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1.
BMC Infect Dis ; 20(1): 139, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32059707

RESUMO

BACKGROUND: Diabetes mellitus (DM) is thought to affect tuberculosis (TB) clinical presentation and treatment response. Whether DM impacts radiological manifestations of pulmonary TB is still not clear. This study investigated the impact of glycemic status on radiological manifestations of pulmonary TB cases and its relationship with concentration of biochemical parameters in peripheral blood. METHODS: A retrospective cross-sectional study used data from 132 microbiologically confirmed pulmonary TB patients from Lima, Peru, evaluated in a previous investigation performed between February and December 2017. Chest radiographs were analyzed by a radiologist and a pulmonologist. Radiographic lesions were identified as cavities, alveolar infiltrates and fibrous tracts. Hyperglycemia in TB patients was identified by use of fasting plasma glucose, HbA1c and oral glucose tolerance test. Clinical, biochemical and hematological parameters were also analyzed. RESULTS: TB patients with hyperglycemia presented more frequently with cavities, alveolar infiltrates and fibrous tracts than those with normoglycemia. Hierarchical clustering analysis indicated that patients with more diverse and higher number of lung lesions exhibited a distinct laboratorial profile characterized by heightened white blood cell counts and circulating levels of total cholesterol, triglycerides and transaminases and simultaneously low levels of albumin and hemoglobin. Multivariable regression analyses adjusted for age, sex, prior TB, hemoglobin levels and acid-fast bacilli ≥2+ in sputum smears, demonstrated that presence of prediabetes or diabetes in TB patients was associated with increased odds of having 3 pulmonary lesion types (p = 0.003 and p < 0.01 respectively) or ≥ 4 lesions (p = 0.001 and p = 0.01 respectively). CONCLUSION: Hyperglycemia (both DM and prediabetes) significantly affected the presentation of radiographic manifestations and the number of lesions in pulmonary TB patients as well as the biochemical profile in peripheral blood.


Assuntos
Hiperglicemia/sangue , Hiperglicemia/complicações , Pulmão/patologia , Estado Pré-Diabético/sangue , Tuberculose Pulmonar/diagnóstico por imagem , Adolescente , Adulto , Análise por Conglomerados , Estudos Transversais , Diabetes Mellitus/sangue , Feminino , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/microbiologia , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Peru , Estado Pré-Diabético/complicações , Análise de Regressão , Estudos Retrospectivos , Escarro/microbiologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/patologia
2.
Scand J Immunol ; 91(4): e12866, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31960452

RESUMO

Understanding mechanisms of cavitation in tuberculosis (TB) is the missing link that could advance the field towards better control of the infection. Descriptions of human TB suggest that postprimary TB begins as lipid pneumonia of foamy macrophages that undergoes caseating necrosis and fragmentation to produce cavities. This study aimed to investigate the various mycobacterial antigens accumulating in foamy macrophages and their relation to tissue destruction and necrosis. Pulmonary tissues from mice with slowly progressive TB were studied for histopathology, acid-fast bacilli (AFB) and presence of mycobacterial antigens. Digital quantification using Aperio ImageScope was done. Until week 12 postinfection, mice were healthy, and lesions were small with scarce AFB and mycobacterial antigens. Colony-forming units (CFUs) increased exponentially. At week 16-33, mice were sick, macrophages attained foamy appearance with an increase in antigens (P < .05), 1.5 log increase in CFUs and an approximately onefold increase in AFB. At week 37-41, mice started dying with a shift in morphology towards necrosis. A >20-fold increase in mycobacterial antigens was observed with only less than one log increase in CFUs and sevenfold increase in AFB. Secreted antigens were significantly (P < .05) higher compared to cell-wall antigens throughout infection. Focal areas of necrosis were associated with an approximately 40-fold increase in antigen MPT46, functionally active thioredoxin, and a significant increase in all secreted antigens. In conclusion, mycobacterial antigens accumulate in the foamy macrophages in TB lesions during slowly progressive murine pulmonary TB. Secreted antigens and MPT46 correlated with necrosis, thereby implying that they might trigger the formation of cavities.


