ABSTRACT
Older adults with lower limb fractures often harbor concerns about losing their mobility, fearing a loss of independence. It is vital to develop strategies that foster their active engagement in the rehabilitation process. The present protocol aims to create a care pathway tailored to motivate individuals with lower limb fractures to adhere to rehabilitation. We will develop an observational, cross-sectional, and descriptive study using the Delphi data-gathering approach. Purposive sampling will recruit a panel of healthcare professionals and experts who care for patients with lower limb fractures. Aligned with the Delphi method, a series of iterative rounds will be developed to gather consensus around the motivational strategies used by health professionals in the rehabilitation of people with lower limb fractures. We will employ the Qualtrics platform for data collection and analysis, and a consensus target of 75% has been predetermined. For quantitative data analysis, we will use descriptive statistics encompassing a range of measures, including count, mean, standard deviation, median, minimum, maximum, and range. An inductive thematic analysis procedure will be employed to extract meaningful themes and patterns from qualitative data. The study results are expected to significantly impact clinical practice by creating a specialized care pathway to motivate individuals with lower limb fractures to adhere to rehabilitation. Adopting these explicit standards by professionals will ensure uniform and high-quality care.
Subject(s)
Delphi Technique , Fractures, Bone , Motivation , Humans , Cross-Sectional Studies , Fractures, Bone/rehabilitation , Consensus , Lower Extremity/injuries , Male , FemaleABSTRACT
Introduction: Cognitive and motor impairments are common among stroke survivors. Physical therapy is often used to improve the functional capacity of stroke survivors. However, limited adherence to rehabilitation programs is a challenge. Motivation plays a crucial role in the success of rehabilitation programs as it influences individual adherence to treatment and overall health outcomes. This review aims to identify current trends in motivational strategies used by healthcare professionals for stroke survivor rehabilitation. Methods: Following the framework developed by Arksey and O'Malley, a scoping review was conducted. We performed a literature search using MEDLINE, CINAHL, the Cochrane Central Register of Controlled Trials, Nursing & Allied Health, and MedicLatina databases. Results: A total of 906 papers were identified. After selecting and analyzing the articles, 17 papers were included in this review. Health professionals use various strategies to motivate stroke survivors. These approaches include establishing a therapeutic alliance, improving patients' health literacy, defining realistic goals, fostering problem-solving skills, personalizing the rehabilitation program, showcasing success stories, utilizing persuasive techniques, offering encouragement and compliments, providing emotional support, and effectively managing symptoms. Conclusion: The knowledge gathered in this review can guide healthcare professionals in helping patients overcome barriers to rehabilitation, improve their motivation, and ultimately enhance their recovery outcomes.
ABSTRACT
An outcome of dementia is a progressive decline in cognitive function. Implementing psychotherapies and psychosocial interventions is crucial for bolstering cognitive abilities, promoting independence, and elevating the quality of life for individuals with dementia. This review aims to identify current trends in psychotherapies and psychosocial interventions for people with dementia. A Scoping review was developed based on the framework proposed by Arksey and O'Malley. The literature search was conducted on electronic databases, including Scopus, Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, Nursing & Allied Health Collection, and MedicLatina. Executed in June 2023, the search focused on articles published in English, Portuguese, and Spanish between 2013 and 2023. Through this search, 1409 articles were initially identified. After selecting and analyzing the reports, sixteen trials were included in this review. Eight distinct categories were identified, covering different strategies. These categories run from computerized game-based cognitive training and reminiscence therapy to compensatory and restorative strategies, memory and attention training, calculation training, dual-task training, counseling, and personalized goal attainment. The findings of this scoping review highlight the diverse landscape of psychotherapies and psychosocial interventions for people with dementia.
