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Our systematic review highlights that multiparametric PAI score assessment is a consistent tool with high sensitivity and specificity for prenatal prediction for placenta accreta spectrum (PAS) in high-risk population with anterior placenta previa or low-lying placenta and prior cesarean deliveries. A systematic search was conducted on November 1, 2022, of MEDLINE via PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar to identify relevant studies (PROSPERO ID # CRD42022368211). A total of 11 articles met our inclusion criteria, representing the data of a total of 1,044 cases. Women with PAS had an increased mean PAI total score, compared to those without PAS. Limitations of the PAI are most studies were conducted in developing countries in high-risk population which limit the global generalizability of findings. Heterogeneity of reported data did not allow to perform meta-analysis.
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Placenta Acreta , Valor Preditivo dos Testes , Ultrassonografia Pré-Natal , Humanos , Feminino , Placenta Acreta/diagnóstico por imagem , Gravidez , Ultrassonografia Pré-Natal/métodos , Sensibilidade e Especificidade , Placenta/diagnóstico por imagemRESUMO
OBJECTIVE: This study aimed to investigate the impact of race/ethnicity and insurance status on obstetric outcomes in nulliparous women. STUDY DESIGN: Secondary analysis of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-To-Be. Obstetric outcomes included the development of a hypertensive event during pregnancy, need for a cesarean section, delivery of a preterm neonate, and postpartum hemorrhage. RESULTS: Of 7,887 nulliparous women, 64.7% were non-Hispanic White (White), 13.4% non-Hispanic Black (Black), 17.8% Hispanic, and 4.1% were Asian. Black women had the highest rates of developing new-onset hypertension (32%) and delivering preterm (11%). Cesarean deliveries were the highest in Asian (32%) and Black women (32%). Individuals with government insurance were more likely to deliver preterm (11%) and/or experience hemorrhage after delivery. In multivariable analyses, race/ethnicity was associated with hypertension and cesarean delivery. More important, the adjusted odds ratios for preventable risk factors, such as obesity, diabetes, and severe anemia were greater than the adjusted odds ratios for race/ethnicity in terms of poor maternal outcome. CONCLUSION: Although disparities were observed between race/ethnicity and obstetric outcomes, other modifiable risk factors played a larger role in clinical differences. KEY POINTS: · Race or insurance alone had mixed associations with maternal morbidities.. · Race and insurance had low associations with maternal morbidities.. · Other, modifiable risk factors may be more important.. · Both social and biological factors impact health disparities..
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Thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-SCT) can pose significant problems in management of patients. Eltrombopag is a small-molecule thrombopoietin receptor agonist that has been approved for use in immune thrombocytopenic purpura and aplastic anemia; but its use after allo-SCT is limited. Between 2014 and 2017, we treated 13 patients with eltrombopag for poor platelet engraftment without evidence of relapse at the time of initiation, including 6 patients with primary platelet engraftment failure and 7 with secondary platelet engraftment failure. Eltrombopag was started at an initial dose of 25 or 50 mg per day, and dose adjustments were made in accordance with the manufacturer's recommendation. The cumulative incidence of platelet recovery to ≥50,000/µL without the need for transfusion for at least 7 days was defined as response. The overall response rate was 62% (nâ¯=â¯8). Of the 6 patients with primary isolated platelet failure, 3 (50%) responded, and of the 7 patients with secondary platelet failure, 5 (71%) responded. The median time to response was 33 days (range, 11 to 68 days). In addition, no significant differences in platelet recovery were noted in patients with adequate and decreased bone marrow megakaryocytic reserve (60% and 67%, respectively). Although eltrombopag was well tolerated, and no patient discontinued treatment because of adverse events, only 3 patients were alive at the end of the observation period, with relapse and graft-versus-host disease accounting for majority of the deaths. This suggested that despite the relatively good overall response rate to eltrombopag, inadequate platelet engraftment is a harbinger of poor outcome in allo-SCT.
