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1.
Zhongguo Zhong Yao Za Zhi ; 48(10): 2606-2612, 2023 May.
Artigo em Chinês | MEDLINE | ID: covidwho-20244902

RESUMO

Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic herbal formula. All of them are derived from Treatise on Cold Damage(Shang Han Lun) by ZHANG Zhong-jing. This combination has the effects of harmonizing lesser yang, relieving exterior syndrome, clearing lung heat, and relieving panting. It is mainly used for treating the disease involving the triple-Yang combination of diseases and accumulation of pathogenic heat in the lung. Xiao Chaihu Decoction combined with Maxing Shigan Decoction is a classic combination for the treatment of exogenous diseases involving the triple-Yang combination. They are commonly used in exogenous diseases, especially in the north of China. This combination is also the main treatment strategy for coronavirus disease 2019(COVID-19) accompanied by fever and cough. Maxing Shigan Decoction is a classical herbal formula for treating the syndrome of phlegm-heat obstructing the lung. "Dyspnea after sweating" suggests the accumulation of pathogenic heat in the lung. Patients with mild symptoms may develop cough and asthma along with forehead sweating, and those in critical severe may develop whole-body sweating, especially the front chest. Modern medicine believes that the above situation is related to lung infection. "Mild fever" refers to syndromes rather than pathogenesis. It does not mean that the heat syndrome is not heavy, instead, it suggests that severe heat and inflammation have occurred. The indications of Xiao Chaihu Decoction combined with Maxing Shigan Decoction are as follows.(1) In terms of diseases, it is suitable for the treatment of viral pneumonia, bronchopneumonia, lobar pneumonia, mycoplasma pneumonia, COVID-19 infection, measles with pneumonia, severe acute respiratory syndrome(SARS), avian influenza, H1N1 influenza, chronic obstructive pulmonary disease with acute exacerbation, pertussis, and other influenza and pneumonia.(2) In terms of syndromes, it can be used for the syndromes of bitter mouth, dry pharynx, vertigo, loss of appetite, vexation, vomiting, and fullness and discomfort in the chest and hypochondrium. It can also be used to treat alternate attacks of chill and fever and different degrees of fever, as well as chest tightness, cough, asthma, expectoration, dry mouth, wanting cold drinks, feeling agitated, sweating, yellow urine, dry stool, red tongue, yellow or white fur, and floating, smooth, and powerful pulse, especially the right wrist pulse.


Assuntos
Asma , COVID-19 , Medicamentos de Ervas Chinesas , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Doença Pulmonar Obstrutiva Crônica , Animais , Humanos , Tosse , Síndrome , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Pulmão , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Cuidados Críticos , Medicina Tradicional Chinesa
2.
Microbiol Spectr ; : e0427522, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: covidwho-2255440

RESUMO

Colistin is a bactericidal antibiotic identified decades ago which is active against a number of Gram-negative pathogens. After early elimination from clinical use due to toxicity issues, colistin has been reintroduced as a last-resort treatment for antibiotic-resistant Gram-negative infections lacking other therapeutic options. Inevitably, colistin resistance has emerged among clinical isolates, making the development of colistin adjuvants extremely beneficial. Clofoctol is a synthetic antibiotic active against Gram-positive bacteria, with low toxicity and high tropism for the airways. Interestingly, clofoctol has been found to have multiple biological activities and has been proposed for the treatment of several obstructive lung diseases, including asthma, lung cancer, and SARS-CoV-2 infection. In this study, the activity of clofoctol as a colistin adjuvant was investigated in Gram-negative lung pathogens that are critical for the high prevalence of multidrug-resistant isolates, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Clofoctol potentiated the bactericidal effect of colistin in all tested strains and reduced colistin MICs below the susceptibility breakpoint in nearly all colistin-resistant strains. Overall, this observation supports the development of inhaled clofoctol-colistin formulations for the treatment of difficult-to-treat airway infections caused by Gram-negative pathogens. IMPORTANCE Colistin is used as a last-resort antibiotic against extensively drug-resistant Gram-negative pathogens. However, colistin resistance is on the rise. Clofoctol is an antibiotic used against Gram-positive bacteria, with low toxicity and high penetration and storage in the airways. Here, a strong synergistic activity of the colistin-clofoctol combination against colistin-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii isolates is reported, supporting the development of clofoctol-colistin formulations for the therapy of difficult-to-treat airways infections caused by these Gram-negative pathogens.

