69 research outputs found

    Comparison of the structural dynamic and mitochondrial electron-transfer properties of the proapoptotic human cytochrome c variants, G41S, Y48H and A51V

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    Mitochondrial cytochrome c is associated with electron transfer in the respiratory chain and in apoptosis. Four cytochrome c variants have been identified in families that suffer from mild autosomal dominant thrombocytopenia, a platelet disorder associated with increased apoptosis. Three out of the four substitutions, G41S, Y48H and A51V are located on the 40–57 Ω-loop. The G41S and Y48H variants perturb key physicochemical and dynamic properties that result in enhanced functional features associated with apoptotic activity. Herein we characterise the ferric A51V variant. We show by chemical denaturation that this variant causes the native state to be destabilized. Through azide binding kinetics, the population of a pentacoordinate heme form, whereby the Met80 axial ligand is dissociated, is estimated to be of equal magnitude to that found in the Y48H variant. This pentacoordinate form gives rise to peroxidase activity, which despite the similar pentacoordinate population of the A51V variant to that of the Y48H variant, the peroxidase activity of the A51V variant is suppressed. Far-UV circular dichroism spectroscopy and pH jump studies, suggest that a combination of structural and dynamic features in addition to the population of the pentacoordinate form regulate peroxidase activity in these disease variants. Additionally, the steady-state ratio of ferric/ferrous cytochrome c when in turnover with cytochrome c oxidase has been investigated for all 40–57 Ω-loop variants. These studies show that the lower pKa of the alkaline transition for the disease causing variants increases the ferric to ferrous heme ratio, indicating a possible influence on respiration in vivo

    Notfallmedizinische Aspekte bei Laufveranstaltungen

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    Background!#!The number of short- and long-distance running events in Germany is increasing. Running as a popular sport is practiced by a large number of people of different ages, risk groups, and degrees of professionalism, which results in a wide range of medical emergencies.!##!Objective!#!The present article elucidates incidence, pathophysiology and therapy of relevant emergencies during running events. Aim was the optimization of work processes of emergency personnel.!##!Materials and methods!#!A literature search was conducted in PubMed.!##!Results!#!Exercise-associated muscle cramps, gastrointestinal symptoms, collapse, compartment syndrome, and tendinopathy are common clinical manifestations. Cardiac arrest and sudden cardiac death are rare events. Consciousness and seizures are major complications. Disseminated intravascular coagulation, exercise-associated hyponatremia, heat stroke, rhabdomyolysis, and thromboembolism are associated with high morbidity and mortality. Substances increasing pain resilience as well as performance-enhancing substances are popular among amateur and professional runners and are associated with a high incidence of side effects.!##!Conclusion!#!General symptoms including vomiting, fever, collapse, muscle-pain, nausea and weakness are the leading symptoms during running events. A careful anamnesis is important for targeted clinical therapy. Symptom control is the main task. Fluid management the most challenging task for healthcare providers in the prehospital setting

    Medical emergencies during running events

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    Background The number of short- and long-distance running events in Germany is increasing. Running as a popular sport is practiced by a large number of people of different ages, risk groups, and degrees of professionalism, which results in a wide range of medical emergencies. Objective The present article elucidates incidence, pathophysiology and therapy of relevant emergencies during running events. Aim was the optimization of work processes of emergency personnel. Materials and methods A literature search was conducted in PubMed. Results Exercise-associated muscle cramps, gastrointestinal symptoms, collapse, compartment syndrome, and tendinopathy are common clinical manifestations. Cardiac arrest and sudden cardiac death are rare events. Consciousness and seizures are major complications. Disseminated intravascular coagulation, exercise-associated hyponatremia, heat stroke, rhabdomyolysis, and thromboembolism are associated with high morbidity and mortality. Substances increasing pain resilience as well as performance-enhancing substances are popular among amateur and professional runners and are associated with a high incidence of side effects. Conclusion General symptoms including vomiting, fever, collapse, muscle-pain, nausea and weakness are the leading symptoms during running events. A careful anamnesis is important for targeted clinical therapy. Symptom control is the main task. Fluid management the most challenging task for healthcare providers in the prehospital setting
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