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Benzoatos/administração & dosagem , Transtornos Plaquetários/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Hidrazinas/administração & dosagem , Pirazóis/administração & dosagem , Adulto , Idoso , Aloenxertos , Benzoatos/efeitos adversos , Transtornos Plaquetários/sangue , Transtornos Plaquetários/etiologia , Feminino , Humanos , Hidrazinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Pirazóis/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVE: Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this review is to identify risk factors, present signs and symptoms, identify methods of diagnosis, and identify best management practices on the basis of published case reviews. DATA SOURCES: PubMed and MEDLINE (Ovid) databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period from database inception until the study date of December 18, 2023. Key words included "liver infarction" or "hepatic infarction" and "pregnancy" or "obstetrics." STUDY ELIGIBILITY CRITERIA: Case reviews or case series published in the English language were included. Our study was registered with the Prospective Register of Systematic Reviews (registration number CRD42023488176) and was conducted in accordance with the published Prospective Register of Systematic Reviews and Meta-analyses Of Observational Studies in Epidemiology guidelines. METHODS: Included papers were evaluated for bias using a previously published tool. RESULTS: A total of 38 citations documenting 50 pregnancies published between 1979 and 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome, and 22% had a history of thrombus. Of those without a preexisting diagnosis of antiphospholipid syndrome, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%), and 32% and 16% had severe blood pressure or mild blood pressure, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm, and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. Computed tomography scans were used to confirm diagnosis of hepatic infarction in 58% of cases, magnetic resonance imaging in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases. CONCLUSION: Hepatic infarction should be considered in all cases of hemolysis, elevated liver enzymes, and low platelets syndrome, but specifically in patients with a history of antiphospholipid syndrome who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with a computed tomography scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.
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Infarto , Humanos , Gravidez , Feminino , Infarto/diagnóstico , Infarto/epidemiologia , Fatores de Risco , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/fisiopatologia , Síndrome Antifosfolipídica/terapia , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/terapia , Fígado/diagnóstico por imagem , Síndrome HELLP/diagnóstico , Síndrome HELLP/epidemiologia , Síndrome HELLP/terapia , Síndrome HELLP/fisiopatologiaRESUMO
BACKGROUND: Recent studies suggest that the reported protective effects of statins (HMG-CoA reductase inhibitors) against community-acquired pneumonia (CAP) and sepsis in humans may be due to confounders and a healthy user-effect. To directly test whether statins are protective against Streptococcus pneumoniae, the leading cause of CAP, we examined the impact of prolonged oral simvastatin therapy at physiologically relevant doses in a mouse model of pneumococcal pneumonia. BALB/c mice were placed on rodent chow containing 0 mg/kg (control), 12 mg/kg (low simvastatin diet [LSD]; corresponds to 1.0 mg/kg/day), or 120 mg/kg (high simvastatin diet [HSD]; corresponds to 10 mg/kg/day) simvastatin for four weeks, infected intratracheally with S. pneumoniae serotype 4 strain TIGR4, and sacrificed at 24, 36, or 42 h post-infection for assessment of lung histology, cytokine production, vascular leakage and edema, bacterial burden and bloodstream dissemination. Some mice received ampicillin at 12-h intervals beginning at 48 h post-infection and were monitored for survival. Immunoblots of homogenized lung samples was used to assess ICAM-1 production. RESULTS: Mice receiving HSD had reduced lung consolidation characterized by less macrophage and neutrophil infiltration and a significant reduction in the chemokines MCP-1 (P = 0.03) and KC (P = 0.02) and ICAM-1 in the lungs compared to control mice. HSD mice also had significantly lower bacterial titers in the blood at 36 (P = 0.007) and 42 (P = 0.03) hours post-infection versus controls. LSD had a more modest effect against S. pneumoniae but also resulted in reduced bacterial titers in the lungs and blood of mice after 42 h and a reduced number of infiltrated neutrophils. Neither LSD nor HSD mice had reduced mortality in a pneumonia model where mice received ampicillin 48 h after challenge. CONCLUSIONS: Prolonged oral simvastatin therapy had a strong dose-dependent effect on protection against S. pneumoniae as evidenced by reduced neutrophil infiltration, maintenance of vascular integrity, and lowered chemokine production in the lungs of mice on HSD. Statin therapy also protected through reduced bacterial burden in the lungs. Despite these protective correlates, mortality in the simvastatin-receiving cohorts was equivalent to controls. Thus, oral simvastatin at physiologically relevant doses only modestly protects against pneumococcal pneumonia.
