Experimental pathology of local tissue damage induced by Bothrops asper snake venom

Envenomations by Bothrops asper are often associated with complex and severe local pathological manifestations, including edema, blistering, dermonecrosis, myonecrosis and hemorrhage. The pathogenesis of these alterations has been investigated at the experimental level. These effects are mostly the consequence of the direct action of zinc-dependent metalloproteinases (SVMPs) and myotoxic phospholipases A2 (PLA2s). SVMPs induce hemorrhage, blistering, dermonecrosis and general extracellular matrix degradation, whereas PLA2s induce myonecrosis and also affect lymphatic vessels. In addition, the prominent vascular alterations leading to hemorrhage and edema may contribute to ischemia and further tissue necrosis. The mechanisms of action of SVMPs and PLA2s are discussed in detail in this review. Venom-induced tissue damage plays also a role in promoting bacterial infection. A prominent inflammatory reaction develops as a consequence of these local pathological alterations, with the synthesis and release of abundant mediators, resulting in edema and pain. However, whether inflammatory cells and mediators contribute to further tissue damage is not clear at present. Muscle tissue regeneration after venom-induced pathological effects is often impaired, thus resulting in permanent tissue loss and dysfunction. SVMP-induced microvessel damage is likely to be responsible of this poor regenerative outcome. Antivenoms are only partially effective in the neutralization of B. asper-induced local effects, and the search for novel toxin inhibitors represents a potential avenue for improving the treatment of this serious aspect of snakebite envenomation.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP

Rheumatoid arthritis and the cardiovascular risk, a retrospective data analysis

Hintergrund: Die Rheumatoide Arthritis (RA) ist eine chronisch entzündliche und autoimmune Systemerkrankung. Patienten, die unter rheumatoider Arthritis leiden, haben ein erhöhtes Risiko kardiovaskulär zu erkranken. Dieses erhöhte Risiko für kardiovaskuläre Ereignisse inkludiert den zusätzlichen negativen Einfluss des chronischen Entzündungszustands auf die traditionellen kardiovaskulären Risikofaktoren. Ziel: Das Hauptziel dieser Studie ist es, die Rheumatoide Arthritis im Zusammenhang mit der Entwicklung von kardiovaskulären Erkrankungen zu beurteilen und das kardiovaskuläre Risiko zu evaluieren mit besonderem Hinblick auf die kardiovaskulären Risikofaktoren. Methodik: Es wurde eine retrospektive Datenanalyse von 550 RA Patienten des Allgemeinen Krankenhauses Wien durchgeführt mit besonderem Fokus auf das Vorkommen von kardiovaskulären Erkrankungen. Bei der Auswertung dieser Daten, wurde gezielt auf den Status der Erkrankung, die medikamentöse Therapie, das Auftreten von kardiovaskulären Risikofaktoren und Erkrankungen geachtet. Das Patientenkollektiv wurde zur 1. Auswertung in folgende Gruppen unterteilt: RA Patienten mit einem CRP Wert 1mg/dl. Eine weitere Untersuchung der Patientendaten wurde durchgeführt mit einer Einteilung in Gruppe 1: Patienten mit einem ACPA Wert 20 U/ml. Resultate: Signifikant erhöhte CRP Werte wurden bei RA Patienten mit Diabetes mellitus (p= 0.000) und mit arterieller Hypertonie (p=0.003) beobachtet. Ein signifikant erhöhter ACPA Wert wurde bei aktiven Rauchern im Vergleich zu Nichtrauchern ermittelt (p=0.001). Es konnte kein signifikant erhöhtes Risiko festgestellt werden, kardiovaskulär zu erkranken, bei Patienten mit kardiovaskulären Risikofaktoren und einem erhöhten CRP Wert (CRP>1mg/dl) im Vergleich zu Patienten mit kardiovaskulären Risikofaktoren und einem normalen Wert (CRP20U/ml) konnte ein erhöhtes Auftreten von Myokardinfarkt gezeigt werden (p=0.020; OR: 3.589; 95%CI:1.224-10.522). Schlussfolgerung: Die Ergebnisse dieser Studie konnten ein erhöhtes kardiovaskuläres Risiko nicht durch die Kombination von kardiovaskulären Risikofaktoren und erhöhten CRP Werten erklären. Jedoch konnte ein Zusammenhang zwischen erhöhten ACPA Werten und Nikotinabusus mit dem Auftreten eines Myokardinfarktes in RA Patienten beobachtet werden. Das kardiovaskuläre Risiko an sich, scheint den größten Einfluss auf das Auftreten eines kardiovaskulären Events zu haben. Zusammenfassend ist eine regelmäßige Kontrolle der kardiovaskulären Risikofaktoren für RA Patienten zu empfehlen.Background: Rheumatoid arthritis (RA) is a chronic, autoimmune and inflammatory disease. Patients with rheumatoid arthritis have a higher risk for cardiovascular events. This increased risk for cardiovascular events implies the additive adverse affect of the chronic inflammatory state to traditional cardiovascular risk factors. Aim: The aim of the present study was to evaluate the cardiovascular risk of rheumatoid patients and to determine the influence of a chronic inflammatory state and cardiovascular risk factors on the occurrence of coronary heart disease and acute myocardial infarction. Methods: A retrospective data analysis of 550 rheumatoid arthritis patients was performed. The population comprises RA patients, who underwent diagnosis and treatment between 1998 and September 2017 at the Vienna General hospital. Special focus was set on: the cardiovascular risk profile, status of the disease, medical treatment, incidence and outcome of cardiovascular diseases. At first the RA patients were grouped in an inflammatory group (serum CRP level over 1mg/dl) and a non inflammatory group (serum CRP level under 1mg/dl) for further analysis on the study endpoints. For the second analysis the RA patients were grouped in a high serum ACPA level group (over 20 U/ml) and normal ACPA level group (under 20 U/ml). Results: CRP levels were significantly increased in RA patients with arterial hypertension (p=0.003) and diabetes mellitus (p=0.000). Another significant result showed that the ACPA levels of active smokers were higher compared to non smokers (p=0.001). There was no association of coronary heart disease or acute myocardial infarction with a chronic inflammatory state as depicted by elevated CRP levels. However we could observe that patients with elevated ACPA levels at baseline and additional nicotine abuse have increased incidences of acute myocardial infarction (p=0.020; OR: 3.589; 95%CI:1.224-10.522) compared to patients with nicotine abuse and normal ACPA levels (p=0.120, OR: 2.673, 95%CI 0.774-9.226) or compared to patients without nicotine abuse and elevated ACPA levels (p=0.406, OR: 0.539, 95%CI 0.126-2.316). Conclusion: In the present study we observed that in patients with rheumatoid arthritis, solely increased inflammatory markers do not increase the risk for future cardiovascular events but an association was observed between increased risk of acute myocardial infarction and the combination of nicotine abuse and elevated ACPA levels. As in general population traditional cardiovascular risk factors seem to be the major determinant of cardiovascular outcome in RA patients. However out data suggest that a chronic inflammatory burden exacerbates the risk for cardiovascular disease in the present of other risk factors. Taken together our findings favor the strict control of cardiovascular risk factors in RA patients.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersArbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftMedizinische Universität Wien, Diplomarb., 2019(VLID)447787

