Chronic musculoskeletal pain involves connective tissue remodeling triggered by inflammatory mediators, such as bradykinin. Fibroblast cells signaling involve changes in intracellular Ca2+ ([Ca2+]i). ATP has been related to connective tissue mechanotransduction, remodeling and chronic inflammatory pain, via P2 purinoceptors activation. Here, we investigated the involvement of ATP in bradykinin-induced Ca2+ signals in human subcutaneous fibroblasts. Bradykinin, via B2 receptors, caused an abrupt rise in [Ca2+]i to a peak that declined to a plateau, which concentration remained constant until washout. The plateau phase was absent in Ca2+-free medium; [Ca2+]i signal was substantially reduced after depleting intracellular Ca2+ stores with thapsigargin. Extracellular ATP inactivation with apyrase decreased the [Ca2+]i plateau. Human subcutaneous fibroblasts respond to bradykinin by releasing ATP via connexin and pannexin hemichannels, since blockade of connexins, with 2-octanol or carbenoxolone, and pannexin-1, with 10Panx, attenuated bradykinin-induced [Ca2+]i plateau, whereas inhibitors of vesicular exocytosis, such as brefeldin A and bafilomycin A1, were inactive. The kinetics of extracellular ATP catabolism favors ADP accumulation in human fibroblast cultures. Inhibition of ectonucleotidase activity and, thus, ADP formation from released ATP with POM-1 or by Mg2+ removal from media reduced bradykinin-induced [Ca2+]i plateau. Selective blockade of the ADP-sensitive P2Y12 receptor with AR-C66096 attenuated bradykinin [Ca2+]i plateau, whereas the P2Y1 and P2Y13 receptor antagonists, respectively MRS 2179 and MRS 2211, were inactive. Human fibroblasts exhibited immunoreactivity against connexin-43, pannexin-1 and P2Y12 receptor. Bradykinin induces ATP release from human subcutaneous fibroblasts via connexin and pannexin-1-containing hemichannels leading to [Ca2+]i mobilization through the cooperation of B2 and P2Y12 receptors.
Changes in the regulation of connective tissue ATP-mediated mechano-transduction and remodeling may be an important link to the pathogenesis of chronic pain. It has been demonstrated that mast cell-derived histamine plays an important role in painful fibrotic diseases. Here we analyzed the involvement of ATP in the response of human subcutaneous fibroblasts to histamine. Acute histamine application caused a rise in intracellular Ca(2+) ([Ca(2+)]i) and ATP release from human subcutaneous fibroblasts via H1 receptor activation. Histamine-induced [Ca(2+)]i rise was partially attenuated by apyrase, an enzyme that inactivates extracellular ATP, and by blocking P2 purinoceptors with pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt and reactive blue 2. [Ca(2+)]i accumulation caused by histamine was also reduced upon blocking pannexin-1 hemichannels with (10)Panx, probenecid, or carbenoxolone but not when connexin hemichannels were inhibited with mefloquine or 2-octanol. Brefeldin A, an inhibitor of vesicular exocytosis, also did not block histamine-induced [Ca(2+)]i mobilization. Prolonged exposure of human subcutaneous fibroblast cultures to histamine favored cell growth and type I collagen synthesis via the activation of H1 receptor. This effect was mimicked by ATP and its metabolite, ADP, whereas the selective P2Y1 receptor antagonist, MRS2179, partially attenuated histamine-induced cell growth and type I collagen production. Expression of pannexin-1 and ADP-sensitive P2Y1 receptor on human subcutaneous fibroblasts was confirmed by immunofluorescence confocal microscopy and Western blot analysis. In conclusion, histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca(2+)]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors.
Ações de prevenção e de manutenção da saúde do idoso, na sua comunidade e no seu domicílio, devem ser resultado de um esforço de parcerias públicas e/ou privadas, academia e serviço. O programa intitulado, VintANGEING+Felizes, tem como finalidade realizar um trabalho multidisciplinar de intervenção comunitária, disponibilizando o conhecimento científico e contribuindo para o cumprimento das diretrizes e das políticas de atenção pública à saúde do idoso, na direção do envelhecimento ativo e saudável.
