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INTRODUCTION: Health disparities in the Asian and Pacific Islander Americans (APIAs) community have not been well described, unlike non-Hispanic Black and Hispanic communities. However, there has been a rise in violence against the APIA community. This study explores and characterizes violent death by incident (e.g., homicide, suicide), weapon (e.g., firearm, strangulation), and location types among APIAs as they compare with other racial or ethnic groups. METHODS: We used the National Violent Death Reporting System from 2003 to 2018 to characterize violent deaths among APIA and compared them to all other races. We compared these racial categories in two ways. First, we compared all races as a categorical variable that included six non-Hispanic racial categories including "Other or unspecified" and "two or more races. We then created a binary variable of APIA versus All Other Races for analysis. We explored the incident type of death, substance abuse disorders, mental health history, and gang involvement among other variables. We used Chi-square tests for categorical variables and Mann-Whitney U-tests for continuous variables. RESULTS: Overall, APIAs had a unique pattern of violent death. APIAs were more likely to commit suicide (71.74%-62.21%, P<0.001) and less likely to die of homicide than other races (17.56%-24.31%, P<0.001). In the cases of homicide, APIAs were more likely to have their deaths precipitated by another crime (40.87% versus 27.87%, P < 0.001). APIAs were more than twice as likely to die of strangulation than other races (39.93%-18.06%, P<0.001). Conversely, APIAs were less likely to die by firearm than other races (29.69-51.51, P<0.001). CONCLUSIONS: APIAs have a unique pattern of violence based on analysis of data from the National Violent Death Reporting System. Our data reveal a significant difference in the incident, weapon and location type as compared to Americans of other races, which begs further inquiry into the patterns of change in time and factors that contribute to inter-racial differences in death patterns.
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Homicídio , Havaiano Nativo ou Outro Ilhéu do Pacífico , Suicídio , Violência , Humanos , Causas de Morte , Vigilância da População , Estados UnidosRESUMO
BACKGROUND: Length of stay (LOS) and readmissions are common measures to evaluate quality of health care. The objective of this study was to evaluate factors related to hospital LOS and readmission within 90 days following carotid endarterectomy (CEA) in patients who have not had a stroke. METHODS: Using a single institution database, patients who underwent CEA for carotid stenosis between 2014 and 2019 were identified. Asymptomatic carotid stenosis (no history of any stroke or transient ischemic attack (TIA) within 6 months prior to CEA), and patients who had a TIA without stroke were included. Demographic and perioperative factors were collected. Primary outcomes analyzed were increased LOS (>1 day) and readmission within 90 days after surgery. RESULTS: There were 125 patients identified who underwent CEA for 133 carotid stenosis, and 8 patients had bilateral CEA; of which 36.8% were asymptomatic carotid stenosis with the remaining being operated on for TIA without any stroke. The mean age was 68 years old and 36.1% of cases were female. The median postoperative LOS was 2 days. Increased LOS occurred in 81 cases (60.9%). Increased LOS, compared to no increased LOS, occurred more often in patients with diabetes (48.1% vs. 30.8%, P = 0.047), in those with operations starting after 12:00 pm (45.7% vs. 21.2%, P = 0.004) and those with any minor complications such as neck swelling, neck pain, and urinary retention (30.9% vs. 15.4%, P = 0.044). Readmission within 90 days after CEA occurred in 24 (18%) of cases. Readmission within 90 days, compared to no readmission within 90 days, occurred more often in patients with a history of coronary artery disease (58.3% vs. 27.5%, P = 0.004), congestive heart failure (37.5% vs. 11%, P = 0.001), and atrial fibrillation (29.2% vs. 8.3%, P = 0.004). CONCLUSIONS: More than half of patients undergoing CEA for carotid stenosis were discharged after postoperative day 1. Interventions on modifiable clinical risk factors, such as morning CEA scheduling and management of comorbidities, may decrease LOS and 90-day readmission rates.