Assuntos
Antígenos de Bactérias/imunologia , Células Espumosas/imunologia , Células Espumosas/microbiologia , Tuberculose Pulmonar/patologia , Animais , Células Espumosas/patologia , Camundongos , Mycobacterium tuberculosis , Necrose , Tuberculose Pulmonar/imunologia
3.
Monaldi Arch Chest Dis ; 89(3)2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31850696

RESUMO

Parenchymal lung infections occasionally present with clinical symptoms and radiological findings similar to lung malignancy. Pulmonary actinomycosis is a rare condition of its own right, let alone in coexistence with tuberculosis. We report a case of a man presenting with hemoptysis alongside a chest computed tomography compatible with lung cancer. The diagnosis, after removal of a large endobronchial mass with flexible bronchoscopy and cryon, was a concomitant infection with Mycobacterium tuberculosis and Actinomyces odontoliticus. In the literature, there are few reported cases with concomitant tuberculosis and actinomycosis. To our knowledge, such radical treatment without surgical intervention has not been reported in the past.


Assuntos
Actinomicose/complicações , Pneumonia Bacteriana/complicações , Tuberculose Pulmonar/complicações , Actinomicose/diagnóstico por imagem , Actinomicose/tratamento farmacológico , Actinomicose/patologia , Broncoscopia , Coinfecção , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Bacteriana/diagnóstico por imagem , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/patologia , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/patologia
4.
BMC Infect Dis ; 19(1): 1006, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779590

RESUMO

BACKGROUND: Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis. METHODS: We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay. RESULTS: Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14-CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16- (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment. CONCLUSIONS: Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Monócitos/metabolismo , Receptores de Superfície Celular/análise , Tuberculose/diagnóstico , Adulto , Idoso , Antígenos CD/sangue , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/metabolismo , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Inata , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia , Prognóstico , Curva ROC , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/metabolismo , Receptores de IgG/metabolismo , Índice de Gravidade de Doença , Tuberculose/imunologia , Tuberculose/patologia , Tuberculose Pleural/imunologia , Tuberculose Pleural/patologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia
5.
BMC Infect Dis ; 19(1): 844, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615433

RESUMO

BACKGROUND: In settings such as China, where universal implementation of directly observed therapy (DOT) is not feasible, innovative approaches are needed to support patient adherence to TB treatment. The electronic medication monitor (EMM) is one of the digital technologies recommended by the World Health Organization (WHO), but evidence from implementation studies remains sparse. In this study, we evaluated acceptance of the EMM among health care workers and patients while implementing the device for differential TB patient management at the community level. METHODS: Zhenjiang City in Jiangsu Province was purposively selected for the study. All participating patients were allowed to select their preferred management approach. If patients declined to use the EMM, DOT was offered. The EMM was designed to hold 1 month of anti-TB drugs for once-daily dosing of fixed-dose combination (FDC) tablets. Patient EMM records were monitored monthly by a physician; if 20 to 50% of doses were missed twice, or more than 50% of doses were missed once, the patient was switched to DOT. The four physicians and five nurses involved in the study at four designated hospitals were surveyed using a structured questionnaire to assess their acceptance of the EMM. RESULTS: From October 2017 through January 2018, 316 pulmonary TB patients were notified in the TB information management system, and 231 (73.1%) met the study enrollment criteria. Although 186 patients (80.5%) initially consented to use the EMM, 17 later refused to use it. Among the 169 patients who used the EMM, 15 (8.9%) were switched to DOT due to poor adherence, and the other 154 completed the treatment course. The median adherence rate was 99.3%. Surveyed health care workers from designated hospitals found the EMM acceptable, although eight of nine felt use of the device moderately increased their workload. However, the EMM program significantly reduced the workload of community physicians by reducing patient visits by 87.9%. CONCLUSIONS: This study demonstrated the acceptability of using an indigenously developed EMM for differential management of TB patients at the community level. However, more operational research should be conducted before introducing and scaling the technology throughout China.