3.
Trop Med Infect Dis ; 7(12)2022 Dec 11.
Artigo em Inglês | MEDLINE | ID: covidwho-2155274

RESUMO

OBJECTIVES: In COVID-19 patients, bacterial and fungal pulmonary coinfections, such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, or Aspergillus, have been reported, but to our knowledge, no case has been reported due to Pasteurella multocida. PATIENTS AND METHODS: We describe three cases of Pasteurella multocida coinfections occurring during the 4th wave of COVID-19 in Martinique (French West Indies). RESULTS: All three cases were fatal; thus, Pasteurella multocida has to be considered as a potentially severe coinfection agent. CONCLUSIONS: Alteration of the epithelial-endothelial barrier due to a SARS-CoV-2 infection probably promotes the expression of a Pasteurella infection. In addition, the SARS-CoV-2 infection induced immunosuppression, and an inflammatory cascade could explain the infection's severity. The use of corticosteroids, which are part of the first-line therapeutic arsenal against COVID-19, may also promote the pathogenicity of this agent.

4.
Diagnostics (Basel) ; 12(4)2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1785561

RESUMO

Intra-vesical instillations with bacillus Calmette-Guerin (BCG) are the established adjuvant therapy for superficial bladder cancer. Although generally safe and well tolerated, they may cause a range of different, local, and systemic complications. We present a patient treated with BCG instillations for three years, who was admitted to our hospital due to fever, hemoptysis, pleuritic chest pain and progressive dyspnea. Chest computed tomography (CT) showed massive bilateral ground glass opacities, partly consolidated, localized in the middle and lower parts of the lungs, bronchial walls thickening, and bilateral hilar lymphadenopathy. PCR tests for SARS-CoV-2 as well as sputum, blood, and urine for general bacteriology-were negative. Initial empiric antibiotic therapy was ineffective and respiratory failure progressed. After a few weeks, a culture of M. tuberculosis complex was obtained from the patient's specimens; the cultured strain was identified as Mycobacterium bovis BCG. Anti-tuberculous treatment with rifampin (RMP), isoniazid (INH) and ethambutol (EMB) was implemented together with systemic corticosteroids, resulting in the quick improvement of the patient's clinical condition. Due to hepatotoxicity and finally reported resistance of the BCG strain to INH, levofloxacin was used instead of INH with good tolerance. Follow-up CT scans showed partial resolution of the pulmonary infiltrates. BCG infection in the lungs must be taken into consideration in every patient treated with intra-vesical BCG instillations and symptoms of protracted infection.

5.
Methods Cell Biol ; 168: 329-341, 2022.
Artigo em Inglês | MEDLINE | ID: covidwho-1628694

RESUMO

As more infectious viruses emerge that result in respiratory illness, there is a significant need to standardize airway harvests and maximize data acquisition. Animal models of respiratory viral infections have been outlined to allow for the analysis of the host immune response and viral pathogenesis kinetics. This chapter outlines two separate tissue harvest protocols following the intranasal infection of mice to investigate both the host immune response and viral pathogenesis. These protocols combine standard laboratory techniques for the analysis of the samples, making it easily integrable for labs without the need for specialized training. In offering two separate yet parallel tissue collection techniques, investigators can ultimately decide which technique will yield the best data for their particular research questions and can maximize data from each animal study.


Assuntos
Pneumonia , Vírus , Animais , Imunidade , Camundongos
6.
Front Biosci (Landmark Ed) ; 26(12): 1607-1612, 2021 12 30.
Artigo em Inglês | MEDLINE | ID: covidwho-1614663