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Estenose das Carótidas , Endarterectomia das Carótidas , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Endarterectomia das Carótidas/efeitos adversos , Estenose das Carótidas/cirurgia , Ataque Isquêmico Transitório/etiologia , Tempo de Internação , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Management of antithrombotic therapy with warfarin in patients undergoing fistulograms and possible interventions is controversial and difficult because of lack of adequate outpatient bridging options. Our goal was to assess periprocedural outcomes in patients managed using different anticoagulation strategies. METHODS: A retrospective, single-institution analysis of all patients on chronic anticoagulation with warfarin undergoing fistulograms from 2011 to 2017 was performed. Anticoagulation management strategies were classified as suspended warfarin (SW), continued warfarin (CW), and a heparin bridge with suspended warfarin (HB). Periprocedural outcomes were analyzed. RESULTS: There were 87 patients on chronic anticoagulation with warfarin who underwent 175 fistulograms. Median age was 63 years, and 43.4% were women. Indications for warfarin included atrial fibrillation (53%), prior pulmonary embolism/deep vein thrombosis (29%), and hypercoagulable state (14%). Distribution was SW (60%), CW (26%), and HB (14%). Approximately half (53%) were same-day procedures, 30% occurred during access-related admissions, and 14% were performed during nonaccess-related admissions. Common indications for a fistulogram included difficulty with dialysis (63.4%), access thrombosis (20.6%), and poor maturation (10.3%). Interventions included angioplasty (82.9%), thrombectomy/embolectomy (20.6%), and stenting (8.6%). Thirty-day outcomes for SW versus CW versus HB were similar for bleeding complications (5.7%, 6.5%, 8.3%; P = 0.89), systemic thrombotic complications (3.8%, 2.2%, 0%; P = 0.569), access rethrombosis (7.6%, 13%, 12.5%; P = 0.517), and tunneled dialysis catheter placement (11.4%, 13%, 12.5%; P = 0.958). After excluding procedures performed during a nonaccess-related admission, length of stay (LOS) was highest among HB (9.6 ± 7.8 days) compared with SW (2.6 ± 5.9 days) and CW (1 ± 2.8 days), (P < 0.0001). CONCLUSIONS: CW therapy in patients undergoing fistulograms was not associated with increased morbidity and was associated with shorter LOS. Bridging with heparin is not associated with improved outcomes, warranting a thorough consideration of continuing warfarin is safe and may streamline preservation of dialysis accesses without significantly increasing resource utilization.
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Anticoagulantes/administração & dosagem , Derivação Arteriovenosa Cirúrgica , Substituição de Medicamentos , Heparina/administração & dosagem , Falência Renal Crônica/terapia , Diálise Renal , Trombose/prevenção & controle , Varfarina/administração & dosagem , Adulto , Idoso , Anticoagulantes/efeitos adversos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Esquema de Medicação , Feminino , Heparina/efeitos adversos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Complicações Pós-Operatórias/etiologia , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Varfarina/efeitos adversosRESUMO
BACKGROUND: Mast cells are present in the airways of patients who have severe asthma despite glucocorticoid treatment; these cells are associated with disease characteristics including poor quality of life and inadequate asthma control. Stem cell factor and its receptor, KIT, are central to mast-cell homeostasis. We conducted a proof-of-principle trial to evaluate the effect of imatinib, a KIT inhibitor, on airway hyperresponsiveness, a physiological marker of severe asthma, as well as on airway mast-cell numbers and activation in patients with severe asthma. METHODS: We conducted a randomized, double-blind, placebo-controlled, 24-week trial of imatinib in patients with poorly controlled severe asthma who had airway hyperresponsiveness despite receiving maximal medical therapy. The primary end point was the change in airway hyperresponsiveness, measured as the concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20% (PC20). Patients also underwent bronchoscopy. RESULTS: Among the 62 patients who underwent randomization, imatinib treatment reduced airway hyperresponsiveness to a greater extent than did placebo. At 6 months, the methacholine PC20 increased by a mean (±SD) of 1.73±0.60 doubling doses in the imatinib group, as compared with 1.07±0.60 doubling doses in the placebo group (P=0.048). Imatinib also reduced levels of serum tryptase, a marker of mast-cell activation, to a greater extent than did placebo (decrease of 2.02±2.32 vs. 0.56±1.39 ng per milliliter, P=0.02). Airway mast-cell counts declined in both groups. Muscle cramps and hypophosphatemia were more common in the imatinib group than in the placebo group. CONCLUSIONS: In patients with severe asthma, imatinib decreased airway hyperresponsiveness, mast-cell counts, and tryptase release. These results suggest that KIT-dependent processes and mast cells contribute to the pathobiologic basis of severe asthma. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01097694 .).