Assuntos
Monitoramento de Medicamentos/métodos , Tuberculose Pulmonar/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Criança , China , Terapia Diretamente Observada , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Tuberculose Pulmonar/tratamento farmacológico , Adulto Jovem
6.
BMC Infect Dis ; 19(1): 909, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664931

RESUMO

BACKGROUND: Disseminated nontuberculous mycobacteria (NTM) infections occur mostly in immunocompromised patients. Therefore, it is difficult to diagnose disseminated NTM infections in patients without history of immunocompromised diseases or using immunosuppressant. Patients with anti-interferon-γ (IFN-γ) autoantibodies are vulnerable to intracellular infections, such as disseminated NTM. Currently, there is no widely used and efficient technique for the detection of anti-IFN-γ autoantibodies. Herein, we report a case of an apparently healthy patient with disseminated Mycobacterium avium complex (MAC) infection who tested positive for anti-IFN-γ autoantibodies. CASE PRESENTATION: A 64-year-old non-immunocompromised and apparently healthy Asian male presented to the emergency department with complaints of progressive chest pain for about 6 months and weight loss. A bulging tumour was found in the anterior chest wall. Chest computed tomography showed a lung mass over the right lower lobe and an osteolytic lesion with a soft tissue component at the sternum. Sonography-guided biopsies for the osteolytic lesion and sputum culture confirmed the presence of disseminated MAC infection. In addition, positive test result of anti-IFN-γ autoantibodies was noted. The patient was prescribed antibiotics. The lesions over the right lower lobe and sternum attenuated following the antibiotic treatment. CONCLUSION: Detection of anti-IFN-γ autoantibodies is important among previously healthy people with disseminated NTM infection. Presence of anti-IFN-γ autoantibodies may suggest a high risk of severe intracellular infection, such as disseminated NTM infection.


Assuntos
Autoanticorpos/análise , Interferon gama/imunologia , Neoplasias Pulmonares/diagnóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Complexo Mycobacterium avium , Tuberculose Pulmonar/diagnóstico por imagem , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Biópsia/métodos , Diagnóstico Diferencial , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/patologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Escarro/microbiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
7.
Pan Afr Med J ; 32: 170, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31303939

RESUMO

Tuberculosis is a disease caused by tubercle bacillus infection. It can affect all of the body's organs. Pulmonary tuberculosis accounts for a little more than 50% of its occurrences. It is a public health problem worldwide, and developing countries in particular. Pseudotumoral bronchopulmonary tuberculosis is a particular form of tuberculosis in immunocompetent subject. It can manifests as a bronchial or pulmonary lesion, suggesting a neoplasia visible on chest CT scan or bronchoscopy. This similarity can confuse clinicians, making diagnosis challenging and requiring the use of invasive diagnostic techniques, since traditional means are often lacking. This increases burden of care and causes delayed treatment. This study aims to educate clinicians about this particular and uncommon form of tuberculosis, which should be suspected in patient with radiological findings compatible with the disease, especially since they live in a highly endemic country. Therapy and treatment duration are the same as for common forms of tuberculosis.


Assuntos
Neoplasias Brônquicas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adulto , Broncoscopia/métodos , Diagnóstico Diferencial , Humanos , Imunocompetência , Masculino , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/patologia
8.
Arch Med Res ; 50(2): 71-78, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31349956

RESUMO

Type-2 Diabetes (T2D) is a predisposing cause for developing tuberculosis (TB) in low- and middle-income countries. TB-T2D comorbidity worsens clinical control and prognosis of the affected individuals. The underlying metabolic alterations for this infectious-metabolic disease are still largely unknown. Possible mediators of the increased susceptibility to TB in diabetic patients are lipids levels, which are altered in individuals with T2D. To evaluate the modulation of glycerophospholipids in patients with TB-T2D, an untargeted lipidomic approach was developed by means of ultra-performance liquid chromatography (UPLC) coupled to electrospray ionization/quadrupole time-of-flight mass spectrometry (ESI-QToF). In addition, tandem mass spectrometry was performed to determine the identity of the differentially expressed metabolites. We found that TB infected individuals with or without T2D share a common glycerophospholipid profile characterized by a decrease in phosphatidylcholines. A total of 14 glycerophospholipids were differentially deregulated in TB and TB-T2D patients and could potentially be considered biomarkers. It is necessary to further validate these identified lipids as biomarkers, focusing on the anticipate diagnosis for TB development in T2D predisposed individuals.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Glicerofosfolipídeos/sangue , Tuberculose Pulmonar/patologia , Biomarcadores/sangue , Cromatografia Líquida , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Tuberculose Pulmonar/diagnóstico
9.
BMJ Case Rep ; 12(6)2019 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-31160302

