Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.056
Filtrar
1.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639212

RESUMO

Healthy human lungs have traditionally been considered to be a sterile organ. However, culture-independent molecular techniques have reported that large numbers of microbes coexist in the lung and airways. The lungs harbor diverse microbial composition that are undetected by previous approaches. Many studies have found significant differences in microbial composition between during health and respiratory disease. The lung microbiome is likely to not only influence susceptibility or causes of diseases but be affected by disease activities or responses to treatment. Although lung microbiome research has some limitations from study design to reporting, it can add further dimensionality to host-microbe interactions. Moreover, there is a possibility that extending understanding to the lung microbiome with new multiple omics approaches would be useful for developing both diagnostic and prognostic biomarkers for respiratory diseases in clinical settings.


Assuntos
Interações Hospedeiro-Patógeno , Pneumopatias/microbiologia , Pulmão/microbiologia , Microbiota , Animais , Humanos
2.
BMC Vet Res ; 17(1): 327, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645427

RESUMO

BACKGROUND: Bashbay sheep (Bbs) has a certain degree of resistance to Mycoplasma ovipneumoniae (Mo), however, Argali hybrid sheep (Ahs) is susceptible to Mo. To understand the molecular mechanisms underlying the difference of the susceptibility for Mo infection, RNA-sequencing technology was used to compare the transcriptomic response of the lung tissue of Mo-infected Bbs and Ahs. RESULTS: Six Bbs and six Ahs were divided into experimental group and control group respectively, all of them were experimentally infected with Mo by intratracheal injection. For collecting lung tissue samples, three Bbs and three Ahs were sacrificed on day 4 post-infection, and the others were sacrificed on day 14 post-infection. Total RNA extracted from lung tissue were used for transcriptome analyses based on high-throughput sequencing technique and bioinformatics. The results showed that 212 (146 up-regulated, 66 down-regulated) DEGs were found when comparing transcriptomic data of Bbs and Ahs at 4th dpi, besides, 311 (158 up-regulated, 153 down-regulated) DEGs were found at 14th dpi. After GO analysis, three main GO items protein glycosylation, immune response and positive regulation of gene expression were found related to Mo infection. In addition, there were 20 DEGs enriched in these above items, such as SPLUC1 (BPIFA1), P2X7R, DQA, HO-1 and SP-A (SFTPA-1). CONCLUSIONS: These selected 20 DEGs associated with Mo infection laid the foundation for further study on the underlying molecular mechanism involved in high level of resistance to Mo expressed by Bbs, meanwhile, provided deeper understandings about the development of pathogenicity and host-pathogen interactions.


Assuntos
Predisposição Genética para Doença , Pulmão/microbiologia , Infecções por Mycoplasma/veterinária , Mycoplasma ovipneumoniae/fisiologia , Doenças dos Ovinos/parasitologia , Transcriptoma , Animais , Perfilação da Expressão Gênica/veterinária , Hibridização Genética , Pulmão/metabolismo , Pneumopatias/metabolismo , Pneumopatias/microbiologia , Pneumopatias/veterinária , Infecções por Mycoplasma/microbiologia , RNA/genética , RNA/metabolismo , Ovinos , Doenças dos Ovinos/genética , Transcriptoma/genética
3.
Int J Mol Sci ; 22(18)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34575864

RESUMO

The importance of a healthy microbiome cannot be overemphasized. Disturbances in its composition can lead to a variety of symptoms that can extend to other organs. Likewise, acute or chronic conditions in other organs can affect the composition and physiology of the gut microbiome. Here, we discuss interorgan communication along the gut-lung axis, as well as interactions between lung and coronary heart diseases and between cardiovascular disease and the gut microbiome. This triangle of organs, which also affects the clinical outcome of COVID-19 infections, is connected by means of numerous receptors and effectors, including immune cells and immune-modulating factors such as short chain fatty acids (SCFA) and trimethlamine-N-oxide (TMAO). The gut microbiome plays an important role in each of these, thus affecting the health of the lungs and the heart, and this interplay occurs in both directions. The gut microbiome can be influenced by the oral uptake of probiotics. With an improved understanding of the mechanisms responsible for interorgan communication, we can start to define what requirements an 'ideal' probiotic should have and its role in this triangle.