RESUMO

PURPOSE: The aim of this observational study was to highlight high resolution CT scan characteristics of COVID-19-associated pulmonary aspergillosis (CAPA) with a focus on the detection of de-novo appeared or evolved bronchiectasis. METHODS: From March 2020 to May 2021, we enrolled 350 consecutive mechanically ventilated ICU patients with COVID-19. Patients with CAPA and at least one chest CT scan performed within 15 days from the diagnosis were included. Two radiologists were asked to identify typical and atypical signs of COVID-19 pneumonia. Bronchiectasis locations were described and a modified Reiff score was calculated, as severity score. A total of 19 CAPA patients (median age 71.0, Interquartile range (IQR) 62.5-75.0; male 16, 84.2%) were included. RESULTS: According to the 2020 ECMM/ISHAM criteria, 18 patients had probable CAPA and one had proven CAPA. The median time between hospital admission and CT scan was 21 days (IQR 14.5-25.0). The incidence of bronchiectasis in the study population was 57.9% (n = 11). Tubular bronchiectasis was detected in 10 patients and were scored as follows: three patients had a score of 1, three patients had a score of score 2, one patient had a score of 5 and four patients had a score of 6. Eight patients had a previous CT scan (performed at hospital admission), among them: 5 patients developed de-novo bronchiectasis, while 2 patients demonstrated a volumetric increase of bronchiectasis. At the 6-months follow-up, the mortality rate for patients with CAPA was >60%. CONCLUSION: the radiologic detection of de-novo appearance or volumetric increase of bronchiectasis in COVID-19 should lead clinicians to search for fungal superinfections.


Assuntos
Bronquiectasia , COVID-19 , Aspergilose Pulmonar Invasiva , Aspergilose Pulmonar , Idoso , Bronquiectasia/diagnóstico por imagem , Humanos , Masculino , SARS-CoV-2 , Tomografia , Tomografia Computadorizada por Raios X
7.
Int Immunopharmacol ; 99: 107961, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: covidwho-1300823

RESUMO

BACKGROUND: COVID-19, which is a disease caused by the SARS-CoV-2 virus, has spread around the world since late 2019. Studies have found associations between the rising levels of TNF-α and severe COVID-19 cases. Hence, TNF-α blocking can possibly be a favorable intervention in modifying COVID-19. To this end, in order to manage pneumonia caused by COVID-19, adalimumab may potentially be considered as a potential therapeutic agent. The present study aimed to investigate the potential therapeutic role of adalimumab in treating COVID-19 cases in combination therapy with remdesivir and dexamethasone. METHODS: Among the 68 patients who were included in the current randomized controlled trial, 34 were assigned to the adalimumab group and the remaining 34 were assigned to the control group. Adalimumab at a dose of 40 mg, subcutaneous for once, was used for the intervention group. Both the intervention and control groups received remdesivir, dexamethasone, and supportive care. The data gathered to make comparisons of the groups included demographic information, the rate of mortality, mechanical ventilation requirement, length of stay in hospital and Intensive Care Unit (ICU), and imaging findings. RESULTS: There was no significant difference between the two groups in the terms of mortality rate (P-value = 1) and mechanical ventilation requirement (P-value = 1). The length of hospital and ICU stay as well as radiologic changes were not affected either (P-value = 1, 0.27, and 0.53, respectively). CONCLUSIONS: Our findings did not support the use of adalimumab in combination with remdesivir and dexamethasone in the treatment of severe COVID-19 cases.


Assuntos
Adalimumab/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Dexametasona/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Respiração Artificial
8.
Microb Pathog ; 156: 104903, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-1211071

RESUMO

To investigate the distribution and risk factors of pathogens in secondary pulmonary infection in patients with COVID-19.142 patients with confirmed COVID-19 from Shanghai Public Health Clinical Center were collected, and 32 patients with pulmonary infection were taken as the infection group. The distribution of pathogens in the sputum specimens was applied for retrospective analysis. Meanwhile, 110 patients diagnosed with COVID-19, but without pulmonary infection were regarded as the asymptomatic group. The risk factors of pulmonary infection were analyzed with generalized linear models and logistic regression. The pathogens in the lung infection group were mainly gram-negative bacteria (22, 68.8%), especially Klebsiella pneumoniae. Gram-positive bacteria and fungi accounted for 13 (40.6%), mainly Staphylococcus aureus, and 11 (34.4%), mainly Candida albicans. There were 14 cases (43.8%) infected with two or more pathogens. The comparison between the two groups found that, patients with elder age, underlying diseases, more lung lesions and low protein contents, were more likely to develop lung infections. At last, univariate analysis showed that 6 factors, including indwelling gastric catheter, the number of deep vein catheters, tracheal intubation tracheotomy, invasive mechanical ventilation, hormonal application, and the use of more than three antibacterial drugs, are risk factors for COVID-19 secondary pulmonary infection. Generalized linear models and logistic regression analysis showed antimicrobial use as an independent risk factor for COVID-19 secondary lung infection. There are many risk factors for secondary lung infection in severe COVID-19 patients, and it is recommended to use antibiotics reasonably.