RESUMO

Although not frequent, thromboembolic events occurring in patient presenting tuberculosis may be observed. Frequency of such thromboembolic events seems correlated with the severity of tuberculosis. We herein report a case of venous thrombosis revealing an asymptomatic tuberculosis. A man aged 32 years was admitted for deep and superficial vein thrombosis of the left arm. Chest CT angiography ruled out pulmonary embolism and showed a mediastinal and pulmonary heterogeneous necrotic mass at the apical segment of the left lung. Histological study of a CT scan-guided pulmonary biopsy showed signs of caseating granuloma compatible with tuberculosis. Diagnosis of venous thrombosis due to pulmonary tuberculosis with lymph nodes involvement was made. Antituberculosis treatment was initiated and required an adjustment of anticoagulant therapy. Our observation highlights the possibility of causative effect between tuberculosis and venous thrombosis.


Assuntos
Veia Axilar , Veia Subclávia , Tuberculose Pulmonar/diagnóstico , Trombose Venosa/diagnóstico , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Braço/irrigação sanguínea , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Quimioterapia Combinada , Humanos , Masculino , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/patologia , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem
10.
Cell Prolif ; 52(4): e12649, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31199047

RESUMO

Mycobacterium tuberculosis (Mtb) leads to approximately 1.5 million human deaths every year. In pulmonary tuberculosis (TB), Mtb must drive host tissue destruction to cause pulmonary cavitation and dissemination in the tissues. Matrix metalloproteinases (MMPs) are endopeptidases capable of degrading all components of pulmonary extracellular matrix (ECM). It is well established that Mtb infection leads to upregulation of MMPs and also causes disturbance in the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thus altering the extracellular matrix deposition. In TB, secretion of MMPs is mainly regulated by NF-κB, p38 and MAPK signalling pathways. In addition, recent studies have demonstrated the immunomodulatory roles of MMPs in Mtb pathogenesis. Researchers have proposed a new regimen of improved TB treatment by inhibition of MMP activity to hinder matrix destruction and to minimize the TB-associated morbidity and mortality. The proposed regimen involves adjunctive use of MMP inhibitors such as doxycycline, marimastat and other related drugs along with front-line anti-TB drugs to reduce granuloma formation and bacterial load. These findings implicate the possible addition of economical and well-tolerated MMP inhibitors to current multidrug regimens as an attractive mean to increase the drug potency. Here, we will summarize the recent advancements regarding expression of MMPs in TB, their immunomodulatory role, as well as their potential as therapeutic targets to control the deadly disease.


Assuntos
Metaloproteinases da Matriz/metabolismo , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/patologia , Animais , Matriz Extracelular/metabolismo , Humanos , Pulmão/metabolismo , Pulmão/patologia , Transdução de Sinais/fisiologia
12.
BMC Womens Health ; 19(1): 79, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215419

RESUMO

BACKGROUND: Ganglionic tuberculosis is the most common extrapulmonary localization in Morocco. It is still a diagnostic and therapeutic problem especially when the infection is concomitant to the management of a cancer. CASE PRESENTATION: Here, we report the uncommon case of a fortuitous discovery of ganglionic tuberculosis in the anatomopathological analysis of an axillary node dissection after conservative treatment of breast cancer for a 29-year-old patient without medical history. Her file was discussed in a multidisciplinary consultation meeting during which several decisions were made. We decided to start her antituberculosis treatment then after three weeks her adjuvant chemotherapy with radiotherapy and hormone therapy. Furthermore, giver her young age, she had an oncogenetic consultation. Despite difficulties of therapeutic compliance, the patient completed her cancer treatments after two years, she also cured of her tuberculosis. Being in remission, she is still on hormone therapy and consults every 3-months as part of her follow-up. CONCLUSIONS: Cancer and tuberculosis presenting simultaneously creates clinical and histopathological difficulties for differential diagnosis and for therapeutic decisions. Anticancer chemotherapy is not an obstacle in anti-tuberculosis treatment but the compliance of patients to receive both at the same time with the associated side effects is one to consider.


