusion, LAS induced reversible deleterious effects on hepatorenal functions and various hematological parameters in a dose-dependent manner.

Pregnancy Outcome in Mice with Protein S Complete Deficiency

Introduction:Pregnancy is associated with a shift of the coagulation balance with increased concentration of procoagulant factors, decreased concentration of some anticoagulants and diminished fibrinolytic activity. These changes provoke a state of hypercoagulability that protects pregnant women from fatal hemorrhage during delivery but predispose them to thromboembolism.Protein S (PS) is a natural anticoagulant that acts as a cofactor of activated protein C and tissue factor pathway inhibitor. PS complete deficiency leads to life threatening skin necrosis and disseminated intravascular coagulation (DIC) named purpura fulminans (PF) that leads to death if untreated. Pregnant women with partial PS deficiency are at high risk of late fetal loss. The beneficial role of thromboprophylaxis in ameliorating pregnancy outcome in patients with inherited thrombophilia is debated.Here, we used mice with complete PS deficiency (Pros1-/-) fully rescued from lethality by the lack of factor VIII (F8-/-Pros1-/-). Characterization of F8-/-Pros1-/- mice revealed no signs of PF or DIC. These mice were used to investigate the effect of PS complete deficiency on pregnancy.Methods:Timed matings were set to generate E9-E17.5 embryos from F8-/-Pros1-/-, F8-/-Pros1+/+ and F8+/+Pros1+/+ pregnant mice (n=3-9/genotype). Embryos viability and genotype were evaluated. At the time of sacrifice, blood was drawn from pregnant female to evaluate blood cells count profile and coagulation parameters (fibrinogen, thrombin anti-thrombin complex; TAT) were measured. Anti-fibrin immunostaining was performed in collected embryos and placentas.F8-/-Pros1-/- pregnant females were treated with low-dose aspirin (200mg/kg Lysine acetylsalicylate) or LMWH (Clexane, 100μg/mL delivered by osmotic pump 0.25 μL/hour) from E7 until E20 to assess if thromboprophylaxis could be beneficial for pregnancy.Results:No litters were produced from F8-/-Pros1-/- crosses.F8-/-Pros1-/- females were then mate with F8-/-Pros1+/- male and sacrificed at different gestational stages. A progressively high number of macerated and necrotic embryos were found after E9-E10 in comparison with pregnantcontrols: 0% (E9-10), 57% (E11-E12), 64% (E14-E15) and 67% (E16-E17). In parallel, number of embryos per gestation decreased in F8-/-Pros1-/- compared to F8-/-Pros1+/+ females (4±1 vs 9±1 at E11-E12, 3±1 vs 7±1 at E14-E15, 2±1 vs 7±2 at E16-E17, respectively). Macroscopically, the majority of alive embryos showed the presence of hemorrhages without PF. F8-/-Pros1-/- genotype was underrepresented among alive embryos (33% vs the expected 50%) and it disappeared from those collected after E12.5.The evaluation of DIC parameters in F8-/-Pros1-/- pregnant females during the period of experienced high embryonic mortality (E12-15) showed a significative reduction of platelet counts (486±105 vs 806±134 G/L F8-/-Pros1+/+, P<0.03), fibrinogen (1±0.1 vs 2±0.2 g/L, respectively, P<0.001) and increased TAT (33.2±5.1, 16.6±2.8 ng/L, respectively, P<0.02).Although these results suggest an activated state of blood coagulation, fibrin staining did not reveal fibrin deposition in lungs, liver and placenta from F8-/-Pros1-/- pregnant mice.Treatment of F8-/-Pros1-/- pregnant mice with LMWH or aspirin had a positive pregnancy outcome (n=4/female/treatment). However, litter size was reduced in comparison to F8-/-Pros1+/+ control mice. In particular, the aspirin group showed the lowest litter size while the LMWH group had increased pups number (3±1 vs 6±1, P<0.03). F8-/-Pros1-/- genotype was rescued only among newborns from LMWH treated group (n=1 over 7). Preliminary data from pups monitoring indicated that some pups were smaller, experienced hemorrhages and died after birth.Conclusion:Targeting F8 did not prevent pregnancy loss in F8-/-Pros1-/- mice. Only few F8-/-Pros1+/- embryos survived until E17 indicating that PS expression in the uteroplacental unit is indispensable for embryos development. F8-/-Pros1-/- pregnant mice displayed coagulation activation. However, further investigations are needed if the observed DIC is due to the lack of PS anticoagulant activity or to retained dead embryos. Aspirin or better LMWH partially prevented pregnancy loss indicating that thromboprophylaxis might be beneficial for pregnancy development with very low PS plasma levels. DisclosuresNo relevant conflicts of interest to declare.