Assuntos
COVID-19 , Doença das Coronárias , Microbioma Gastrointestinal/efeitos dos fármacos , Pneumopatias , Probióticos/administração & dosagem , Animais , COVID-19/microbiologia , COVID-19/patologia , Doença das Coronárias/microbiologia , Doença das Coronárias/patologia , Humanos , Pneumopatias/microbiologia , Pneumopatias/patologia
4.
Pol J Microbiol ; 70(3): 315-320, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34584525

RESUMO

Mycobacterium chimaera is the newly described species belonging to Mycobacterium avium complex (MAC), with morphology and growth characteristics closely related to Mycobacterium intracellulare. The aim of this retrospective study was to analyze the frequency and clinical significance of M. chimaera identification in the population of patients with previous positive respiratory cultures for M. intracellulare or MAC. 200 strains of M. intracellulare or MAC, isolated from respiratory specimens of patients hospitalized in pulmonary wards, between 2011 and 2020, were retrospectively analyzed with GenoType NTM-DR test. 88 (44%) of strains were re-classified to M. chimaera species. Analysis of clinical data in 30 patients with positive M. chimaera isolates revealed that they were diagnosed with chronic obstructive pulmonary disease (COPD) - 27%, past tuberculosis - 20%, or interstitial lung diseases - 17%, respectively. Non-tuberculous mycobacterial lung disease (NTMLD) caused by M. chimaera has been recognized in 53% of patients, most often in those presenting with post-tuberculous lung lesions. M. chimaera was almost exclusively isolated from respiratory specimens of patients with underlying lung diseases, especially those with COPD and/or past tuberculosis. NTMLD due to M. chimaera was diagnosed predominantly in patients with past tuberculosis.


Assuntos
Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium/fisiologia , Hospitalização/estatística & dados numéricos , Humanos , Pulmão/microbiologia , Pulmão/patologia , Infecções por Mycobacterium não Tuberculosas/patologia , Estudos Retrospectivos
5.
Nutrients ; 13(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34444684

RESUMO

Research on vitamin D in patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) is limited. We aimed to compare the vitamin D parameters of patients with NTM-PD to those of a healthy control group, and to assess the possible predictive markers for a clinical response. We prospectively enrolled 53 patients with NTM-PD between January 2014 and December 2016. The clinical data and vitamin D indices, including total, free, bioavailable 25-(OH)D, and vitamin D binding protein (VDBP) genotyping, were measured at baseline and six months after enrollment. An external dataset of 226 healthy controls was compared with the NTM-PD group. The mean age of subjects was 53 years; 54.5% were male. The NTM-PD group was older, predominantly female, and had a lower body mass index (BMI) than the controls. The proportion of patients with vitamin D concentration <50 nmol/L was 52.8% in the NTM-PD group and 54.9% in the control group (p = 0.789). The bioavailable 25-(OH)D concentrations of the NTM-PD group and the controls were similar (6.9 nmol/L vs. 7.6 nmol/L, p = 0.280). In the multivariable analysis, bioavailable 25-(OH)D concentrations were associated with NTM-PD, adjusting for age, sex, BMI, and VDBP levels. Bioavailable 25-(OH)D concentrations were significantly associated with susceptibility to NTM-PD, but not with treatment outcomes. Lower bioavailable 25-(OH)D might be a risk factor for NTM-PD.


Assuntos
Biomarcadores/sangue , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/sangue , Estado Nutricional/fisiologia , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Disponibilidade Biológica , Estudos de Coortes , Feminino , Genótipo , Humanos , Pneumopatias/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética
6.
J Clin Invest ; 131(15)2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338230

RESUMO

The healthy lung was long thought of as sterile, but recent advances using molecular sequencing approaches have detected bacteria at low levels. Healthy lung bacteria largely reflect communities present in the upper respiratory tract that enter the lung via microaspiration, which is balanced by mechanical and immune clearance and likely involves limited local replication. The nature and dynamics of the lung microbiome, therefore, differ from those of ecological niches with robust self-sustaining microbial communities. Aberrant populations (dysbiosis) have been demonstrated in many pulmonary diseases not traditionally considered microbial in origin, and potential pathways of microbe-host crosstalk are emerging. The question now is whether and how dysbiotic microbiota contribute to initiation or perpetuation of injury. The fungal microbiome and virome are less well studied. This Review highlights features of the lung microbiome, unique considerations in studying it, examples of dysbiosis in selected disease, emerging concepts in lung microbiome-host interactions, and critical areas for investigation.