Assuntos
Neoplasias da Mama/patologia , Tuberculose dos Linfonodos/patologia , Tuberculose Pulmonar/patologia , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Tratamento Conservador , Feminino , Humanos , Marrocos , Tuberculose dos Linfonodos/complicações , Tuberculose Pulmonar/complicações
14.
Tuberculosis (Edinb) ; 116S: S118-S122, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31072690

RESUMO

Mycobacterium tuberculosis (MTB) is a pathogen that infects and kills millions yearly. The mycobacterium's cell wall glycolipid trehalose 6,6'-dimycolate (TDM) has been used historically to model MTB induced inflammation and granuloma formation. Alterations to the model can significantly influence the induced pathology. One such method incorporates intraperitoneal pre-exposure, after which the intravenous injection of TDM generates pathological damage effectively mimicking the hypercoagulation, thrombus formation, and tissue remodeling apparent in lungs of infected individuals. The purpose of these experiments is to examine the histological inflammation involved in the TDM mouse model that induces development of the hemorrhagic response. TDM induced lungs of C57BL/6 mice to undergo granulomatous inflammation. Further histological examination of the peak response demonstrated tissue remodeling consistent with hypercoagulation. The observed vascular occlusion indicates that obstruction likely occurs due to subendothelial localized activity leading to restriction of blood vessel lumens. Trichrome staining revealed that associated damage in the hypercoagulation model is consistent with intra endothelial cell accumulation of innate cells, bordered by collagen deposition in the underlying parenchyma. Overall, the hypercoagulation model represents a comparative pathological instrument for understanding mechanisms underlying development of hemorrhage and vascular occlusion seen during MTB infection.


Assuntos
Fatores Corda/metabolismo , Endotélio Vascular/patologia , Granuloma do Sistema Respiratório/patologia , Pulmão/irrigação sanguínea , Mycobacterium tuberculosis/metabolismo , Pneumonia/patologia , Tuberculose Pulmonar/patologia , Animais , Coagulação Sanguínea , Modelos Animais de Doenças , Endotélio Vascular/microbiologia , Feminino , Granuloma do Sistema Respiratório/sangue , Granuloma do Sistema Respiratório/induzido quimicamente , Granuloma do Sistema Respiratório/microbiologia , Pulmão/microbiologia , Camundongos Endogâmicos C57BL , Pneumonia/sangue , Pneumonia/induzido quimicamente , Pneumonia/microbiologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/induzido quimicamente , Tuberculose Pulmonar/microbiologia , Remodelação Vascular
15.
Immunopharmacol Immunotoxicol ; 41(2): 292-298, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31046503

RESUMO

Objective: The current therapeutic regimens for tuberculosis (TB) are complex and involve the prolonged use of multiple antibiotics with diverse side effects that lead to therapeutic failure and bacterial resistance. The standard appliance of immunotherapy may aid as a powerful tool to combat the ensuing threat of TB. We have earlier reported the immunotherapeutic potential of N-formylated peptides of two secretory proteins of Mycobacterium tuberculosis H37Rv. Here, we investigated the immunotherapeutic effect of an N-formylated peptide from Listeria monocytogenes in experimental TB. Methods: The N-terminally formylated listerial peptide with amino acid sequence 'f-MIGWII' was tested for its adjunctive therapeutic efficacy in combination with anti-tuberculosis drugs (ATDs) in the mouse model of TB. In addition, its potential to generate reactive oxygen species (ROS) in murine neutrophils was also evaluated. Results: The LemA peptide (f-MIGWII) induced a significant increase in the intracellular ROS levels of mouse neutrophils (p ≤ .05). The ATD treatment reduced the colony forming units (CFU) in lungs and spleen of infected mice by 2.39 and 1.67 log10 units, respectively (p < .001). Treatment of the infected mice with combination of ATDs and LemA peptide elicited higher therapeutic efficacy over ATDs alone. The histopathological changes in the lungs of infected mice also correlated well with the CFU data. Conclusions: Our results clearly indicate that LemA peptide conferred an additional therapeutic effect when given in combination with the ATDss (p < .01) and hence can be used as adjunct to the conventional chemotherapy against TB.


Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias/farmacologia , Listeria monocytogenes/classificação , Oligopeptídeos/farmacologia , Tuberculose Pulmonar/tratamento farmacológico , Animais , Proteínas de Bactérias/química , Quimioterapia Combinada , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos/imunologia , Neutrófilos/patologia , Oligopeptídeos/química , Espécies Reativas de Oxigênio/imunologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia
16.
J Clin Lab Anal ; 33(6): e22916, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31074534

RESUMO

BACKGROUND: The retrospective study aimed to compare computed tomography (CT)-guided percutaneous needle biopsy (PNB) and endobronchial biopsy (EB) in the diagnosis of multifocal pulmonary lesions with endobronchial involvement. METHODS: Between November 2014 and June 2017, consecutive patients who had underwent both CT-guided PNB and EB via bronchoscopy for diagnosis of pulmonary lesions were evaluated retrospectively. Tissue samples were submitted for pathological examination, acid-fast bacilli, TB RT-PCR, and mycobacterial culture. Sensitivities of the two methods alone or in combination were calculated and compared using Fisher's exact test. RESULTS: Sixty-seven patients (46 men and 21 women) were enrolled and could be diagnosed (32 malignant, 18 TB, and 17 benign). A final diagnosis of either malignant or TB diseases was made in 34 (68.0%) patients for CT-guided PNBs, 19 (38.0%) patients for EBs, and 42 (84.0%) patients for the combination of both methods. Further statistical analysis showed significant difference in sensitivity between CT-guided PNBs, or the combination of both methods, and EBs (all P < 0.05), and no difference between CT-guided PNBs and the combination (P > 0.05). However, the combination of both methods appears to have the highest sensitivity in the detection of malignancies or TB diseases. CONCLUSION: Compared with EB, CT-guided PNB has a high diagnostic yield for the detection of TB and malignancy in patients with multifocal pulmonary lesions with endobronchial involvement. When the two biopsies are combined, it appears to provide an incremental diagnostic value for the pulmonary lesions.


Assuntos
Biópsia por Agulha/métodos , Broncoscopia/métodos , Biópsia Guiada por Imagem/métodos , Pneumopatias/patologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biópsia por Agulha/efeitos adversos , Broncoscopia/efeitos adversos , Feminino , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Pneumotórax/terapia , Estudos Retrospectivos , Sensibilidade e Especificidade , Tuberculose Pulmonar/patologia
17.
PLoS One ; 14(5): e0217457, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31145751

RESUMO

For many years, tuberculosis (TB) has been a major public health problem worldwide. Advances for treatment and eradication have been very limited. Silymarin (Sm) is a natural product with antioxidant and hepatoprotective activities that has been proposed as a complementary medicine to reduce the liver injury produced by the conventional anti-TB chemotherapy. Sm also has immunoregulatory and microbicide properties. In this study, we determined the effect of Sm on the growth control of mycobacteria. In vitro studies showed that Sm and Silibinin (the principal active compound of Sm) have microbicidal activity against drug-sensitive and multidrug-resistant (MDR) mycobacteria, induce the production of protective cytokines from infected macrophages, and improve the growth control of mycobacteria (p ≤ 0.0001). Studies in vivo using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive or MDR mycobacteria have shown that Sm induces significant expression of Th-1 cytokines such as IFN-γ and IL-12 as well as TNFα, which produce significant therapeutic activity when administered alone and apparently have a synergistic effect with chemotherapy. These results suggest that Sm has a bactericidal effect and can contribute to the control and establishment of a TH1 protective immune response against mycobacterial infection. Thus, it seems that this flavonoid has a promising potential as adjuvant therapy in the treatment of TB.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Silimarina/farmacologia , Tuberculose Pulmonar/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antituberculosos/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Tuberculose Extensivamente Resistente a Medicamentos/patologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/patogenicidade , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
18.
PLoS One ; 14(4): e0214131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31039160

