RESUMO
Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We measured viral load, levels of various cytokines, urokinase plasminogen activator (uPA), and plasminogen activator inhibitor-1 (PAI-1). We found significantly elevated levels of proinflammatory cytokines and PAI-1 in five end-stage cases. There was no difference between the expression of active uPA in survivors' and decedents' cases. However, total uPA in decedents' cases was significantly higher compared to survivors'. In some end-stage cases, uPA was refractory to PAI-1 inhibition as measured by zymography, where uPA and PAI-1 were strongly correlated to lymphocyte counts and IFN-γ. We also found bacterial co-infection influencing the etiology and outcome of immune response in two cases. Unsupervised Principal Component Analysis and hierarchical cluster analyses resolved separate waves of correlated immune mediators expressed in one case patient due to a sequential co-infection of bacteria and SNV. Overall, a robust proinflammatory immune response, characterized by an imbalance in T helper 17 (Th17) and regulatory T-cells (Treg) subsets, was correlated with dysregulated inflammation and mortality. Our sample size is small; however, the core differences correlated to survivors and end-stage HCPS are instructive.
Assuntos
Citocinas/genética , Citocinas/imunologia , Infecções por Hantavirus/complicações , Infecções por Hantavirus/imunologia , Síndrome Pulmonar por Hantavirus/imunologia , Plasminogênio/genética , Vírus Sin Nombre/patogenicidade , Adolescente , Adulto , Coinfecção/complicações , Coinfecção/microbiologia , Coinfecção/virologia , Citocinas/classificação , Feminino , Infecções por Hantavirus/fisiopatologia , Síndrome Pulmonar por Hantavirus/fisiopatologia , Humanos , Inflamação/imunologia , Inflamação/virologia , Estudos Longitudinais , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Plasminogênio/análise , Plasminogênio/imunologia , Estudos Retrospectivos , Vírus Sin Nombre/imunologia , Adulto JovemRESUMO
COVID-19 is announced as a global pandemic in 2020. Its mortality and morbidity rate are rapidly increasing, with limited medications. The emergent outbreak of COVID-19 prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps spreading. In this infection, a patient's immune response plays pivotal role in the pathogenesis. This inflammatory factor was shown by its mediators that, in severe cases, reach the cytokine at peaks. Hyperinflammatory state may sparks significant imbalances in transporters and drug metabolic machinery, and subsequent alteration of drug pharmacokinetics may result in unexpected therapeutic response. The present scenario has accounted for the requirement for therapeutic opportunities to relive and overcome this pandemic. Despite the diminishing developments of COVID-19, there is no drug still approved to have significant effects with no side effect on the treatment for COVID-19 patients. Based on the evidence, many antiviral and anti-inflammatory drugs have been authorized by the Food and Drug Administration (FDA) to treat the COVID-19 patients even though not knowing the possible drug-drug interactions (DDI). Remdesivir, favipiravir, and molnupiravir are deemed the most hopeful antiviral agents by improving infected patient's health. Dexamethasone is the first known steroid medicine that saved the lives of seriously ill patients. Some oligopeptides and proteins have also been using. The current review summarizes medication updates to treat COVID-19 patients in an inflammatory state and their interaction with drug transporters and drug-metabolizing enzymes. It gives an opinion on the potential DDI that may permit the individualization of these drugs, thereby enhancing the safety and efficacy.
Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Inflamação/tratamento farmacológico , Animais , COVID-19/complicações , Interações Medicamentosas , Humanos , Inflamação/virologia , Medição de RiscoRESUMO
The high mortality rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is a critical concern of the coronavirus disease 2019 (COVID-19) pandemic. Strikingly, men account for the majority of COVID-19 deaths, with current figures ranging from 59% to 75% of total mortality. However, despite clear implications in relation to COVID-19 mortality, most research has not considered sex as a critical factor in data analysis. Here, we highlight fundamental biological differences that exist between males and females, and how these may make significant contributions to the male-biased COVID-19 mortality. We present preclinical evidence identifying the influence of biological sex on the expression and regulation of angiotensin-converting enzyme 2 (ACE2), which is the main receptor used by SARS-CoV-2 to enter cells. However, we note that there is a lack of reports showing that sexual dimorphism of ACE2 expression exists and is of functional relevance in humans. In contrast, there is strong evidence, especially in the context of viral infections, that sexual dimorphism plays a central role in the genetic and hormonal regulation of immune responses, both of the innate and the adaptive immune system. We review evidence supporting that ineffective anti-SARS-CoV-2 responses, coupled with a predisposition for inappropriate hyperinflammatory responses, could provide a biological explanation for the male bias in COVID-19 mortality. A prominent finding in COVID-19 is the increased risk of death with pre-existing cardiovascular comorbidities, such as hypertension, obesity, and age. We contextualize how important features of sexual dimorphism and inflammation in COVID-19 may exhibit a reciprocal relationship with comorbidities, and explain their increased mortality risk. Ultimately, we demonstrate that biological sex is a fundamental variable of critical relevance to our mechanistic understanding of SARS-CoV-2 infection and the pursuit of effective COVID-19 preventative and therapeutic strategies.
Assuntos
COVID-19/mortalidade , Doenças Cardiovasculares/mortalidade , Disparidades nos Níveis de Saúde , Inflamação/mortalidade , SARS-CoV-2/imunologia , Animais , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/virologia , Comorbidade , Feminino , Interações Hospedeiro-Patógeno , Humanos , Inflamação/diagnóstico , Inflamação/imunologia , Inflamação/virologia , Masculino , Prognóstico , Medição de Risco , Fatores de Risco , Caracteres Sexuais , Fatores SexuaisAssuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/epidemiologia , Otolaringologia/organização & administração , Pneumonia Viral/epidemiologia , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Atenção à Saúde/organização & administração , Disgeusia/diagnóstico , Disgeusia/etiologia , Epistaxe/diagnóstico , Epistaxe/etiologia , Humanos , Inflamação/complicações , Inflamação/virologia , Mucosa Nasal/patologia , Programas Nacionais de Saúde/organização & administração , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Pandemias , Publicações Periódicas como Assunto , Equipamento de Proteção Individual/normas , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , SARS-CoV-2 , Reino Unido/epidemiologiaRESUMO
BACKGROUND: The aim of this study was to determine the presence of HPV in patients with Prostate cancer (PCa) and its possible association with cancer progression. METHODS: In this case-control study, fresh prostate tissues and blood samples were collected from 90 individuals, including 58 cases samples with PCa and 32 non-malignant prostate tissue samples as a control group. The expression level of viral genes (E2, E6, and E7) and cellular factors including tumor suppressor proteins (Rb and p53), anti-apoptotic mediators (Bcl-2 and survivin), and some mediators involved in inflammation and angiogenesis was evaluated. RESULTS: The presence of the HPV genome was identified in 19 out of the 58 cases (32.7%) and five out of the 32 controls (15.6%). However, there was not any statistically significant relationship between the presence of the HPV genome and PCa (OR = 2.63, 95% C.I = 0.89-7.91, P-value = 0.078). Moreover, the HPV high-risk genotypes 16 and 18 were detected in 47.4% and 31.6% of HPV-infected PCa tissues, respectively. The expression level of the tumor suppressor proteins (Rb and p53) significantly decreased in the HPV-infected samples compared to the HPV negative specimens (P-value = 0.01, P-value = 0.01, respectively). However, the expression level of the anti-apoptotic mediators and those involved in angiogenesis and inflammation significantly increased in the HPV-infected PCa group compared to the HPV-negative PCa and control groups (P-value < 0.05, respectively). CONCLUSION: Our study suggests that although it is not definitely known whether HPV causes PCa, this virus probably modulates PCa cell behavior by affecting inflammation, angiogenesis, and apoptosis mechanisms, which, in turn, promotes tumorigenesis.
