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1.
South Med J ; 117(2): 88-92, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307504

RESUMO

OBJECTIVES: Inflammatory bowel disease (IBD) encompasses Crohn's disease (CD) and ulcerative colitis (UC). These two chronic inflammatory conditions can differ in severity, presentation, and anatomical localization, and can greatly affect quality of life if not managed properly. Given the many healthcare challenges during the coronavirus disease 2019 pandemic, we studied the effects of the pandemic and corresponding changes to medical resources on surgical outcomes for patients with IBD. METHODS: Deidentified data from patients who underwent a colectomy for CD or UC were collected from the National Surgical Quality Improvement Program database of the American College of Surgeons. We analyzed clinical factors and surgical outcomes between 2019 and 2020. RESULTS: Patients with IBD were more likely to have lost >10% of their body mass before the operation in 2020. Operations for patients with UC were significantly shorter in the first year of the pandemic. Patients with CD were less likely to have a urinary tract infection or sepsis postoperatively in 2020, whereas patients with UC were more likely to require a repeat operation. Interestingly, both patient populations were less likely to undergo an emergency operation in 2020 than in 2019. CONCLUSIONS: Colectomy outcomes for patients with CD in 2020 were similar or improved in comparison with those seen in 2019, whereas colectomies for UC saw a statistically but not clinically significant increase in the rate of repeat operations. Overall, these patients seem to have been well managed despite the coronavirus disease 2019 pandemic-induced strain on the healthcare system.


Assuntos
COVID-19 , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Pandemias , Qualidade de Vida , COVID-19/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Colite Ulcerativa/cirurgia , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , Colectomia
2.
South Med J ; 117(5): 284-288, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701852

RESUMO

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 has been described as eliciting a powerful immune response. The association of coronavirus disease 2019 (COVID-19) infection with diseases requiring emergent or urgent colectomies may exacerbate the risk of surgical complications. We investigated the effect of preoperative COVID-19 infection on the clinical outcomes of patients who underwent a nonelective colectomy in 2021. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program Targeted Colectomy database for all of the patients who underwent a colectomy in 2021 and filtered for patients classified as "Urgent" or "Emergent." Two groups were created based on preoperative COVID-19 status: COVID+ (n = 242) and COVID- cohorts (n = 11,049). Several clinical variables were compared. RESULTS: Before filtering for urgent/emergent operations, a large percentage of COVID+ patients were found to have undergone an urgent or emergency colectomy (68.36% vs 25.05%). Preoperatively, these patients were more likely to be taking steroids (21.49% vs 12.41%) or have a bleeding issue requiring a transfusion (19.42% vs 11.00%). A larger percentage of infected patients returned to the operating room (14.05% vs 8.13%) and had a hospital stay >30 days (18.18% vs 5.35%). COVID-19 infection was associated with a higher rate of mortality (14.05% vs 8.08%) but did not independently predict it (odds ratio 1.25, P = 0.233), with all P ≤ 0.001. CONCLUSIONS: Urgent or emergent colectomy patients who were COVID-19+ preoperatively were more likely to present with comorbidities, which, along with the recent viral infection, contributed to markedly worse clinical outcomes, including an increased rate of mortality.


Assuntos
COVID-19 , Colectomia , Complicações Pós-Operatórias , Humanos , COVID-19/epidemiologia , Colectomia/métodos , Colectomia/estatística & dados numéricos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , SARS-CoV-2 , Emergências , Período Pré-Operatório , Estados Unidos/epidemiologia , Estudos Retrospectivos , Tempo de Internação/estatística & dados numéricos
3.
J Trauma Nurs ; 31(3): 123-128, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742718