RESUMO

BACKGROUND: Assessing Mycobacterium tuberculosis (TB) viability by fluorescein diacetate (FDA) microscopy can predict TB culture results, treatment response and infectiousness. However, diverse methods have been published. We aimed to optimise FDA microscopy, minimising sputum processing, biohazard and complexity for use in resource-constrained settings. METHODS AND RESULTS: Optimization: Patients with smear-positive pulmonary TB before treatment and healthy control participants provided sputa. These were divided into equal aliquots that were tested directly or after NaOH centrifuge-decontamination. Each aliquot was cultured and used to prepare slides (n = 80). FDA microscopy used: 1 or 3 drops of sputum; with/out acid-alcohol wash; with/out phenol sterilization; with 0/30/60 seconds KMnO4 quenching. Control samples all had negative culture and microscopy results. FDA microscopy had higher sensitivity when performed directly (without centrifuge-decontamination) on 1 drop of sputum (P<0.001), because 3 drops obscured microscopy. Acid-alcohol wash and KMnO4 quenching made bacilli easier to identity (P = 0.005). Phenol sterilization did not impair microscopy (P>0.1). Validation: The 2 protocols that performed best in the optimization experiments were reassessed operationally by comparing duplicate slides (n = 412) stained with KMnO4 quenching for 30 versus 60 seconds. FDA microscopy results were similar (P = 0.4) and highly reproducible, with 97% of counts agreeing within +/-1 logarithm. Storage: Smear microscopy slides and aliquots of the sputum from which they were made were stored for 4 weeks. Twice-weekly, paired slides (n = 80) were stained with freshly prepared versus stored FDA and read quantitatively. Storing sputum, microscopy slides or FDA solution at 4°C or room temperature had no effect on FDA microscopy results (all P>0.2). Cost: Material costs for each slide tested by FDA microscopy using reagents purchased locally were USD $0.05 and required the same equipment, time and skills as auramine acid-fast microscopy. CONCLUSIONS: We recommend a simple, bio-secure protocol for FDA microscopy that provides sensitive and repeatable results without requiring centrifugation.


Assuntos
Fluoresceína/química , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Testes Diagnósticos de Rotina , Feminino , Humanos , Microscopia , Mycobacterium tuberculosis/patogenicidade , Escarro/química , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
19.
Intern Med ; 58(17): 2443-2449, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31118378

RESUMO

Objective Although rare, pulmonary tuberculosis occasionally develops in patients with interstitial pneumonia (IP). In this study, we aimed to evaluate the clinicoradiological features of pulmonary tuberculosis associated with IP. Methods In this retrospective, observational, single-center study, the medical charts, high-resolution computed tomography (HRCT) findings, and bacteriological test results of patients with IP who also tested positive for Mycobacterium tuberculosis were reviewed. Patients The study included 20 patients with IP out of 329 who tested positive for M. tuberculosis in sputum or bronchoalveolar lavage fluid cultures at Toranomon Hospital between January 2006 and December 2017. Results The HRCT patterns were usual interstitial pneumonia (UIP) in 11 patients and non-UIP in 9 patients. Consolidations (80%) were the most frequent HRCT findings, followed by cavities (60%) and nodules (45%), which are generally characteristic of pulmonary tuberculosis. Consolidations often developed in relation to fibrotic or emphysematous lesions. Tuberculosis lesions could not be identified in one patient. All patients were treated with anti-tuberculosis drugs according to WHO guidelines, and 13 patients achieved a WHO category of "Treatment success." No patient died of tuberculosis, and the median survival time for the 20 patients was 1,196 days. Conclusion Although the HRCT findings for pulmonary tuberculosis associated with IP are atypical, appropriate tuberculosis treatments can lead to favorable outcomes.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/epidemiologia , Tuberculose Pulmonar/diagnóstico por imagem , Tuberculose Pulmonar/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Líquido da Lavagem Broncoalveolar , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Estudos Retrospectivos , Escarro/microbiologia , Tomografia Computadorizada por Raios X , Tuberculose Pulmonar/patologia
20.
Arch Med Res ; 50(1): 19-20, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31101238

RESUMO

There are severa influencing factors that affect the burden of tuberculosis (TB), including host immune responses and migration. For example, co-infection of parasitic infections with TB suppresses protective immune response against TB. As such, migration is one of the important influencing factors that affect the TB burden, especially in multidrug-resistant (MDR-TB). In this article, these important and neglected factors are discussed.


Assuntos
Antituberculosos/uso terapêutico , Helmintíase/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/imunologia , África ao Sul do Saara , Animais , Europa Oriental , Helmintos/imunologia , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/patologia
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