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1.
Sci Transl Med ; 11(499)2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31270271

RESUMO

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor best known for regulating cell proliferation and metabolism. PTEN forms a complex with the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) at the plasma membrane, and this complex is known to be functionally impaired in CF. Here, we demonstrated that the combined effect of PTEN and CFTR dysfunction stimulates mitochondrial activity, resulting in excessive release of succinate and reactive oxygen species. This environment promoted the colonization of the airway by Pseudomonas aeruginosa, bacteria that preferentially metabolize succinate, and stimulated an anti-inflammatory host response dominated by immune-responsive gene 1 (IRG1) and itaconate. The recruitment of myeloid cells induced by these strains was inefficient in clearing the infection and increased numbers of phagocytes accumulated under CFTR-PTEN axis dysfunction. This central metabolic defect in mitochondrial function due to impaired PTEN activity contributes to P. aeruginosa infection in CF.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Pulmão/microbiologia , Mitocôndrias/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Infecções por Pseudomonas/metabolismo , Animais , Carboxiliases/metabolismo , Contagem de Colônia Microbiana , Fibrose Cística/patologia , Células HCT116 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imunidade , Interleucina-1beta/metabolismo , Pulmão/imunologia , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Oxidantes/metabolismo , Estresse Oxidativo , PTEN Fosfo-Hidrolase/deficiência , Pseudomonas aeruginosa/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Succinatos/metabolismo
2.
Genome Announc ; 5(46)2017 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-29146850

RESUMO

The draft genome sequences of two Nocardia farcinica strains isolated from two patients with cystic fibrosis (CF), resistant to trimethoprim/sulfamethoxazole and linezolid, are reported here. The estimated genome sizes were 5.8 Mb with a 70.63% G+C content. Transposases from Tn916 were detected, but not 23S rRNA mutation (G2576T) related to linezolid resistance.

3.
Infect Dis (Lond) ; 47(5): 277-82, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25835092

RESUMO

Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Síndrome da Imunodeficiência Adquirida/complicações , Infecções por HIV/complicações , Toxoplasma/isolamento & purificação , Toxoplasmose/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/terapia , Terapia Antirretroviral de Alta Atividade , Humanos , Masculino , Pessoa de Meia-Idade , Mielite/complicações , Mielite/diagnóstico , Mielite/terapia , Doenças do Sistema Nervoso/patologia , Medula Espinal/patologia , Toxoplasmose/diagnóstico , Toxoplasmose/terapia , Toxoplasmose Cerebral/complicações , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/terapia
4.
Travel Med Infect Dis ; 11(5): 329-31, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23267716

RESUMO

Tuberculosis is an infectious disease caused by the acid-fast bacilli Mycobacterium tuberculosis that usually affects the lungs although it may affect any organ. Tuberculous osteitis of the cranial bones is an uncommon manifestation of disseminated tuberculosis known as calvarial tuberculosis. Cases with parenchymal involvement are infrequent in the literature. We report a case of a patient with multiple osteolytic cranial lesions and a tuberculoma.


Assuntos
Encefalopatias/metabolismo , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Osteoarticular/patologia , Encefalopatias/diagnóstico por imagem , Encefalopatias/patologia , Cotovelo/microbiologia , Feminino , Osso Frontal/diagnóstico por imagem , Osso Frontal/patologia , Humanos , Pessoa de Meia-Idade , Paquistão , Couro Cabeludo/diagnóstico por imagem , Couro Cabeludo/patologia , Tomografia Computadorizada por Raios X , Tuberculose Osteoarticular/diagnóstico por imagem , Tuberculose Osteoarticular/microbiologia
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