Assuntos
Inflamação , Neovascularização Patológica , Infecções por Papillomavirus , Neoplasias da Próstata , Adulto , Idoso , Alphapapillomavirus/genética , Apoptose , Citocinas/sangue , DNA Viral , Genoma Viral , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/patologia , Inflamação/virologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica/sangue , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Neovascularização Patológica/virologia , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Próstata/imunologia , Próstata/patologia , Próstata/virologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/virologiaRESUMO
Italy was the first European nation to be affected by COVID-19. The biggest cluster of cases occurred in Lombardy, the most populous Italian region, and elderly men were the population hit in the hardest way. Besides its high infectivity, COVID-19 causes a severe cytokine storm and old people, especially those with comorbidities, appear to be the most vulnerable, presumably in connection to inflammaging. In centenarians inflammaging is much lower than predicted by their chronological age and females, presenting survival advantage in almost all centenarian populations, outnumber males, a phenomenon particularly evident in Northern Italy. Within this scenario, we wondered if: a) the COVID-19 mortality in centenarians was lower than that in people aged between 50 and 80 and b) the mortality from COVID-19 in nonagenarians and centenarians highlighted gender differences.We checked COVID-19-related vulnerability/mortality at the peak of infection (March 2020), using data on total deaths (i.e. not only confirmed COVID-19 cases). Our conclusion is that excess mortality increases steadily up to very old ages and at the same time men older than 90 years become relatively more resilient than age-matched females.
Assuntos
Envelhecimento , Betacoronavirus/fisiologia , Infecções por Coronavirus , Serviços de Saúde para Idosos/estatística & dados numéricos , Inflamação , Mortalidade , Pandemias , Pneumonia Viral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Envelhecimento/psicologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Feminino , Necessidades e Demandas de Serviços de Saúde , Disparidades nos Níveis de Saúde , Humanos , Inflamação/epidemiologia , Inflamação/virologia , Itália/epidemiologia , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Saúde Pública/métodos , SARS-CoV-2 , Fatores Sexuais , Populações VulneráveisRESUMO
AIMS: The use of direct-acting anti-viral agents (DAAs) has resulted in extremely high sustained virological response (SVR) rates in patients being treated while on liver transplantation (LT) waiting lists. The aim of this study was to evaluate the histological findings of hepatitis C virus (HCV) patients who achieved SVR after receiving DAA treatment [SVR(+)] prior to LT, and compare them with HCV patients who had not achieved SVR [SVR(-)]. METHODS AND RESULTS: Fifty-eight adult HCV patients who underwent LT at our institution from 2014 to 2016 were included in the study. Two pathologists, blinded to SVR status, simultaneously evaluated the histological sections. Assessment included the Histology Activity Index (HAI/modified Knodell score), fibrosis stage (Ishak score), and Laennec cirrhosis stage. The study group comprised 25 SVR(+) patients (56% male; mean age, 63.8 years), and the control group comprised 33 SVR(-) patients (69% male; mean age, 61.7 years). There was no significant difference in HAI between the groups (P = 0.414). Patients who achieved SVR also did not show less portal inflammation (P = 0.787), interface hepatitis (P = 0.999), confluent necrosis (P = 0.627) or spotty necrosis (P = 0.093) than the control group. There was a trend towards a higher degree of inflammation in patients who achieved SVR in <24 weeks (P = 0.07). The degree of focal lytic necrosis/apoptosis and portal inflammation was more prominent in SVR(+) patients with shorter SVR-LT intervals. CONCLUSIONS: Our study is the first to report persistent inflammation in HCV patients who received DAAs prior to LT. This supports the notion that inflammation is immunologically driven and that inflammation persists despite the absence of virus.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Adulto , Idoso , Benzimidazóis/uso terapêutico , Feminino , Fluorenos/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/virologia , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Uridina Monofosfato/análogos & derivados , Uridina Monofosfato/uso terapêuticoRESUMO