RESUMO

BACKGROUND: Studies have indicated that patients infected with the SARS-CoV-2 virus fare worse clinically after a traumatic injury, especially those who are older and have other comorbidities. OBJECTIVE: This study aims to understand the effects of Corona Virus Disease 19 (COVID-19) diagnosis on patients undergoing surgery for hip fractures. METHODS: This is a retrospective review of the 2021 American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Targeted Hip Fracture database for patients who underwent surgery. Two cohorts were formed based on patients' preoperative COVID-19 status, as tested within 14 days prior to the operation. Several clinical factors were compared. RESULTS: The COVID-positive cohort consisted of 184 patients, all of whom had a laboratory-confirmed or clinically suspected SARS-CoV-2 infection, while the COVID-negative cohort consisted of 12,211 patients with no infection. A lower proportion of COVID-positive patients had an emergent operation compared to the COVID-negative cohort (58.70% vs. 73.09%, p < .001). Preoperatively, the COVID-positive cohort showed higher rates of coagulopathy/bleeding disorders (22.83% vs. 14.12%), congestive heart failure (16.30% vs. 9.84%), diabetes mellitus (28.26% vs. 19.24%), and dementia (42.39% vs. 28.07%), with p ≤ .005 for all. Postoperatively, a higher proportion of COVID-positive patients died (9.78% vs. 5.40%) or had pneumonia (8.70% vs. 3.65%), hospital readmission within 30 days (10.87% vs. 6.76%), and pressure sores (8.15% vs. 4.55%), with p ≤ .033 for all. CONCLUSION: The diagnosis of COVID-19 in hip fracture patients was associated with higher rates of postoperative complications, including mortality, when compared to COVID-negative patients, indicating the severity of the viral infection.


Assuntos
COVID-19 , Fraturas do Quadril , Melhoria de Qualidade , Humanos , COVID-19/epidemiologia , Feminino , Masculino , Fraturas do Quadril/cirurgia , Fraturas do Quadril/mortalidade , Estudos Retrospectivos , Idoso , Idoso de 80 Anos ou mais , Estados Unidos/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Pessoa de Meia-Idade , SARS-CoV-2 , Estudos de Coortes
4.
J Biol Chem ; 298(5): 101888, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35367412

RESUMO

Adenosine A2A receptor (A2AR)-dependent signaling in macrophages plays a key role in the regulation of inflammation. However, the processes regulating A2AR targeting to the cell surface and degradation in macrophages are incompletely understood. For example, the C-terminal domain of the A2AR and proteins interacting with it are known to regulate receptor recycling, although it is unclear what role potential A2AR-interacting partners have in macrophages. Here, we aimed to identify A2AR-interacting partners in macrophages that may effect receptor trafficking and activity. To this end, we performed a yeast two-hybrid screen using the C-terminal tail of A2AR as the "bait" and a macrophage expression library as the "prey." We found that the lysosomal protease cathepsin D (CtsD) was a robust hit. The A2AR-CtsD interaction was validated in vitro and in cellular models, including RAW 264.7 and mouse peritoneal macrophage (IPMΦ) cells. We also demonstrated that the A2AR is a substrate of CtsD and that the blockade of CtsD activity increases the density and cell surface targeting of A2AR in macrophages. Conversely, we demonstrate that A2AR activation prompts the maturation and enzymatic activity of CtsD in macrophages. In summary, we conclude that CtsD is a novel A2AR-interacting partner and thus describe molecular and functional interplay that may be crucial for adenosine-mediated macrophage regulation in inflammatory processes.


Assuntos
Adenosina , Catepsina D/metabolismo , Receptor A2A de Adenosina , Adenosina/metabolismo , Animais , Proteínas de Transporte/metabolismo , Catepsina D/genética , Macrófagos/metabolismo , Camundongos , Receptor A2A de Adenosina/genética , Receptor A2A de Adenosina/metabolismo , Transdução de Sinais
5.
Respir Res ; 24(1): 186, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37438813