ABSTRACT
There is a lack of studies analyzing if universal school-based Social and Emotional Learning programs can reduce social withdrawal and social anxiety. This study analyzed the effectiveness of one such program on those variables, and the role of individual school climate perceptions. In this nationwide study, 704 seventh to eighth-grade Portuguese students (Mage = 12.96, SD = 1.09, 48% girls), of which 215 (30.6%) in the comparison group, were assessed at pretest, post-test, and follow-up seven months later. Analyses showed positive intervention results in self- and teacher-reported social withdrawal and social anxiety. Regarding school climate, intervention group students with more positive teacher-student relationships benefitted more from program participation in social anxiety. These results support the program's effectiveness for addressing social withdrawal and social anxiety.
Subject(s)
Cognition , Emotions , Female , Adolescent , Humans , Child , Male , Ethnicity , Social Isolation , AnxietyABSTRACT
Resumo A regulação da prática de telemedicina no Brasil tem se mostrado tortuosa desde seu reconhecimento pela Resolução nº 1.643/2002, do Conselho Federal de Medicina (CFM), havendo questionamentos quanto à competência deste para inserção da prática. Em 2018, o conselho editou nova resolução, mas que foi revogada em função da repercussão negativa. A pandemia de covid-19 pressionou os serviços de saúde de tal forma que o Poder Legislativo Federal foi impelido ao conflito e editou a Lei nº 13.989/2020, permitindo a prática de telemedicina durante o período da crise sanitária. O art. 6º da lei delegou ao CFM a competência para regulação da prática pós-pandemia, acirrando ainda mais as discussões. Este trabalho constitui um estudo de caso sobre a regulação da telemedicina no Brasil, buscando identificar os conflitos jurídicos impostos pela atuação do CFM em substituição ao Poder Legislativo. Utiliza o modelo político de implementação de políticas públicas de William Clune como base da análise, empregando o método da pesquisa documental qualitativa. Conclui-se que a implementação da telemedicina deve considerar as forças políticas em atuação, compreendendo o papel do CFM no processo normativo, para que se obtenha, no texto legal, uma política pública compatível com a realidade e apta a ser implementada.
Abstract The regulation of telemedicine in Brazil has been tortuous since its recognition by the Resolution No. 1,643/2002, of the Federal Council of Medicine (CFM), with issues regarding its competence to insert this practice. In 2018, the council issued a new resolution but it was revoked due to negative repercussions. The covid-19 pandemic put pressure on health services in such a way that the National Congress was pushed into conflict and enacted the Federal Law No. 13,989/2020, which allowed the practice of telemedicine during the period of health crisis. The article 6 of the law delegated the competence to regulate the post-pandemic practice to the CFM, further intensifying the discussions. This work is a case study on the regulation of telemedicine in Brazil, seeking to identify the legal conflicts imposed by the action of CFM in substitution of the Legislative Power. It uses the political model of implementation of public policies by William Clune as the basis for the analysis, using the qualitative documentary research method. In conclusion, the implementation of telemedicine must consider the political forces involved, understanding the CFM's role in the normative process, to obtain, in the legal text, a public policy compatible with reality and capable of being implemented.
Subject(s)
Humans , Male , Female , Professional Competence/standards , Social Control, Formal , Telemedicine/legislation & jurisprudence , COVID-19 , Health Occupations/legislation & jurisprudence , Public Policy , LegislativeABSTRACT
O presente trabalho analisou, sob a perspectiva econômica da concretização do direito à saúde, o Projeto de Lei dos Planos de Saúde Acessíveis (PL n. 7.419/2006), apensado ao projeto geral de reforma da Lei n. 9.656/1998, desenvolvido pelo Ministério da Saúde em 2016 e atualmente em tramitação na Câmara dos Deputados. Para isso, os documentos oficiais da proposta foram analisados à luz de suas justificativas econômicas e da amplitude do acesso a serviços. As principais diretrizes do projeto, destacando-se os novos modelos de planos, evidenciam a criação de entraves burocráticos à realização de procedimentos, além da flexibilização do rol de cobertura dos planos de acordo com a infraestrutura local, em desacordo com a cobertura mínima prevista na regulação atual. A proposta favorece economicamente as operadoras de planos de saúde ao estabelecer a coparticipação de 50% e o reajuste conforme tabela de custos. Além disso, na prática, o projeto apresenta um duplo prejuízo: ao beneficiário, que arca com os custos do plano e, no momento de maior necessidade, de procedimentos de urgência ou de maior complexidade por não estar amparado pela cobertura; e ao sistema público, que deve suprir as deficiências da cobertura privada, o que, em um momento de maior demanda e recursos limitados, pode levá-lo à sobrecarga.
