Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis.

BACKGROUND: The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis. METHODS: We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity. RESULTS: One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-ß in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity. CONCLUSIONS: Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.

Biomineralization potential and biological properties of a new tantalum oxide (Ta2O5)-containing calcium silicate cement.

OBJECTIVE: The present study evaluated the biological effects and biomineralization potential of a new tantalum oxide (Ta2O5)-containing material designed for vital pulp therapy or perforation repair (NeoMTA 2), compared to NeoMTA Plus and Bio-C Repair. MATERIAL AND METHODS: Human dental pulp stem cells (hDPSCs) were exposed to different eluates from NeoMTA Plus, NeoMTA 2, and Bio-C Repair. Ion release from each material was determined using inductively coupled plasma-optical emission spectrometry (ICP-MS). The biological experiments performed were MTT assays, apoptosis/necrosis assays, adhesion assays, migration assays, morphology evaluation, and reactive oxygen species (ROS) production analysis. Biomineralization was assessed by Alizarin red S staining. Finally, osteo/odontogenic gene expression was determined by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Data were analyzed using one-way ANOVA followed by Tukey's multiple comparison test. RESULTS: NeoMTA 2 displayed a significantly higher calcium release compared to the other materials (p < 0.05). When hDPSCs were cultured in presence of the different material eluates, all groups exhibited similar hDPSC viability and migration rates when compared to untreated cells. Substantial cell attachment and spreading were observed in all materials' surfaces, without significant differences. hDPSCs treated with NeoMTA 2 displayed an upregulation of ALP, Col1A1, RUNX2 (p < 0.001), ON, and DSPP genes (p < 0.05), and showed the highest mineralization potential compared to other groups (p < 0.001). Finally, the more concentrated eluates from these materials, specially NeoMTA Plus and NeoMTA 2, promoted higher ROS production in hDPSCs compared to Bio-C Repair and control cells (p < 0.001), although these ROS levels did not result in increased cell death. CONCLUSIONS: The new tantalum oxide (Ta2O5)-containing material shows an adequate cytocompatibility and the ability to promote biomineralization without using chemical osteogenic inducers, showing great potential as a new material for vital pulp therapy. CLINICAL RELEVANCE: NeoMTA 2 seems to be a promising material for vital pulp therapy. Further studies considering its biocompatibility and biomineralization potential are necessary.

In Vitro Biocompatibility of CPP-ACP and Fluoride-containing Desensitizers on Human Gingival Cells.

OBJECTIVES: To analyze the biocompatibility of different desensitizers containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride in their composition: MI Varnish (MV), Clinpro White Varnish (3M Oral Care), Profluorid Varnish (VOCO), Duraphat (Colgate) and Embrace Varnish (Pulpdent) on human gingival fibroblast cells (hGF). METHODS AND MATERIALS: Human gingival fibroblast (hGF) cells were exposed to several desensitizer extracts at different concentrations (0.1%, 1%, and 4% eluates). Then, in vitro biocompatibility was studied by analyzing the IC50 value, cell proliferation (MTT assay and cell cycle), cell migration (wound healing assay), cell morphology and F-actin content (immunocytofluorescence), and induction of apoptosis/necrosis (flow cytometry). Data were analyzed by one-way analysis of variance (ANOVA) followed by Tukey test. RESULTS: The lowest cell viability and IC50 were observed in all concentrations of Embrace Varnish-treated hGFs (p<0.001), whereas the highest were exhibited by those treated with Clinpro White Varnish. Similar effects were evidenced when induction of apoptosis/necrosis and cell migration assays were assessed. Finally, MI Varnish, Profluorid Varnish, Duraphat, and Embrace Varnish extracts showed lower numbers of attached cells, some of them with an unusual fibroblastic morphology when cultured with 4% concentration of the varnishes, while Clinpro White Varnish exhibited a similar number of cells with an evident actin cytoskeleton compared to the control group. CONCLUSIONS: The results obtained in this study indicate that hGFs show better in vitro biocompatibility after exposure to Clinpro White Varnish, even at the highest concentration employed, making it the most eligible for topical applications. In contrast, Embrace Varnish exhibited a high cytotoxicity towards hGFs that could potentially delay the healing process and regeneration of the oral mucosa, although more studies are needed to confirm this hypothesis.

Cytocompatibility and bioactive properties of the new dual-curing resin-modified calcium silicate-based material for vital pulp therapy.