RESUMO

BACKGROUND: Trauma and a subsequent hemorrhagic shock (T/HS) result in insufficient oxygen delivery to tissues and multiple organ failure. Extracellular adenosine, which is a product of the extracellular degradation of adenosine 5' triphosphate (ATP) by the membrane-embedded enzymes CD39 and CD73, is organ protective, as it participates in signaling pathways, which promote cell survival and suppress inflammation through adenosine receptors including the A2BR. The aim of this study was to evaluate the role of CD39 and CD73 delivering adenosine to A2BRs in regulating the host's response to T/HS. METHODS: T/HS shock was induced by blood withdrawal from the femoral artery in wild-type, global knockout (CD39, CD73, A2BR) and conditional knockout (intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl) mice. At 3 three hours after resuscitation, blood and tissue samples were collected to analyze organ injury. RESULTS: T/HS upregulated the expression of CD39, CD73, and the A2BR in organs. ATP and adenosine levels increased after T/HS in bronchoalveolar lavage fluid. CD39, CD73, and A2BR mimics/agonists alleviated lung and liver injury. Antagonists or the CD39, CD73, and A2BR knockout (KO) exacerbated lung injury, inflammatory cytokines, and chemokines as well as macrophage and neutrophil infiltration and accumulation in the lung. Agonists reduced the levels of the liver enzymes aspartate transferase and alanine transaminase in the blood, whereas antagonist administration or CD39, CD73, and A2BR KO enhanced enzyme levels. In addition, intestinal epithelial cell-specific deficient VillinCre-A2BRfl/fl mice showed increased intestinal injury compared to their wild-type VillinCre controls. CONCLUSION: In conclusion, the CD39-CD73-A2BR axis protects against T/HS-induced multiple organ failure.


Assuntos
Adenosina , Insuficiência de Múltiplos Órgãos , Animais , Camundongos , Trifosfato de Adenosina , Transdução de Sinais , Líquido da Lavagem Broncoalveolar
6.
Inorg Chem ; 62(16): 6397-6410, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37039430

RESUMO

The properties of transition-metal complexes and their chemical dynamics can be effectively modified with ligand substitutions, and theory can be a great aid to such molecular engineering. In this paper, we first theoretically explored how substitution with a Cl atom at different positions of the terpyridine ligand affects the electronic structure of the [Fe(terpy)2]2+ complex. We found that besides the substitution at position 4', the next most promising candidate to cause substantial electronic effects is that where the side pyridine ring is substituted at position 5 (ß). Therefore, next, we examined in detail the Fe(II) complexes of the 5-chloro and 5,5″-dichloro derivatives of terpy, theoretically and experimentally, to reveal how these substitutions modify the ground state properties and the lifetime of the excited quintet state in such complexes. In addition, we extend the investigation to the complexes of the analogously substituted derivatives of 4'-SMe-terpy. The substitution at position(s) 5 (and 5″) with Cl lowers the energy of the quintet state and increases its lifetime; the results on the 4'-SMe-substituted complexes show similar changes with these two substitutions, verifying that these effects are more or less additive. This study contributes to the enhancement of our molecular engineering toolset for modifying the potential energy landscape of similar complexes.

7.
Int Urogynecol J ; 34(4): 921-927, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35841400

RESUMO

INTRODUCTION AND HYPOTHESIS: Loss of anatomical support for the pelvic organs results in pelvic organ prolapse (POP). We hypothesized that daily self-management of a cube pessary might be a safe, feasible long-term treatment in women with symptomatic POP. METHODS: A cohort of 214 symptomatic POP patients (stage 2+) were enrolled prospectively (January to December 2015). Each patient was size-fitted with a space-filling cube pessary and completed a questionnaire online or by phone ≥5 years after her initial fitting. Change in quality of life (QoL) was measured with the Patient Global Impression of Improvement (PGI-I). RESULTS: Of 185 women included in our analyses, 174 (94%) were continuing to use their pessary 4 weeks post-insertion. Among those, 143 (82.2%) used the pessary successfully for ≥5 years. A large majority of these patients (88.8% [127 out of 143]) described their condition as much or very much improved compared with their pretreatment status (PGI-I). Adverse secondary effects (ASEs) were infrequent [15.4% (22 out of 143)]; when they did occur, they were mild, including smelly vaginal discharge (15 out of 22) and slight vaginal bleeding caused by the fitting procedure (6 out of 22). CONCLUSIONS: Daily self-management of cube pessaries was found to be a safe and effective treatment for improving POP-related symptoms and QoL in the long term.