The present work analyzed, from the economic perspective of the realization of the right to health, the Accessible Health Insurance Bill (PL No. 7,419/2006), attached to the general project of reform of Law No. 9,656/1998, developed by the Ministry of Health in 2016 and currently being processed in the Chamber of Deputies. For this, the official documents of the proposal were analyzed in light of its economic justifications and the scope of access to services. The main guidelines of the project, highlighting the new models of plans, show the creation of bureaucratic obstacles to the performance of procedures, in addition to the flexibility of the coverage list of the plans according to the local infrastructure, in disagreement with the minimum coverage in the current regulation. The proposal economically favors the health insurance companies by establishing the 50% coparticipation and adjustment according to the cost table. Moreover, in practice, the project presents a double loss: to the beneficiary, who bears plan costs and, at the moment of greatest need, emergency procedures or of greater complexity, because he is not protected by the coverage; and to the public system, which must supply the deficiencies of private coverage, which, at a time of greater demand and limited resources, can lead to overload.
Subject(s)
Unified Health System , Health Programs and Plans , Supplemental HealthABSTRACT
Plant-based biomass (CFB (carnauba fruit biomass)) obtained from the fruit exocarp of the species Copernicia prunifera (Mill.) H.E. Moore (carnauba) was evaluated for its viability as an adsorbent of potentially toxic metals in aqueous medium. The CFB was characterized by powder X-ray spectroscopy (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and zeta potential to investigate the morphology of the biosorbent and its interaction with water soluble metal ions of Pb and Cd. The biomass presents an amorphous structure, with negative zeta potential (- 2.59 mV), and the presence of functional groups such as O-H, C-O-C, C-H, and C=O. The removal potential of Pb(II) and Cd(II) was performed in a batch system, and monoelement solutions were tested to assess the effects of adsorbent dose and initial metal ion concentration, pH at the point of zero charge (pHPZC), sorption kinetics, and adsorption capacity. The most appropriate adsorbent concentration was 5 g/L, and sorption studies were carried out at pH 5.0 (pHPZC = 4.68), in which the surface of the adsorbent shows negative charges and favors the adsorption of metal ions. Kinetic studies showed that the pseudo-second order model best fit the experimental data, and equilibrium was reached at 120 min of contact time. The experimental sorption capacity (SCexp) for Pb and Cd was around 28 and 34 mg/g, respectively, and six different non-linear isotherm models were used to describe the sorption phenomena, among them, four with 2 parameters, i.e., Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich (DR), respectively, and two with 3 parameters, namely, SIPS and Hill. The non-linear Temkin and Freundlich isotherm models best fit the experimental data for Pb(II) and Cd(II), respectively. According to the Langmuir model, Qmax was 26 mg/g and 58 mg/g for Pb(II) and Cd(II), respectively, indicating the efficiency of CFB as a new alternative to conventional methods for the removal of potentially toxic metals from aqueous medium.
Subject(s)
Cadmium , Water Pollutants, Chemical , Adsorption , Biomass , Cadmium/analysis , Hydrogen-Ion Concentration , Kinetics , Lead , Spectroscopy, Fourier Transform Infrared , Trees , Water , Water Pollutants, Chemical/analysisABSTRACT
O objetivo deste artigo é analisar o financiamento da saúde pública no Brasil, em especial as consequências da adoção do novo regime fiscal. Para isso, o método utilizado foi o levantamento bibliográfico nas principais bases de dados disponíveis, complementado por textos jornalísticos e análise das Ações Diretas de Inconstitucionalidade n. 5.595 e n. 5.658, que discutiram o tema. O artigo é dividido em quatro partes: (i) introdução sobre a constitucionalização do direito à saúde; (ii) exposição sobre os modos de financiamento da saúde pública, com enfoque nas Emendas Constitucionais n. 29/2000, n. 86/2015 e n. 95/2016; (iii) exame dos impactos do novo regime fiscal no setor da saúde, com destaque para suas implicações na judicialização da saúde; e (iv) a conclusão de que o novo regime fiscal trouxe medidas de austeridade que, além de reduzirem os recursos disponíveis para a saúde, impedem a expansão dos serviços de atendimento à população e têm grande potencial de aumentar as demandas judiciais por tratamentos e medicamentos.
