Effect of VAChT reduction on lung alterations induced by exposure to iron particles in an asthma model.

INTRODUCTION: Pollution harms the health of people with asthma. The effect of the anti-inflammatory cholinergic pathway in chronic allergic inflammation associated to pollution is poorly understood. METHODS: One hundred eight animals were divided into 18 groups (6 animals). Groups included: wild type mice (WT), genetically modified with reduced VAChT (VAChTKD), and those sensitized with ovalbumin (VAChTKDA), exposed to metal powder due to iron pelletizing in mining company (Local1) or 3.21 miles away from a mining company (Local2) in their locations for 2 weeks during summer and winter seasons. It was analyzed for hyperresponsivity, inflammation, remodeling, oxidative stress responses and the cholinergic system. RESULTS: During summer, animals without changes in the cholinergic system revealed that Local1 exposure increased the hyperresponsiveness (%Rrs, %Raw), and inflammation (IL-17) relative to vivarium animals, while animals exposed to Local2 also exhibited elevated IL-17. During winter, animals without changes in the cholinergic system revealed that Local2 exposure increased the hyperresponsiveness (%Rrs) relative to vivarium animals. Comparing the exposure local of these animals during summer, animals exposed to Local1 showed elevated %Rrs, Raw, and IL-5 compared to Local 2, while in winter, Local2 exposure led to more IL-17 than Local1. Animals with VAChT attenuation displayed increased %Rrs, NFkappaB, IL-5, and IL-13 but reduced alpha-7 compared to animals without changes in the cholinergic system WT. Animals with VAChT attenuation and asthma showed increased the hyperresponsiveness, all inflammatory markers, remodeling and oxidative stress compared to animals without chronic lung inflammation. Exposure to Local1 exacerbated the hyperresponsiveness, oxidative stressand inflammation in animals with VAChT attenuation associated asthma, while Local2 exposure led to increased inflammation, remodeling and oxidative stress. CONCLUSIONS: Reduced cholinergic signaling amplifies lung inflammation in a model of chronic allergic lung inflammation. Furthermore, when associated with pollution, it can aggravate specific responses related to inflammation, oxidative stress, and remodeling.

Investigating the Effects of a New Peptide, Derived from the Enterolobium contortisiliquum Proteinase Inhibitor (EcTI), on Inflammation, Remodeling, and Oxidative Stress in an Experimental Mouse Model of Asthma-Chronic Obstructive Pulmonary Disease Overlap (ACO).

The synthesized peptide derived from Enterolobium contortisiliquum (pep3-EcTI) has been associated with potent anti-inflammatory and antioxidant effects, and it may be a potential new treatment for asthma-COPD overlap-ACO). Purpose: To investigate the primary sequence effects of pep3-EcTI in an experimental ACO. BALB/c mice were divided into eight groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep3-EcTI (treated with inhibitor), ACO-DX (treated with dexamethasone), ACO-DX-pep3-EcTI (treated with dexamethasone and inhibitor), and SAL-pep3-EcTI (saline group treated with inhibitor). We evaluated the hyperresponsiveness to methacholine, exhaled nitric oxide, bronchoalveolar lavage fluid (BALF), mean linear intercept (Lm), inflammatory markers, tumor necrosis factor (TNF-α), interferon (IFN)), matrix metalloproteinases (MMPs), growth factor (TGF-ß), collagen fibers, the oxidative stress marker inducible nitric oxide synthase (iNOS), transcription factors, and the signaling pathway NF-κB in the airways (AW) and alveolar septa (AS). Statistical analysis was conducted using one-way ANOVA and t-tests, significant when p < 0.05. ACO caused alterations in the airways and alveolar septa. Compared with SAL, ACO-pep3-EcTI reversed the changes in the percentage of resistance of the respiratory system (%Rrs), the elastance of the respiratory system (%Ers), tissue resistance (%Gtis), tissue elastance (%Htis), airway resistance (%Raw), Lm, exhaled nitric oxide (ENO), lymphocytes, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, transforming growth factor (TGF)-ß, collagen fibers, and iNOS. ACO-DX reversed the changes in %Rrs, %Ers, %Gtis, %Htis, %Raw, total cells, eosinophils, neutrophils, lymphocytes, macrophages, IL-1ß, IL-6, IL-10, IL-13, IL-17, TNF-α, INF-γ, MMP-12, TGF-ß, collagen fibers, and iNOS. ACO-DX-pep3-EcTI reversed the changes, as was also observed for the pep3-EcTI and the ACO-DX-pep3-EcTI. Significance: The pep3-EcTI was revealed to be a promising strategy for the treatment of ACO, asthma, and COPD.

Effects of a Peptide Derived from the Primary Sequence of a Kallikrein Inhibitor Isolated from Bauhinia bauhinioides (pep-BbKI) in an Asthma-COPD Overlap (ACO) Model.