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Lesão Pulmonar Aguda/patologia , Anticolesterolemiantes/administração & dosagem , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/patologia , Sinvastatina/administração & dosagem , Administração Oral , Animais , Citocinas/análise , Modelos Animais de Doenças , Edema/patologia , Feminino , Histocitoquímica , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Streptococcus pneumoniae/patogenicidade , Análise de SobrevidaRESUMO
OBJECTIVE: To create an antibiogram derived exclusively from our obstetric population and compare the clinical isolates and susceptibilities to our institutional antibiogram. METHODS: Data collected by the University Hospital Clinical Microbiology Laboratory in SSC Soft from 01/01/2018 to 12/31/2018 was used to generate our institutional antibiogram. For comparison, we created an obstetric (OB) antibiogram using all clinical isolates collected during the same time interval from OB triage, labor & delivery, antepartum and postpartum wards. The antibiotic susceptibilities of the OB clinical isolates were compared to the institutional clinical isolates. RESULTS: In total, we identified 929 clinical isolates from our OB population in 2018. Urine was the predominant source of clinical isolates (76.3%). The remaining sources included wound (10.1%), genital (9.0%), blood and other fluids (4.6%). Escherichia coli (E. coli) accounted for nearly half of all isolates (48.7%) followed by Group B Streptococcus (10.7%), Enterococcus spp. (9%), and Klebsiella pneumoniae (7.2%). There was no difference in susceptibilities of Gram-positive organisms in the OB antibiogram compared to the institutional antibiogram. Conversely, common Gram-negative organisms demonstrated less antibiotic resistance in the OB antibiogram compared to the institutional antibiogram. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were significantly more susceptible in the OB antibiogram compared to the institutional antibiogram to most antimicrobials tested. CONCLUSION: Compared to our institutional antibiogram, gram-negative clinical isolates in our OB population exhibit less antibiotic resistance. Creation of an OB-specific antibiogram, which more accurately reflects antibiotic resistance patterns within our unique patient population, may promote appropriate antimicrobial use by assisting in more informed antibiotic selection and limit unnecessary use of broad-spectrum antibiotics.
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Gestão de Antimicrobianos , Infecções por Escherichia coli , Feminino , Humanos , Escherichia coli , Testes de Sensibilidade Microbiana , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológicoRESUMO
OBJECTIVE: COVID-19 vaccination rates among pregnant women remain low, despite increased risk of COVID-19-related illness and death and demonstrated vaccine safety and efficacy in this population. The objective of this study is to identify sociodemographic predictors of COVID-19 vaccine hesitancy and elucidate important concerns among the pregnant population in light of evolving conversations regarding COVID-19. METHODS: A prospective survey of pregnant women at a single urban clinic in South Texas was conducted August to September 2021 to identify predictors of COVID-19 vaccine hesitancy among the pregnant population. Collected variables included demographics, COVID-19 beliefs, tetanus-diphtheria-pertussis (Tdap)/influenza vaccine hesitancy, and primary vaccine concerns. Statistical analyses included Fisher's exact test, asymptotic two-sample Brown-Mood median test, and multinomial logistic regression. RESULTS: One hundred and nine participants completed the survey, 35 vaccinated and 74 unvaccinated, with a response rate of 91.6%. Women who were COVID-19 vaccine hesitant were more likely to be younger (28.0 vs. 31.0 years, p < .004) and further along in pregnancy (30.0 vs. 20.0 weeks, p = .001). They were also more likely to report influenza (odds ratio (OR) 6.3; 95% confidence interval (CI) 2.5-17.1) and Tdap (OR 4.1; 95% CI 1.75-10.7) vaccine hesitancy. Furthermore, women who were vaccine hesitant were more likely to believe they did not have enough information to confidently make their decision (OR 4.0; 95% CI 1.4-11.4). Primary concerns with COVID-19 vaccines included: short- and long-term side effects on the pregnancy, personal long-term side effects, and harmful ingredients. CONCLUSIONS: COVID-19 vaccine hesitant pregnant women were more likely to be younger, hesitant toward other vaccines, and concerned with pregnancy impact and harmful ingredients. Personal knowledge of other vaccinated pregnant women was associated with significantly higher vaccine acceptance rates. Access to vaccines and concerns about quality control were not cited as reasons for vaccine hesitancy, in contrast to earlier studies on this topic.