Acute HIV infection (AHI) is the period prior to seroconversion characterized by high viral replication, hyper-transmission potential and commonly, non-specific febrile illness. AHI detection requires HIV-RNA viral load (VL) determination, which has very limited access in low-income countries due to restrictive costs and implementation constraints. We sought to identify a biomarker that could enable AHI diagnosis in scarce-resource settings, and to evaluate the feasibility of its implementation. HIV-seronegative adults presenting at the Manhiça District Hospital, Mozambique, with reported-fever were tested for VL. Plasma levels of 49 inflammatory biomarkers from AHI (n = 61) and non-HIV infected outpatients (n = 65) were determined by Luminex and ELISA. IP-10 demonstrated the best predictive power for AHI detection (AUC = 0.88 [95%CI 0.80-0.96]). A cut-off value of IP-10 ≥ 161.6 pg/mL provided a sensitivity of 95.5% (95%CI 85.5-99.5) and a specificity of 76.5% (95%CI 62.5-87.2). The implementation of an IP-10 screening test could avert from 21 to 84 new infections and save from US$176,609 to US$533,467 to the health system per 1,000 tested patients. We conclude that IP-10 is an accurate biomarker to screen febrile HIV-seronegative individuals for subsequent AHI diagnosis with VL. Such an algorithm is a cost-effective strategy to prevent disease progression and a substantial number of further HIV infections.
Assuntos
Quimiocina CXCL10/sangue , Quimiocina CXCL10/metabolismo , Infecções por HIV/sangue , Infecções por HIV/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Análise Custo-Benefício/métodos , Progressão da Doença , Feminino , Febre/sangue , Febre/metabolismo , HIV-1/patogenicidade , Recursos em Saúde , Humanos , Inflamação/sangue , Inflamação/metabolismo , Inflamação/virologia , Masculino , Programas de Rastreamento/métodos , Moçambique , Sensibilidade e Especificidade , Carga Viral/fisiologia , Replicação Viral/fisiologiaRESUMO
PROBLEM: Stability over time of systemic and mucosal immunity and their associations with bacterial vaginosis (BV) and HIV-specific parameters were assessed. METHOD OF STUDY: Immune mediators and HIV viral load in plasma and cervicovaginal lavage (CVL), E. coli inhibition, and Nugent score were measured at three semiannual visits among 94 participants in the Women's Interagency HIV Study. Mixed models identified the factors associated with immune mediators. RESULTS: There was higher E. coli inhibition and lower inflammation over time in the genital tract and systemically. BV was consistently associated with higher CVL inflammatory mediators and lower CVL E. coli inhibition. HIV-infected women with higher CD4 counts had lower systemic and genital inflammatory mediators, and genital HIV shedding was associated with higher CVL inflammatory mediators. Use of antiretroviral therapy (ART) was associated with lower plasma and CVL mediators, but higher E. coli inhibition. CONCLUSION: HIV and BV are linked to inflammation, and ART may be associated with improved vaginal health.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Escherichia coli/imunologia , Genitália Feminina/imunologia , Infecções por HIV/imunologia , HIV/fisiologia , Inflamação/imunologia , Vaginose Bacteriana/imunologia , Adulto , Antirretrovirais/uso terapêutico , Processos de Crescimento Celular , Citocinas/sangue , Feminino , Seguimentos , Genitália Feminina/microbiologia , Genitália Feminina/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/microbiologia , Humanos , Imunidade nas Mucosas , Inflamação/microbiologia , Inflamação/virologia , Mediadores da Inflamação/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Vaginose Bacteriana/virologia , Carga Viral/imunologia , Eliminação de Partículas Virais/imunologiaRESUMO
Mortality from influenza infections continues as a global public health issue, with the host inflammatory response contributing to fatalities related to the primary infection. Based on Ordinary Differential Equation (ODE) formalism, a computational model was developed for the in-host response to influenza A virus, merging inflammatory, innate, adaptive and humoral responses to virus and linking severity of infection, the inflammatory response, and mortality. The model was calibrated using dense cytokine and cell data from adult BALB/c mice infected with the H1N1 influenza strain A/PR/8/34 in sublethal and lethal doses. Uncertainty in model parameters and disease mechanisms was quantified using Bayesian inference and ensemble model methodology that generates probabilistic predictions of survival, defined as viral clearance and recovery of the respiratory epithelium. The ensemble recovers the expected relationship between magnitude of viral exposure and the duration of survival, and suggests mechanisms primarily responsible for survival, which could guide the development of immuno-modulatory interventions as adjuncts to current anti-viral treatments. The model is employed to extrapolate from available data survival curves for the population and their dependence on initial viral aliquot. In addition, the model allows us to illustrate the positive effect of controlled inflammation on influenza survival.