The objective of this article is to analyze public health funding in Brazil, especially the consequences of the newly adopted fiscal regime. The method used was bibliographical survey, gathering articles from the main available databases, newspaper articles and the analysis of the Direct Actions of Unconstitutionality no. 5595 and no. 5658, which discussed the matter. The article is divided into four parts: (i) an introduction on the constitutionalization of the right to health; (ii) an exposition on public health funding approaches focusing on the Constitutional Amendments number 29/2000, 86/2015 and 95/2016; (iii) the examination of the impacts of the new fiscal regime on the health sector and a highlight of the impact of these measures in cases of health judicialization; and (iv) with the conclusion that the new fiscal regime has introduced austerity measures, which, in addition to reducing the health resources available, discourage the expansion of public health care, leading to a great potential of increasing legal demands for treatments and medicines.
Subject(s)
Capital FinancingABSTRACT
Despite their inherent proximity to circulating oxygen and nutrients, endothelial cells (ECs) oxidize only a minor fraction of glucose in mitochondria, a metabolic specialization that is poorly understood. Here we show that the glycolytic enzyme pyruvate kinase M2 (PKM2) limits glucose oxidation, and maintains the growth and epigenetic state of ECs. We find that loss of PKM2 alters mitochondrial substrate utilization and impairs EC proliferation and migration in vivo. Mechanistically, we show that the NF-κB transcription factor RELB is responsive to PKM2 loss, limiting EC growth through the regulation of P53. Furthermore, S-adenosylmethionine synthesis is impaired in the absence of PKM2, resulting in DNA hypomethylation, de-repression of endogenous retroviral elements (ERVs) and activation of antiviral innate immune signalling. This work reveals the metabolic and functional consequences of glucose oxidation in the endothelium, highlights the importance of PKM2 for endothelial growth and links metabolic dysfunction with autoimmune activation in ECs.
Subject(s)
Carrier Proteins/metabolism , Endothelial Cells/cytology , Endothelial Cells/metabolism , Membrane Proteins/metabolism , Pyruvate Kinase/metabolism , Signal Transduction , Thyroid Hormones/metabolism , Animals , Cell Proliferation , DNA Methylation , Endogenous Retroviruses/metabolism , Gene Deletion , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice, Inbred C57BL , Mitochondria/metabolism , Neovascularization, Physiologic , Transcription Factor RelB/metabolism , Tumor Suppressor Protein p53/metabolism , Thyroid Hormone-Binding ProteinsABSTRACT
Objectives A single-blinded, randomized, parallel clinical trial evaluated the use of 37% carbamide peroxide (CP) on bleaching effectiveness and tooth sensitivity reported by patients undergoing in-office tooth bleaching, in comparison with the results of using 35% hydrogen peroxide. Material and Methods Forty patients were allocated to receive two sessions of in-office tooth bleaching using either 35% hydrogen peroxide (HP) or 37% CP. Each patient's sensitivity level was evaluated during and up to 24 h after bleaching. The effectiveness of the bleaching procedures was evaluated with a spectrophotometer one week after each session and 30 days after the last session. The impact of tooth bleaching on the patients' perceptions regarding smile changes, in addition to the bleaching procedures and their results, were also recorded. Absolute and relative sensitivity risks were calculated. Data on sensitivity level were analyzed using the Mann-Whitney or T-test, and data from the color evaluation were subjected to 2-way repeated measures ANOVA. Results The use of CP reduced the risk and level of tooth sensitivity to values close to zero, whereas the difference between the bleaching agents disappeared after 24 h. An increased bleaching effect was observed for HP, mainly due to an improved reduction of redness and yellowness. Participants perceived improved tooth bleaching for HP and reduced sensitivity for CP, but no differences regarding the comfort of the techniques were noted. Conclusions In our study, 37% CP resulted in reduced tooth sensitivity but decreased the tooth bleaching effectiveness. However, both bleaching agents resulted in high levels of patient satisfaction.