Detection of genetically modified corn (Bt176) in spiked cow blood samples by polymerase chain reaction and immunoassay methods

International audienceThe fate of DNA and protein transgenic sequences in products derived from animals fed transgenic crops has recently raised public interest. Sensitive molecular tests targeting the Bt176 genetic construct and the transgenic Cry1Ab protein were developed to determine whether plant sequences, especially transgenic sequences, are present in animal products. A protocol for total DNA extraction and purification from cow whole blood samples was first drawn up and assessed by spiking with known amounts of DNA from Bt176 maize. The limit of detection for transgenic sequences (35S promoter and Bt176-specific junction sequence) was determined by both the polymerase chain reaction–enzyme-linked immunosorbent assay (PCR–ELISA) and the 5′-nuclease PCR assay. Four additional PCR systems were built to substantiate the results. The first detects a mono-copy maize-specific sequence (ADH promoter). Two others target multi-copy sequences from plant nucleus (26S rRNA gene) and chloroplast (psaB gene). The last one, used as a positive control, targets a mono-copy animal sequence (αs1-casein gene). Both methods detected a minimum spiking at 25 copies of Bt176 maize/mL in 10 mL whole blood samples. The sandwich ELISA kit used detected down to 1 ng transgenic Cry1Ab protein/mL spiked whole bloo

Detection of genetically modified corn (Bt176) in spiked cow blood samples by polymerase chain reaction and immunoassay methods

International audienceThe fate of DNA and protein transgenic sequences in products derived from animals fed transgenic crops has recently raised public interest. Sensitive molecular tests targeting the Bt176 genetic construct and the transgenic Cry1Ab protein were developed to determine whether plant sequences, especially transgenic sequences, are present in animal products. A protocol for total DNA extraction and purification from cow whole blood samples was first drawn up and assessed by spiking with known amounts of DNA from Bt176 maize. The limit of detection for transgenic sequences (35S promoter and Bt176-specific junction sequence) was determined by both the polymerase chain reaction–enzyme-linked immunosorbent assay (PCR–ELISA) and the 5′-nuclease PCR assay. Four additional PCR systems were built to substantiate the results. The first detects a mono-copy maize-specific sequence (ADH promoter). Two others target multi-copy sequences from plant nucleus (26S rRNA gene) and chloroplast (psaB gene). The last one, used as a positive control, targets a mono-copy animal sequence (αs1-casein gene). Both methods detected a minimum spiking at 25 copies of Bt176 maize/mL in 10 mL whole blood samples. The sandwich ELISA kit used detected down to 1 ng transgenic Cry1Ab protein/mL spiked whole bloo