Assuntos
Inflamação/virologia , Vírus da Influenza A Subtipo H1N1/fisiologia , Modelos Biológicos , Infecções por Orthomyxoviridae/imunologia , Animais , Teorema de Bayes , Simulação por Computador , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Influenza Humana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Método de Monte Carlo , Probabilidade , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: It is disputed whether recurrent episodes of wheeze in preschool-aged children comprise a distinct asthma phenotype. OBJECTIVE: We sought to prospectively assess airflow limitation and airway inflammation in children 4 to 6 years old with episodic virus-induced wheeze. METHODS: Ninety-three children 4 to 6 years old with a history of mild, virus-induced episodes of wheeze who were able to perform acceptable fraction of exhaled nitric oxide (Feno) maneuvers and spirometry (with forced expiratory time ≥0.5 seconds) were followed prospectively. Lung function and Feno values were measured every 6 weeks (baseline) within the first 48 hours of an acute wheezing episode (day 0) and 10 and 30 days later. Symptom scores and peak flow measurement were recorded daily. RESULTS: Forty-three children experienced a wheezing episode. At day 0, Feno values were significantly increased, whereas forced expiratory volume at 0.5 seconds (FEV(0.5)) significantly decreased compared with baseline (16 ppb [interquartile range {IQR}, 13-20 ppb] vs 9 ppb IQR, 7-11 ppb] and 0.84 L [IQR, 0.75-0.99 L] vs 0.99 L [IQR, 0.9-1.07 L], respectively; both P < .001). Airflow limitation at day 0 was reversible after bronchodilation. FEV(0.5) and Feno values were significantly associated with each other and with lower and upper respiratory tract symptoms when assessed longitudinally but not cross-sectionally at all time points independently of atopy. Feno and FEV(0.5) values returned to baseline levels within 10 days. CONCLUSIONS: Mild episodes of wheeze in preschoolers are characterized by enhanced airway inflammation, reversible airflow limitation, and asthma-related symptoms. Feno values increase significantly during the first 48 hours and return to personal baseline within 10 days from the initiation of the episode. Longitudinal follow-up suggests that symptoms, inflammation, and lung function correlate well in this phenotype of asthma.