Assuntos
COVID-19 , Idoso , China/epidemiologia , Humanos , Pulmão , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
9.
Wien Klin Wochenschr ; 133(17-18): 979-982, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: covidwho-1188097

RESUMO

The potential mid-term and long-term consequences after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are as yet unknown. This is the first report of bronchoscopically verified organizing pneumonia as a complication of coronavirus disease 2019 (Covid19). It caused persisting dyspnea, impaired pulmonary function, and radiological abnormalities over 5 weeks after onset of symptoms. While organizing pneumonia frequently requires treatment with systemic corticosteroids, in this case it resolved spontaneously without treatment after 6 weeks. Healthcare professionals should consider organizing pneumonia in patients with persisting respiratory symptoms after Covid19.


Assuntos
COVID-19 , Pneumonia , Humanos , Pulmão , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , SARS-CoV-2
10.
J Control Release ; 330: 284-292, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: covidwho-932122

RESUMO

Pulmonary melioidosis is a bacterial disease with high morbidity and a mortality rate that can be as high as 40% in resource-poor regions of South Asia. This disease burden is linked to the pathogen's intrinsic antibiotic resistance and protected intracellular localization in alveolar macrophages. Current treatment regimens require several antibiotics with multi-month oral and intravenous administrations that are difficult to implement in under-resourced settings. Herein, we report that a macrophage-targeted polyciprofloxacin prodrug acts as a surprisingly effective pre-exposure prophylactic in highly lethal murine models of aerosolized human pulmonary melioidosis. A single dose of the polymeric prodrug maintained high lung drug levels and targeted an intracellular depot of ciprofloxacin to the alveolar macrophage compartment that was sustained over a period of 7 days above minimal inhibitory concentrations. This intracellular pharmacokinetic profile provided complete pre-exposure protection in a BSL-3 model with an aerosolized clinical isolate of Burkholderia pseudomallei from Thailand. This total protection was achieved despite the bacteria's relative resistance to ciprofloxacin and where an equivalent dose of pulmonary-administered ciprofloxacin was ineffective. For the first time, we demonstrate that targeting the intracellular macrophage compartment with extended antibiotic dosing can achieve pre-exposure prophylaxis in a model of pulmonary melioidosis. This fully synthetic and modular therapeutic platform could be an important therapeutic approach with new or re-purposed antibiotics for melioidosis prevention and treatment, especially as portable inhalation devices in high-risk, resource-poor settings.


Assuntos
Melioidose , Pró-Fármacos , Animais , Humanos , Pulmão , Macrófagos Alveolares , Melioidose/tratamento farmacológico , Melioidose/prevenção & controle , Camundongos , Polímeros
11.
Pol J Radiol ; 86: e172-e176, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1173027

RESUMO

PURPOSE: In December 2019, a new coronavirus (SARS-CoV-2) was identified as being responsible for the pulmonary infection called COVID-19. On 21 February 2020, the first autochthonous case of COVID-19 was detected in Italy. Our goal is to report the most common chest computed tomography (CT) findings identified in 64 patients, in the initial phase of COVID-19. METHODS: Sixty-four chest high-resolution computed tomography (HRCT) examinations performed at the Radiology Unit of the Hospital of Cremona, from 22 to 29 February 2020, of 64 patients during first week of hospitalization for COVID-19 were retrospectively evaluated. All cases were confirmed by real-time RT-PCR for SARS-CoV-2. Image analysis was independently conducted by 2 radiologists with 10 years and 1 year of experience in chest imaging. The inter-observer agreement was obtained by applying a Cohen's κ test. RESULTS: The average age of patients was 67.1 years (± 12.2); men 42 (66%). HRCT was performed on the 5th (± 1.5) day of hospitalization. More frequently, the initial CT changes of the lung show more or less extensive areas of ground-glass, as single pattern or with parenchymal consolidations. Coronavirus lung involvement appears very frequently multi-lobar, bilateral, and it concerns both subpleural and central regions. An excellent agreement (κ: 0.88-1, CI: 0.79-1.01, p < 0.05) concerning CT findings between the 2 operators was reached. CONCLUSIONS: Our data suggest that detection of the most frequent pulmonary CT-scan changes, in the early stages of COVID-19, can be performed, with excellent agreement, among readers with different experience, and consequently attribute their exact diagnostic value, in an appropriate clinical and environmental exposure setting.