Subject(s)
Dentin Sensitivity/prevention & control , Dentin/drug effects , Hydrogen Peroxide/administration & dosage , Peroxides/administration & dosage , Tooth Bleaching Agents/administration & dosage , Tooth Bleaching/methods , Urea/analogs & derivatives , Adult , Analysis of Variance , Carbamide Peroxide , Dentin Sensitivity/chemically induced , Female , Humans , Hydrogen Peroxide/adverse effects , Male , Peroxides/adverse effects , Reproducibility of Results , Risk Assessment , Risk Factors , Single-Blind Method , Statistics, Nonparametric , Time Factors , Tooth Bleaching/adverse effects , Tooth Bleaching Agents/adverse effects , Treatment Outcome , Urea/administration & dosage , Urea/adverse effects , Visual Analog Scale , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Rescue of F508del-cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the most common CF mutation, requires small molecules that overcome protein processing, stability and channel gating defects. Here, we investigate F508del-CFTR rescue by CFFT-004, a small molecule designed to independently correct protein processing and channel gating defects. EXPERIMENTAL APPROACH: Using CFTR-expressing recombinant cells and CF patient-derived bronchial epithelial cells, we studied CFTR expression by Western blotting and channel gating and stability with the patch-clamp and Ussing chamber techniques. KEY RESULTS: Chronic treatment with CFFT-004 improved modestly F508del-CFTR processing, but not its plasma membrane stability. By contrast, CFFT-004 rescued F508del-CFTR channel gating better than C18, an analogue of the clinically used CFTR corrector lumacaftor. Subsequent acute addition of CFFT-004, but not C18, potentiated F508del-CFTR channel gating. However, CFFT-004 was without effect on A561E-CFTR, a CF mutation with a comparable mechanism of CFTR dysfunction as F508del-CFTR. To investigate the mechanism of action of CFFT-004, we used F508del-CFTR revertant mutations. Potentiation by CFFT-004 was unaffected by revertant mutations, but correction was abolished by the revertant mutation G550E. These data suggest that correction, but not potentiation, by CFFT-004 might involve nucleotide-binding domain 1 of CFTR. CONCLUSIONS AND IMPLICATIONS: CFFT-004 is a dual-acting small molecule with independent corrector and potentiator activities that partially rescues F508del-CFTR in recombinant cells and native airway epithelia. The limited efficacy and potency of CFFT-004 suggests that combinations of small molecules targeting different defects in F508del-CFTR might be a more effective therapeutic strategy than a single agent.
Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/physiology , Animals , Cell Line , Cell Membrane/physiology , Cells, Cultured , Cricetinae , Epithelial Cells/physiology , Humans , Ion Channel Gating , Mice , Protein Processing, Post-Translational , Protein StabilityABSTRACT
Abstract Objectives A single-blinded, randomized, parallel clinical trial evaluated the use of 37% carbamide peroxide (CP) on bleaching effectiveness and tooth sensitivity reported by patients undergoing in-office tooth bleaching, in comparison with the results of using 35% hydrogen peroxide. Material and Methods Forty patients were allocated to receive two sessions of in-office tooth bleaching using either 35% hydrogen peroxide (HP) or 37% CP. Each patient's sensitivity level was evaluated during and up to 24 h after bleaching. The effectiveness of the bleaching procedures was evaluated with a spectrophotometer one week after each session and 30 days after the last session. The impact of tooth bleaching on the patients' perceptions regarding smile changes, in addition to the bleaching procedures and their results, were also recorded. Absolute and relative sensitivity risks were calculated. Data on sensitivity level were analyzed using the Mann-Whitney or T-test, and data from the color evaluation were subjected to 2-way repeated measures ANOVA. Results The use of CP reduced the risk and level of tooth sensitivity to values close to zero, whereas the difference between the bleaching agents disappeared after 24 h. An increased bleaching effect was observed for HP, mainly due to an improved reduction of redness and yellowness. Participants perceived improved tooth bleaching for HP and reduced sensitivity for CP, but no differences regarding the comfort of the techniques were noted. Conclusions In our study, 37% CP resulted in reduced tooth sensitivity but decreased the tooth bleaching effectiveness. However, both bleaching agents resulted in high levels of patient satisfaction.