OBJECTIVE: The aim of the present study was to evaluate the in vitro biocompatibility of Theracal PT, Theracal LC, and MTA Angelus, considered as bioactive materials used for vital pulp treatment, on human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: Human dental pulp stem cells (hDPSCs) were isolated from third molars, and material eluates were prepared (undiluted, 1:2, and 1:4 ratios). The hDPSC cytotoxicity, adhesion, morphology, viability, and cell migration were assessed. The mineralization nodule formation was determined by Alizarin red S staining (ARS). The odonto/osteogenic differentiation potential was assessed by osteo/odontogenic marker expression real-time qPCR. The chemical composition and ion release of the vital pulp materials were determined by energy dispersive X-ray (EDX) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Statistical differences were assessed by ANOVA and Tukey's test (p < 0.05). RESULTS: The three vital pulp materials showed variable levels of calcium, tungsten, silicon, and zirconium release and in their chemical composition. Cytocompatibility assays revealed higher hDPSC viability and migration rates when treated with Theracal PT than with Theracal LC. The lowest cell adhesion and spreading were observed in all Theracal LC-treated groups, whereas the highest were observed when treated with MTA. Theracal PT and MTA promoted the upregulation of DSPP and RUNX2 gene expression (p < 0.05). After 21 days, both MTA Angelus and Theracal PT-treated cells exhibited a significantly higher mineralized nodule formation than the negative control (p < 0.05). CONCLUSIONS: This study demonstrates the favorable in vitro cytocompatibility and bioactive properties of the recently introduced Theracal PT and the well-established MTA Angelus on hDPSCs, as opposed to Theracal LC. More studies, including in vivo animal testing are suggested before these new formulations might be used in the clinical setting. CLINICAL RELEVANCE: Theracal PT is a new material that could be clinically suitable for vital pulp therapy. Further studies considering its biocompatibility and bioactivity are necessary.

Chemical composition and bioactivity potential of the new Endosequence BC Sealer formulation HiFlow.

AIM: To evaluate in a laboratory setting the effects of Endosequence BC Sealer HiFlow (Brasseler USA, Savannah, GA, USA), a novel calcium silicate-based sealer developed for use in warm canal filling techniques, on human periodontal ligament stem cells (hPDLSCs). METHODOLOGY: Eluates of EndoSequence BC Sealer HiFlow (BCHiF) (Brasseler USA), EndoSequence BC Sealer (BCS) (Brasseler USA) and AH Plus (AHP) (Dentsply DeTrey GmbH, Konstanz, Germany) were placed in contact with hPDLSCs. The characterization of the chemical elements of the root canal sealers was assessed using scanning electron microscopy and energy-dispersive X-ray analysis (SEM-EDX). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to determine the ion release of the sealers. MTT assay and wound healing techniques were used to determine cell viability and migration, respectively. Cell morphology and cell attachment were assessed using a direct contact technique of hPDLSCs onto the surface of the sealers and analysed by SEM. The bioactivity potential was carried out with the Alizarin Red and qPCR testing methods. The statistical differences were evaluated using one-way anova and Tukey's test (P < 0.05). RESULTS: ICP-MS and EDX revealed significantly more zirconium in BCHiF than BCS (P < 0.05), whereas BCS had slightly higher levels of Ca2+ than BCHiF (P < 0.05). The cell viability assay revealed no relevant differences between BCS and BCHiF when compared with the control group (P > 0.05). Both BCS and BCHiF had similar rates of cell migration to the control group at 24 and 48 h. Cell morphology and adhesion capacity were also similar for BCS and BCHiF groups, whilst the AHP group was associated with reduced adhesion capacity. The Alizarin Red assay revealed a significant difference between the BCS and the control group (P < 0.001), as well as for the BCHiF group (P < 0.001). Finally, BCS and BCHiF promoted overexpression of osteo/cementogenic genes. CONCLUSIONS: In general, EndoSequence BC Sealer HiFlow possesses suitable biological properties to be safely used as a root canal filling material and promote increased expression of oste/cementogenic genes by hPDLSCs.

El paradigma del ozono en el tratamiento del dolor / The ozone paradigm in pain treatment

No disponible

Cytocompatibility, bioactivity potential, and ion release of three premixed calcium silicate-based sealers.