12.
PeerJ Comput Sci ; 7: e349, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1097462

RESUMO

Currently, the new coronavirus disease (COVID-19) is one of the biggest health crises threatening the world. Automatic detection from computed tomography (CT) scans is a classic method to detect lung infection, but it faces problems such as high variations in intensity, indistinct edges near lung infected region and noise due to data acquisition process. Therefore, this article proposes a new COVID-19 pulmonary infection segmentation depth network referred as the Attention Gate-Dense Network- Improved Dilation Convolution-UNET (ADID-UNET). The dense network replaces convolution and maximum pooling function to enhance feature propagation and solves gradient disappearance problem. An improved dilation convolution is used to increase the receptive field of the encoder output to further obtain more edge features from the small infected regions. The integration of attention gate into the model suppresses the background and improves prediction accuracy. The experimental results show that the ADID-UNET model can accurately segment COVID-19 lung infected areas, with performance measures greater than 80% for metrics like Accuracy, Specificity and Dice Coefficient (DC). Further when compared to other state-of-the-art architectures, the proposed model showed excellent segmentation effects with a high DC and F1 score of 0.8031 and 0.82 respectively.

13.
Int Immunopharmacol ; 90: 107205, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: covidwho-1065216

RESUMO

BACKGROUND: The newly discovered coronavirus has turned into coronavirus disease 2019 (COVID-19) pandemic and it rages at an unprecedented rate. Considering the findings of previous studies on the use of Intravenous Immunoglobulin (IVIg) for treating severe H1N1 infection and the satisfying results for reducing viral load and mortality, this study aimed to investigate the potential usefulness of IVIg for the management of severe cases. METHODS: In this randomized controlled trial, 84 patients were included: 52 in the IVIg group and 32 in the control group. The intervention group received IVIg at a dose of 400 mg/kg, IV, daily for three days. Both groups received hydroxychloroquine, lopinavir/ritonavir and supportive care. The demographic data, mortality rate, the need for mechanical ventilation, length of stay in hospital and in Intensive Care Unit (ICU), and imaging findings were recorded and compared in terms of the mentioned factors. RESULTS: The mean time from admission to IVIg initiation was 3.84 ± 3.35 days. There was no significant difference between the two groups in terms of mortality rate (P-value = 0.8) and the need for mechanical ventilation (P-value = 0.39). The length of hospital stay was significantly lower for the control group than that of the intervention group (P-value = 0.003). There was a significant positive relationship between the time from hospital admission to IVIg initiation and the length of stay in the hospital and ICU among the survivors (P-value < 0.001 and =0.01, respectively). CONCLUSIONS: Our findings did not support the use of IVIg in combination with hydroxychloroquine and lopinavir/ritonavir in treatment of severe COVID-19 cases.


Assuntos
Tratamento Farmacológico da COVID-19 , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , SARS-CoV-2 , Adulto , Idoso , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Tempo de Internação , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ritonavir/uso terapêutico , Resultado do Tratamento
14.
Antioxidants (Basel) ; 10(1)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: covidwho-1042079

RESUMO

Supplemental oxygen therapy with supraphysiological concentrations of oxygen (hyperoxia; >21% O2) is a life-saving intervention for patients experiencing respiratory distress. However, prolonged exposure to hyperoxia can compromise bacterial clearance processes, due to oxidative stress-mediated impairment of macrophages, contributing to the increased susceptibility to pulmonary infections. This study reports that the activation of the α7 nicotinic acetylcholine receptor (α7nAChR) with the delete allosteric agonistic-positive allosteric modulator, GAT107, decreases the bacterial burden in mouse lungs by improving hyperoxia-induced lung redox imbalance. The incubation of RAW 264.7 cells with GAT107 (3.3 µM) rescues hyperoxia-compromised phagocytic functions in cultured macrophages, RAW 264.7 cells, and primary bone marrow-derived macrophages. Similarly, GAT107 (3.3 µM) also attenuated oxidative stress in hyperoxia-exposed macrophages, which prevents oxidation and hyper-polymerization of phagosome filamentous actin (F-actin) from oxidation. Furthermore, GAT107 (3.3 µM) increases the (1) activity of superoxide dismutase 1; (2) activation of Nrf2 and (3) the expression of heme oxygenase-1 (HO-1) in macrophages exposed to hyperoxia. Overall, these data suggest that the novel α7nAChR compound, GAT107, could be used to improve host defense functions in patients, such as those with COVID-19, who are exposed to prolonged periods of hyperoxia.