Assuntos
Prolapso de Órgão Pélvico , Autogestão , Humanos , Feminino , Pessários/efeitos adversos , Seguimentos , Qualidade de Vida , Prolapso de Órgão Pélvico/etiologia , Resultado do Tratamento
8.
Int Urogynecol J ; 34(6): 1187-1194, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35972523

RESUMO

INTRODUCTION AND HYPOTHESIS: The aims of the study were the translation, cultural adaptation, and validation of self-administered Australian Pelvic Floor Questionnaire (APFQ) on a Hungarian population. METHODS: The validation was performed in 294 women over 18 who agreed to answer the Hungarian version of the APFQ. The validation of the questionnaire included evaluation of content/face validity, internal consistency, construct validity, test-retest reproducibility, discriminant validity and convergent validity. RESULTS: Acceptable and good internal consistency was observed in all four dimensions [McDonald's ω (95% confidence interval) coefficients were > 0.7 for each dimension: bladder 0.888, bowel 0.790, prolapse 0.895 and sexual function 0.738]. Test-retest analyses revealed high reproducibility with intraclass correlation coefficients (bladder 0.83, bowel 0.92, prolapse 0.96 and sexual function 0.87). Prolapse symptom score correlated significantly with Pelvic Organ Prolapse Quantification (POP-Q), and bladder score correlated significantly with the results of the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ UI SF) (convergent validity). Scores distinguished between patients with pelvic floor disorders and controls (high discriminant validity). CONCLUSIONS: Hungarian version of the self-administered APFQ is a reliable and valid instrument for evaluating symptom severity and impact of pelvic floor dysfunction on the quality of life of Hungarian women.


Assuntos
Distúrbios do Assoalho Pélvico , Incontinência Urinária , Feminino , Humanos , Austrália , Hungria , Diafragma da Pelve , Distúrbios do Assoalho Pélvico/diagnóstico , Prolapso de Órgão Pélvico/diagnóstico , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Incontinência Urinária/diagnóstico , Tradução
9.
South Med J ; 116(10): 828-832, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37788818

RESUMO

OBJECTIVES: The literature suggests that there are ongoing racial disparities in healthcare outcomes between patients in White and non-White populations. As such, we examined the outcomes of patients who underwent an emergency colectomy for diverticulitis. METHODS: We identified 4841 White and 590 non-White patients, which include Black/African American and Asian patients, using the 2016-2019 American College of Surgeons National Surgical Quality Improvement Program databases. We compared Black/African American and Asian patients with White patients for differences in surgical outcomes. RESULTS: Non-White patients had more comorbidities than White patients (P < 0.05). These patients underwent longer operations, developed more postoperative complications, and were more likely to have lengths of stay >30 days. When controlling for all of the covariates in multivariate logistic regression models, White race was independently associated with a 22.14% lower odds of a hospital stay >30 days compared with non-White patients (P = 0.001). CONCLUSIONS: In this study, non-White patients developed more complications than did White patients and had longer hospitalizations. These disparities represent a more complex societal issue that cannot be managed perioperatively alone.


Assuntos
Colectomia , Diverticulite , Grupos Raciais , Humanos , Negro ou Afro-Americano , Diverticulite/cirurgia , Disparidades em Assistência à Saúde , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Brancos , Asiático , Disparidades nos Níveis de Saúde
10.
J Trauma Nurs ; 30(6): 334-339, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37937874

RESUMO

BACKGROUND: Little is known about the distribution and outcomes of hip fractures in pediatric patients during the COVID-19 pandemic. OBJECTIVE: To study the clinical outcomes of both pediatric and adult patients who underwent hip fracture surgeries and determine the effects of changes surrounding the COVID-19 pandemic. METHODS: Both pediatric and adult surgical hip fracture cases were analyzed from the pandemic year (2020) and the control year (2019) using the American College of Surgeons National Surgical Quality Improvement Program database. RESULTS: Between the prepandemic (control) and pandemic years, a total of 2,438 pediatric and 28,180 adult cases were compared. Pediatric patients had similar perioperative characteristics and outcomes between the two years. Significantly fewer hip fractures were reported among adults during the pandemic (p < .001). Preoperatively, more adult patients had ventilator dependence (p = .020), transfusions (p = .029), and systemic inflammatory response syndrome (p < .001) in 2020. Adult operations were more likely to be emergent in 2020 (p < .001) and adults had more severe disease states. Length of stay (p < .001) and the time from operation to discharge (p < .001) were significantly longer for the adult cohort in 2020. Mortality was also higher for adults during the first year of the pandemic (p = .003), and superficial surgical site infections became more common (p = .036). CONCLUSION: Pediatric hip fracture patients had similar clinical outcomes between 2019 and 2020. Adults with hip fractures presented in more serious clinical conditions, which resulted in higher mortality in 2020. Further studies could better clarify the reasons as to why adult hip fracture patients had markedly worse clinical course during the COVID year than pediatric patients.