Assuntos
Pneumopatias , Pulmão , Micobioma , Viroma , Animais , Humanos , Pulmão/microbiologia , Pulmão/virologia , Pneumopatias/microbiologia , Pneumopatias/virologia
7.
BMC Infect Dis ; 21(1): 776, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372796

RESUMO

BACKGROUND: Nocardiosis is known as an opportunistic infection in immunocompromised hosts, but it occasionally has been reported in immunocompetent patient. The Nocardia exalbida is first-reported in 2006 from Japan, and a few cases of have been reported in only immunocompromised host, and the characteristic is still unclear. We herein describe the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. CASE PRESENTATION: A77 -year-old Japanese man was admitted to our hospital on November 2, 2018. He was a lifelong non-smoker with no childhood history of respiratory disease. He had a medical history of dyslipidemia. One month before this admission fevers, sputum, mild cough were developed and he was evaluated in a clinic near our hospital. His diagnosis was community acquired pneumonia within his right middle lobe. He was treated with ceftriaxone 1 g/day intravenously for a week, however his symptoms relapsed a few days later. So, the physician retried ceftriaxone for another 3 days, but his symptoms did not improve. He was referred to our hospital. He was treated with sitafloxacin as an outpatient for a week, however his symptoms got worse. The chest CT showed consolidation and atelectasis in his right middle lobe. Low density area was scattered in consolidation, and right pleural effusion was observed. The patient was diagnosed with pulmonary abscess and he was admitted. Administration of piperacillin/tazobactam improved his condition. We switched antibiotics to amoxicillin/clavulanate, and he was discharged. After 2 weeks, he relapsed and was admitted again. After administration of piperacillin/tazobactam for 3 weeks, we perform bronchoscopy and Nocardia species were cultured from samples of the bronchial wash. The isolates were identified as N. exalbida using 16S rRNA gene sequencing. We prescribed Trimethoprim / Sulfamethoxazole (TMP/SMX) for 4 months. Then we switched to minocycline for renal dysfunction caused from TMP-SMX for 1 more month. After 5 months therapy, Consolidation on CT disappeared, and Nocardiosis was cured. CONCLUSION: we reported the first case of pulmonary nocardiosis caused by N. exalbida in an immunocompetent patient. N. exalbida infection might be associated with a good response to treatment.


Assuntos
Pneumopatias , Nocardiose , Nocardia , Idoso , Humanos , Pneumopatias/microbiologia , Masculino , Nocardia/genética , Nocardia/patogenicidade , Nocardiose/diagnóstico , Nocardiose/tratamento farmacológico , RNA Ribossômico 16S , Combinação Trimetoprima e Sulfametoxazol
8.
BMC Infect Dis ; 21(1): 698, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284734

RESUMO

BACKGROUND: The incidence and prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) are reportedly increasing in many parts of the world. However, there are few published data on NTM-PD-related death. Using data from a national inpatient database in Japan, we aimed in this study to identify the characteristics of patients with NTM-PD and clinical deterioration and to identify risk factors for in-hospital mortality. METHODS: We examined data from the Diagnosis Procedure Combination (DPC) database in Japan from July 2010 to March 2014. We extracted data for HIV-negative NTM-PD patients who required unscheduled hospitalization. We evaluated these patients' characteristics and performed multivariable logistic regression analysis to identify risk factors for all-cause in-hospital mortality. RESULTS: A total of 16,192 patients (median age: 78 years; women: 61.2%) were identified. The median body mass index (BMI) was 17.5 kg/m2 (IQR 15.4-20.0). All cause In-hospital death occurred in 3166 patients (19.6%). The median BMI of the patients who had died was 16.0 kg/m2 (IQR 14.2-18.4). Multivariable analysis revealed that increased mortality was associated with male sex, lower BMI, lower activities of daily living scores on the Barthel index, hemoptysis, and comorbidities, including pulmonary infection other than NTM, interstitial lung disease, pneumothorax, and malignant disease. CONCLUSIONS: We found associations between being underweight and having several comorbidities and increased in-hospital mortality in patients with NTM-PD. Preventing weight loss and management of comorbidities may have a crucial role in improving this disease's prognosis.