Subject(s)
Humans , Male , Female , Adult , Young Adult , Peroxides/administration & dosage , Tooth Bleaching/methods , Urea/analogs & derivatives , Dentin/drug effects , Dentin Sensitivity/prevention & control , Tooth Bleaching Agents/administration & dosage , Hydrogen Peroxide/administration & dosage , Peroxides/adverse effects , Time Factors , Tooth Bleaching/adverse effects , Urea/administration & dosage , Urea/adverse effects , Single-Blind Method , Reproducibility of Results , Risk Factors , Analysis of Variance , Treatment Outcome , Statistics, Nonparametric , Risk Assessment , Dentin Sensitivity/chemically induced , Tooth Bleaching Agents/adverse effects , Visual Analog Scale , Carbamide Peroxide , Hydrogen Peroxide/adverse effectsABSTRACT
Transition from elementary to middle school is commonly seen as a period of stress, impacting students' school adjustment. The present longitudinal study aimed to analyze the difference in stress levels between the end of 4th grade and 5th grade, while also analyzing gender differences and 5th grade retention. Two hundred fifty-eight 4th grade students (M age = 9.55; SD = 0.77) from six Portuguese public schools, from the municipality of Torres Vedras, participated in this study. Self-report questionnaires were administered at the end of the 4th and 5th grades, and 5th grade school records were also collected. Results showed that 5th graders present higher levels of Academic Stress (d = .29) and Teacher/Rules Stress (d = .28). Girls had a greater increase of Peer-related Stress with the transition (p < .01). Students who were retained at the end of 5th grade showed higher increases of Teacher/Rules Stress (p < .05). Intervention programs that aim to support the transition from elementary to middle school are needed, in order to reduce the increase of stress levels at 5th grade and to promote a better school adjustment in the first year of middle school.
ABSTRACT
Transition from elementary to middle school is commonly seen as a period of stress, impacting students school adjustment. The present longitudinal study aimed to analyze the difference in stress levels between the end of 4th grade and 5th grade, while also analyzing gender differences and 5th grade retention. Two hundred fifty-eight 4th grade students (Mage = 9.55; SD = 0.77) from six Portuguese public schools, from the municipality of Torres Vedras, participated in this study. Self-report questionnaires were administered at the end of the 4th and 5th grades, and 5th grade school records were also collected. Results showed that 5th graders present higher levels of Academic Stress (d = .29) and Teacher/Rules Stress (d = .28). Girls had a greater increase of Peer-related Stress with the transition (p < .01). Students who were retained at the end of 5th grade showed higher increases of Teacher/Rules Stress (p < .05). Intervention programs that aim to support the transition from elementary to middle school are needed, in order to reduce the increase of stress levels at 5th grade and to promote a better school adjustment in the first year of middle school (AU)
No disponible
Subject(s)
Humans , Male , Female , Stress, Psychological/epidemiology , Stress, Psychological/psychology , Life Change Events , Gender Identity , Interpersonal Relations , Students/psychology , Portugal/epidemiology , Multilevel Analysis/instrumentation , Multilevel Analysis/methodsABSTRACT
Purinergic P2X7 receptors (P2X7R) are fundamental to innate immune response. In macrophages, transient stimulation of P2X7R activates several transport mechanisms and induces the scrambling of phospholipids with subsequent membrane blebbing and apoptosis. These processes support phagocytosis and subsequent killing of phagocytosed bacteria. Here we demonstrate that the stimulation of P2X7 receptors activates anoctamin 6 (ANO6, TMEM16F), a protein that functions as Ca(2+) dependent phospholipid scramblase and Ca(2+)-activated Cl(-) channel. Inhibition or knockdown of ANO6 attenuates ATP-induced cell shrinkage, cell migration and phospholipid scrambling. In mouse macrophages, Ano6 produces large ion currents by stimulation of P2X7 receptors and contributes to ATP-induced membrane blebbing and apoptosis, which is largely reduced in macrophages from Ano6-/- mice. ANO6 supports bacterial phagocytosis and killing by mouse and human THP-1 macrophages. Our data demonstrate that anoctamin 6 is an essential component of the immune defense by macrophages.