Assuntos
COVID-19 , Fraturas do Quadril , Humanos , Adulto , Criança , Pandemias , Estudos Retrospectivos , Tempo de Internação , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia
11.
Eur J Orthop Surg Traumatol ; 33(1): 177-183, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34855003

RESUMO

INTRODUCTION: In trauma care, pelvic fractures contribute to morbidity and mortality. Since men and women have different pelvic structures and hormonal milieu, we studied if these gender differences affect clinical outcomes after pelvic fractures. METHODS: Using the 2016 American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) database, we stratified 24,425 patients with pelvic fractures by gender. Male and female patients were analyzed for differences in comorbidities,  mechanism of injury, complications, and other clinical parameters. RESULTS: Female patients were older (p < 0.001) and had more comorbidities (p < 0.001), such as bleeding disorder, congestive heart failure, chronic obstructive pulmonary disorder, dementia, chronic renal failure, diabetes mellitus, and hypertension. Although female patients were sicker before sustaining pelvic fractures, male patients had higher rates of post-trauma complications (p < 0.001), such as acute kidney injury, deep vein thrombosis, unplanned admission to the intensive care unit (ICU), and unplanned return to the operating room (OR). Multivariate logistic regression further supports this as male gender was independently associated with a 26.1% higher risk of developing at least one complication (p < 0.001), despite having a higher average Injury Severity Score (ISS) (21.91 ± 0.09 versus 20.71 ± 0.11, p < 0.001). Interestingly, male patients also had a longer hospital length of stay than female patients (13.36 ± 0.12 days versus 11.8 2± 0.14 days, p < 0.001). CONCLUSION: Even though female patients were older and had more pre-existing comorbidities, male patients developed more complications and had longer hospital stays. Trial registration number Not a clinical trial.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Humanos , Masculino , Feminino , Estudos Retrospectivos , Fraturas Ósseas/cirurgia , Ossos Pélvicos/lesões , Hospitalização , Comorbidade , Tempo de Internação , Escala de Gravidade do Ferimento
12.
J Synchrotron Radiat ; 29(Pt 5): 1216-1222, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36073880

RESUMO

The present work demonstrates the performance of a von Hámos high-energy-resolution X-ray spectrometer based on a non-conventional conical Si single-crystal analyzer. The analyzer is tested with different primary and secondary X-ray sources as well as a hard X-ray sensitive CCD camera. The spectrometer setup is also characterized with ray-tracing simulations. Both experimental and simulated results affirm that the conical spectrometer can efficiently detect and resolve the two pairs of two elements (Ni and Cu) Kα X-ray emission spectroscopy (XES) peaks simultaneously, requiring a less than 2 cm-wide array on a single position-sensitive detector. The possible applications of this simple yet broad-energy-spectrum crystal spectrometer range from quickly adapting it as another probe for complex experiments at synchrotron beamlines to analyzing X-ray emission from plasma generated by ultrashort laser pulses at modern laser facilities.

13.
Am J Physiol Regul Integr Comp Physiol ; 323(5): R763-R775, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36189990