OBJECTIVE: Compositional modifications may alter the biological and physicochemical characteristics of calcium silicate-based sealers (CSBS) and, ultimately, their bioactivity. The main objective of this study was to evaluate the biological properties of three CSBS: EndoSequence BC Sealer, Ceraseal, and Endoseal mineral trioxide aggregate. MATERIALS AND METHODS: Human periodontal ligament stem cells (hPDLSCs) were exposed to several eluates of CSBS. The ion release profile and pH were determined, and metabolic activity and cell migration were assessed using the MTT and wound healing assays. hPDLSCs were cultured in direct contact with the surface of each material, and cell morphology and attachment were analyzed by scanning electron microscopy (SEM). Bioactivity potential was assessed by RT-qPCR and mineralization assays. Statistical differences between biomaterials were assessed using one- or two-way ANOVA (α < 0.05). RESULTS: All materials showed an alkaline pH, although Endoseal exhibited a significantly higher pH compared with the other CSBS (p < 0.05). Ceraseal released significantly more Ca2+ (p < 0.05) than EndoSequence BC Sealer and Endoseal. Interestingly, Endoseal induced a significant reduction in cell viability and cell migration compared with the control (p < 0.001). Moreover, SEM showed abundant cells adhering to EndoSequence BC Sealer and Ceraseal surfaces, whereas very few round cells were detected on the surface of Endoseal. Finally, Ceraseal and EndoSequence induced ALP, CAP, and CEMP-1 expression and a significantly higher mineralization capacity than Endoseal (***p < 0.001). CONCLUSIONS: The eluates from EndoSequence BC Sealer and Ceraseal displayed higher cell viability, cell attachment, cell migration rates, and ion release rates than Endoseal. Ceraseal and EndoSequence BC Sealer exhibited significantly more gene expression and mineralization capacity than Endoseal. CLINICAL RELEVANCE: The results obtained in the present work suggest that EndoSequence BC Sealer and Ceraseal possess biological properties that make them suitable materials for root canal treatment.

Valoración de la efectividad y seguridad de dos técnicas de radiofrecuencia para el tratamiento de la gonalgia secundaria a gonartrosis. Estudio prospectivo randomizado doble ciego / Assessment of the effectiveness and safety of two radiofrequency techniques for the treatment of knee pain secondary to gonarthrosis. Prospective randomized double blind study

Antecedentes y objetivo: En los pacientes con gonalgia por gonartrosis, disponemos de tratamientos no exentos de efectos secundarios. Objetivo: evaluar la eficacia analgésica de la radiofrecuencia (pulsada y convencional) sobre el nervio safeno a nivel subsartorial y los nervios geniculares de la rodilla, mediante la localización por ultrasonografía. Materiales y métodos: Ensayo clínico prospectivo, aleatorizado, doble ciego. G1 (RDF1): sujetos sometidos a radiofrecuencia, G2 (PLCB): sujetos sometidos a placebo. Se consideró clínicamente relevante una disminución ≥30% del dolor, según escala visual numérica y en el Western Ontario and McMaster Universities Osteoartritis Index, cuestionario de impresión global del paciente (PGIC) y cuestionario de estado de salud (SF-12) en la evaluación al mes, a los tres meses y a los seis meses de la realización de la técnica. Resultados: Veintiocho pacientes (G1: 12, G2: 16), 72% mujeres, edad: 75,2 (9,1) años, índice de masa corporal: 29,9 (4,64). El análisis no mostró una reducción del dolor, ni estadísticamente significativa, ni clínicamente relevante, al mes, tres, o seis meses respecto al inicio del tratamiento, en el cuestionario Western Ontario and McMaster Universities Osteoartritis Index y en la escala visual numérica (reposo, movimiento). Respecto al PGIC y al cuestionario SF-12, tampoco existieron diferencias estadísticamente significativas entre G1 y G2 antes ni después del tratamiento. Conclusiones: La combinación de dos técnicas de radiofrecuencia, no provoca una reducción en la intensidad de la gonalgia, al mes, tres, ni a los seis meses después de su realización. Es necesario cambiar la técnica de radiofrecuencia e incluir más variables para proseguir con el estudio de eficacia

Background and objective: In patients with knee pain due to gonarthrosis, we have treatments that are not free of side effects. Objective: to evaluate the analgesic efficacy of radiofrequency (pulsed and conventional) on the saphenous nerve at the subsartorial level and the genicular nerves of the knee, by ultrasonography. Materials and methods: Prospective, randomized, double-blind clinical trial. G1 (RDF1): subjects subjected to radiofrequency, G2 (PLCB): subjects subjected to placebo. A decrease ≥30% of the pain was considered clinically relevant, according to numerical rating scale and in the Western Ontario and McMaster Universities Osteoarthritis Index, global patient impression questionnaire (PGIC) and health status questionnaire (SF-12) in the evaluation at month, three months and six months after the completion of the technique. Results: 28 patients (G1: 12, G2: 16), 72% women, age: 75.2+/-9.1 years, body mass index: 29.9+/-4.64. The analysis did not show a pain reduction, neither statistically significant, not clinically relevant, at one month, three, or six months with respect to the start of treatment, in the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire and numerical rating scale (rest, movement). Regarding PGIC and the SF-12 questionnaire, there were no statistically significant differences between G1 and G2 either before or after treatment. Conclusions: The combination of two radiofrequency techniques, does not cause a reduction in the intensity of the knee pain, at month, three, or at six months after its completion. It is necessary to change the radiofrequency technique and include more variables to continue with the efficacy study