Oral aspirin or low dose of intravenous lysine acetylsalicylate in ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

To compare the pharmacodynamic effect of an oral loading dose of 'noncoated' ASA 300 mg vs. an intravenous bolus injection of lysine acetylsalicylate 150 mg in patients with STEMI undergoing pPCI. This was a prospective single-center, open label, pharmacodynamic study, including nonconsecutive patients presenting at our catheterization laboratory with STEMI undergoing pPCI and not receiving ASA within the previous 7 days. Pharmacodynamic analyses were performed at five time points: baseline, and 1, 2, 4 and 12 h after the loading dose, and measured as ASA reaction units (ARU) by the Verify Now System. An ARU more than 550 was considered as nonresponsiveness to study drugs. The primary end point was the different rate of patients with ARU more than 550 at 2 h after the loading dose of oral vs. intravenous ASA. Secondary end points included the comparison of ARU more than 550 at the other time points and the comparison of continuous ARU at each time point. The study was planned with a sample size of 68 patients, but it was prematurely stopped due to slow enrollment after the inclusion of 23 patients, 12 randomized to oral ASA and 11 to intravenous lysine acetylsalicylate. At 2 h the rate of patients with ARU more than 550 was numerically but not significantly higher in patients receiving oral ASA as compared with intravenous lysine acetylsalicylate (33 vs. 14.2%; Δ -0.19, 95% confidence interval -0.59-0.21, P = 0.58). The difference over time was NS (P = 0.98), though the prevalence of ARU more than 550 was higher at the other time points. Both routes of administration reduced ARU values over time, though with no overall significant difference between profiles (P overall = 0.48). In patients with STEMI undergoing pPCI the rate of nonresponsiveness to ASA was not different comparing an oral 'noncoated' loading dose of ASA with an intravenous bolus injection of lysine acetylsalicylate. However, as patient enrollment was prematurely terminated, this study is underpowered to draw a definite conclusion.

A Comparison of Lysine Acetylsalicylate to Anti-IL4/13 and Anti-IL5 Agents in the Management of Type 2 Asthma

This systematic and literature review directly compares the various outcomes including pharmacokinetics, asthma forced expiratory volume in one second (FEV1), quality of life, sinusitis exacerbations, and required polyp surgery for three potential asthma medications: lysine acetylsalicylate (L-ASA), dupilumab (anti-IL-4/13), and mepolizumab (anti-IL-5).

Effect of LTRA in L-ASA Challenge for Aspirin-Exacerbated Respiratory Disease Diagnosis

Aspirin-exacerbated respiratory disease (AERD) consists of asthma, chronic rhinosinusitis with polyps, and hypersensitivity to aspirin and/or nonsteroidal anti-inflammatory drugs (NSAIDs). Nasal Lysine Aspirin Challenge is an effective tool for the diagnosis of hypersensitivity to aspirin and/or NSAIDs in patients with AERD. However, there is no unified international consensus version to perform nasal provocation tests (NPTs). To investigate the effect of a leukotriene receptor antagonist (LTRA), montelukast, on the lysine-acetylsalicylate (L-ASA) nasal challenge. We included 86 patients divided into 3 samples: group A (AERD without LTRA), group B (AERD with LTRA), and the control group (NSAID-tolerant asthmatics). NPT with L-ASA was performed with 25 mg of L-ASA every 30 minutes 4 times followed by rhinomanometry and spirometric measurements and evaluation of symptoms using a novel clinical scale. In group A, 94.5% of patients (35 of 37) developed a positive response to NPT (drop >40% in total nasal flow), whereas only 46% of group B subjects (13 of 28) showed a positive response to the nasal challenge (P < .001). Control subjects did not show any response to the L-ASA challenge. A novel clinical score demonstrated accuracy in classifying the hypersensitivity to aspirin and/or NSAIDs when patients avoid LTRA (33 of 37). Patients with AERD without LTRA showed a greater positive response to the L-ASA challenge than those taking this drug; therefore, LTRA treatment should be discontinued before the challenge for optimal diagnostic accuracy.