RESUMO

Migration of monocytes-macrophages plays an important role in phagocytosis of pathogens and cellular debris in a variety of pathophysiological conditions. Although epithelial Na+ channels (ENaCs) are required for normal migratory responses in other cell types, their role in macrophage migration signaling is unknown. To address this possibility, we determined whether ENaC message is present in several peripheral blood monocyte cell populations and tissue-resident macrophages in healthy humans using the Human Protein Atlas database (www.proteinatlas.org) and the mouse monocyte cell line RAW 264.7 using RT-PCR. We then determined that selective ENaC inhibition with amiloride inhibited chemotactic migration (∼50%), but not phagocytosis, of the mouse monocyte-macrophage cell line RAW 264.7. Furthermore, we generated a cell line stably expressing an NH2-terminal truncated αENaC to interrupt normal channel trafficking and found it suppressed migration. Prolonged exposure (48 h) of RAW 264.7 cells to proinflammatory cytokines interferon γ (IFNγ) and/or tumor necrosis factor α (TNFα) inhibited RAW 264.7 migration and abolished the amiloride (1 µM)-sensitive component of migration, a finding consistent with ENaC downregulation. To determine if proinflammatory cytokines regulate αENaC protein expression, cells were exposed to proinflammatory cytokines IFNγ (10 ng/mL, last 48 h) and TNFα (10 ng/mL, last 24 h). By Western blot analysis, we found whole cell αENaC protein is reduced ≥50%. Immunofluorescence demonstrated heterogeneous αENaC inhibition. Finally, we found that overnight exposure to amiloride stimulated morphological changes and increased polarization marker expression. Our findings suggest that ENaC may be a critical molecule in macrophage migration and polarization.


Assuntos
Canais Epiteliais de Sódio , Fator de Necrose Tumoral alfa , Camundongos , Animais , Humanos , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Amilorida/farmacologia , Interferon gama/farmacologia , Interferon gama/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo
14.
FASEB J ; 35(11): e21935, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34591327

RESUMO

Inosine monophosphate (IMP) is the intracellular precursor for both adenosine monophosphate and guanosine monophosphate and thus plays a central role in intracellular purine metabolism. IMP can also serve as an extracellular signaling molecule, and can regulate diverse processes such as taste sensation, neutrophil function, and ischemia-reperfusion injury. How IMP regulates inflammation induced by bacterial products or bacteria is unknown. In this study, we demonstrate that IMP suppressed tumor necrosis factor (TNF)-α production and augmented IL-10 production in endotoxemic mice. IMP exerted its effects through metabolism to inosine, as IMP only suppressed TNF-α following its CD73-mediated degradation to inosine in lipopolysaccharide-activated macrophages. Studies with gene targeted mice and pharmacological antagonism indicated that A2A , A2B, and A3 adenosine receptors are not required for the inosine suppression of TNF-α production. The inosine suppression of TNF-α production did not require its metabolism to hypoxanthine through purine nucleoside phosphorylase or its uptake into cells through concentrative nucleoside transporters indicating a role for alternative metabolic/uptake pathways. Inosine augmented IL-ß production by macrophages in which inflammasome was activated by lipopolysaccharide and ATP. In contrast to its effects in endotoxemia, IMP failed to affect the inflammatory response to abdominal sepsis and pneumonia. We conclude that extracellular IMP and inosine differentially regulate the inflammatory response.


Assuntos
Endotoxemia/metabolismo , Inosina Monofosfato/metabolismo , Inosina/metabolismo , Pneumonia Pneumocócica/metabolismo , Streptococcus pneumoniae , Antagonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A3 de Adenosina/farmacologia , Animais , Modelos Animais de Doenças , Interleucina-10/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia Pneumocócica/microbiologia , Quinazolinas/farmacologia , Receptor A2A de Adenosina/metabolismo , Receptor A2B de Adenosina/metabolismo , Receptor A3 de Adenosina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triazóis/farmacologia , Fator de Necrose Tumoral alfa/biossíntese
15.
Purinergic Signal ; 18(3): 345-358, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35838900

RESUMO

Extracellular adenosine is a biologically active signaling molecule that accumulates at sites of metabolic stress in sepsis. Extracellular adenosine has potent immunosuppressive effects by binding to and activating G protein-coupled A2A adenosine receptors (A2AARs) on the surface of neutrophils. A2AAR signaling reproduces many of the phenotypic changes in neutrophils that are characteristic of sepsis, including decreased degranulation, impaired chemotaxis, and diminished ability to ingest and kill bacteria. We hypothesized that A2AARs also suppress neutrophil aging, which precedes cell death, and N1 to N2 polarization. Using human neutrophils isolated from healthy subjects, we demonstrate that A2AAR stimulation slows neutrophil aging, suppresses cell death, and promotes the polarization of neutrophils from an N1 to N2 phenotype. Using genetic knockout and pharmacological blockade, we confirmed that A2AARs decrease neutrophil aging in murine sepsis induced by cecal ligation and puncture. A2AARs expression is increased in neutrophils from septic patients compared to healthy subject but A2AAR expression fails to correlate with aging or N1/N2 polarization. Our data reveals that A2AARs regulate neutrophil aging in healthy but not septic neutrophils.


