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1.
J Assoc Physicians India ; 69(4): 11-12, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34470194

RESUMO

For decades, short acting beta agonists (SABAs) have been prescribed for giving symptomatic relief to asthmatics. However, this symptomatic benefit perceived by the patient leads to the overuse and dependency of the patient to the SABA inhaler and underusage of the inhaled corticosteroid (ICS) containing controller inhalers resulting in destabilizing disease control and increased risk of exacerbations. In order to address this issue, the 2019 update of the Global Initiative for Asthma (GINA) strategy document no longer recommends the use of SABA inhalers as the preferred reliever for asthma due to concerns around poor outcomes and safety. Instead, it strongly supports the use of a combined ICS-fast acting beta agonist as a reliever also termed as an Anti-inflammatory Reliever Therapy (AIR). In this review we discuss the extent of SABA overusage and its impact on asthma outcomes, the resultant change in the recommendations in the GINA document and finally the evidence supporting the use of formoterol- budesonide as AIR therapy.


Assuntos
Antiasmáticos , Asma , Administração por Inalação , Corticosteroides , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Budesonida/uso terapêutico , Combinação de Medicamentos , Etanolaminas/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Humanos , Nebulizadores e Vaporizadores
2.
Rev Med Suisse ; 17(749): 1515-1519, 2021 Sep 08.
Artigo em Francês | MEDLINE | ID: mdl-34495587

RESUMO

Inhaled medication is the cornerstone of medical treatment of COPD. The efficacy of these treatments depends on the optimal use of inhalation devices. This requires not only an impeccable inhalation technique, but above all the selection of an inhaler adapted to the patient. In this article, we describe the specificities of the different inhalation devices and some of the patient's characteristics to be taken into account when selecting an inhaler, in particular the presence of cognitive disorders, impaired dexterity or insufficient inspiratory force.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Aerossóis/uso terapêutico , Desenho de Equipamento , Humanos , Nebulizadores e Vaporizadores , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
3.
Mater Sci Eng C Mater Biol Appl ; 128: 112324, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474875

RESUMO

Pulmonary drug delivery is governed by several biophysical parameters of delivery carriers, such as particle size, shape, density, charge, and surface modifications. Although much attention has been given to other parameters, particle shape effects have rarely been explored. In this work, we assess the influence of particle shape of inhaled delivery carriers on their aerodynamic properties and macrophage uptake by using polymeric microparticles of different geometries ranging in various sizes. Doxorubicin was conjugated to the polymer particles and the bioconjugates were characterized. Interestingly, the results of in-vitro lung deposition, performed using a next generation impactor, demonstrated a significant improvement in the aerodynamic properties of the rod-shaped particles with a high aspect ratio as compared to spherical particles with the same equivalent volume. The results of a macrophage uptake experiment demonstrate that the high aspect ratio particles were phagocytosed less than spherical particles. Furthermore, the cytotoxicity of these doxorubicin-conjugated particles was determined against murine macrophages, resulting in reduced toxicity when treated with high aspect ratio particles as compared to spherical particles. This project provides valuable insights into the influence of particle shape on aerodynamic properties and primary defense mechanisms in the peripheral lungs, while using polymeric microparticles of various sizes and geometries. Further systematic development can help translate these findings to preclinical and clinical studies for designing efficient inhalable delivery carriers.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Administração por Inalação , Animais , Portadores de Fármacos , Pulmão , Camundongos , Tamanho da Partícula
4.
BMC Pulm Med ; 21(1): 278, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465321

RESUMO

BACKGROUND: There are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report. CASE PRESENTATION: A 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive. CONCLUSION: Our case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico , Diagnóstico Tardio , Nasofaringe/virologia , SARS-CoV-2/isolamento & purificação , Administração por Inalação , Corticosteroides/uso terapêutico , Asma/complicações , Asma/tratamento farmacológico , Asma/patologia , Lavagem Broncoalveolar , COVID-19/complicações , COVID-19/terapia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
5.
Nutrients ; 13(8)2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34444947

