Lipid emulsion exerts rapid, positive inotropic and positive lusitropic effects in both intact animal and isolated heart models. We hypothesize that this inotropy and the resulting increase in tissue blood flow contribute to the phenomenon of lipid reversal of cardiac toxicity caused by drug overdose.

Triglyceride micro-emulsions such as Intralipid® have been used to reverse cardiac toxicity induced by a number of drugs but reservations about their broad-spectrum applicability remain because of the poorly understood mechanism of action. Herein we report an integrated mechanism of reversal of bupivacaine toxicity that includes both transient drug scavenging and a cardiotonic effect that couple to accelerate movement of the toxin away from sites of toxicity. We thus propose a multi-modal therapeutic paradigm for colloidal bio-detoxification whereby a micro-emulsion both improves cardiac output and rapidly ferries the drug away from organs subject to toxicity. In vivo and in silico models of toxicity were combined to test the contribution of individual mechanisms and reveal the multi-modal role played by the cardiotonic and scavenging actions of the triglyceride suspension. These results suggest a method to predict which drug toxicities are most amenable to treatment and inform the design of next-generation therapeutics for drug overdose.

Superwarfarins were developed following the emergence of warfarin resistance in rodents. Superwarfarins have much longer half-lives and stronger affinity to vitamin K epoxide reductase versus warfarin, and therefore can cause death in warfarin-resistant rodents. By the mid-1970s, the superwarfarins brodifacoum (BDF) and difenacoum (DiF) were the most widely used rodenticides throughout the world. Unfortunately, increased use was accompanied by a rise in accidental poisonings, reaching >16,000 per year in the United States. Risk of exposure has become a concern since large quantities, up to hundreds of kilograms of rodent bait, are applied by aerial dispersion over regions with rodent infestations. Reports of intentional use of superwarfarins in civilian and military scenarios raises the specter of larger incidents or mass casualties. Unlike warfarin overdose, for which 1–2 days of treatment with vitamin K is effective, treatment of superwarfarin poisoning with vitamin K is limited by extremely high cost and can require daily treatment for a year or longer. Furthermore, superwarfarins have actions that are independent of their anticoagulant effects, including both vitamin K–dependent and –independent effects, which are not mitigated by vitamin K therapy. In this review, we will summarize superwarfarin development, biology and pathophysiology, their threat as weapons, and possible therapeutic approaches.

In patients taking a statin and admitted to the hospital for investigation of a coronary event, treatment with Eze/Simva 10/40 mg for 12 weeks produced greater improvements in lipids with a similar safety profile compared with doubling of the statin dose.

BackgroundAn allergy to mango is extremely rare. The antigenic composition of the fruit is not fully known. Profilin from mango has a structure similar to birch tree profiling: it is responsible for cross-reactions between mango and pear, apple, and peach. A panallergen with a structure similar to mugwort defensin (Art v 1) which cross-reacts with celery, carrot, peanuts, pepper, aniseed, and caraway has been previously described.Case studyA female patient, 30 years old, was admitted in February 2017 because of recurrent allergic reactions following consumption of various foods. The most severe allergic reaction in the patient’s life occurred after eating a mango fruit. Within several minutes the patient developed a generalised urticaria, followed by facial oedema, strong stomach pain and watery diarrhoea. The diagnostics involved skin tests with a set of inhalatory and food allergens, including native skin tests. The patient also experienced symptoms of recurrent, generalized urticaria in connection with consumption of various types of food, especially complex dishes containing many different ingredients. Additionally, an interview revealed that the patient was experiencing symptoms of the oral allergy syndrome after ingesting various fruit and vegetables, especially during late summer and fall. Diagnostics was extended by determining the levels of IgE specific for allergen components, using the ImmunoCap ISAC method. In order to confirm the occurence of a cross-reaction between mugwort and mango allergens, we performed the inhibition test of IgE specific for mugwort using a mango allergen extract and ImmunoCap matrix.ResultsSkin prick tests (SPT) were positive for allergens of grass 7 mm; weeds 8 mm; cat’s fur 5 mm; mugwort 6 mm. SPT were also positive for mango. The level of specific IgE was increased for allergens of mugwort, grass, celery, pepper, carrot, mango, banana, peach, and apple. The ImmunoCap ISAC test demonstrated a high level of specific IgE rPhl p 1 (timothy grass) and Art v 1 (mugwort). We also performed the IgE inhibition test using both mango extract and ImmunoCap matrix and confirmed a cross-reaction with Art v 1 in the pathogenesis of symptoms observed in the patient.ConclusionsAn anaphylactic reaction to consumed mango, resulting from cross-allergy with mugwort Art v 1 was diagnosed in the patient. Acute urticarial in this case is a manifestation of IgE-mediated food allergy. During in vitro diagnostic procedures we found an elevated concentration of IgE specific to several food allergens (including celery, peppers, carrot, banana, peach, apple, shrimp). The elimination diet removing allergens the patient was allergic to was recommended. Considering the anaphylactic reaction the patient was instructed to carry a rescue set composed of an adrenaline autosyringe, steroids, and antihistamines.