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Asma/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Mastócitos/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Asma/imunologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/tratamento farmacológico , Testes de Provocação Brônquica , Contagem de Células , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Cloreto de Metacolina , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida , Triptases/sangue , Triptases/metabolismoRESUMO
Cysteinyl leukotrienes (cysLTs) facilitate mucosal type 2 immunopathology by incompletely understood mechanisms. Aspirin-exacerbated respiratory disease, a severe asthma subtype, is characterized by exaggerated eosinophilic respiratory inflammation and reactions to aspirin, each involving the marked overproduction of cysLTs. Here we demonstrate that the type 2 cysLT receptor (CysLT2R), which is not targeted by available drugs, is required in two different models to amplify eosinophilic airway inflammation via induced expression of IL-33 by lung epithelial cells. Endogenously generated cysLTs induced eosinophilia and expanded group 2 innate lymphoid cells (ILC2s) in aspirin-exacerbated respiratory disease-like Ptges-/- mice. These responses were mitigated by deletions of either Cysltr2 or leukotriene C4 synthase (Ltc4s). Administrations of either LTC4 (the parent cysLT) or the selective CysLT2R agonist N-methyl LTC4 to allergen sensitized wild-type mice markedly boosted ILC2 expansion and IL-5/IL-13 generation in a CysLT2R-dependent manner. Expansion of ILC2s and IL-5/IL-13 generation reflected CysLT2R-dependent production of IL-33 by alveolar type 2 cells, which engaged in a bilateral feed-forward loop with ILC2s. Deletion of Cysltr1 blunted LTC4-induced ILC2 expansion and eosinophilia but did not alter IL-33 induction. Pharmacological blockade of CysLT2R prior to inhalation challenge of Ptges-/- mice with aspirin blocked IL-33-dependent mast cell activation, mediator release, and changes in lung function. Thus, CysLT2R signaling, IL-33-dependent ILC2 expansion, and IL-33-driven mast cell activation are necessary for induction of type 2 immunopathology and aspirin sensitivity. CysLT2R-targeted drugs may interrupt these processes.
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Aspirina/imunologia , Asma Induzida por Aspirina/patologia , Interleucina-33/imunologia , Mastócitos/imunologia , Receptores de Leucotrienos/imunologia , Animais , Asma Induzida por Aspirina/imunologia , Cisteína/biossíntese , Eosinofilia/imunologia , Eosinofilia/patologia , Células Epiteliais/metabolismo , Glutationa Transferase/genética , Interleucina-13/biossíntese , Interleucina-33/biossíntese , Interleucina-5/biossíntese , Leucotrieno E4/biossíntese , Leucotrienos/biossíntese , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Prostaglandina-E Sintases/genética , Receptores de Leucotrienos/genéticaRESUMO
OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort nâ¯=â¯1196, and Japan cohort nâ¯=â¯495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (Pâ¯=â¯0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, Pâ¯=â¯0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, Pâ¯=â¯0.805), overall survival (HR not estimated, Pâ¯=â¯0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, Pâ¯=â¯0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, Pâ¯=â¯0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, Pâ¯=â¯0.021), but was not associated with overall survival (HR not estimated, Pâ¯=â¯0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9â¯years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.
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Carcinoma Endometrioide/epidemiologia , Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/terapia , Segunda Neoplasia Primária/epidemiologia , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Ovário/fisiologia , Adulto , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia/métodos , Histerectomia/estatística & dados numéricos , Japão/epidemiologia , Gradação de Tumores , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Cysteinyl leukotrienes (cysLTs) are bronchoconstricting lipid mediators that amplify eosinophilic airway inflammation by incompletely understood mechanisms. We recently found that LTC4, the parent cysLT, potently activates platelets in vitro and induces airway eosinophilia in allergen-sensitized and -challenged mice by a platelet- and type 2 cysLT receptor-dependent pathway. We now demonstrate that this pathway requires production of thromboxane A2 and signaling through both hematopoietic and lung tissue-associated T prostanoid (TP) receptors. Intranasal administration of LTC4 to OVA-sensitized C57BL/6 mice markedly increased the numbers of eosinophils in the bronchoalveolar lavage fluid, while simultaneously decreasing the percentages of eosinophils in the blood by a TP receptor-dependent mechanism. LTC4 upregulated the expressions of ICAM-1 and VCAM-1 in an aspirin-sensitive and TP receptor-dependent manner. Both hematopoietic and nonhematopoietic TP receptors were essential for LTC4 to induce eosinophil recruitment. Thus, the autocrine and paracrine functions of thromboxane A2 act downstream of LTC4/type 2 cysLT receptor signaling on platelets to markedly amplify eosinophil recruitment through pulmonary vascular adhesion pathways. The findings suggest applications for TP receptor antagonists in cases of asthma with high levels of cysLT production.