Paso de guardia en enfermería: Una revisión sistemática / Nursing shift handover: A systematic review / Passagem de plantão em enfermagem: Uma revisão sistemática

Resumen El paso de guardia en enfermería es una actividad fundamental para dar continuidad al cuidado de los pacientes, se realiza como cumplimiento obligatorio de una tarea en el quehacer laboral. Objetivo Describir la producción científica publicada entre 2007-2017, referente a la temática de paso de guardia de enfermería en los servicios de urgencias. Metodología Se desarrolló una revisión sistemática en seis bases de datos, se incluyeron estudios en idiomas inglés, español y portugués que estuvieran publicados en revistas indexadas con acceso a texto completo. Se realizó un análisis crítico de cada uno de los artículos con las Herramientas CASPe y STROBE, los resultados se ordenaron en una matriz que facilitó la obtención de información y categorías. Resultados De un total de 430 artículos, se incluyeron a la investigación únicamente 19, de los cuales 17 están escritos en idioma inglés y dos en español. Después del análisis de los artículos seleccionados se estructuraron dos categorías: Características del paso de guardia y Estandarización del proceso. Conclusiones Las brechas en la comunicación se perfilan como uno de los principales aspectos a tener en cuenta, para mejorar el paso de guardia. El lugar más recomendable para que se lleve a cabo el proceso debe ser en la habitación del paciente y verificado por los dos equipos de enfermería. En la actualidad es necesario realizar investigaciones para mejorar el nivel de evidencia de los estudios.

Abstract Nursing shift handover is an obligatory and a fundamental activity to ensure continuity in the process of patient care. Objective To describe the scientific production published between 2007-2017 regarding nursing shift handover within medical emergency services. Methodology A systematic review was conducted on six databases. Articles with full texts written in English, Spanish, and Portuguese, and published in indexed journals were included. A critical analysis on each article was conducted using the Critical Appraisal Skills Programme spanish, and the Strengthening the Reporting of Observational Studies in Epidemiology tools. Articles were clustered in a matrix of categories. Results From a total of 430 possible articles, 19 were included for this study - 17 written in English and 2 written in Spanish. From the corresponding analysis, two categories were structured: Nursing Shift Handover Characteristics, and Process Standardization. Conclusions Communication gaps seem to be one of the main issues to address while improving the nursing shift handover process. The patient room should be the place for the shift handover, and this process must be acknowledged by both nursing teams.

Resumo A passagem de plantão em enfermagem é uma atividade fundamental para dar continuidade ao cuidado dos pacientes, realiza-se como cumprimento obrigatório de uma tarefa no trabalho laboral. Objetivo Descrever a produção científica publicada entre 2007-2017, referente à temática de passagem de plantão de enfermagem nos serviços de urgências. Metodologia Desenvolveu-se uma revisão sistemática em seis bases de dados, incluíram-se estudos em idiomas inglês, espanhol e português que estiveram publicados em revistas indexadas com acesso a texto completo. Realizou-se uma análise crítica de cada um dos artigos com as Ferramentas CASPe e STROBE, os resultados ordenaram-se em uma matriz que facilitou a obtenção de informação e categorias. Resultados De um total de 430 artigos, incluíram-se à pesquisa unicamente 19, dos quais 17 estão escritos em idioma inglês e dois em espanhol. Depois da análise dos artigos selecionados estruturaram-se duas categorias: Caraterísticas da passagem de plantão e Padronização do processo. Conclusões Os abismos na comunicação perfilam-se como um dos principais aspectos a ter em conta, para melhorar a passagem de plantão. O lugar mais recomendável para se efetuar o processo deve ser no quarto do paciente e verificado pelas duas equipes de enfermagem. Na atualidade é necessário realizar pesquisas para melhorar o nível de evidência dos estudos.

Comparison of diffusion, cytotoxicity and tissue inflammatory reactions of four commercial bleaching products against human dental pulp stem cells.

Multiple side effects related to bleaching were found to occur in the dental pulp tissue, including decreased cell metabolism and viability. In this work we evaluated the in vitro diffusion capacity, cytotoxicity and biocompatibility of four commercial bleaching products on stem cells from human dental pulp (hDPSCs). Two commercial bleaching gels hydrogen peroxide-based (HP), Norblanc Office 37.5% (Nor-HP) and Opalescence Boost 40% (Opal-HP) were applied for 30 min to enamel/dentine discs. Another two gels from the same manufacturers, 16% carbamide peroxide-based (CP), Norblanc Home (Nor-CP) and Opalescence CP 16% (Opal-CP), were applied for 90 min. The diffusion of HP was analysed by fluorometry. Cytotoxicity was determined using the MTT assays, the determination of apoptosis, immunofluorescence assays and intracellular reactive oxygen species (ROS) level. Tissue inflammatory reactions were evaluated histopathologically in rats. Statistical differences were performed by one-way ANOVA and Bonferroni post-test (α < 0.05). Normon products showed lower cytotoxicity and diffusion capacity than the Ultradent products. A high intracellular ROS level was measured in hDPSCs after exposure to Opal-HP. Finally, a severe necrosis of both coronal and radicular pulp was observed with Opal-HP. Similar concentrations of hydrogen peroxide and carbamide peroxide in a variety of bleaching products exhibited different responses in cells and dental pulp tissue, suggesting that bleaching products contain unknown agents that could influence their toxicity.