BackgroundComponent resolved allergen diagnosis allows for a precise evaluation of the sensitization profiles of patients sensitized to felines and canines. An accurate interpretation of these results allows better insight into the evolution of a given patients sensitizations, and allows for a more precise evaluation of their prognoses.Methods70 patients (42 women and 28 men, aged 18–65, with the average of 35.5) with a positive feline or canine allergy diagnosis were included in the research group. 30 patients with a negative allergy diagnosis were included in the control group. The total IgE levels of all patients with allergies as well as their allergen-specific IgE to feline and canine allergens were measured. Specific IgE levels to canine (Can f 1, Can f 2, Can f 3, Can f 5) and feline (Fel d 1, Fel d 2, Fel d 4) allergen components were also measured with the use of the ImmunoCap method.ResultsMonosensitization for only one canine or feline component was found in 30% of patients. As predicted, the main feline allergen was Fel d 1, which sensitized as many as 93.9% of patients sensitized to felines. Among 65 patients sensitized to at least one feline component, for 30 patients (46.2%) the only sensitizing feline component was Fel d 1. Only 19 patients in that group (63.3%) were not simultaneously sensitized to dogs and 11 (36.7%), the isolated sensitization to feline Fel d 1 notwithstanding, displayed concurrent sensitizations to one of the canine allergen components. Fel d 4 sensitized 49.2% of the research group.64.3% of patients sensitized to canine components had heightened levels of specific IgE to Can f 1. Monosensitization in that group occurred for 32.1% of the patients. Sensitization to Can f 5 was observed among 52.4% of the patients.ConclusionsConcurrent sensitizations to a few allergic components, not only cross-reactive but also originating in different protein families, are a significant problem for patients sensitized to animals.

Preference is a composite, patient-oriented endpoint incorporating efficacy, tolerability, formulation, and convenience of medications. The objective of this study was to compare patient preference for rizatriptan 10-mg wafer vs. eletriptan 40-mg tablet for acute treatment of migraine. In this multicentre, open-label, two-period, crossover study, out-patients were randomly assigned to treat the first of two moderate to severe migraines with rizatriptan or eletriptan and the second with the alternate therapy. Patients completed diary assessments at baseline and up to 24 h after taking study medication. At the last visit, patients completed a psychometrically validated preference questionnaire. A total of 372 patients (mean age 38 years, 85% female) treated two migraine attacks, and 342 patients (92%) expressed a preference for treatment. Significantly more (P < or = 0.001) patients preferred rizatriptan 10-mg wafer [61.1%; 95% confidence interval (CI) 55.7, 66.3] to eletriptan 40-mg tablet (38.9%; 95% CI 33.7, 44.3). The most common reason given for preference of either treatment was speed of headache relief. At 2 h, 80% and 69% of patients reported that rizatriptan and eletriptan, respectively, was convenient or very convenient to take (mean convenience score 1.99 vs. 2.31, respectively; P < or = 0.001). Both triptans were well tolerated. In this head-to-head study designed to evaluate global patient preference, significantly more patients preferred the rizatriptan 10-mg wafer to the eletriptan 40-mg tablet for acute treatment of migraine. The single most important reason for preference was speed of relief, consistent with results from previous preference studies.

SummaryBackgroundThe aim of this study was to evaluate the concentration of malondialdehyde (MDA) in erythrocytes and in blood plasma and the activity of blood paraoxonase (PON1) of patients with osteoarthrosis (OA) submitted to endoprosthesis implantation for evaluating oxidative stress.Material/MethodsStudy was conducted on 55 patients with OA and on 54 total movement-efficient volunteers. The material for the study was venous blood plasma, serum and erythrocytes.ResultsIncreased concentration of MDAe before surgery was observed in the group of men and in patients with a degenerative process affecting hip joints. After an implantation of endoprosthesis, MDAe decreased to the level observed in the control groups. In the study group MDA concentration in plasma was slightly lower before surgery, and after an operation it reached the value of the parameter of the reference groups. Regardless of sex or age, paraoxonase activity was almost twice as high in almost all subgroups as in the reference group. A positive correlation between PON 1 activity and MDAe concentration was demonstrated both before and after surgery in the group of men.ConclusionsThe increase of PON1 activity in patients’ serum in relation to the control groups indicates a probable pathogenic role of the increased formation of reactive oxygen species in the course of OA and may suggest acute inflammation of the synovial joint. The high level of PON 1 activity after endoprosthesis implantation indicates that surgical treatment may additionally stimulate ROS generation. MDAe concentration indicate more intensive process of lipid peroxidation in the elderly.