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Aspirina/farmacologia , Plaquetas/imunologia , Cisteína/imunologia , Leucotrieno C4/imunologia , Leucotrienos/imunologia , Ativação Plaquetária/imunologia , Alérgenos/imunologia , Animais , Asma/tratamento farmacológico , Asma/imunologia , Transplante de Medula Óssea , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Eosinofilia/sangue , Eosinofilia/imunologia , Inflamação/imunologia , Molécula 1 de Adesão Intercelular/biossíntese , Antagonistas de Leucotrienos/farmacologia , Leucotrieno C4/farmacologia , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina , Receptores de Prostaglandina/genética , Receptores de Prostaglandina/metabolismo , Tromboxano A2/biossíntese , Tromboxano A2/imunologia , Molécula 1 de Adesão de Célula Vascular/biossínteseRESUMO
Aspirin-exacerbated respiratory disease (AERD), a severe eosinophilic inflammatory disorder of the airways, involves overproduction of cysteinyl leukotrienes (cysLTs), activation of airway mast cells (MCs), and bronchoconstriction in response to nonselective cyclooxygenase inhibitors that deplete homeostatic PGE2. The mechanistic basis for MC activation in this disorder is unknown. We now demonstrate that patients with AERD have markedly increased epithelial expression of the alarmin-like cytokine IL-33 in nasal polyps, as compared with polyps from aspirin-tolerant control subjects. The murine model of AERD, generated by dust mite priming of mice lacking microsomal PGE2 synthase (ptges(-/-) mice), shows a similar upregulation of IL-33 protein in the airway epithelium, along with marked eosinophilic bronchovascular inflammation. Deletion of leukotriene C4 synthase, the terminal enzyme needed to generate cysLTs, eliminates the increased IL-33 content of the ptges(-/-) lungs and sharply reduces pulmonary eosinophilia and basal secretion of MC products. Challenges of dust mite-primed ptges(-/-) mice with lysine aspirin induce IL-33-dependent MC activation and bronchoconstriction. Thus, IL-33 is a component of a cysLT-driven innate type 2 immune response that drives pathogenic MC activation and contributes substantially to AERD pathogenesis.
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Asma Induzida por Aspirina/imunologia , Imunidade Inata , Interleucina-33/imunologia , Leucotrienos/imunologia , Mastócitos/imunologia , Adolescente , Adulto , Idoso , Animais , Asma Induzida por Aspirina/genética , Asma Induzida por Aspirina/patologia , Dinoprostona/genética , Dinoprostona/imunologia , Feminino , Humanos , Interleucina-33/genética , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/imunologia , Leucotrienos/genética , Masculino , Mastócitos/patologia , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Prostaglandina-E Sintases , Eosinofilia Pulmonar/genética , Eosinofilia Pulmonar/imunologia , Eosinofilia Pulmonar/patologiaRESUMO
INTRODUCTION: Ventral hernias can be repaired electively; however, many circumstances require emergency repair. The association between sociodemographic status and rate of emergency repair are unclear and the Social Vulnerability Index may be a useful tool to better understanding this association. The purpose of this study was to investigate the association between Social Vulnerability Index and emergency ventral hernia repair. METHODS: This was a retrospective cohort study using the National Surgical Quality Improvement Program (2012-2018) data for patients at a level 1 trauma center. We included patients who had an open ventral hernia repair. Social Vulnerability Index was based on residential address at the time of surgery. We conducted univariate and bivariate statistics, including χ2 and Mann-Whitney U tests to compare high and low social vulnerability. RESULTS: Our sample had 1,017 patients. Patients who underwent emergency operations were older (P = .025) and had higher Social Vulnerability Index (P = .029). Patients in the high Social Vulnerability Index group were 1.5 times more likely to receive emergency surgery (P = .047). Emergency repair was also associated with increased frequency of nonhome discharge (9% vs 2%, P = .001) and higher mean work relative value unit (15.4 vs 11.9, P < .001). CONCLUSION: Patients requiring emergency ventral hernia repair have significantly higher Social Vulnerability Index than those undergoing elective repair. This vulnerable population also has increased cost associated with the repair and higher rates of nonhome discharge. This work provides a foundation for efforts to reach patients in high Social Vulnerability Index environments at an earlier stage to achieve earlier elective repair.