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COVID-19 , Influenza Humana , Gravidez , Feminino , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Gestantes , Estudos Prospectivos , Texas/epidemiologia , Hesitação Vacinal , VacinaçãoRESUMO
Posterior reversible encephalopathy syndrome (PRES) is a neurological condition with a wide range of symptoms, including visual disturbances, headache, vomiting, seizures, and altered consciousness. This review describes the pathophysiology of PRES, as well as the clinical, diagnostic, and therapeutic intervention during pregnancy. The gold standard for diagnosis of PRES is Magnetic Resonance Imaging (MRI), helping to differentiate it from other similar conditions. The aim of this paper is to review the principal aspects of PRES, general care, blood pressure control, and seizures prevention while avoiding potential injuries to the mother and fetus in the event of pregnancy. We concluded that PRES can be effectively treated and reversed if prompt diagnostic action is made, and adequate care is initiated.
Assuntos
Síndrome da Leucoencefalopatia Posterior , Gravidez , Feminino , Humanos , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/terapia , Imageamento por Ressonância Magnética , Pressão Sanguínea , Convulsões , CefaleiaRESUMO
OBJECTIVE: Pain and depression are common in cancer patients. As these are both highly prevalent, the issue of a possible interdependent association has been raised. The aim of this systematic review was to examine the available literature and explore whether there is any evidence to support a causal relationship between cancer pain and depression. METHODS: An extensive literature search was undertaken. The following databases were searched electronically: Medline (1950-2007), Embase (1988-2007), CINAHL (1982-2007) and the Cochrane Database of Systematic Reviews (Issue 2 2007). The initial literature search revealed 892 articles. Following initial screening 41 articles were independently reviewed in detail. Fourteen articles were eligible for inclusion. RESULTS: The mean prevalence of both depression and pain was 36.5% (range 22.1-49.0). In 9 out of 14 studies a statistically significant association was demonstrated between pain and depression. Pain intensity positively correlated with depression (P<0.05). Items such as 'worst pain' and 'enjoyment of life' (on the Brief Pain Inventory) correlated significantly with depression. When using the McGill Pain Questionnaire, depressed patients used more affective pain descriptors. It was also shown that the longer the duration of pain, the higher the risk of depression. CONCLUSIONS: Pain and depression are highly prevalent in cancer patients; however, there have been no appropriately designed studies to examine a causal relationship. Although associations exist, the evidence available is not sufficient to support an interdependent relationship between pain and depression. A suitably designed longitudinal study to examine causality would be a relevant step in the research agenda.
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Transtorno Depressivo Maior , Neoplasias/complicações , Neoplasias/epidemiologia , Dor/epidemiologia , Dor/etiologia , Dor/psicologia , Comorbidade , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/etiologia , Humanos , Prevalência , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Cervical cancer is one of the most frequently encountered malignancies in pregnancy. For early-stage disease arising in late second/third trimester, treatment may be delayed until delivery. However, in advanced disease, data are lacking. CASE: A 26-year-old woman presented at 21 weeks gestation with a stage IIB high-grade clear cell cervical carcinoma. At 25 + 1 weeks gestation, cisplatin 100 mg/m(2) every 21 days was commenced. One month after cycle 3, a healthy infant was delivered. Thereafter, further cisplatin, intracavity cesium, and chemoradiation were administered. Findings from subsequent clinical examination and magnetic resonance imaging were normal. Fifteen months post treatment, both patient and baby remain well. CONCLUSION: Neoadjuvant cisplatin chemotherapy can be used in stage IIB cervical carcinoma during pregnancy to allow fetal development and prevent disease progression before delivery.