Assuntos
Neutrófilos , Sepse , Adenosina , Envelhecimento , Animais , Humanos , Camundongos , Camundongos Knockout , Neutrófilos/metabolismo , Fenótipo , Receptor A2A de Adenosina/metabolismo
16.
J Chem Phys ; 157(22): 224201, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36546808

RESUMO

We present a sub-picosecond resolved investigation of the structural solvent reorganization and geminate recombination dynamics following 400 nm two-photon excitation and photodetachment of a valence p electron from the aqueous atomic solute, I-(aq). The measurements utilized time-resolved X-ray Absorption Near Edge Structure (TR-XANES) spectroscopy and X-ray Solution Scattering (TR-XSS) at the Linac Coherent Light Source x-ray free electron laser in a laser pump/x-ray probe experiment. The XANES measurements around the L1-edge of the generated nascent iodine atoms (I0) yield an average electron ejection distance from the iodine parent of 7.4 ± 1.5 Å with an excitation yield of about 1/3 of the 0.1M NaI aqueous solution. The kinetic traces of the XANES measurement are in agreement with a purely diffusion-driven geminate iodine-electron recombination model without the need for a long-lived (I0:e-) contact pair. Nonequilibrium classical molecular dynamics simulations indicate a delayed response of the caging H2O solvent shell and this is supported by the structural analysis of the XSS data: We identify a two-step process exhibiting a 0.1 ps delayed solvent shell reorganization time within the tight H-bond network and a 0.3 ps time constant for the mean iodine-oxygen distance changes. The results indicate that most of the reorganization can be explained classically by a transition from a hydrophilic cavity with a well-ordered first solvation shell (hydrogens pointing toward I-) to an expanded cavity around I0 with a more random orientation of the H2O molecules in a broadened first solvation shell.

17.
South Med J ; 115(5): 304-309, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35504610

RESUMO

OBJECTIVES: Thyroidectomies involve meticulous dissection of a highly vascularized organ and complications may develop, such as hematoma, hypocalcemia, and even hypoparathyroidism. Because some of these complications may be fatal, we sought to identify the differences in postthyroidectomy outcomes when the use of a vessel sealant device (VSD) such, as LigaSure or Harmonic scalpel, is compared with more traditional techniques, such as ligatures and clips. METHODS: Using the 2016 American College of Surgeons National Surgical Quality Improvement Program Targeted Thyroidectomy database, we compared patients who underwent a thyroidectomy using a VSD with patients without a VSD for differences in postoperative complications. RESULTS: A total of 5146 cases were identified and 3452 of those cases used a VSD, whose use was associated with significantly lower rates of hematoma, deep vein thrombosis, and hypocalcemia before discharge, as well as a shorter length of stay and longer operation time. Multivariate logistic regression showed that VSD was associated with 32.27% and 39.15% lower odds of hypocalcemia and hematoma, respectively. VSDs also were used more frequently in cases that had multinodular, severe, or substernal goiter or Graves disease as the primary indication for surgery and in patients with a higher body mass index. There was no significant difference in the incidence of recurrent laryngeal nerve injury between the two groups. CONCLUSIONS: Analysis of the American College of Surgeons National Surgical Quality Improvement Program data indicates that VSDs are associated with a lower risk of complications, such as hypocalcemia, hematoma, and deep vein thrombosis, suggesting that VSDs may be a more effective method of hemostasis than traditional techniques.