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OBJECTIVE: The purpose of this study was to determine if an association between Social Vulnerability Index (SVI) and risk-adjusted complications exists in a broad spectrum of surgical patients. SUMMARY BACKGROUND DATA: Growing evidence supports the impact of social circumstances on surgical outcomes. SVI is a neighborhood-based measure accounting for sociodemographic factors putting communities at risk. METHODS: This was a multi-hospital, retrospective cohort study including a sample of patients within one healthcare system (2012-2017). Patient addresses were geocoded to determine census tract of residence and estimate SVI. Patients were grouped into low SVI (score<75) and high SVI (score≥75) cohorts. Perioperative variables and postoperative outcomes were tracked and compared using local ACS-NSQIP data. Multivariable logistic regression was performed to generate risk-adjusted odds ratios of postoperative complications in the high SVI cohort. RESULTS: Overall, 31,224 patients from five hospitals were included. Patients with high SVI were more likely to be racial minorities, have 12/18 medical comorbidities, have high ASA class, be functionally dependent, be treated at academic hospitals, and undergo emergency operations (all p â< â0.05). Patients with high SVI had significantly higher rates of 30-day mortality, overall morbidity, respiratory, cardiac and infectious complications, urinary tract infections, postoperative bleeding, non-home discharge, and unplanned readmissions (all p â< â0.05). After risk-adjustment, only the associations between high SVI and mortality and unplanned readmission became non-significant. CONCLUSIONS: High SVI was associated with multiple adverse outcomes even after risk adjustment for preoperative clinical factors. Targeted preventative interventions to mitigate risk of these specific complications should be considered in this high-risk population.
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Melhoria de Qualidade , Vulnerabilidade Social , Humanos , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Hemorragia Pós-OperatóriaRESUMO
Chagas disease, caused by the Trypanosoma cruzi parasitic protozoan, is a neglected tropical disease (NTD) of significant incidence in Latin America. Transmission to humans and other mammals is mainly via the vector insect from the Reduviidae family, popularly known as the kissing bug. There are other transmission means, such as through congenital transmission, blood transfusions, organ transplantations, and the consumption of contaminated food. For more than 50 years, the disease has been treated with benznidazole and nifurtimox, which are only effective during the acute phase of the disease. In addition to their low efficacy in the chronic phase, they cause many adverse effects and are somewhat selective. The use of nanocarriers has received significant attention due to their ability to encapsulate and release therapeutic agents in a controlled manner. Generally, their diameter ranges from 100 to 300 nanometers. The objective of this scoping review was to perform a search of the literature for the use of nanocarriers as an alternative for improving the treatment of Chagas disease and to suggest future research. Bibliographic searches were carried out in the Web of Science and PubMed scientific databases from January 2012 to May 2023, using the "Chagas disease and Trypanosoma cruzi and nanoparticles" keywords, seeking to gather the largest number of articles, which were evaluated using the inclusion and exclusion criteria. After analyzing the papers, the results showed that nanocarriers offer physiological stability and safety for the transport and controlled release of drugs. They can increase solubility and selectivity against the parasite. The in vitro assays showed that the trypanocidal activity of the drug was not impaired after encapsulation. In the in vivo assays, parasitemia reduction and high survival and cure rates in animals were obtained during both phases of the disease using lower doses when compared to the standard treatment. The scoping review showed that nanocarriers are a promising alternative for the treatment of Chagas disease.
