In the present work, a sterically constrained noncoded amino acid, 1-aminocyclohexane-1-carboxylic acid (Acc), was substituted in position 8 of the peptide chain of bradykinin (BK) and position 6, 7, or 8 of its B2 receptor antagonist [D-Arg0,Hyp3,Thi,(5,8)D-Phe7]BK, previously synthesized by Stewart's group, to reduce the flexibility of the peptides, thus forcing the peptide backbone and side chains to adopt specific orientations. Knowing that acylation of the N-terminus of several known B2 blockers with a variety of bulky groups has consistently improved their antagonistic potency in the rat blood pressure assay, the Acc substituted analogues were also synthesized in the N-acylated form with 1-adamantaneacetic acid (Aaa). The activity of eight new analogues was assayed in isolated rat uterus and in rat blood pressure tests. The results clearly demonstrated the importance of the position in the peptide chain into which the sterically restricted Acc residue was inserted. Meanwhile, Acc at positions 6 and 7 led to reduction of antagonistic qualities or even restored the agonism, respectively. Acc at position 8 enhanced antagonistic qualities in both tests. The Acc at position 8 of BK strongly reduced the agonistic potency. In most cases acylation of the N-terminus led either to enhancement of antagonistic potencies or to further decrease of agonistic potency. Our findings offer new possibilities for designing new potent and selective B2 blockers.
A sterically constrained non-coded amino acid, 1-aminocyclopentane-1-carboxylic acid (Apc), was introduced in position 7 or 8 of the bradykinin (BK) B(2) receptor antagonist, [D-Arg(0), Hyp(3), Thi(5, 8), D-Phe(7)]BK, previously synthesized by Stewart's group. This modification is believed to reduce the flexibility of the peptides, thereby forcing the peptide backbone and side chains to adopt specific orientations. Apc substitution was combined with acylation of the N-terminus with 1-adamantaneacetic acid (Aaa). The activity of four new analogues was assayed in isolated rat uterus and in rat blood pressure tests. The results clearly demonstrated that the Apc residue inserted in position 7 led to a reduction of antagonistic properties in the rat uterus assay or even restored the agonism in the blood pressure test, whereas Apc at position 8 enhanced antagonistic potency in both the tests. In both cases, acylation of the N-terminus led to the enhancement of the antagonistic potency. On the basis of these findings, new potent and selective B(2) blockers might be designed.
Our previous studies suggested that acylation of the N-terminus of several known B2 antagonists with various kinds of bulky acyl groups consistently improved their antagonistic potency in rat blood pressure assay. On the other hand, our earlier observations also seemed to suggest that the effects of acylation on the contractility of isolated rat uterus depended substantially on the chemical character of the acyl group, as we observed that this modification might either change the range of antagonism or even transform it into agonism. Bearing all this in mind, we decided to synthesize seven new analogues of bradykinin by N-terminal acylation with various acyl groups of a moderately potent B2 antagonist, previously synthesized by Stewart's group, D-Arg-Arg-Pro-Hyp-Gly-Thr-Ser-D-Phe-Thi-Arg. The analogues were tested in vitro for their blood pressure-lowering and uterotonic activities. The modifications either preserved or increased the antagonistic potency in the rat blood pressure test. On the other hand, all seven substituents negatively influenced the interaction with the rat uterine receptors. Our results may be helpful for designing new B2 agonists and antagonists.
This article presents an overview of contemporary risk assessment systems used in patients with myocardial infarction. The full range of risk scales, both recommended by the European Society of Cardiology and others published in recent years, is presented. Scales for assessing the risk of ischemia/death as well as for assessing the risk of bleeding are presented. A separate section is devoted to systems assessing the integrated risk associated with both ischemia and bleeding. In the first part of the work, each of the risk scales is described in detail, including the clinical trials/registers on the basis of which they were created, the statistical methods used to develop them, as well as the specification of their individual parameters. The next chapter presents the practical application of a given scale in the patient risk assessment process, the timing of its application on the timeline of myocardial infarction, as well as a critical assessment of its potential advantages and limitations. The last part of the work is devoted to the presentation of potential directions for the development of risk assessment systems in the future.
Background and Objectives: The guidelines of the European Society of Cardiology (ESC) recommend the use of telematic methods in the diagnosis of myocardial infarction, allowing for transtelephonic electrocardiography (TTECG) from the emergency scene to centers performing percutaneous coronary interventions (PCI center). It has been proven that such a procedure has a beneficial effect on the survival of patients with ST elevation myocardial infarction (STEMI). Fewer data can be found on the correct use of these methods in everyday clinical practice. The aim of this study was to indicate potential indications and contraindications for the use of the TTECG system, and provide recommendations for proper collaboration between emergency medical systems (EMS) teams and PCI centers. Materials and Methods: The article is a systematic review of cardiological emergencies, with an assessment of indications for the use of the TTECG system. The authors introduced their own grading of the validity of indications for transmission of the TTECG, similar to those used in the official ESC guidelines.: Results:: The authors described individual cardiological emergencies occurring in the practice of EMS, considering specific indications or contraindications for the transmission of the TTECG. The article also discusses individual practical recommendations for proper cooperation between EMS teams and PCI centers in detail. All of the recommendations are compiled in a handy table to facilitate its use in everyday clinical practice. Conclusions: The summary presents a comparison of the realities of the functioning of the telematic support system in Poland in the field of STEMI diagnostics, with the model’s recommendations. The necessity of further educating the members of individual teams included in the network dealing with STEMI treatment was indicated, as well as the necessity of introducing legal regulations sanctioning the functioning of telematic systems in modern medicine.
For many years, the importance of using telematic technologies in medicine has been growing, especially in the period of the coronavirus pandemic, when direct contact and supervision of medical personnel over the patient is difficult. The existing possibilities of modern information and communication technologies (ICTs) are not fully used. The aim of the study is to identify the telemedicine technologies that can be used in future implementation projects of the posthospital patient care process after total hip arthroplasty (THA). The literature search is reported according to PRISMA 2020. The search strategy included databases and gray literature. In total, 28 articles (EMBASE, PubMed, PEDro) and 24 records from gray literature (Google Search and Technology presentations) were included in the research. This multi-source study analyzes the possibilities of using different technologies useful in the patient care process. The conducted research resulted in defining visual and wearable types of telemedicine technologies for the original posthospital patient care process after THA. As the needs of stakeholders in the posthospital patient care process after THA differ, the awareness of appropriate technologies selection, information flow, and its management importance are prerequisites for effective posthospital patient care with the use of telemedicine technologies.
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