Histamine exerts cAMP-dependent positive inotropic effects (PIE) and positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic mice which overexpress the human ...H
2
-receptor in the heart (=H
2
-TG). To determine whether these effects are antagonized by phosphodiesterases (PDEs), contractile studies were done in isolated left and right atrial preparations of H
2
-TG. The contractile effects of histamine were tested in the additional presence of the PDE-inhibitors
erythro
-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA, 1 μM, PDE2-inhibitor) or cilostamide (1 μM, PDE3-inhibitor), rolipram (10 μM, a PDE4-inhibitor), and their combinations. Cilostamide (1 μM) and EHNA (1 μM), rolipram (1 μM), and EHNA (1 μM) and the combination of rolipram (0.1 μM) and cilostamide (1 μM) each increased the potency of histamine to elevate the force of contraction (FOC) in H
2
-TG. Cilostamide (1 μM) and rolipram (10 μM) alone increased and EHNA (1 μM) decreased alone, and their combination increased the potency of histamine to increase the FOC in H
2
-TG indicating that PDE3 and PDE4 regulate the inotropic effects of histamine in H
2
-TG. The PDE inhibitors (EHNA, cilostamide, rolipram) alone did not alter the potency of histamine to increase the heart beat in H
2
-TG whereas a combination of rolipram, cilostamide, and EHNA, or of rolipram and EHNA increased the potency of histamine to act on the beating rate. In summary, the data suggest that the PCE of histamine in H
2
-TG atrium involves PDE 2 and 4 activities, whereas the PIE of histamine are diminished by activity of PDE 3 and 4.
Histamine exerts cAMP-dependent positive inotropic effects (PIE) and positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic mice which overexpress the human ...H
-receptor in the heart (=H
-TG). To determine whether these effects are antagonized by phosphodiesterases (PDEs), contractile studies were done in isolated left and right atrial preparations of H
-TG. The contractile effects of histamine were tested in the additional presence of the PDE-inhibitorserythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA, 1 μM, PDE2-inhibitor) or cilostamide (1 μM, PDE3-inhibitor), rolipram (10 μM, a PDE4-inhibitor), and their combinations. Cilostamide (1 μM) and EHNA (1 μM), rolipram (1 μM), and EHNA (1 μM) and the combination of rolipram (0.1 μM) and cilostamide (1 μM) each increased the potency of histamine to elevate the force of contraction (FOC) in H
-TG. Cilostamide (1 μM) and rolipram (10 μM) alone increased and EHNA (1 μM) decreased alone, and their combination increased the potency of histamine to increase the FOC in H
-TG indicating that PDE3 and PDE4 regulate the inotropic effects of histamine in H
-TG. The PDE inhibitors (EHNA, cilostamide, rolipram) alone did not alter the potency of histamine to increase the heart beat in H
-TG whereas a combination of rolipram, cilostamide, and EHNA, or of rolipram and EHNA increased the potency of histamine to act on the beating rate. In summary, the data suggest that the PCE of histamine in H
-TG atrium involves PDE 2 and 4 activities, whereas the PIE of histamine are diminished by activity of PDE 3 and 4.
Sedation in Palliative Care Klein, Carsten; Voss, Rafaela; Ostgathe, Christoph ...
Deutsches Ärzteblatt international,
04/2023, Volume:
120, Issue:
14
Journal Article
Peer reviewed
Open access
The appropriate provision of sedation as a last resort for the relief of suffering in palliative care is dealt with variably in actual practice. This article is intended as an overview of practically ...relevant information found in treatment recommendations and guidelines.
A systematic literature search was conducted in the PubMed, Scopus, and Google Scholar databases, and a manual search was carried out online. Recommendations that were not available in either German or English, or that were specific to pediatric practice, were excluded. Publication quality was assessed with the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II). The recommendations in the documents were qualitatively evaluated.
29 publications (11 journal articles, 18 other) of varying quality according to AGREE II were included. All recommendations and guidelines were essentially based on expert consensus. The common indications for sedation are otherwise intractable delirium, dyspnea, and pain, in patients with a life expectancy of no more than two weeks. Existential distress is a controversial indication. The drug of first choice is midazolam. As the sedating effect of opioids is hard to predict, they should not be used as sedatives. The risks of sedation include respiratory and circulatory depression, as well as the loss of communicative ability, control, and autonomy. It is generally recommended that the patient's symptom burden and depth of sedation should be monitored; clinical and technically supported monitoring are recommended in some publications as well, depending on the situation.
There is a broad consensus in favor of sedation to relieve suffering in the last days and hours of life. Recommendations vary for patients with a longer life expectancy and for those with existential distress, and with respect to monitoring.
BACKGROUNDThe appropriate provision of sedation as a last resort for the relief of suffering in palliative care is dealt with variably in actual practice. This article is intended as an overview of ...practically relevant information found in treatment recommendations and guidelines. METHODSA systematic literature search was conducted in the PubMed, Scopus, and Google Scholar databases, and a manual search was carried out online. Recommendations that were not available in either German or English, or that were specific to pediatric practice, were excluded. Publication quality was assessed with the AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II). The recommendations in the documents were qualitatively evaluated. RESULTS29 publications (11 journal articles, 18 other) of varying quality according to AGREE II were included. All recommendations and guidelines were essentially based on expert consensus. The common indications for sedation are otherwise intractable delirium, dyspnea, and pain, in patients with a life expectancy of no more than two weeks. Existential distress is a controversial indication. The drug of first choice is midazolam. As the sedating effect of opioids is hard to predict, they should not be used as sedatives. The risks of sedation include respiratory and circulatory depression, as well as the loss of communicative ability, control, and autonomy. It is generally recommended that the patient's symptom burden and depth of sedation should be monitored; clinical and technically supported monitoring are recommended in some publications as well, depending on the situation. CONCLUSIONThere is a broad consensus in favor of sedation to relieve suffering in the last days and hours of life. Recommendations vary for patients with a longer life expectancy and for those with existential distress, and with respect to monitoring.
Os jogos sérios vêm se destacando como ferramentas de grande potencial para a educação, pois oferecem aos estudantes a possibilidade de exercitar seus conhecimentos em cenários virtuais, permitindo ...maior interatividade, tentativas e erros, respeitando o tempo cognitivo do educando e enfatizando a aplicação prática de seu aprendizado. Além de serem alternativas para simulação de ambientes reais, que em sua essência são críticos ou caros. Este artigo apresenta a aplicação do jogo sério CyberCIEGE diante de uma turma de Segurança para RC. Ao mesmo tempo, discute possíveis melhorias no Design Instrucional da disciplina de acordo com os pareceres dos estudantes.
With the technological progress, new alternatives that help complement the activities carried out in the educational context, such as virtual worlds have emerged. This paper presents a proposal to ...use the virtual world OpenSim in education, in conjunction with Moodle through Sloodle plug in. A virtual laboratory with various activities related to Software Engineering was built, in which GenMyModel tool was used for educational practice of diagrams and UML modeling. The lab was used by students and evaluated to verify its potential as an educational alternative that can help both teachers and students in the process of knowledge construction in this area of domain.
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