Dual energy CT in the management of antiplatelet therapy in patients with acute ischemic stroke for carotid obstruction.

Acute tandem occlusions often require carotid stenting. Combination of mechanical and pharmacologic therapies in addition to antiplatelet drugs administered to prevent acute stent thrombosis might increase the risk of intracerebral hemorrhage. We present a protocol of antiplatelet regimen based on early post-procedural dual-energy CT (DE-CT). Fifty consecutive stroke patients with tandem occlusions treated with acute carotid stenting after intracranial thrombectomy and TICI 2b/3 were reviewed. All patients received intravenous lysine acetylsalicylate during the procedure. Dual (aspirin+clopidogrel with or without clopidogrel load, groups A and B, respectively) or mono (aspirin) antiplatelet regimen (group C) was administered 12-24 h later according to brain DE-CT findings. Carotid ultrasonography was performed at 24 h and before discharge. We evaluated the rate of subsequent symptomatic intracranial hemorrhage (SICH) and acute stent thrombosis in each group. Between June 2014 and December 2016, 50 patients were included (mean age 66 years, 76% men, baseline NIHSS 16, median time from symptom onset to recanalization 266 min). According to DE-CT, 24 patients were assigned to group A, 19 to group B and 7 to group C (4 of them had SICH at that time). One patient suffered a subsequent SICH (belonging to group B). There was only one stent thrombosis without clinical repercussions in group B. DE-CT may contribute to select antiplatelet regimen after acute carotid stenting in tandem occlusions.

NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs

Non-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDs-exacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the current classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n = 138), who had a higher percentage of underlying rhinitis (p < 0.0001) and asthma (p < 0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT.

The dentin permeability of anti-inflammatory and antibacterial drugs: In vitro study

Stimuli from the oral cavity may penetrate through exposed dentinal tubules and evoke inflammatory pulp response. Anti-bacterial and anti-inflammatory drugs applied to exposed dentin may infiltrate through the dentinal tubules and cause pulp recovery. This study investigated the dentin permeability of anti-bacterial and anti-inflammation drugs via an in-vitro transwell dentin disc tube model. Twenty-seven dentin discs prepared from extracted human molars were collected. Nine kinds of drugs were investigated with three dentin discs in each group. These nine drugs included two anti-bacterial drugs (ampicillin sodium and clindamycin phosphate), two corticosteroids (betamethasone sodium phosphate and hydrocortisone sodium succinate), three non-steroidal anti-inflammatory drugs (NSAIDs, piroxicam, lysine acetylsalicylate, and diclofenac sodium), and two natural extracts with anti-inflammatory effect (Ginsenoside Rg1 and Hinokitol). The drugs were introduced to the transwell dentin disc tube model and the 4-hour cumulative release of the drug was detected and recorded by UV-visible spectroscopy. We found that ampicilin sodium had better dentin permeability than clindamycin phosphate. Betamethasone sodium phosphate revealed better dentin permeability than hydrocortisone sodium succinate. Lysine acetylsalicylate showed the best dentin permeability among the three NSAIDs. Ginsenoside Rg1 had the best dentin permeability among the nine drugs tested. However, Hinokitiol could not penetrate the dentin disc after 4h. Regarding the dentin permeability, Ginsenoside Rg1 is the best among the seven anti-inflammatory drugs tested and ampicilin sodium is the better one between the two anti-bacterial drugs tested. Therefore, these two drugs may have high potential for treating exposed dentinal tubule diseases.