Assessment of the effectiveness and safety of two radiofrequency techniques for the treatment of knee pain secondary to gonarthrosis. Prospective randomized double blind study. / Valoración de la efectividad y seguridad de dos técnicas de radiofrecuencia para el tratamiento de la gonalgia secundaria a gonartrosis. Estudio prospectivo randomizado doble ciego.

BACKGROUND AND OBJECTIVE: In patients with knee pain due to gonarthrosis, we have treatments that are not free of side effects. OBJECTIVE: to evaluate the analgesic efficacy of radiofrequency (pulsed and conventional) on the saphenous nerve at the subsartorial level and the genicular nerves of the knee, by ultrasonography. MATERIALS AND METHODS: Prospective, randomized, double-blind clinical trial. G1 (RDF1): subjects subjected to radiofrequency, G2 (PLCB): subjects subjected to placebo. A decrease ≥30% of the pain was considered clinically relevant, according to numerical rating scale and in the Western Ontario and McMaster Universities Osteoarthritis Index, global patient impression questionnaire (PGIC) and health status questionnaire (SF-12) in the evaluation at month, three months and six months after the completion of the technique. RESULTS: 28 patients (G1: 12, G2: 16), 72% women, age: 75.2±9.1 years, body mass index: 29.9±4.64. The analysis did not show a pain reduction, neither statistically significant, not clinically relevant, at one month, three, or six months with respect to the start of treatment, in the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire and numerical rating scale (rest, movement). Regarding PGIC and the SF-12 questionnaire, there were no statistically significant differences between G1 and G2 either before or after treatment. CONCLUSIONS: The combination of two radiofrequency techniques, does not cause a reduction in the intensity of the knee pain, at month, three, or at six months after its completion. It is necessary to change the radiofrequency technique and include more variables to continue with the efficacy study.

Evaluation of changes in ion release and biological properties of NeoMTA-Plus and Endocem-MTA exposed to an acidic environment.

AIM: To analyse in vitro changes in ion release and biological properties of Endocem-MTA (Maruchi, Wonju, Korea) and NeoMTA-Plus (Avalon Biomed Inc, Bradenton, FL, USA) exposed to acidic or neutral environment on human dental periodontal ligament stem cells (hPDLSCs). METHODOLOGY: Cell viability and wound healing assays were performed using eluates of each material. Cell death and changes in phenotype induced by the set endodontic sealer eluates were evaluated through flow cytometry. To evaluate cell attachment to the different materials, hPDLSCs were directly seeded onto the material surfaces and analysed by scanning electron microscopy. The chemical composition of the materials was determined by energy-dispersive X-ray (EDX), and ion release was evaluated by inductively coupled plasma-mass spectrometry. Statistical analysis was performed with analysis of variance and a Bonferroni or Tukey post-test (α < 0.05). RESULTS: The MTT assay revealed non-cytotoxic effects of NeoMTA-Plus and Endocem-MTA at pH 5.2 and 7.4. However, there were minor differences compared with the control, especially at pH 5.2, where both materials were associated with significantly greater cell viability (P < 0.05). In both environments, the materials stimulated hPDLSCs to migrate. hPDLSCs were attached to the bioactive cements, with multiple prolongations proliferated on the surface of the samples. Moreover, there were no changes to cell phenotype or apoptosis/necrosis rates, indicating that the acidic environment did not induce cell death. Prismatic crystalline structures were seen on the surface of the cements exposed to butyric acid and EDX analysis identified a marked peak of Ca2+ from NeoMTA-Plus and Endocem-MTA in acidic and physiological environments. CONCLUSIONS: An acidic environment favoured the release of Ca2+ ions from both bioactive cements, and the cytotoxicity of these bioactive cements was low in both environments studied.