(1) There are several patients with asthma-COPD overlap (ACO). A peptide derived from the primary sequence of a kallikrein inhibitor isolated from Bauhinia bauhinioides (pep-BbKI) has potent anti-inflammatory and antioxidant effects. Purpose: To investigate the effects of pep-BbKI treatment in an ACO model and compare them with those of corticosteroids. (2) BALB/c mice were divided into groups: SAL (saline), OVA (ovalbumin), ELA (elastase), ACO (ovalbumin + elastase), ACO-pep-BbKI (treated with inhibitor), ACO-DX (dexamethasone treatment), ACO-DX-pep-BbKI (both treatments), and SAL-pep-BbKI (saline group treated with inhibitor). We evaluated: hyperresponsiveness to methacholine, bronchoalveolar lavage fluid (BALF), exhaled nitric oxide (eNO), IL-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, IFN-γ, TNF-α, MMP-9, MMP-12, TGF-ß, collagen fibers, iNOS, eNO, linear mean intercept (Lm), and NF-κB in airways (AW) and alveolar septa (AS). (3) ACO-pep-BbKI reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, neutrophils, IL-5, IL-10, IL-17, IFN-γ, TNF-α, MMP-12 (AW), collagen fibers, iNOS (AW), and eNO (p > 0.05). ACO-DX reversed ACO alterations and was similar to SAL in all mechanical parameters, Lm, total cells and differentials, IL-1ß(AS), IL-5 (AS), IL-6 (AS), IL-10 (AS), IL-13 (AS), IFN-γ, MMP-12 (AS), TGF-ß (AS), collagen fibers (AW), iNOS, and eNO (p > 0.05). SAL was similar to SAL-pep-BbKI for all comparisons (p > 0.05). (4) Pep-BbKI was similar to dexamethasone in reducing the majority of alterations of this ACO model.

A retrospective chart review to identify the involvement of palliative care with glioblastoma multiforme patients.

Background: Glioblastoma Multiforme is a deadly brain cancer that is very challenging for patients and their families. It is associated with rapid progression, cognitive decline, and a low survival rate. Objective: To determine whether deceased Glioblastoma Multiforme patients had received follow-up service from the palliative care team before their death, whether invasive measures had been reduced, and whether the last antineoplastic treatment was given within 14-30 days before death. Method: A retrospective study utilizing chart data from January 2020 to March 2022 from an institutional project. Data were gathered to reflect selected indicators of quality of care for palliative care patients. Results: Of the 30 hospitalized patients with Glioblastoma Multiforme who had died while in hospital, 50% had received support from the palliative care team. Two patients (6.7%) had undergone antineoplastic treatment in the last 14 days of life and 13 (43.3%) had an order limiting invasive measures defined in the last two weeks of life. Conclusion: In half of the patients monitored by a palliative care team, antineoplastic treatment and limitation of invasive measures occurred in the last 14 days of life. This may be associated with increased suffering of patients, family members, and professionals. Discussions about end-of-life care-related choices and goals of care need to be respected.

Cateter venoso central de inserção periférica e trombose: experiência em hospital de alta complexidade / Catéter venoso central de inserción periférica y trombosis: una experiencia en un hospital de alta complejidad / Peripherally-inserted central venous catheter: an experience in a high-complexity hospital

RESUMO Objetivo: descrever as variáveis associadas à trombose nos pacientes com cateter venoso central de inserção periférica. Método: estudo de coorte, retrospectivo, com dados coletados em 2016, no sistema de informação Research Eletronic Data Capture de um hospital de alta complexidade em São Paulo, Brasil. Resultados: o paciente crítico foi o que mais apresentou trombose (77,3%). O paciente que tinha o cateter venoso central de inserção periférica com ocupação do vaso sanguíneo maior que 33%, quando puncionado mais de uma vez (15,4%), evoluiu com trombose. Referente à área de punção, não houve resultado significativo já que 96,2% dos pacientes estavam com o cateter na zona ideal de punção no braço. Conclusão: a incidência de pacientes com Cateter Venoso Central de Inserção Periférica que evoluíram com trombose foi de 1,2%, considerada baixa em comparação com outros estudos, contribuindo para fortalecer as políticas de boas práticas para o sucesso da terapia intravenosa com seu uso.

RESUMEN: Objetivo: describir las variables asociadas a la trombosis en pacientes con un catéter venoso central de inserción periférica. Método: estudio de cohorte, retrospectivo, realizado con datos recolectados en el año 2016, en el sistema de información Research Eletronic Data Capture de un hospital de alta complejidad en San Pablo, Brasil. Resultados: los pacientes críticos fueron los que presentaron más casos de trombosis (77,3%). Cuando se realizó más de una punción (15,4%) en pacientes en los que el catéter venoso central de inserción periférica ocupaba más del 33% del vaso sanguíneo, el cuadro clínico evolucionó con trombosis. En relación al área de punción, no se registró un resultado significativo, puesto que el 96,2% de los pacientes tenía el catéter en la zona ideal de punción en el brazo. Conclusión: la incidencia de pacientes con un Catéter Venoso Central de Inserción Periférica que evolucionaron con trombosis fue del 1,2%, considerada baja en comparación con otros estudios, lo que contribuye a fortalecer las políticas de buenas prácticas para el buen resultado de la terapia intravenosa con su uso.

ABSTRACT Objective: to describe the variables associated with thrombosis in patients with peripherally-inserted central venous catheters. Method: a retrospective cohort study with data collected in 2016, in the Research Electronic Data Capture information system of a high-complexity hospital in São Paulo, Brazil. Results: the critical patient was the one who presented more thrombosis (77.3%). The patient who had a peripherally-inserted central venous catheter taking more than 33% of the blood vessel, when punctured more than once (15.4%), evolved with thrombosis. Regarding the puncture area, there was no significant result since 96.2% of the patients had the catheter in the ideal puncture zone in the arm. Conclusion: the incidence of patients with Peripherally-Inserted Central Venous Catheters who evolved with thrombosis was 1.2%, considered low compared to other studies, contributing to strengthen the policies of good practices for the success of the intravenous therapy with its use.