Intravitreal Administration of Lysine-Acetylsalicylate Could be an Effective Approach to Preserve Retinal Vessels and to Inhibit Leukostasis in Experimental Diabetic Retinopathy

Leukostasis and the loss of retinal capillaries associated with inflammation play a central role in the development of diabetic retinopathy. The oral administration of acetylsalicylic acid (ASA) at high doses has been associated with therapeutic benefits in experimental diabetic retinopathy. Although, its utility in humans remains controversial. We explore the ability of intravitreal injection of lysine acetylsalicylate to preserve retinal vessels and to inhibit the presence of leukocytes in the retinal ganglion cell (GCL) layer and the outer plexiform layer (OPL) using an experimental model of diabetic retinopathy induced with streptozotocin. The diabetic animals were assigned to two groups, one of them received 2 doses of intravitreal lysine acetylsalicylate (lysine-group) while the other group received 2 intravitreal injections of saline (control-group). The two injections in each group were administered with an interval of 4 weeks. The immunohistochemical labeling revealed a greater number of intact vessels in the lysine-group in the GCL and in the OPL (P<0.001), both in the central and peripheral retina. There was also a lower leukocyte count in the lysinegroup compared to the control-group in the GCL of the central retina (P<0.001). The correlation study between both variables was significant in the GCL of the central and peripheral retina as well as in the OPL of the central retina. These results suggest a protective effect of the drug on the capillary network of the retina and a reduction of leukostasis. Intravitreal administration could maximize the action of salicylate and minimize its systemic adverse effects.

Lysine acetylsalicylate

Lysine acetylsalicylate

Facilitated Transport of Lysine Acetylsalicylate Through Supported Liquid Membrane Using Methyl Cholate as Carrier: Parameters and Mechanism

Transport of lysine acetylsalicylate (LAS) through supported liquid membrane was investigated using methyl cholate (MC) as extractive agent. Kinetic and thermodynamic models were developed, based on the interaction of the substrate LAS with the extractive agent T, and the diffusion of the formed entity (TS) through the membrane. The experimental results verify the models and enable the determination of macroscopic parameters (permeabilities (<i>P</i>) and initial fluxes (<i>J</i>₀)), as well as microscopic parameters (association constants (<i>K</i>_ass), and apparent diffusion coefficients (<i>D</i>^*)), relating to formed entity (TS) and its diffusion through the membrane organic phase. Parameters such as initial concentration of the substrate in the feed phase, pH of the feed and stripping phases and temperature of the extraction medium were studied. The results obtain indicate that the mechanism of the migration of LAS through the membrane organic phase cannot be a pure diffusion movement but it takes place by successive jumps from one site to another of the extractive agent, via interaction reactions with LAS.

Nonsteroidal anti‐inflammatory drugs enhance IgE‐mediated activation of human basophils in patients with food anaphylaxis dependent on and independent of nonsteroidal anti‐inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) act as cofactors worsening the allergic reactions induced by food allergens. The aim of this study was to evaluate the effect of both lysine acetylsalicylate (L-ASA) (non-selective cyclooxygenase (COX) inhibitor) and valdecoxib (selective COX-2 inhibitor) in basophils activated by peach lipid transfer protein (Pru p 3) in patients with food-dependent NSAID-induced anaphylaxis (FDNIA). Twenty Pru p 3-allergic patients with FDNIA group, eleven peach anaphylaxis not exacerbated by NSAIDs (no-NSAID group) and 5 healthy volunteers were recruited. Basophil activation (BA) was measured as expression of CD63 (Flow(2) CAST(™) ; Bühlmann(®) ), after stimulation with Pru p 3, both alone and in combination with L-ASA (1.13, 3.38 and 6.78 mm) or valdecoxib (0.87, 7.8 and 31.25 μm). Basophils from no-NSAID group were significantly more reactive and sensitive to Pru p 3 than those from the FDNIA group. In both groups, an increase in BA was observed when basophils were exposed to Pru p 3 and L-ASA. In the FDNIA group, valdecoxib partially terminates the BA induced by Pru p 3, whereas in the no-NSAID group, a dual effect was observed depending on the concentration tested. This study indicates that subjects with food-induced anaphylaxis differ from FDNIA subjects in the higher reactivity and sensitivity of their basophils to allergen challenge. We have shown a direct effect of NSAIDs on basophils using a human model of FDNIA. Our results also suggest that selective COX2 inhibitors might be a safe alternative. BA test may be a useful tool in the study of the pathogenic mechanism of the cofactor phenomenon.