Documento de consenso sobre el uso de la combinación paracetamol/tramadol en pacientes con dolor moderado-intenso / Consensus statement on the use of acetaminophen/tramadol in patients with moderate-severe pain

OBJETIVOS: Desarrollar recomendaciones sobre el uso de la combinación paracetamol/tramadol (P/T) en pacientes con dolor moderado-intenso, basadas en la mejor evidencia y experiencia. MÉTODOS: Se siguió la metodología de grupos nominales y Delphi apoyados por una revisión sistemática de la literatura (RSL). Se seleccionó un panel multidisciplinar de 12 expertos en el manejo del dolor. En la primera reunión de grupo nominal se definió el objetivo, alcance, usuarios, apartados del documento de consenso, así como recomendaciones generales preliminares. Para la RSL se definieron los criterios de inclusión y exclusión, y las estrategias de búsqueda. Dos revisores seleccionaron y analizaron los artículos. Esta evidencia se discutió en una segunda reunión de grupo nominal y se generaron las recomendaciones definitivas. Para cada recomendación, el nivel de evidencia y el grado de recomendación se clasificaron según el modelo de Oxford, y el grado de acuerdo por técnica Delphi. Se definió acuerdo si al menos el 70% de los participantes contestaron ≥ 7 en cada recomendación (1 = total desacuerdo a 10 = total acuerdo). RESULTADOS: Se generaron 20 recomendaciones que cubren aspectos generales, como la evaluación del dolor, y específicos del manejo de P/T. Estos últimos abarcan la indicación de la combinación P/T (perfil de paciente, dosificación, pauta, formulaciones), gestión del riesgo (contraindicaciones, precauciones, interacciones, uso concomitante con otras medicaciones, seguimiento, situaciones especiales) y la educación del paciente. CONCLUSIONES: Estas recomendaciones pretenden resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones respecto al uso de la combinación P/T en pacientes con dolor moderado-intenso

OBJECTIVES: To present recommendations on the use of the paracetamol/tramadol (P/T) combination in patients with moderate-intense pain based on best evidence and experience. METHODS: The method of nominal groups and Delphi was followed, and supported by a systematic literature review (SLR). A multidisciplinary panel of 12 experts in pain management was selected. In the first nominal group meeting, the aim, scope, users, and sections of the consensus document, were defined, along with the preliminary general recommendations. For the SLR, the inclusion and exclusion criteria, as well as the search strategies, were defined. Two reviewers selected and analysed the articles. This evidence was discussed in a second nominal group meeting, and definitive recommendations were developed. For each recommendation, the evidence levels and grade of recommendation grades were classified according to the Oxford model, and the grade according to the Delphi technique. It was defined as an agreement if at least 70% of the participants scored ≥ 7 for each recommendation (1 = total disagreement to 10 = total agreement). RESULTS: A total of 20 recommendations were produced, which covered general aspects, such as the assessment of pain, and those specific to P/T management. These latter included the indications of the P/T combination (patient profile, dosing, prescription, formulations), risk management (contraindications, precautions, interactions, concomitant use with other medications, follow-up, special situations), and patient education. CONCLUSIONS: These recommendations attempt to resolve any of the routine clinical questions, and help in the making of decisions on the use of the P/T combination in patients with moderate-intense pain

[Consensus statement on the use of acetaminophen/tramadol in patients with moderate-severe pain]. / Documento de consenso sobre el uso de la combinación paracetamol/tramadol en pacientes con dolor moderado-intenso.

OBJECTIVES: To present recommendations on the use of the paracetamol/tramadol (P/T) combination in patients with moderate-intense pain based on best evidence and experience. METHODS: The method of nominal groups and Delphi was followed, and supported by a systematic literature review (SLR). A multidisciplinary panel of 12 experts in pain management was selected. In the first nominal group meeting, the aim, scope, users, and sections of the consensus document, were defined, along with the preliminary general recommendations. For the SLR, the inclusion and exclusion criteria, as well as the search strategies, were defined. Two reviewers selected and analysed the articles. This evidence was discussed in a second nominal group meeting, and definitive recommendations were developed. For each recommendation, the evidence levels and grade of recommendation grades were classified according to the Oxford model, and the grade according to the Delphi technique. It was defined as an agreement if at least 70% of the participants scored ≥7 for each recommendation (1=total disagreement to 10=total agreement). RESULTS: A total of 20 recommendations were produced, which covered general aspects, such as the assessment of pain, and those specific to P/T management. These latter included the indications of the P/T combination (patient profile, dosing, prescription, formulations), risk management (contraindications, precautions, interactions, concomitant use with other medications, follow-up, special situations), and patient education. CONCLUSIONS: These recommendations attempt to resolve any of the routine clinical questions, and help in the making of decisions on the use of the P/T combination in patients with moderate-intense pain.

GuttaFlow Bioseal promotes spontaneous differentiation of human periodontal ligament stem cells into cementoblast-like cells.