Assuntos
Mortalidade Hospitalar , Pneumopatias/mortalidade , Infecções por Mycobacterium não Tuberculosas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Japão/epidemiologia , Pneumopatias/microbiologia , Pneumopatias/terapia , Masculino , Infecções por Mycobacterium não Tuberculosas/terapia , Prognóstico , Fatores de Risco
9.
Acta Biochim Pol ; 68(2): 207-215, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33945245

RESUMO

Pseudomonas aeruginosa, is an opportunistic bacterium with a high prevalence in diverse pulmonary infections. Although several genes are involved in the system of resistance and evasion of the immunological response of the host, little is known about the inflammatory, degradative, and cell-binding response induced by P. aeruginosa in human lung alveolar epithelial cells. The purpose of this study was to determine the cytokine expression (IL-1ß and TNFα), pro matrix metalloproteinases activation (proMMP-2 and proMMP-9), and the effects on the cell-binding adhesion protein (E-cadherin) in an in vitro model of human lung alveolar epithelial cells. A549 cells were stimulated with a different number of colony-forming units of P. aeruginosa for 3, 6, and 24 hours. Subsequently, the culture medium was collected, IL-1ß and TNFα levels were evaluated by ELISA; proMMP-2 and -9 levels were determined by substrate gel zymography, and the MMP-9 and E-cadherin assessed by immunostaining of A549 cells. Our results demonstrated that P. aeruginosa induces mainly the secretion of TNFα, increases actMMP-9 level, and significantly reduces the level of E-cadherin in the A549 cells. In summary, the inflammatory/degradative process induced by P. aeruginosa modulates the expression of the E-cadherin protein. The probable clinical implications of this study suggest the use of inhibitors that reduce the degradative activity of proMMP-9 which will be further explored in the next phase of this study.


Assuntos
Caderinas/metabolismo , Precursores Enzimáticos/metabolismo , Interleucina-1beta/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pseudomonas aeruginosa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Células A549 , Células Epiteliais Alveolares/metabolismo , Sobrevivência Celular , Citocinas/metabolismo , Gelatinases/metabolismo , Humanos , Pulmão/metabolismo , Pneumopatias/metabolismo , Pneumopatias/microbiologia , Infecções por Pseudomonas/metabolismo
10.
Vet Microbiol ; 258: 109123, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34023636

RESUMO

Infections with Mycoplasma hyopneumoniae (Mhyo), Mycoplasma hyorhinis (Mhr) and Mycoplasma flocculare (Mfloc) are common in swine. However, the degree of co-infections and the correlations between these mycoplasma co-infection and the severity of macroscopic lung consolidation lesions (MLCL) have not yet been explored in Brazil.The objectives were to quantify Mhyo, Mhr, and Mfloc in MLCL of slaughter pigs in Brazil, and to assess correlations with the degree of MLCL in slaughter pigs. To this end, five groups of lungs were made based on severity of lung lesions, and 80 lungs were collected for each group (400 lungs in total). The Mycoplasmas were quantified using a multiplex qPCR. Statistical differences and comparison between the groups were evaluated, respectively, by the Kruskal-Wallis test (p < 0.05) and Dunn's test (p < 0.05), and the correlation between the data was performed by Spearman's method (p < 0.05). The results revealed that the extent of MLCL showed a positive correlation with the Mhyo estimate (rho = 0.26; p < 0.05), a negative correlation with the Mfloc estimate (rho= -0.15; p < 0.05), and no significant correlation with the Mhr estimate (p = 0, 12). The extension of MLCL showed a positive correlation with the co-infection by Mfloc and Mhr (rho = 0.17; p < 0.05), and no significant correlation with Mhyo and Mhr (p = 0.87), and a negative correlation with Mhyo and Mfloc (rho= -0.28; p < 0.05). This study allowed to infer that, regarding the extension of MLCL, Mhr and Mfloc did not present opportunistic activity in relation to primary infection by Mhyo, but revealed some potential aggravation of these lesions. In addition, Mhyo expressed inhibitory behavior towards Mfloc, suggesting that one can compete with the other's presence.