RESUMO

Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with airways inflammation and lung parenchyma fibrosis. The primary goals of COPD treatment are to reduce symptoms and risk of exacerbations, therefore pulmonary rehabilitation is considered the key component of managing COPD patients. Oxidative airway damage, inflammation and reduction of endogenous antioxidant enzymes are known to play a crucial role in the pathogenesis of COPD. Recently, also natural antioxidants have been considered as they play an important role in metabolism, DNA repair and fighting the effects of oxidative stress. In this paper we evaluated the response of 105 elderly COPD patients to pulmonary rehabilitation (PR), based on high or low vegetable consumption, by analyzing clinical parameters and biological measurements at baseline and after completion of the three weeks PR. We found that daily vegetable intake in normal diet, without any specific intervention, can increase the probability to successfully respond to rehabilitation (65.4% of responders ate vegetables daily vs. 40.0% of non-responders, p = 0.033). The association was especially evident in subjects ≥ 80 year of age (OR = 17.0; p < 0.019). Three weeks of pulmonary rehabilitation are probably too short to reveal a reduction of the oxidative stress and DNA damage, but are enough to show an improvement in the patient's inflammatory state.


Assuntos
Dieta Saudável/métodos , Ingestão de Alimentos/fisiologia , Fenômenos Fisiológicos da Nutrição do Idoso/fisiologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Verduras , Administração por Inalação , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/administração & dosagem , Dano ao DNA/fisiologia , Inquéritos sobre Dietas , Feminino , Humanos , Inflamação , Pulmão/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Resultado do Tratamento
6.
Am J Nurs ; 121(9): 56, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438430

RESUMO

According to this study: In patients with moderate to severe asthma, triple therapy was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control compared with dual therapy.No significant differences were found in quality of life or mortality between triple and dual therapy.


Assuntos
Asma , Qualidade de Vida , Administração por Inalação , Asma/tratamento farmacológico , Quimioterapia Combinada , Humanos
7.
Artigo em Inglês | MEDLINE | ID: mdl-34444206

RESUMO

Environmental pollution is a worldwide problem recognized by the World Health Organization as a major health risk factor that affects low-, middle- and high-income countries. Suspended particulate matter is among the most dangerous pollutants, since it contains toxicologically relevant agents, such as metals, including vanadium. Vanadium is a transition metal that is emitted into the atmosphere especially by the burning of fossil fuels to which dwellers are exposed. The objective of this literature review is to describe the toxic effects of vanadium and its compounds when they enter the body by inhalation, based especially on the results of a murine experimental model that elucidates the systemic effects that vanadium has on living organisms. To achieve this goal, we reviewed 85 articles on the relevance of vanadium as a component of particulate matter and its toxic effects. Throughout several years of research with the murine experimental model, we have shown that this element generates adverse effects in all the systems evaluated, because it causes immunotoxicity, hematotoxicity, neurotoxicity, nephrotoxicity and reprotoxicity, among other noxious effects. The results with this experimental model add evidence of the effects generated by environmental pollutants and increase the body of evidence that can lead us to make more intelligent environmental decisions for the welfare of all living beings.


Assuntos
Poluentes Atmosféricos , Síndromes Neurotóxicas , Administração por Inalação , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Animais , Combustíveis Fósseis , Camundongos , Material Particulado/análise , Material Particulado/toxicidade , Vanádio/toxicidade
8.
BMJ Open ; 11(8): e049675, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348953

RESUMO

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting ß2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands. METHODS: A previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV1), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively. RESULTS: Treatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer's incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries. CONCLUSIONS: Based on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Benzoxazinas , Broncodilatadores/uso terapêutico , Análise Custo-Benefício , Finlândia , Humanos , Países Baixos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Suécia , Brometo de Tiotrópio/uso terapêutico , Resultado do Tratamento
10.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360708