Subject(s)
Immunity, Innate , Macrophages/immunology , Phospholipid Transfer Proteins/immunology , Receptors, Purinergic P2X7/immunology , Animals , Anoctamins , Apoptosis/genetics , Apoptosis/immunology , Calcium/metabolism , Cell Movement , Cell Size , Gene Expression Regulation , Humans , Ion Transport , Macrophage Activation , Macrophages/cytology , Mice , Mice, Knockout , Oocytes/cytology , Oocytes/metabolism , Patch-Clamp Techniques , Phagocytosis/genetics , Phospholipid Transfer Proteins/antagonists & inhibitors , Phospholipid Transfer Proteins/deficiency , Phospholipid Transfer Proteins/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Receptors, Purinergic P2X7/genetics , Signal Transduction , Xenopus laevisABSTRACT
The role of calcium-activated chloride channels for renal function is unknown. By immunohistochemistry we demonstrate dominant expression of the recently identified calcium-activated chloride channels, Anoctamin 1 (Ano1, TMEM16A) in human and mouse proximal tubular epithelial (PTE) cells, with some expression in podocytes and other tubular segments. Ano1-null mice had proteinuria and numerous large reabsorption vesicles in PTE cells. Selective knockout of Ano1 in podocytes (Ano1-/-/Nphs2-Cre) did not impair renal function, whereas tubular knockout in Ano1-/-/Ksp-Cre mice increased urine protein excretion and decreased urine electrolyte concentrations. Purinergic stimulation activated calcium-dependent chloride currents in isolated proximal tubule epithelial cells from wild-type but not from Ano1-/-/Ksp-Cre mice. Ano1 currents were activated by acidic pH, suggesting parallel stimulation of Ano1 chloride secretion with activation of the proton-ATPase. Lack of calcium-dependent chloride secretion in cells from Ano1-/-/Ksp-Cre mice was paralleled by attenuated proton secretion and reduced endosomal acidification, which compromised proximal tubular albumin uptake. Tubular knockout of Ano1 enhanced serum renin and aldosterone concentrations, probably leading to enhanced compensatory distal tubular reabsorption, thus maintaining normal blood pressure levels. Thus, Ano1 has a role in proximal tubular proton secretion and protein reabsorption. The results correspond to regulation of the proton-ATPase by the Ano1-homolog Ist2 in yeast.