15.
Open Forum Infect Dis ; 8(7): ofab016, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: covidwho-1033836

RESUMO

We report 2 cases of severe coronavirus disease 2019 requiring prolonged hospitalization complicated by the late onset of opportunistic fungal infections, histoplasmosis, and cryptococcosis.

16.
Int J Environ Res Public Health ; 17(21)2020 10 22.
Artigo em Inglês | MEDLINE | ID: covidwho-983192

RESUMO

Osteoporosis is a public health concern all over the world. As a chronic condition, it generally requires prolonged medical interventions to limit the risks of further bone loss, impaired skeletal integrity and the onset of fractures. This problem is further complicated by the fact that the abrupt cessation of some therapies may be associated with an increased risk of harm. It is in this context that the COVID-19 pandemic has caused an unprecedented disruption to the provision of healthcare worldwide, exceeding our worst expectations in terms of the number of lives lost and the rapidity at which consolidated economies and healthcare systems are being significantly damaged. In this review, we assessed the challenges and strategies used in the management of osteoporosis and fragility fracture care during the COVID-19 pandemic. We also examined the available evidence and provided clinical recommendations that will require reassessment as the worldwide response to COVID-19 evolves.


Assuntos
Infecções por Coronavirus/epidemiologia , Osteoporose/terapia , Fraturas por Osteoporose/terapia , Pneumonia Viral/epidemiologia , Betacoronavirus , COVID-19 , Humanos , Fraturas por Osteoporose/prevenção & controle , Pandemias , SARS-CoV-2
17.
Mol Med ; 26(1): 98, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: covidwho-894987

RESUMO

BACKGROUND: Mechanical ventilation, in combination with supraphysiological concentrations of oxygen (i.e., hyperoxia), is routinely used to treat patients with respiratory distress, such as COVID-19. However, prolonged exposure to hyperoxia compromises the clearance of invading pathogens by impairing macrophage phagocytosis. Previously, we have shown that the exposure of mice to hyperoxia induces the release of the nuclear protein high mobility group box-1 (HMGB1) into the pulmonary airways. Furthermore, extracellular HMGB1 impairs macrophage phagocytosis and increases the mortality of mice infected with Pseudomonas aeruginosa (PA). The aim of this study was to determine whether GTS-21 (3-(2,4-dimethoxybenzylidene) anabaseine), an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, could (1) inhibit hyperoxia-induced HMGB1 release into the airways; (2) enhance macrophage phagocytosis and (3) increase bacterial clearance from the lungs in a mouse model of ventilator-associated pneumonia. METHOD: GTS-21 (0.04, 0.4, and 4 mg/kg) or saline were administered by intraperitoneal injection to mice that were exposed to hyperoxia (≥ 99% O2) and subsequently challenged with PA. RESULTS: The systemic administration of 4 mg/kg i.p. of GTS-21 significantly increased bacterial clearance, decreased acute lung injury and decreased accumulation of airway HMGB1 compared to the saline control. To determine the mechanism of action of GTS-21, RAW 264.7 cells, a macrophage-like cell line, were incubated with different concentrations of GTS-21 in the presence of 95% O2. The phagocytic activity of macrophages was significantly increased by GTS-21 in a dose-dependent manner. In addition, GTS-21 significantly inhibited the cytoplasmic translocation and release of HMGB1 from RAW 264.7 cells and attenuated hyperoxia-induced NF-κB activation in macrophages and mouse lungs exposed to hyperoxia and infected with PA. CONCLUSIONS: Our results indicate that GTS-21 is efficacious in improving bacterial clearance and reducing acute lung injury via enhancing macrophage function by inhibiting the release of nuclear HMGB1. Therefore, the α7nAChR represents a possible pharmacological target to improve the clinical outcome of patients on ventilators by augmenting host defense against bacterial infections.