RESUMO

BACKGROUND: exposure to environmental contaminants has been linked to an increased risk of neurological diseases and poor outcomes. Chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Several studies have demonstrated that ATR has the potential to be harmful to the brain's neuronal circuits. Until today nobody has explored the effect of ATR inhalation on young and aged mice. METHODS: young and aged mice were subject to 25 mg of ATR in a vehicle made with saline and 10% of Dimethyl sulfoxide (DMSO) every day for 28 days. At the end of experiment different behavioral test were made and brain was collected. RESULTS: exposure to ATR induced the same response in terms of behavioral alterations and motor and memory impairment in mice but in aged group was more marked. Additionally, in both young and aged mice ATR inhalations induced oxidative stress with impairment in physiological antioxidant response, lipid peroxidation, nuclear factor kappa-light-chain-enhancer of activated B cells (nf-κb) pathways activation with consequences of pro-inflammatory cytokines release and apoptosis. However, the older group was shown to be more sensitive to ATR inhalation. CONCLUSIONS: our results showed that aged mice were more susceptible compared to young mice to air pollutants exposure, put in place a minor physiologically response was seen when exposed to it.


Assuntos
Envelhecimento/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Atrazina/efeitos adversos , Encéfalo/metabolismo , Administração por Inalação , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Atrazina/farmacologia , Encéfalo/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos
12.
Front Public Health ; 9: 713258, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395374

RESUMO

Objectives: This study analyzed the long-term cost-effectiveness of fluticasone/umeclidinium/vilanterol triple combination (FF/UMEC/VI) vs. budesonide/formoterol double combination (BUD/FOR) in the treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD) and provides evidence for COPD treatment decisions. Methods: From the perspective of the healthcare system, a Markov model was established that consists of four states-stable period, non-severely deteriorating period, severely deteriorating period, and death-according to real-world COPD progression. The model period comprises 6 months, with a cycle length of 14 years. The initial state, transition probabilities, costs, and utility data were collected from the FULFIL trial, published literature, hospital record surveys, and China Health Statistics Yearbook. The discount rate was 5%, and the threshold was set as the Chinese per capita GDP in 2020 (¥72,447). The cost, utility, transition probabilities, and discount rate were calculated through TreeagePro11 software. The results were analyzed via one-way factor analysis and probability sensitivity analysis. Results: The baseline study shows that the 14-year treatment for FF/UMEC/VI and BUD/FOR groups are ¥199,765.55 and ¥173,030.05 with effectiveness at 8.54 quality-adjusted life years (QALYs) and 7.73 QALYs, respectively. The incremental cost-effectiveness ratio is ¥33,006.80/QALY, which is below the threshold. A tornado diagram of a one-way sensitivity analysis shows that the top three factors that affected the results are the non-severe deterioration rates of FF/UMEC/VI, the cost of FF/UMEC/VI and the non-severe deterioration rates of BUD/FOR. Probabilistic sensitivity analysis shows that FF/UMEC/VI (compared to BUD/FOR) can be made cost-effective under the willingness-to-pay (WTP) threshold (¥38,000). Furthermore, the likelihood of cost-effectiveness increases with a higher WTP. Conclusions: Compared with the double combination (BUD/FOR), the triple combination (FF/UMEC/VI) is more cost-effective under the Chinese per capita GDP threshold.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Androstadienos/uso terapêutico , Broncodilatadores/uso terapêutico , Análise Custo-Benefício , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
14.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34234013

RESUMO

Development of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the development and initial evaluation of two targeted phage-based vaccination approaches against SARS-CoV-2: dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. For peptide-targeted phage, we performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein. One of these epitopes displayed on the major capsid protein pVIII of phage induced a specific and sustained humoral response when injected in mice. These phage were further engineered to simultaneously display the peptide CAKSMGDIVC on the minor capsid protein pIII to enable their transport from the lung epithelium into the systemic circulation. Aerosolization of these "dual-display" phage into the lungs of mice generated a systemic and specific antibody response. In the second approach, targeted AAVP particles were engineered to deliver the entire S protein gene under the control of a constitutive CMV promoter. This induced tissue-specific transgene expression, stimulating a systemic S protein-specific antibody response in mice. With these proof-of-concept preclinical experiments, we show that both targeted phage- and AAVP-based particles serve as robust yet versatile platforms that can promptly yield COVID-19 vaccine prototypes for translational development.