OBJECTIVES: To evaluate in vitro the cementogenic potential and the biological effects of GuttaFlow Bioseal, GuttaFlow 2, MTA Fillapex and AH Plus on human periodontal ligament stem cells (hPDLSCs). METHODS: Cell viability, cell migration and cell morphology assays were performed using eluates of each material. To evaluate cell attachment, hPDLSCs were directly seeded onto the material surfaces and analyzed by scanning electron microscopy (SEM). The effects of endodontic sealers on cementum protein 1 (CEMP1), cementum-derived attachment protein (CAP), bone sialoprotein (BSP), ameloblastin (AMBN), amelogenin (AMELX) and alkaline phosphatase (ALP) gene expression on hPDLSCs were investigated by qPCR and immunofluorescence (IF). Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post-test (α<0.05). RESULTS: More than 90% of viable cells were obtained using extracts of GuttaFlow Bioseal and GuttaFlow2 after 72h of culture. By contrast, AH Plus and MTA Fillapex induced significantly lower levels of cell viability. GuttaFlow2 and GuttaFlow Bioseal promoted wound closure in a concentration-dependent manner, comparable to that observed with control extracts (*p<0.05). However, with AH Plus and MTA Fillapex, cell migration was significantly lower than in the control (***p<0.0001). SEM analysis pointed to an organized stress fiber assembly and high degree of cell adhesion on GuttaFlow Bioseal disks but low rates on GuttaFlow2, MTA Fillapex and AH Plus. When hPDLSCs were cultured with GuttaFlow Bioseal-conditioned media, qPCR assays and IF showed a higher level of AMELX, AMBN, CEMP1 and CAP expression than the control (*p<0.05)), whereas no such expression was observed in the other sealers. SIGNIFICANCE: Our results showed that GuttaFlow sealers were more cytocompatible than AH Plus and MTA Fillapex, while GuttaFlow Bioseal favored cementoblast differentiation of hPDLSCs in the absence of any growth factors.

Intraperitoneal administration of the anti-IL-23 antibody prevents the establishment of intestinal nematodes in mice.

Previous studies have established that an increased Th-9 response creates a hostile environment for nematode parasites. Given that IL-23, a cytokine required for maintenance of the IL-17-secreting phenotype, has inhibitory effects on IL-9 production, we hypothesized that reducing circulating IL-23 by treatment with anti-IL-23 antibodies would reduce the establishment and development of parasitic intestinal nematodes. In this study, we show that animals treated with anti-IL-23 monoclonal antibodies showed a drastic reduction in the number of mouse pinworms (Aspiculuris tetraptera) recovered from the intestine (p < 0.001) at 23 days post-infection compared to the untreated animals. The cytokine levels in Peyer's patches (PP) in treated and infected animals increase the expression of interleukins such as IL-25, IL-21, and IL-9, augmenting mucus production in the crypts, and boosting chemokines, such as OX40 and CCL20 in the mucosa. Our results suggest that the Th17/Th2 regulatory mechanism provoked by the administration of the anti-IL-23 antibody prevents the implantation of the intestinal nematode in mice. The diminished inflammatory IL-17 levels alter the Th9 environment perhaps as a consequence of IL-17 inhibiting IL-9 expression. These Th9 conditions may explain the successful treatment against Inflammatory Bowel Disease (IBD) both with antibodies against IL-23 or through parasitization with nematodes.

Biological effects of silk fibroin 3D scaffolds on stem cells from human exfoliated deciduous teeth (SHEDs).

The aim is to investigate in vitro biological effects of silk fibroin 3D scaffolds on stem cells from human exfoliated deciduous teeth (SHEDs) in terms of proliferation, morphological appearance, cell viability, and expression of mesenchymal stem cell markers. Silk fibroin 3D scaffolding materials may represent promising suitable scaffolds for their application in regenerative endodontic therapy approaches. SHEDs were cultured in silk fibroin 3D scaffolds. Then, cell numbers were counted and the Alamar blue colorimetric assay was used to analyse cell proliferation after 24, 48, 72, and 168 h of culture. The morphological features of SHEDs cultured on silk fibroin scaffolds were evaluated by scanning electron microscopy (SEM). Finally, cell viability and the expression of mesenchymal stem cell markers were analysed by flow cytometry. One-way analysis of variance (ANOVA) followed by a Bonferroni post-test was performed (P < 0.05). At 24 and 48 h of culture, SHED proliferation on scaffolds was modest compared to the control although still significant (p < 0.05). However, cell proliferation progressively increased from 72 to 168 h compared with the control (p < 0.001; p < 0.01). In addition, flow cytometry analysis showed that the culture of SHEDs on silk fibroin scaffolds did not significantly alter the level of expression of the mesenchymal markers CD73, CD90, or CD105 up to 168 h; in addition, cell viability in silk fibroin was similar to than obtained in plastic. Moreover, SEM studies revealed a suitable degree of proliferation, cell spreading, and attachment, especially after 168 h of culture. The findings from the current study suggest that silk fibroin 3D scaffolds had a favourable effect on the biological responses of SHEDs. Further in vivo investigations are required to confirm these results.