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Adenocarcinoma de Células Claras/tratamento farmacológico , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/radioterapia , Adulto , Progressão da Doença , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Gravidez , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapiaRESUMO
Advanced age is associated with chronic low-grade inflammation (i.e. inflamm-aging) and poor macrophage function that includes a weak pro-inflammatory cytokine response to bacteria and diminished phagocytosis (i.e. age-dependent macrophage dysfunction [ADMD]). One reason for this is that ADMD is associated with poor NFκB and MAPK activation following Toll-like receptor stimulation. Herein, we tested the hypothesis that inflamm-aging induces production of A20, a cytosolic and homeostatic suppressor of the NFκB and MAPK signaling cascades that deubiquitinates (i.e. inactivates) the common upstream signaling molecule TRAF6, and this is responsible for ADMD. Western blots and immunohistochemistry comparing tissues from young, mature, and aged C57BL/6 mice indicated that A20 was strongly elevated in the lungs of aged mice but not in other tissues. Elevated A20 was also detected in alveolar macrophages (AM) from aged mice. In contrast CYLD, a second deubiquitinase that also negatively regulates the NFκB pathway was decreased with aging. Following co-incubation of AM with the bacteria Streptococcus pneumoniae, TRAF6 polyubiquitination was diminished in AM isolated from aged versus young mice. A20 production was inducible in the J774A.1 macrophage cell line and C57BL/6AM by overnight incubation with TNFα but not IL-6. Retrovirus-induced expression of A20 in J774A.1 cells resulted in their diminished production of IL-6 following exposure to S. pneumoniae but had no effect on levels of phagocytosis. Overnight incubation of AM from young mice with TNFα also resulted in a dampened IL-6 response to S. pneumoniae. Finally, dietary supplementation of aged mice with anti-inflammatory n-3 polyunsaturated fatty acids in the form of fish oil lowered lung A20 levels and enhanced resistance, including a 100-fold reduction in bacterial titers in the lungs, to experimental challenge with S. pneumoniae. We conclude that elevated A20 due to TNFα partially explains the ADMD phenotype and that ADMD is potentially reversible.
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Cisteína Endopeptidases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos Alveolares/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Células Cultivadas , Senescência Celular/fisiologia , Citocinas/farmacologia , Feminino , Óleos de Peixe/farmacologia , Imunidade Inata/fisiologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fagocitose/fisiologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/prevenção & controle , Streptococcus pneumoniae , Fator 6 Associado a Receptor de TNF/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/metabolismo , Ubiquitinação/fisiologiaRESUMO
PURPOSE: The purpose of this study was to explicate and interpret common experiences of diabetes educators (DEs) with patient goal setting for patients with type 2 diabetes in diabetes education. METHODS: Transcripts (n = 10) from semi-structured interviews were analyzed using a hermeneutic phenomenological approach to more deeply explore the accounts of DEs' goal setting with patients with type 2 diabetes. RESULTS: The overarching pattern that emerged was "Striking a Balance," which subsumed 4 subthemes: Applying Theoretical-Practical Principles When Setting Goals, Identifying Idealistic-Realistic Expectations, Creating Patient-Educator-Centered Plans, and Readying-Living With Goal Setting. The pattern, "Striking a Balance," revealed a common meaning of DEs as experiences requiring balance and nuance in goal setting with patients. IMPLICATIONS: The results of this study combined with the tenets of the self-determination theory can provide the DEs with real-life exemplars and a theoretical framework to encourage their patients to self-manage, increase intrinsic motivation, and improve adherence related to their lifestyle changes and glycemic control. DEs, as facilitators of change, can implement these changes with flexible and reciprocal activities with their patients. The DEs owned these activities and they are: "building the bond," "sharing the session," "readying for change," "sending them home," and "bringing them back."