Assuntos
Bacteriófagos/genética , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Programas de Imunização , Administração por Inalação , Animais , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Dependovirus/genética , Armazenamento de Medicamentos , Feminino , Programas de Imunização/métodos , Imunogenicidade da Vacina , Camundongos , Camundongos Endogâmicos BALB C , Estudo de Prova de Conceito , Temperatura
15.
J Pharm Biomed Anal ; 204: 114253, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34271287

RESUMO

A simple and rapid on-line SFE/SFC/quadrupole TOF-MS method to simultaneously analyze active pharmaceutical ingredients and impurities from metered-dose inhalers (MDIs) was developed using ciclesonide MDI (CIC-MDI) as an example. CIC-MDI, as drug Alvesco®, has been approved for the treatment of bronchial asthma, and its major impurities are listed in the European Pharmacopoeia and in the supplementary package inserts of Alvesco® (called as "Pharmaceutical interview form" in Japan). In the developed method, CIC-MDI was manually sprayed only once on a glass disc prior to the SFE/SFC/quadrupole TOF-MS. In the SFE, CIC and its impurities and other impurities having various polarities and hydrophobicity, were extracted in 3.5 min and subsequently separated on a CHIRALPAK IE-3 column to be detected by quadrupole TOF-MS in 6.5 min. This method would be applicable to the analysis of other inhalable pharmaceutical products whose sample preparation requires complicated procedures, as well as to the analysis of general pharmaceutical products for profiling impurities.


Assuntos
Cromatografia com Fluido Supercrítico , Administração por Inalação , Espectrometria de Massas , Inaladores Dosimetrados , Pregnenodionas
16.
Sci Signal ; 14(690)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230209

RESUMO

Inorganic polyphosphates (polyPs) are linear polymers composed of repeated phosphate (PO4 3-) units linked together by multiple high-energy phosphoanhydride bonds. In addition to being a source of energy, polyPs have cytoprotective and antiviral activities. Here, we investigated the antiviral activities of long-chain polyPs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In molecular docking analyses, polyPs interacted with several conserved amino acid residues in angiotensin-converting enzyme 2 (ACE2), the host receptor that facilitates virus entry, and in viral RNA-dependent RNA polymerase (RdRp). ELISA and limited proteolysis assays using nano- LC-MS/MS mapped polyP120 binding to ACE2, and site-directed mutagenesis confirmed interactions between ACE2 and SARS-CoV-2 RdRp and identified the specific amino acid residues involved. PolyP120 enhanced the proteasomal degradation of both ACE2 and RdRp, thus impairing replication of the British B.1.1.7 SARS-CoV-2 variant. We thus tested polyPs for functional interactions with the virus in SARS-CoV-2-infected Vero E6 and Caco2 cells and in primary human nasal epithelial cells. Delivery of a nebulized form of polyP120 reduced the amounts of viral positive-sense genomic and subgenomic RNAs, of RNA transcripts encoding proinflammatory cytokines, and of viral structural proteins, thereby presenting SARS-CoV-2 infection in cells in vitro.