Decreasing the toxicity of paraquat through the complexation with sodium salicylate: Stoichiometric analysis.

Over the last decades, paraquat (1,1'-dimethyl-4,4'-bipyridilium dichloride; PQ) has been involved in numerous fatalities especially attributed to suicide attempts. Previously, it was shown that salicylates, namely sodium salicylate (NaSAL) and lysine acetylsalicylate (LAS) may form complexes with PQ, which may contribute to prevent its toxicity. The direct chemical reactivity between PQ and NaSAL was previously studied by liquid chromatography/electrospray ionization/mass spectrometry/mass spectrometry, showing the formation of complexes, though reported data was not fully conclusive. In the present study, the structure of the complex of PQ with NaSAL is fully characterized by crystallography. It was observed that PQ is complexed with 4 NaSAL molecules. Since formulations containing PQ and salicylates have been proposed, these results point that the stoichiometry of 1:4 (PQ:salicylates) should be considered to optimize prevention of PQ-mediated toxic effects.

Anti-inflammatory Activities of Total Leaf Extracts of Ficus sycomorus L. (Moraceae) used in Traditional Medicine in the Treatment of Sickle Cell Disease

Background: This study has been carried out to evaluate the in vivo anti-inflammatory, analgesic and anti-pyretic effects of an aqueous decoction and ethanol extract (95%) of Ficus sycomorus leaves. Methods: The anti-inflammatory effect was evaluated by the carrageenan-induced mice paw oedema model. The non-morphine type analgesic effect was evaluated trough acetic acid-induced writhing test. The morphine type analgesic activity was tested by mouse tail–flick test. The anti-pyretic activity was tested by induced hyperthermia in mice with brewer's yeast. Data analysis used the one way ANOVA test. Results: The anti-inflammatory effects of the two extracts, at doses of 300 and 500 mg/kg b.w., were dose dependent and comparable to those of the reference controls, indomethacin (1 mg/kg b.w.) and hydrocortisone (10 mg/kg b.w.). At the same dose, the analgesic effect of the ethanol extract on abdominal writhings induced by acetic acid, was comparable to those Lysine acetylsalicylate (LAS, 300 mg/kg b.w) and hydrocortisone (10 mg/kg b.w.) used as controls. As for the morphine type analgesic effects of the two extracts tested at doses of 300 and 500 mg / kg both were significantly higher in comparison with the blank control (p Key words: Anti-inflammatory, Analgesic, Antipyretic, Antinociceptive, Ficus sycomorus, Sickle cell disease.

À l’ère de l’automédication, que savent les femmes enceintes des anti-inflammatoires ?

Non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated in pregnancy because of the many foetalmaternal complications they can induce. Yet, NSAIDs can be massively found in family medicine cabinets and they are over the-counter drugs for most of them. Because of the actual trend of empowerment and public authorities encouraging self-medication, NSAIDs might be used. Our aim was to assess pregnant women's knowledge of NSAIDs. A descriptive study, through the distribution of 330 questionnaires to all pregnant women consulting at the Teaching hospital of Saint-Etienne, during a week, from February 11(th), 2014 to 19(th), 2014. The answering rate was 96.4%. Around 46% of pregnant women declared self-medicating. More than 1 in 3 women considered NSAIDs without danger starting from their 6th month of pregnancy. Eighty-six percent of women recognized ibuprofen as belonging to NSAISs. However, 1 in 2 women didn't consider Rhinadvil® (ibuprofene/pseudoephedrine) as such and approximately 40% for Aspegic® (lysine acetylsalicylate) and Aspirin® (acetylsalicylic acid). Danger's perception varied according to the galenic and the trade name: 60% of them thought that Rhinadvil® was without risks and around 1 in 2 women thought the same for Aspirin® and Aspegic®. Eighty-six per cent of women recognized ibuprofen as belonging to NSAIDs. However, 1 in 2 women didn't consider Rhinadvil® as such and approximately 40% for Apegic® and Aspirin®. Pregnant women's knowledge of NSAIDs is not satisfactory. They are not aware of their danger and do not know how to recognize them. Yet, self-medication is rising and its accessibility is made easier. A work on prevention and information is therefore essential.