Assuntos
Expiração , Inflamação/diagnóstico , Inflamação/virologia , Infecções do Sistema Genital/diagnóstico , Infecções do Sistema Genital/virologia , Sons Respiratórios/diagnóstico , Sons Respiratórios/etiologia , Criança , Pré-Escolar , Feminino , Volume Expiratório Forçado , Humanos , Inflamação/fisiopatologia , Estudos Longitudinais , Masculino , Infecções do Sistema Genital/fisiopatologia , EspirometriaRESUMO
SUMMARY: Up to 30% of patients with hepatitis C virus (HCV) infection and normal serum alanine aminotransferase (NALT) have significant liver disease. Currently, many of these patients undergo a liver biopsy to guide therapeutic decisions. The BreathID continuous online (13)C-methacetin breath test (MBT) reflects hepatic microsomal function and correlates with hepatic fibrosis. To assess its role in identifying intrahepatic inflammation and fibrosis in NALT patients, we tested 100 patients with untreated chronic HCV infection, and 100 age- and sex-matched healthy volunteers using (13)C MBT following ingestion of 75 mg methacetin. All HCV patients had undergone a liver biopsy within 12 months of performing the MBT. Patients with a necroinflammatory grade
Assuntos
Acetamidas , Alanina Transaminase/sangue , Testes Respiratórios/métodos , Hepatite C Crônica/complicações , Inflamação/diagnóstico , Cirrose Hepática/diagnóstico , Adulto , Idoso , Algoritmos , Isótopos de Carbono , Feminino , Hepatite C Crônica/virologia , Humanos , Inflamação/patologia , Inflamação/fisiopatologia , Inflamação/virologia , Fígado/patologia , Fígado/fisiopatologia , Fígado/virologia , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Inflammation plays a key role in coronary artery disease (CAD), but whether it is involved in the pathogenesis of syndrome X (SX) is not known. Thus, we assessed the presence of systemic inflammation in patients with SX and its possible relation to infections from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus. We studied 55 patients with SX (57 +/- 8 years old; 27 women), 49 with stable angina and obstructive CAD (56 +/- 8 years old; 24 women), and 60 healthy controls (57 +/- 11 years old; 24 women). Plasma levels of high-sensitivity C-reactive protein and interleukin-1 receptor antagonist were measured in all patients. Infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus was assessed in 43 patients with SX, 40 patients with CAD, and in 39 controls. Patients with SX had lower serum levels of C-reactive protein than did patients with CAD (4.06 +/- 6.8 vs 5.99 +/- 7.8 mg/L, p = 0.013) but higher levels of C-reactive protein than did controls (1.75 +/- 1.98 mg/L; p = 0.008). Plasma levels of interleukin-1 receptor antagonist were higher in patients with CAD (570 +/- 738 pg/ml) and patients with SX (494 +/- 677 pg/ml) than in controls (254 +/- 174, pg/ml; p = 0.0003 vs CAD and p = 0.013 vs SX) but did not differ significantly between patients with CAD or SX (p = 0.20). There were no differences across groups in the prevalence of infection from Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus, and Epstein-Barr virus and in the prevalence of 1, 2, 3, and 4 infections (p = 0.99). Among patients with SX, no correlation was found between markers of inflammation and indexes of disease activity (angina episodes, exercise test results). Our data show evidence of increased low-grade systemic inflammation in patients with cardiac SX, which was unrelated to an increased infectious pathogen burden.
Assuntos
Doença da Artéria Coronariana/sangue , Inflamação/epidemiologia , Angina Microvascular/sangue , Proteína C-Reativa , Estudos de Casos e Controles , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Chlamydophila pneumoniae , Doença da Artéria Coronariana/complicações , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Inflamação/complicações , Inflamação/microbiologia , Inflamação/virologia , Itália/epidemiologia , Masculino , Angina Microvascular/complicações , Pessoa de Meia-Idade , PrevalênciaRESUMO
HTLV-I-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP), is a chronic inflammatory disease of the spinal cord. Acute cases are uncommon. We report the case of a 41-year-old woman with acute HAM/TSP complicated with encephalitis, an intense inflammatory reaction of the nervous system and lymphocytic infiltration of skeletal muscles, liver, salivary, adrenal and pituitary glands. The immunohistochemical studies of the lymphocytes surrounding blood vessels showed both B- and T-lymphocytes, in similar proportion, with both CD4- and CD8-positive cells. In addition, many perivascular and scattered macrophages were observed. Adult T-cell leukemia/lymphoma (ATL) was ruled out. The marrow aspirate was normal. Serial cerebrospinal fluid (CSF) analysis showed presence of HTLV-I antibodies, but without intrathecal synthesis of specific antibodies. Determination of HTLV-I viral loads demonstrated increased levels in the CSF relative to the peripheral blood and may be associated with widespread inflammation. The pathological and immunological findings may help understand the role of immune-reactive cells in the pathogenesis of HTLV-I-associated myelopathy.