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Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/terapia , Objetivos , Comportamentos Relacionados com a Saúde , Educação de Pacientes como Assunto/organização & administração , Autocuidado , Adulto , Glicemia , Comunicação , Serviços de Saúde Comunitária , Diabetes Mellitus Tipo 2/psicologia , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Motivação , Relações Profissional-Paciente , Autocuidado/psicologia , Inquéritos e Questionários , Estados UnidosRESUMO
Alveolar macrophages (AMs) are the first immune cells to respond to an invading pathogen and coordinate the inflammatory response within the lungs. Studies suggest that macrophages exhibit age-related deficiencies in Toll-like receptor (TLR) function; however, the impact of this dysfunction during pneumonia, the leading cause of infectious death in the elderly, and the underlying mechanisms responsible remain unclear. We examined disease severity in young, mature, and aged BALB/cBy mice following intratracheal infection with the Gram-positive bacteria Streptococcus pneumoniae (Spn). Both mature and aged mice failed to clear bacteria and as a result had increased mortality, tissue damage and vascular leakage. Early production of TNFα, IL-1ß, and IL-6 during pneumonia declined with age and was associated with an inability of isolated AMs to respond to pneumococcal cell wall (CW) and ethanol-killed Spn ex vivo. Total levels of TLR1 were unaffected by age and TLR2 surface expression was slightly yet significantly increased on aged AMs suggesting that intracellular TLR signaling defects were responsible for the age-related decline in cytokine responsiveness. Following infection of isolated AMs with live Spn, a significant age-related decline in TLR2-induced phosphorylation of p65 NFκB, JNK and p38 MAPK, and an increase in ERK phosphorylation was observed by immunoblotting. These data are the first to demonstrate that TLR2-dependent recognition of Spn by aged AMs is impaired and is associated with a delayed pro-inflammatory cytokine response in vivo along with enhanced susceptibility to pneumococcal pneumonia.
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Envelhecimento/imunologia , Citocinas/biossíntese , Macrófagos Alveolares/imunologia , Pneumonia Pneumocócica/imunologia , Receptor 2 Toll-Like/metabolismo , Animais , Células Cultivadas , Contagem de Colônia Microbiana , Suscetibilidade a Doenças , Feminino , Interleucina-6/biossíntese , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Pneumonia Pneumocócica/metabolismo , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/imunologia , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Advances in modern medicine have led to an increase in the median life span and an expansion of the world's population over the age of 65. With increasing numbers of the population surviving to the extreme of age, those at risk for the development of pneumonia will approach 2 billion by the year 2050. Numerous age-related changes in the lung likely contribute to the enhanced occurrence of pneumonia in the elderly. Inflammation in the elderly has been shown to increase risk prior to infection; age-associated inflammation enhances bacterial ligand expression in the lungs which increases the ability of bacteria to attach and invade host cells. Conversely, the elaboration of the acute inflammatory response during early infection has been found to decrease with age resulting in a delayed immune response and diminished bacterial killing. Finally, the resolution of the inflammatory response during the convalescent stage back to "baseline" is often prolonged in the elderly and associated with negative outcomes, such as adverse cardiac events. The focus of this review will be to discuss our current understanding of the potential mechanisms by which dysregulated inflammation (both prior to and following an infectious insult) enhances susceptibility to and severity of community acquired pneumonia (CAP) in the elderly with an emphasis on pneumococcal pneumonia, the leading cause of CAP.