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Biodiversity is a hallmark of the Asteraceae family. Several species are known for their pharmacological potential. The search for new substances has permeated the chemistry of natural products for years. However, the development of a final product is still a challenge. Plant extracts have physicochemical characteristics that sometimes hinder administration, requiring a formulation. In this context, nanotechnology emerges as a tool to improve the pharmacokinetic parameters of several pharmacologically active substances. Nanoemulsions, liposomes, and nanoparticles are used to carry the active ingredients and thus improve therapeutic action, especially for substances with solubility and absorption problems. This paper aimed at compiling all the studies that used nanotechnology to develop formulations from species of the Asteraceae family from 2010 to 2021 in a literature review. The search showed that nanoemulsions are the most developed formulation associated with essential oils. The use of nanotechnology promoted an improvement in the pharmacokinetic parameters of active substances.
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Asteraceae , Nanopartículas , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Nanopartículas/química , Nanotecnologia , BiodiversidadeRESUMO
This article is a report from an experience about a work developed by Farmácia Universitária at UFRJ (FU-UFRJ) during the nCov-19 pandemic period. The aim of this work was to describe its contribution in the production of antiseptic supplies used to prevent contagion by the new coronavirus. The work routine at the pharmacy has been changed to allow the implementation of local workflow during the pandemic, and to adapt the protection rules to meet the safety measures. FU-UFRJ started to manipulate two antiseptic formulations: 70% ethyl alcohol and gel alcohol, which are included in the National Form, manufacturing around 100 L of these formulations, weekly, to donate to different health units. The experience enabled the adaptation to emergency health standards, planning and meaningful guidance to pharmacists and technicians to attend clinics at university hospitals, vaccination center and UFRJ city hall, in order to facilitate the access to adequate hand hygiene to the population.
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COVID-19/prevenção & controle , Higienizadores de Mão/química , Farmacêuticos/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Anti-Infecciosos Locais/química , Anti-Infecciosos Locais/provisão & distribuição , Composição de Medicamentos/métodos , Etanol/química , Géis , Desinfecção das Mãos/métodos , Higiene das Mãos/métodos , Higienizadores de Mão/provisão & distribuição , Humanos , Fluxo de TrabalhoRESUMO
Cysteinyl leukotrienes (cysLTs) facilitate eosinophilic mucosal type 2 immunopathology, especially in aspirin-exacerbated respiratory disease (AERD), by incompletely understood mechanisms. We now demonstrate that platelets, activated through the type 2 cysLT receptor (CysLT2R), cause IL-33-dependent immunopathology through a rapidly inducible mechanism requiring the actions of high mobility box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE). Leukotriene C4 (LTC4) induces surface HMGB1 expression by mouse platelets in a CysLT2R-dependent manner. Blockade of RAGE and neutralization of HMGB1 prevent LTC4-induced platelet activation. Challenges of AERD-like Ptges-/- mice with inhaled lysine aspirin (Lys-ASA) elicit LTC4 synthesis and cause rapid intrapulmonary recruitment of platelets with adherent granulocytes, along with platelet- and CysLT2R-mediated increases in lung IL-33, IL-5, IL-13, and bronchoalveolar lavage fluid HMGB1. The intrapulmonary administration of exogenous LTC4 mimics these effects. Platelet depletion, HMGB1 neutralization, and pharmacologic blockade of RAGE eliminate all manifestations of Lys-ASA challenges, including increase in IL-33, mast cell activation, and changes in airway resistance. Thus, CysLT2R signaling on platelets prominently utilizes RAGE/HMGB1 as a link to downstream type 2 respiratory immunopathology and IL-33-dependent mast cell activation typical of AERD. Antagonists of HMGB1 or RAGE may be useful to treat AERD and other disorders associated with type 2 immunopathology.
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Asma Induzida por Aspirina/imunologia , Plaquetas/imunologia , Proteína HMGB1/metabolismo , Pulmão/imunologia , Mastócitos/imunologia , Receptores de Leucotrienos/metabolismo , Animais , Células Cultivadas , Humanos , Interleucina-33/metabolismo , Leucotrieno C4/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Prostaglandina-E Sintases/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptores de Leucotrienos/genética , Transdução de SinaisRESUMO
Abstract The University Pharmacy Program (FU), from the Federal University of Rio de Janeiro (UFRJ), was created based on the need to offer a curricular internship to students of the Undergraduate Course at the Faculty of Pharmacy. Currently, it is responsible for the care of about 200 patients/day, offering vacancies for curricular internships for students in the Pharmacy course, it has become a reference in the manipulation of many drugs neglected by the pharmaceutical industry and provides access to medicines for low-income users playing an important social function. Research is one of the pillars of FU-UFRJ and several master and doctoral students use the FU research laboratory in the development of dissertations and theses. As of 2002, the Pharmaceutical Care extension projects started to guarantee a rational and safe pharmacotherapy for the medicine users. From its beginning in 1982 until the current quarantine due to the COVID-19 pandemic, FU-UFRJ has been adapting to the new reality and continued to provide patient care services, maintaining its teaching, research, and extension activities. The FU plays a relevant social role in guaranteeing the low-income population access to special and neglected medicines, and to pharmaceutical and education services in health promotion.