Assuntos
Coinfecção/veterinária , Pneumopatias/veterinária , Pulmão/patologia , Infecções por Mycoplasma/veterinária , Mycoplasma/classificação , Doenças dos Suínos/microbiologia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Coinfecção/microbiologia , Regulação Bacteriana da Expressão Gênica/fisiologia , Pulmão/microbiologia , Pneumopatias/microbiologia , Pneumopatias/patologia , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/patologia , Suínos
11.
J Med Microbiol ; 70(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33999797

RESUMO

Introduction. Mycobacterium avium complex (MAC) has been reported as the most common aetiology of lung disease involving nontuberculous mycobacteria.Hypothesis. Antimicrobial susceptibility and clinical characteristics may differ between Mycobacterium avium and Mycobacterium intracellulare.Aim. We aimed to evaluate the differences in antimicrobial susceptibility profiles between two major MAC species (Mycobacterium avium and Mycobacterium intracellulare) from patients with pulmonary infections and to provide epidemiologic data with minimum inhibitory concentration (MIC) distributions.Methodology. Between January 2019 and May 2020, 45 M. avium and 242 M. intracellulare isolates were obtained from Shanghai Pulmonary Hospital. The demographic and clinical characteristics of patients were obtained from their medical records. The MICs of 13 antimicrobials were determined for the MAC isolates using commercial Sensititre SLOWMYCO MIC plates and the broth microdilution method, as recommended by the Clinical and Laboratory Standards Institute (CLSI; Standards M24-A2). MIC50 and MIC90 values were derived from the MIC distributions.Results. M. intracellulare had higher resistance rates than M. avium for most tested antimicrobials except clarithromycin, ethambutol, and ciprofloxacin. Clarithromycin was the most effective antimicrobial against both the M. avium (88.89 %) and M. intracellulare (91.32 %) isolates, with no significant difference between the species (P=0.601). The MIC90 of clarithromycin was higher for M. avium (32 µg ml-1) than M. intracellulare (8 µg ml-1). The MIC50 of rifabutin was more than four times higher for M. intracellulare (1 µg ml-1) than M. avium (≤0.25 µg ml-1). The percentages of patients aged >60 years and patients with sputum, cough, and cavitary lesions were significantly higher than among patients with M. intracellulare infection than M. avium infections.Conclusions. The pulmonary disease caused by distinct MAC species had different antimicrobial susceptibility, symptoms, and radiographic findings.


Assuntos
Antibacterianos/farmacologia , Pneumopatias/microbiologia , Complexo Mycobacterium avium/efeitos dos fármacos , Infecção por Mycobacterium avium-intracellulare/microbiologia , Mycobacterium avium/efeitos dos fármacos , Adulto , Idoso , China , Ciprofloxacina/farmacologia , Claritromicina/farmacologia , Tosse , Doxiciclina/farmacologia , Farmacorresistência Bacteriana , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pneumopatias/fisiopatologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium avium/isolamento & purificação , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/fisiopatologia , Radiografia , Escarro
12.
Nat Commun ; 12(1): 2491, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941780

RESUMO

Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.


Assuntos
Água Potável/microbiologia , Genoma Bacteriano/genética , Pneumopatias/epidemiologia , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Mycobacterium kansasii/genética , Metabolismo Energético/genética , Variação Genética/genética , Genética Populacional/métodos , Genômica , Humanos , Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium kansasii/isolamento & purificação , Virulência/genética , Microbiologia da Água
13.
Int J Antimicrob Agents ; 58(1): 106349, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33905861

RESUMO

Morphologically identified Penicillium (n = 103) and Talaromyces marneffei (n = 8) isolates were collected from various clinical sources between 2016 and 2017 at a medical centre in Beijing, China. Identification to species level was confirmed by sequencing of the internal transcribed spacer (ITS) region, ß-tubulin gene (benA) and RNA polymerase II second largest subunit (RPB2) gene. Of the 111 isolates, 56 (50.5%) were identified as Penicillium spp. and 55 (49.5%) as Talaromyces spp. Eleven species of Penicillium were detected, of which Penicillium oxalicum was the commonest, accounting for 51.8% (29/56), followed by Penicillium rubens (10.7%; 6/56) and Penicillium citrinum (10.7%; 6/56). Among the 55 Talaromyces isolates, nine species were identified, with Talaromyces funiculosus (36.4%; 20/55), Talaromyces stollii (27.3%; 15/55) and Talaromyces marneffei (14.5%; 8/55) being the most common. Of note, 89.3% (50/56) of the Penicillium isolates and 98.2% (54/55) of the Talaromyces isolates exhibited growth at 37°C. The isolates were mainly recovered from patients with pulmonary disorders (56.8%; 63/111), autoimmune disease (12.6%; 14/111) and AIDS (5.4%; 6/111). The azoles and amphotericin B exhibited potent activity against T. marneffei, while various levels of activity were observed against Penicillium and other Talaromyces species The echinocandins had the lowest MECs (MEC90, ≤0.12 mg/L) against most Penicillium and Talaromyces species, with the exception of T. marneffei whose MEC90 (4 mg/L) was five or more dilutions higher than that of the other species tested. These data on the species distribution and antifungal susceptibility expand the current clinical knowledge of Penicillium and Talaromyces species.