Abstract Background Most people with stroke exhibit a variety of impairments that need to be addressed by a multidisciplinary team. Communication and swallowing disorders are common and should be screened very early. To guarantee a patient‐centred approach, all patients, even those with speech and language disorders, must be actively engaged in the healthcare process. Effective communication is essential to success in many of the needed interventions. However, healthcare professionals often do not receive formal training in communicating with these patients, thus increasing the risk of preventable adverse events. Aims To describe the design, implementation and evaluation of a post‐acute stroke multidisciplinary team training using patient actors in a simulation approach. Methods & Procedures A 2‐day course focused on the transdisciplinary knowledge related to communication and swallowing that all members of the multidisciplinary stroke team should acquire was implemented. A case‐based learning methodology used simulation and resorting to patients’ actors. Learning outcomes were evaluated by comparing the results obtained in two knowledge tests, one for each topic, which participants performed before and after each day course. Reaction to the training was gathered concerning the content, teacher quality and course organization. The follow‐up was performed 6 months later to assess training skills transfer to the workplace environment. Outcomes & Results All the participants considered that the programme objectives were relevant or truly relevant and revealed that the programme's dynamic, rhythm and scenarios set were excellent. After the end of the programme, both communication and swallowing knowledge increased. Most participants had the opportunity to employ the acquired training skills in their work environment. The main barriers identified to implementing these skills were the ‘need for additional training’, the ‘lack of time’ or ‘the lack of opportunities’. Conclusions & Implications Simulation is a central method to increase and improve health professionals’ skills when intervening with stroke patients. Using simulation with patient actors allows flexibility and diversification of clinical situations under analysis, which can provide a multiplier effect of reflection and learning. The implemented training achieved its objectives. WHAT THIS PAPER ADDS What is already known on this subject Simulation in the training of health professionals is increasingly used as a good practice, allowing the recreation of scenarios identical to those in the context of professional practice. This strategy is used not only in initial training but also for the development of advanced skills. What this study adds to the existing knowledge This study reports the use of simulation using actor patients for the development of transdisciplinary skills in the topics of communication and swallowing in people with stroke What are the clinical and practical implications of this work? The study demonstrates that in a short period of training, the use of simulation with actor patients favours the development of transdisciplinary skills in the topics of communication and swallowing in people with stroke. At the same time, the skills developed are transferable to professional practice.
Introduction. The beginning of the movement sequence from standing to sitting requires the modulation of plantar flexors activity, including the soleus muscle (SOL), to allow the forward translation of the tibia in relation to the foot, preserving its antigravity function.Purpose. To analyze the SOL activity during the initial phase of standing to sitting in stroke subjects.Methods. Two groups of ten subjects each participated in this study, one composed of healthy subjects and the other with subjects with a history of stroke. Electromyographic activity (EMGa) of SOL was analyzed in the ipsilateral (IPSI) and contralateral (CONTRA) limb to side lesion in stroke subjects, and in one limb in healthy subjects during the initial phase of standing to sitting. A force plate was used to identify the movement sequence phase.Results. The mean values of SOL EMGa were higher in healthy subjects than the ones obtained in the IPSI and CONTRA limb in stroke subjects. Significant differences were only observed between the IPSI and healthy limb (p = 0.035).Conclusion. When compared to the healthy subjects, stroke subjects showed a decreased SOL EMGa in the IPSI limb, which suggests that therapeutic decisions must consider the need to promote a better postural control also in the IPSI limb.
Chronic spinal pain (CSP) is a prevalent condition, and prolonged sitting at work can contribute to it. Ergonomic factors like this can cause changes in motor variability. Variability analysis is a useful method to measure changes in motor performance over time. When performing the same task multiple times, different performance patterns can be observed. This variability is intrinsic to all biological systems and is noticeable in human movement. This study aims to examine whether changes in movement variability and complexity during real-time office work are influenced by CSP. The hypothesis is that individuals with and without pain will have different responses to office work tasks. Six office workers without pain and ten with CSP participated in this study. Participant’s trunk movements were recorded during work for an entire week. Linear and nonlinear measures of trunk kinematic displacement were used to assess movement variability and complexity. A mixed ANOVA was utilized to compare changes in movement variability and complexity between the two groups. The effects indicate that pain-free participants showed more complex and less predictable trunk movements with a lower degree of structure and variability when compared to the participants suffering from CSP. The differences were particularly noticeable in fine movements.
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