Subject(s)
Chloride Channels/metabolism , Kidney Tubules, Proximal/metabolism , Podocytes/metabolism , Renal Reabsorption , Adenosine Triphosphate/pharmacology , Aldosterone/blood , Animals , Anoctamin-1 , Cells, Cultured , Chloride Channels/deficiency , Chloride Channels/drug effects , Chloride Channels/genetics , Female , Genotype , Humans , Hydrogen-Ion Concentration , Ion Channel Gating , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/physiopathology , Male , Mice, 129 Strain , Mice, Inbred C57BL , Mice, Knockout , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Phenotype , Podocytes/drug effects , Proteinuria/genetics , Proteinuria/metabolism , Proteinuria/physiopathology , Renal Reabsorption/drug effects , Renin/blood , Time Factors , Vacuolar Proton-Translocating ATPases/metabolismABSTRACT
OBJECTIVE: To compare the cardiorenal effects of early versus late cyclosporine (CsA) to sirolimus (SRL) conversion, using a novel animal model that mimics these protocols used in the clinical practice, and focusing on blood pressure, heart rate (HR), biochemical data and heart and kidney lipid peroxidation. MATERIALS AND METHODS: The study had five groups. Six male Wistar rats in each group were used during a 9-week study protocol: control, CsA (5 mg/kg/day), SRL (1 mg/kg/day); early conversion and late conversion. Cardiorenal evaluation was assessed by biochemical data, blood pressure, HR, and heart and kidney lipid peroxidation. RESULTS: As expected, CsA promoted cardiorenal impairment, viewed by development of hypertension, tachycardia, increased urea, creatine kinase, and glucose levels, as well as heart and kidney oxidative stress. SRL, as expected, promoted less cardiorenal side effects, namely those related with nephrotoxicity. In agreement, both early and late conversions from CsA to SRL produced less side-effects, namely those related to the CsA-induced nephrotoxicity. CONCLUSIONS: In our model, both early and late CsA to SRL conversion promoted amelioration of the CsA -induced cardiorenal damage. However, early substitution seems to produce more benefits, in particular due to higher improvement of the cardiac profile.
ABSTRACT
The long history of Cannabis sativa had its development stimulated and oriented for medicine after the discovery and chemical characterization of its main active ingredient, the 9-tetrahydrocannabinol (9-THC). Consequently, a binding site for 9-THC was identified in rat brains and the first cannabinoid receptor (CB1) was cloned, followed by the CB2 and by the discover of two endogenous agonists: anandamide and 2-arachidonoyl glycerol. Cannabinoid receptors, endocannabinoids and the enzymes that catalyze its synthesis and degradation constitute the endocannabinoid system (ECS), which plays an important role in the cardiovascular system. In vivo experiments with rats have demonstrated the action of anandamide and 2-AG on the development of atherosclerotic plaque, as well as an effect on heart rate, blood pressure, vasoactivity and energy metabolism (action in dyslipidemia and obesity). Recent studies with an antagonist of CB1 receptors showed that the modulation of ECS can play an important role in reducing cardiovascular risk in obese and dyslipidemic patients. Similarly, studies in rats have demonstrated the action of CB2 receptors in adhesion, migration, proliferation and function of immune cells involved in the atherosclerotic plaque formation process. The evidence so far gathered shows that the modulation of ECS (as agonism or antagonism of its receptors) is an enormous potential field for research and intervention in multiple areas of human pathophysiology. The development of selective drugs for the CB1 and CB2 receptors may open a door to new therapeutic regimens.This review article aims to address the key findings and evidences on the modulation of ECS, in order to prospect future forms of therapeutic intervention at the cardiovascular level. A recent, emerging, controversial and of undoubted scientific interest subject, which states as a potential therapeutic target to reach in the 21(st) century.
ABSTRACT
Flavothione (FT) and a series of 18 hydroxy- and methoxy-substituted flavothiones were screened for photobiological activity. The 5-hydroxy-substituted compounds (group 3) and the methoxy-substituted flavothiones were inactive. FT and the remaining hydroxy-substituted compounds, all displayed photobiological activity. Among these, the 3-hydroxy-substituted compounds (group 2) were the most efficient photosensitizers overall in spite of their concurrent fast photodegradation. FT and all other hydroxyflavothiones, not substituted in the 3- or 5-positions (group 1), were inefficient compared with group 2. Detailed photobiological tests were carried out for four flavothiones of groups 1 and 2. The biological tests included fungi, several strains of Escherichia coli, Salmonella typhimurium and mammalian cells. In addition, the ability of these flavothiones to perform lipid peroxidation was evaluated. FT and 6-hydroxyflavothione (group 1) induce DNA damage via H-atom abstraction from the lowest n, pi* triplet state of the thione (oxygen independent). For 3-hydroxy and 3,6-dihydroxyflavothione (group 2), both DNA and the membrane are targets. The mechanism likely involves both energy transfer and electron transfer from the lowest pi, pi* triplet state to oxygen, to form singlet oxygen and the superoxide anion. Some of these compounds could be considered as models for environmentally safe photopesticides.