Assuntos
Antifúngicos/farmacologia , Pneumopatias/microbiologia , Micoses/microbiologia , Penicillium/efeitos dos fármacos , Talaromyces/efeitos dos fármacos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , DNA Fúngico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Penicillium/classificação , Penicillium/genética , Prevalência , RNA Polimerase II/genética , Talaromyces/classificação , Talaromyces/genética , Tubulina (Proteína)/genética , Adulto Jovem
14.
Chest ; 159(3): e141-e145, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33678281

RESUMO

CASE PRESENTATION: A 51-year-old woman with a medical history of poorly controlled type 1 diabetes mellitus, hyperthyroidism, and tobacco abuse was admitted to the hospital with persistent nausea, vomiting, abdominal discomfort, dry cough, rhinorrhea, and sore throat. She denied fevers, chills, rigors, shortness of breath, hemoptysis, nasal congestion, postnasal drip, and facial pain. She denied any sick contacts, and there was no recent travel outside of Chicago.


Assuntos
Antifúngicos/administração & dosagem , Broncoscopia/métodos , Pneumopatias , Pulmão , Mucormicose , Nitrilas/administração & dosagem , Pneumonectomia/métodos , Piridinas/administração & dosagem , Triazóis/administração & dosagem , Anfotericina B/administração & dosagem , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias/diagnóstico , Pneumopatias/microbiologia , Pneumopatias/fisiopatologia , Pneumopatias/cirurgia , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/cirurgia , Respiração Artificial/métodos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
15.
J Ethnopharmacol ; 277: 114066, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33766755

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liu Shen Wan (LSW) is a traditional Chinese medicine (TCM) with detoxification and antiphlogistic activity; it is composed of bezoar, toad venom, musk, pearl powder, borneol and realgar. In recent years, LSW has been widely used in traditional medicine for the treatment of influenza, tonsillitis, pharyngitis, mumps, cancer and leukaemia. AIM OF STUDY: The anti-influenza virus properties of LSW and its inhibition of the inflammatory response was demonstrated in our previous research; however, the effect and potential mechanism of LSW against influenza induced secondary bacteria have remained obscure. Therefore, in the present study, a model of influenza virus PR8 with secondary infection by Staphylococcus aureus (S. aureus) in vitro and in mice was established to examine the effect and potential mechanism by which LSW inhibits bacterial adhesion and subsequent severe pneumonia after viral infection. MATERIALS AND METHODS: We investigated the effect of LSW on the PR8-induced adhesion of live S. aureus in A549 cells. RT-qPCR was used to detect the expression of adhesion molecules. Western blotting was used to determine the expression of CEACAM1, RIG-1, MDA5, p-NF-κB, and NF-κB in A549 cells. Inflammatory cytokines were detected using a Bio-Plex Pro Human Cytokine Screening Panel (R&D) in A549 cells and Mouse Magnetic Luminex Assays (R&D) in mice infected with PR8 virus and secondarily with S. aureus, respectively. Moreover, the survival rate, lung index, viral titre, bacterial loads and pathological changes in the lung tissue of mice infected with PR8 and S. aureus were investigated to estimate the effect of LSW in inhibiting severe pneumonia. RESULTS: LSW significantly decreased S. aureus adhesion following influenza virus infection in A549 cells, which may have occurred by suppressing expression of the adhesion molecule CEACAM1. In addition, treatment with LSW dramatically suppressed the induction of proinflammatory cytokines (CCL2/MCP-1 and CXCL-9/MIG) and chemokines (IL-6 and TNF-α) by PR8 infection following secondary LPS stimulation in A549 cells. Upregulation of related signalling proteins (RIG-I, MDA5 and NF-κB) induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly decreased the viral titres and bacterial load, prolonged survival time, and ameliorated lung inflammation and injury in mice with S. aureus infection secondary to PR8 infection. CONCLUSIONS: We demonstrated that LSW prevents S. aureus adherence to influenza virus-infected A549 cells, perhaps by inhibiting the expression of the adhesion molecule CEACAM1. The upregulation of proinflammatory cytokines and related signalling proteins induced by viruses and bacteria was suppressed by LSW in A549 cells. LSW significantly ameliorated lung injury caused by viral and secondary bacterial infection. These findings provide a further evaluation of LSW and suggest a beneficial effect of LSW for the prevention of secondary bacterial infection and related complications.