Comparative analysis of the biological effects of the endodontic bioactive cements MTA-Angelus, MTA Repair HP and NeoMTA Plus on human dental pulp stem cells.

AIM: To evaluate the biological effects in vitro of MTA-Angelus (MTA-Ang; Angelus, Londrina, PR, Brazil), MTA Repair HP (MTA-HP; Angelus) and NeoMTA Plus (NeoMTA-P; Avalon Biomed Inc, Bradenton, FL, USA) on human dental pulp stem cells (hDPSCs). METHODOLOGY: Cell viability and cell migration assays were performed using eluates of each material. To evaluate cell morphology and cell attachment to the different materials, hDPSCs were directly seeded onto the material surfaces and analysed by immunocytofluorescence and scanning electron microscopy, respectively. The chemical composition of the materials was determined by energy-dispersive X-ray (EDX), and eluates were analysed by inductively coupled plasma-mass spectrometry (ICP-MS). Statistical analysis was performed with the analysis of variance and Bonferroni or Tukey post-test (α < 0.05). RESULTS: Undiluted MTA-Ang, MTA-HP and NeoMTA-P displayed a significant increase in cell viability greater than that obtained using complete medium alone (control) (*P < 0.05; **P < 0.01; ***P < 0.001). Moreover, a cell migration assay revealed cell migration rates after incubation with extracts of MTA-Ang, MTA-HP and NeoMTA-P that were similar to levels obtained in the control group. In addition, stretched cytoskeletal F-actin fibres were detected in the cells treated with the three material extracts. SEM studies revealed a high degree of cell proliferation and attachment on all three materials. EDX analysis demonstrated similar weight percentages of C, O and Ca in all three materials, whilst other elements such as Al, Si and S were also found. CONCLUSIONS: MTA-Ang, MTA-HP and NeoMTA-P were associated with biological effects on hDPSCs in terms of cell proliferation, morphology, migration and attachment.

Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against Trichuris muris infection.

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other experimental groups. Also, these animals presented significantly different chemokine, CCL20 and CCL11, levels. However, although the number and size of Tuft cells did not vary between groups, the intensity of fluorescence per cell was significant in the group immunized with the rPP2A-OVS. The results of the present study suggest that mice immunized with the lipopeptide are capable of activating a combined Th17/Th9 response. This strategy of immunization may be of great applicability not only in immunotherapy and immunoprophylaxis to control diseases caused by nematodes but also in pathologies necessitating action at the level of the Th9 response in the intestinal mucosa.

Cytotoxicity and bioactivity of various pulpotomy materials on stem cells from human exfoliated primary teeth.

AIMS: To investigate the cytotoxicity and bioactivity of several pulpotomy materials: Biodentine (Septodont, Saint-Maur-des-Fosses, France) MTA (Angelus, Londrina, PR, Brazil), Theracal LC (Bisco Inc., Schamburg, IL, USA) and IRM (Dentsply DeTrey GmbH, Konstanz, Germany), after contact with stem cells isolated from human exfoliated primary teeth (SHEDs). METHODOLOGY: SHEDs were cultured in the presence of the eluates of various pulpotomy materials for 24, 48 and 72 h. Cell viability was determined by mitochondrial dehydrogenase enzymatic (MTT) assay. Apoptosis and changes in cell phenotype were evaluated by flow cytometry. Also, an in vitro scratch wound-healing assay was used to determine their effects on cell migration. To assess cell morphology and attachment to the different pulpotomy materials, SHEDs were directly seeded onto the material surfaces and analysed by scanning electron microscopy (SEM). Finally, the deposition of a calcified matrix in presence of these materials was verified by Alizarin Red staining. Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post-test (α = 0.05). RESULTS: Cell viability in the presence of Biodentine eluates was significantly higher to that obtained using complete medium alone (control; P < 0.01) and was also significantly higher than using MTA Angelus from 48 h of incubation (P < 0.01). However, Theracal LC and IRM were associated with low rates of cell viability (P < 0.001). Similar results were obtained in an apoptosis assay. In addition, SHEDs maintained their mesenchymal phenotype in all conditions although their capacity to migrate was higher in the presence of Biodentine. SEM studies revealed a suitable proliferation rate, cell spreading and attachment, especially when using Biodentine and MTA Angelus discs. Finally, Biodentine eluates significantly induced calcified matrix deposition from 7 days of culture (P < 0.01). CONCLUSIONS: Biodentine exhibited better cytocompatibility and bioactivity than MTA Angelus, Theracal LC and IRM.