Assuntos
Hipocalcemia , Trombose Venosa , Hematoma/complicações , Hematoma/epidemiologia , Humanos , Hipocalcemia/complicações , Hipocalcemia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Instrumentos Cirúrgicos/efeitos adversos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Trombose Venosa/complicações
18.
South Med J ; 115(12): 887-892, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36455896

RESUMO

OBJECTIVES: Robot-assisted laparoscopic surgeries (RLSs) have become increasingly common in the past decade alongside conventional laparoscopic surgeries (CLSs). In general, RLSs have been reported to be superior to CLSs; therefore, we compared both methods among patients undergoing an elective colectomy for differences in perioperative factors and postoperative complications. METHODS: A retrospective analysis was conducted using the 2019 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. We stratified 5879 patients into two cohorts according to their preoperative diagnosis of either colon cancer or chronic diverticulitis. Patients within each group were further stratified by operative approach. RESULTS: Of the 5879 patients, 3210 colon cancer and 2669 chronic diverticulitis patients underwent an elective colectomy. There were no differences in length of stay and time from operation to discharge between RLSs and CLSs. RLSs, however, had significantly longer operation times (minutes; colon cancer: RLS 242.9 ± 91.0 vs CLS 177.4 ± 78.2, P < 0.001; chronic diverticulitis: RLS 226.2 ± 87.4 vs CLS 181.7 ± 74.4, P < 0.001). Among all of the colon cancer patients, RLS had higher rates of unplanned return to the operating room (P = 0.028) and organ space surgical site infection (P = 0.035). Among chronic diverticulitis patients, RLS was associated with higher rates of postoperative sepsis, anastomotic leak, organ space surgical site infection, and unplanned readmission (all P < 0.05). CONCLUSIONS: CLS may be the more efficient operative technique because it was associated with a shorter average operation time and fewer postoperative complications. This paradigm, however, may change as the robotic technology develops and surgeons become more experienced with RLS.


Assuntos
Neoplasias do Colo , Diverticulite , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Melhoria de Qualidade , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Infecção da Ferida Cirúrgica , Estudos Retrospectivos , Colectomia , Neoplasias do Colo/cirurgia , Laparoscopia/efeitos adversos
19.
Int J Mol Sci ; 23(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35955460

RESUMO

In this article, we describe the antimicrobial properties of a new composite based on anodic aluminium oxide (AAO) membranes containing propyl-copper-phosphonate units arranged at a predetermined density inside the AAO channels. The samples were prepared with four concentrations of copper ions and tested as antimicrobial drug on four different strains of Escherichia coli (K12, R2, R3 and R4). For comparison, the same strains were tested with three types of antibiotics using the minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than antibiotics such as ciprofloxacin, bleomycin and cloxacillin. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA. We have also observed that the intermolecular distances between the functional units play an important role for the antimicrobial properties of the used material. Hence, we utilised the idea of the 2D solvent to tailor them.


Assuntos
Cobre , Proteínas de Escherichia coli , Óxido de Alumínio , Antibacterianos/farmacologia , Bactérias , Cobre/farmacologia , DNA Bacteriano , DNA-Formamidopirimidina Glicosilase , Escherichia coli/genética
20.
Molecules ; 27(9)2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35566300

RESUMO

Nowadays, the use of hybrid structures and multi-component materials is gaining ground in the fields of environmental protection, water treatment and removal of organic pollutants. This study describes promising, cheap and photoactive self-supported hybrid membranes as a possible solution for wastewater treatment applications. In the course of this research work, the photocatalytic performance of titania nanowire (TiO2 NW)-based hybrid membranes in the adsorption and degradation of methylene blue (MB) under UV irradiation was investigated. Characterization techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), X-ray powder diffractometry (XRD) were used to study the morphology and surface of the as-prepared hybrid membranes. We tested the photocatalytic efficiency of the as-prepared membranes in decomposing methylene blue (MB) under UV light irradiation. The hybrid membranes achieved the removal of MB with a degradation efficiency of 90% in 60 min. The high efficiency can be attributed to the presence of binary components in the membrane that enhanced both the adsorption capability and the photocatalytic ability of the membranes. The results obtained suggest that multicomponent hybrid membranes could be promising candidates for future photocatalysis-based water treatment technologies that also take into account the principles of circular economy.


Assuntos
Nanofios , Purificação da Água , Azul de Metileno/química , Titânio/química
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