Assuntos
Misturas Complexas/farmacologia , Influenza Humana/complicações , Pneumopatias/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Células A549 , Animais , Citocinas/metabolismo , Cães , Feminino , Humanos , Influenza Humana/tratamento farmacológico , Pneumopatias/microbiologia , Pneumopatias/virologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Taxa de Sobrevida
16.
Clin Drug Investig ; 41(4): 405-412, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33723805

RESUMO

Amikacin liposome inhalation suspension (ALIS) [Arikayce® Liposomal (EU); Arikayce® (USA)], a liposomal suspension of the aminoglycoside amikacin (590 mg) for nebulization via the Lamira® Nebulizer System, is available as add-on therapy for treatment-refractory Mycobacterium avium complex (MAC) lung disease in adults who have little or no alternative treatment options. Its addition to guideline-based therapy (GBT) significantly improved the likelihood of achieving sputum culture conversion (defined as three consecutive monthly MAC-negative sputum cultures) by month 6 relative to GBT alone in adults with treatment-refractory MAC lung disease, with the conversion response maintained over up to 12 months' therapy and at 3 months' post treatment in significantly higher proportions of ALIS plus GBT than GBT alone recipients. ALIS as an add-on therapy to GBT was associated with an increased risk of respiratory adverse reactions compared with GBT alone, but treatment-emergent adverse events associated with systemic amikacin exposure were uncommon.


Assuntos
Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Pneumopatias/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Administração por Inalação , Adulto , Amicacina/efeitos adversos , Humanos , Lipossomos , Pneumopatias/microbiologia , Complexo Mycobacterium avium/efeitos dos fármacos , Escarro/microbiologia
17.
Int J Mol Sci ; 22(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671516

RESUMO

The treatment of lung infection in the context of cystic fibrosis (CF) is limited by a biofilm mode of growth of pathogenic organisms. When compared to planktonically grown bacteria, bacterial biofilms can survive extremely high levels of antimicrobials. Within the lung, bacterial biofilms are aggregates of microorganisms suspended in a matrix of self-secreted proteins within the sputum. These structures offer both physical protection from antibiotics as well as a heterogeneous population of metabolically and phenotypically distinct bacteria. The bacteria themselves and the components of the extracellular matrix, in addition to the signaling pathways that direct their behaviour, are all potential targets for therapeutic intervention discussed in this review. This review touches on the successes and failures of current anti-biofilm strategies, before looking at emerging therapies and the mechanisms by which it is hoped they will overcome current limitations.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Fibrose Cística/microbiologia , Pneumopatias/microbiologia , Alginatos/farmacologia , Antibacterianos/administração & dosagem , Bacteriófagos , Comunicação Celular/efeitos dos fármacos , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Fibrose Cística/complicações , Humanos , Ferro/metabolismo , Pneumopatias/tratamento farmacológico , Percepção de Quorum/efeitos dos fármacos
18.
Eur J Drug Metab Pharmacokinet ; 46(2): 277-287, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33595792