Assuntos
Farmácia/classificação , Educação em Farmácia , COVID-19/classificação , Pacientes/classificação , Assistência Farmacêutica/história , Ensino/ética , Preparações Farmacêuticas/provisão & distribuição , Assistência ao Paciente/éticaRESUMO
Synthesis of asparaginyl-tRNA (Asn-tRNA(Asn)) in bacteria can be formed either by directly ligating Asn to tRNA(Asn) using an asparaginyl-tRNA synthetase (AsnRS) or by synthesizing Asn on the tRNA. In the latter two-step indirect pathway, a non-discriminating aspartyl-tRNA synthetase (ND-AspRS) attaches Asp to tRNA(Asn) and the amidotransferase GatCAB transamidates the Asp to Asn on the tRNA. GatCAB can be similarly used for Gln-tRNA(Gln) formation. Most bacteria are predicted to use only one route for Asn-tRNA(Asn) formation. Given that Bacillus halodurans and Bacillus subtilis encode AsnRS for Asn-tRNA(Asn) formation and Asn synthetases to synthesize Asn and GatCAB for Gln-tRNA(Gln) synthesis, their AspRS enzymes were thought to be specific for tRNA(Asp). However, we demonstrate that the AspRSs are non-discriminating and can be used with GatCAB to synthesize Asn. The results explain why B. subtilis with its Asn synthetase genes knocked out is still an Asn prototroph. Our phylogenetic analysis suggests that this may be common among Firmicutes and 30% of all bacteria. In addition, the phylogeny revealed that discrimination toward tRNA(Asp) by AspRS has evolved independently multiple times. The retention of the indirect pathway in B. subtilis and B. halodurans likely reflects the ancient link between Asn biosynthesis and its use in translation that enabled Asn to be added to the genetic code.
Assuntos
Asparagina/metabolismo , Aspartato-tRNA Ligase/metabolismo , Bacillus/enzimologia , Aminoacil-RNA de Transferência/metabolismo , RNA de Transferência de Asparagina/metabolismo , Bacillus/metabolismo , Bacillus subtilis/enzimologia , Bacillus subtilis/metabolismo , Especificidade por SubstratoRESUMO
The predatory bacterium Bdellovibrio bacteriovorus preys on other Gram-negative bacteria and was predicted to be an asparagine auxotroph. However, despite encoding asparaginyl-tRNA synthetase and glutaminyl-tRNA synthetase, B. bacteriovorus also contains the amidotransferase GatCAB. Deinococcus radiodurans, and Thermus thermophilus also encode both of these aminoacyl-tRNA synthetases with GatCAB. Both also code for a second aspartyl-tRNA synthetase and use the additional aspartyl-tRNA synthetase with GatCAB to synthesize asparagine on tRNAAsn. Unlike those two bacteria, B. bacteriovorus encodes only one aspartyl-tRNA synthetase. Here we demonstrate the lone B. bacteriovorus aspartyl-tRNA synthetase catalyzes aspartyl-tRNAAsn formation that GatCAB can then amidate to asparaginyl-tRNAAsn. This non-discriminating aspartyl-tRNA synthetase with GatCAB thus provides B. bacteriovorus a second route for Asn-tRNAAsn formation with the asparagine synthesized in a tRNA-dependent manner. Thus, in contrast to a previous prediction, B. bacteriovorus codes for a biosynthetic route for asparagine. Analysis of bacterial genomes suggests a significant number of other bacteria may also code for both routes for Asn-tRNAAsn synthesis with only a limited number encoding a second aspartyl-tRNA synthetase.