RESUMO
Cellular senescence is an age-associated phenomenon that promotes tumor invasiveness owing to the secretion of proinflammatory cytokines, proteases, and growth factors. Herein we demonstrate that cellular senescence also potentially increases susceptibility to bacterial pneumonia caused by Streptococcus pneumoniae (the pneumococcus), the leading cause of infectious death in the elderly. Aged mice had increased lung inflammation as determined by cytokine analysis and histopathology of lung sections. Immunoblotting for p16, pRb, and mH2A showed that elderly humans and aged mice had increased levels of these senescence markers in their lungs vs. young controls. Keratin 10 (K10), laminin receptor (LR), and platelet-activating factor receptor (PAFr), host proteins known to be co-opted for bacterial adhesion, were also increased. Aged mice were found to be highly susceptible to pneumococcal challenge in a PsrP, the pneumococcal adhesin that binds K10, dependent manner. In vitro senescent A549 lung epithelial cells had elevated K10 and LR protein levels and were up to 5-fold more permissive for bacterial adhesion. Additionally, exposure of normal cells to conditioned media from senescent cells doubled PAFr levels and pneumococcal adherence. Genotoxic stress induced by bleomycin and oxidative stress enhanced susceptibility of young mice to pneumonia and was positively correlated with enhanced p16, inflammation, and LR levels. These findings suggest that cellular senescence facilitates bacterial adhesion to cells in the lungs and provides an additional molecular mechanism for the increased incidence of community-acquired pneumonia in the elderly. This study is the first to suggest a second negative consequence for the senescence-associated secretory phenotype.
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Senescência Celular , Suscetibilidade a Doenças , Pulmão/microbiologia , Pneumonia Pneumocócica/microbiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Envelhecimento/patologia , Animais , Aderência Bacteriana , Biomarcadores , Bleomicina/administração & dosagem , Bleomicina/farmacologia , Linhagem Celular Tumoral , Citocinas/análise , Citocinas/imunologia , Feminino , Humanos , Immunoblotting , Imuno-Histoquímica , Inflamação/imunologia , Inflamação/patologia , Estimativa de Kaplan-Meier , Queratina-10/imunologia , Queratina-10/metabolismo , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Estresse Oxidativo , Pneumonia Pneumocócica/imunologia , Pneumonia Pneumocócica/patologia , Receptores de Laminina/imunologia , Receptores de Laminina/metabolismo , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/patogenicidadeRESUMO
Rapamycin was administered in food to genetically heterogeneous mice from the age of 9 months and produced significant increases in life span, including maximum life span, at each of three test sites. Median survival was extended by an average of 10% in males and 18% in females. Rapamycin attenuated age-associated decline in spontaneous activity in males but not in females. Causes of death were similar in control and rapamycin-treated mice. Resveratrol (at 300 and 1200 ppm food) and simvastatin (12 and 120 ppm) did not have significant effects on survival in male or female mice. Further evaluation of rapamycin's effects on mice is likely to help delineate the role of the mammalian target of rapamycin complexes in the regulation of aging rate and age-dependent diseases and may help to guide a search for drugs that retard some or all of the diseases of aging.
Assuntos
Longevidade/efeitos dos fármacos , Sinvastatina/administração & dosagem , Sirolimo/administração & dosagem , Estilbenos/administração & dosagem , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Animais , Feminino , Heterogeneidade Genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , ResveratrolRESUMO
Purpose of this study was to determine if the turtle has a consensual pupillary light response (cPLR), and if so, to compare it to its direct pupillary light response (dPLR). One eye was illuminated with different intensities of light over a four log range while keeping the other eye in darkness. In the eye directly illuminated, pupil diameter was reduced by as much as approximately 31%. In the eye not stimulated by light, pupil diameter was also reduced but less to approximately 11%. When compared to the directly illuminated eye, this generated a ratio, cPLR-dPLR, equal to 0.35. Ratio of slopes for log/linear fits to plots of pupil changes versus retinal irradiance for non-illuminated (-1.27) to illuminated (-3.94) eyes closely matched at 0.32. cPLR had time constants ranging from 0.60 to 1.20min; however, they were comparable and not statistically different from those of the dPLR, which ranged from 1.41 to 2.00min. Application of mydriatic drugs to the directly illuminated eye also supported presence of a cPLR. Drugs reduced pupil constriction by approximately 9% for the dPLR and slowed its time constant to 9.58min while simultaneous enhancing constriction by approximately 6% for the cPLR. Time constant for the cPLR at 1.75min, however, was not changed. Results support that turtle possesses a cPLR although less strong than its dPLR.