RESUMO

BACKGROUND AND OBJECTIVES: Use of parenteral amikacin to treat refractory nontuberculous mycobacterial (NTM) lung disease is limited by systemic toxicity. A population pharmacokinetic model was developed using data pooled from two randomized trials to evaluate the pharmacokinetic properties of once-daily amikacin liposome inhalation suspension (ALIS) in patients with treatment-refractory NTM lung disease. METHODS: In phase 2 (TR02-112) and phase 3 (CONVERT) studies, patients with sputum cultures positive for Mycobacterium avium complex (both studies) or M. abscessus (TR02-112) despite ≥ 6 months of guideline-based therapy were treated with once-daily ALIS 590 mg. RESULTS: Fifty-three patients (28 Japanese; 25 White) were assessed. At baseline and ≈ 6 months after daily dosing, median maximum concentration (Cmax) was < 2 mg/L and median area under the concentration-time curve (AUC0-24) was < 20 mg·h/L, suggesting low systemic exposure at both time points. Exposure estimates were similar between Japanese and White patients. The median unchanged amikacin fraction excreted in urine was < 10% of inhaled dose throughout the TR02-112 study, indicating that relatively small amounts reached systemic circulation. Median t1/2 was 5.5 h. Amikacin concentrations were much higher in sputum than in serum, demonstrating the ability to achieve higher drug concentration at the site of infection. Median sputum amikacin concentrations in the CONVERT study were high at 1-4 h postdose (range 242-426 µg/g) and decreased by 8 h (median 7 µg/g). CONCLUSIONS: Systemic exposure to amikacin in serum and urine following once-daily ALIS administration in patients with treatment-refractory NTM lung disease was notably lower than that previously reported for parenteral amikacin. TRIAL REGISTRATION: ClinicalTrials.gov NCT01315236 (registered March 15, 2011) and NCT02344004 (registered January 22, 2015).


Assuntos
Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Pneumopatias/tratamento farmacológico , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Idoso de 80 Anos ou mais , Amicacina/farmacocinética , Antibacterianos/farmacocinética , Área Sob a Curva , Método Duplo-Cego , Feminino , Humanos , Lipossomos , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Complexo Mycobacterium avium/isolamento & purificação , Infecção por Mycobacterium avium-intracellulare/microbiologia , Estudos Prospectivos , Fatores de Tempo , Distribuição Tecidual , Resultado do Tratamento , Adulto Jovem
20.
Benef Microbes ; 12(2): 175-186, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33573506

RESUMO

Allergies are a world increasing health issue and most treatments are oriented to alleviate symptoms. Probiotics have several health benefits including the improvement of the immune system. In previous work we found that consumption of commercial probiotic fermented milk (PFM) significantly reduced specific-immunoglobulin (Ig) E in serum and lungs by increasing specific-IgG and controlled allergic response to ovalbumin (OVA) in an adult mouse respiratory allergy model. Here we continued our study determining the mechanism triggered in the gut by the PFM ingestion that influenced the results previously reported. Five groups of BALB/c mice were assessed: normal-control, basal (drinks PFM five days without OVA sensitisation), sensitisation-control (no PFM intake), previous and continuous-PFM administration. Allergen administration: 3 OVA injections (1% in PBS) followed by aerosols exposure for 7 days. We determined total secretory-IgA and cytokines in small intestine (SI) fluid; CD11b+, CD103+, IgA+ cells and cytokine producing cells in SI tissue. In lungs we analysed co-expression of CD4/interferon (IFN)-γ or CD4/interleukin (IL)-10, IgE+ cells and IL-12 production. Results: continuous intake of PFM increased the expression of CD103 marker and decreased CD11b and pro-inflammatory cytokines. Coexpression of CD4/IFN-γ was confirmed in lungs of animals that consumed PFM continuously. This group had a lower count of IgE+ cells and a higher concentration of IL-12. The consumption of PFM reinforces the mucosal barrier by increasing IgA+ cells and induces signalling from the intestine to the lungs by increasing the expression of CD103+ dendritic cells related to regulatory mechanisms. The results found in this work together with those previously reported demonstrated that the intake of PFM induces a clear balance towards the Th1 response, preventing the Th2 allergic response by controlling the previously reported IgE level. According to our model, the intake of PFM could be a good strategy to alleviate the development of allergies.


Assuntos
Produtos Fermentados do Leite/microbiologia , Hipersensibilidade/tratamento farmacológico , Imunoglobulina E/imunologia , Intestino Delgado/imunologia , Pneumopatias/tratamento farmacológico , Probióticos/administração & dosagem , Animais , Produtos Fermentados do Leite/análise , Células Dendríticas/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Hipersensibilidade/microbiologia , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/genética , Interleucina-10/imunologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/microbiologia , Pneumopatias/genética , Pneumopatias/imunologia , Pneumopatias/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Th1/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...