Assuntos
Compostos de Benzilideno/farmacologia , Hiperóxia/imunologia , Macrófagos Alveolares/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Piridinas/farmacologia , Lesão Pulmonar Induzida por Ventilação Mecânica/tratamento farmacológico , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Proteína HMGB1/metabolismo , Hiperóxia/dietoterapia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Pseudomonas aeruginosa , Células RAW 264.7
18.
Clin Respir J ; 14(2): 78-84, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: covidwho-824769

RESUMO

OBJECTIVES: To demonstrate the value of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) when determining causes of lung infection in immunocompromised children; to investigate differences in causes and radiological features of lung infections following bone marrow transplantation (BMT) compared to other immunosuppressive conditions; to evaluate the reliability of radiological findings when predicting the pathogen. METHODS: We retrospectively evaluated 132 immunosuppressed children who underwent FB and BAL because pulmonary complications between January 1999 and May 2014 at the Hacettepe University Hospital Pediatric Pulmonology Unit. Two groups, Group I (n = 106) and Group II (n = 26), consisted of patients who had primary or secondary immunodeficiency and those who were immunosuppressed because BMT, respectively. Radiological findings before FB and macroscopic and microscopic findings of the procedure were evaluated. RESULTS: FB and BAL were diagnostic in 86/132 patients (65.1%) and the antimicrobial treatment changed for 75/132 patients (56.8%). The most common pathogen was bacteria (Streptococcus pneumoniae was the leading one). Bacteria were more frequent in Group I than Group II (P = .008). No significant difference in radiological findings between Groups I and II was found. Considering all patients, a significant association was detected between viral pathogens and radiologically interstitial infiltration and a ground-glass appearance (P = .003). However, no significant association was detected between bacterial and fungal pathogens and the radiological findings. CONCLUSION: In immunosuppressed patients, FB and BAL should be evaluated early for clarifying the causative agents. Then, appropriate treatments can be utilised and the side effects and high cost of unnecessary treatment may be mitigated.


Assuntos
Lavagem Broncoalveolar/métodos , Broncoscopia/métodos , Rejeição de Enxerto/prevenção & controle , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Infecções Respiratórias/diagnóstico , Adolescente , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
19.
BMC Infect Dis ; 20(1): 434, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: covidwho-610520

RESUMO

BACKGROUND: The novel coronavirus pneumonia (coronavirus disease 2019, COVID-19) has spread around the world. We aimed to recapitulate the clinical and CT imaging features of COVID-19 and their differences in three age groups. METHODS: The clinical and CT data of patients with COVID-19 (n = 307) that had been divided into three groups (Group 1: < 40 years old; Group 2: 40 ≤ age < 60 years old; Group 3: ≥ 60 years old) according to age were analyzed retrospectively. RESULTS: Of all patients, 114 (37.1%) had histories of epidemiological exposure, 48 (15.6%) were severe/critical cases, 31 had hypertension (10.1%), 15 had diabetes mellitus (4.9%), 3 had chronic obstructive pulmonary disease (COPD, 1%). Among the three groups, severe/critical type, hypertension and diabetes occurred more commonly in the elderly group compared with Group 1&2 (P < 0.05, respectively). Cough and chest tightness/pain were more commonly appeared in Group 2&3 compared with Group 1 (P < 0.05, respectively). Compared with Group 1 and 2, there were more abnormal laboratory examination indexes (including CRP increase, abnormal percentage of lymphocytes, neutrophils and monocytes) in Group 3 (P < 0.05, respectively). CT images revealed that more lobes were affected and more subpleural lesions were involved in the elderly group, besides, crazy paving sign, bronchodilatation and pleural thickening were more commonly seen in the elderly group, with significant difference between Group 1&2, Group 2&3 (P < 0.05, respectively). CONCLUSIONS: COVID-19 presented representative clinical manifestations, laboratory examinations and CT findings, but three age groups possessed their own specific characteristics. Grasping the clinical and CT features stratified by age will be helpful for early definite diagnosis of COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Fatores Etários , Idoso , Betacoronavirus/fisiologia , COVID-19 , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2
20.
Res Pract Thromb Haemost ; 4(4): 510-517, 2020 May.
Artigo em Inglês | MEDLINE | ID: covidwho-601438
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