Assuntos
Antivirais/farmacologia , COVID-19/tratamento farmacológico , Polifosfatos/farmacologia , SARS-CoV-2/efeitos dos fármacos , Administração por Inalação , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Antivirais/administração & dosagem , Antivirais/química , COVID-19/metabolismo , COVID-19/virologia , Células CACO-2 , Chlorocebus aethiops , RNA-Polimerase RNA-Dependente de Coronavírus/química , RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA-Polimerase RNA-Dependente de Coronavírus/metabolismo , Citocinas/metabolismo , Células HEK293 , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Técnicas In Vitro , Modelos Biológicos , Simulação de Acoplamento Molecular , Nebulizadores e Vaporizadores , Polifosfatos/administração & dosagem , Polifosfatos/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Domínios e Motivos de Interação entre Proteínas , Proteólise/efeitos dos fármacos , RNA Viral/genética , RNA Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , Homologia de Sequência de Aminoácidos , Transdução de Sinais/efeitos dos fármacos , Células Vero , Replicação Viral/efeitos dos fármacos
17.
Br J Anaesth ; 127(3): 447-457, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34266661

RESUMO

BACKGROUND: Infant anaesthesia causes acute brain cell apoptosis, and later in life cognitive deficits and behavioural alterations, in non-human primates (NHPs). Various brain injuries and neurodegenerative conditions are characterised by chronic astrocyte activation (astrogliosis). Glial fibrillary acidic protein (GFAP), an astrocyte-specific protein, increases during astrogliosis and remains elevated after an injury. Whether infant anaesthesia is associated with a sustained increase in GFAP is unknown. We hypothesised that GFAP is increased in specific brain areas of NHPs 2 yr after infant anaesthesia, consistent with prior injury. METHODS: Eight 6-day-old NHPs per group were exposed to 5 h isoflurane once (1×) or three times (3×), or to room air as a control (Ctr). Two years after exposure, their brains were assessed for GFAP density changes in the primary visual cortex (V1), perirhinal cortex (PRC), hippocampal subiculum, amygdala, and orbitofrontal cortex (OFC). We also assessed concomitant microglia activation and hippocampal neurogenesis. RESULTS: Compared with controls, GFAP densities in V1 were increased in exposed groups (Ctr: 0.208 [0.085-0.427], 1×: 0.313 [0.108-0.533], 3×: 0.389 [0.262-0.652]), whereas the density of activated microglia was unchanged. In addition, GFAP densities were increased in the 3× group in the PRC and the subiculum, and in both exposure groups in the amygdala, but there was no increase in the OFC. There were no differences in hippocampal neurogenesis among groups. CONCLUSIONS: Two years after infant anaesthesia, NHPs show increased GFAP without concomitant microglia activation in specific brain areas. These long-lasting structural changes in the brain caused by infant anaesthesia exposure may be associated with functional alterations at this age.


Assuntos
Anestesia por Inalação/efeitos adversos , Anestésicos Inalatórios/toxicidade , Encéfalo/efeitos dos fármacos , Gliose/induzido quimicamente , Isoflurano/toxicidade , Microglia/efeitos dos fármacos , Administração por Inalação , Fatores Etários , Anestésicos Inalatórios/administração & dosagem , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/metabolismo , Gliose/patologia , Isoflurano/administração & dosagem , Macaca mulatta , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/metabolismo , Microglia/patologia , Fatores de Tempo
20.
J Infect Chemother ; 27(10): 1436-1446, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34226112

RESUMO

INTRODUCTION: We conducted a post-marketing surveillance of laninamivir octanoate hydrate for Inhalation Suspension Set in patients under the age of 5 infected with the influenza virus to evaluate safety and efficacy of the drug. METHODS: Subjects enrolled by the centralized enrollment system were administered laninamivir once using a nebulizer based on the package insert. RESULTS: Safety was evaluated in 1104 patients. The incidence of ADRs was 1.00% (11/1104). Compared to the incidence of ADRs of 2.04% (9/441) in the clinical trials for development, no increase in the frequency of ADRs was noted. Serious ADRs were noted in 3 patients (5 cases): 2 cases of convulsive attack, each 1 case of muscular weakness, a depressed level of consciousness, and pain in extremities. Excluding 2 patients with unknown outcomes, all of the patients recovered or their symptoms were alleviated. To detect risk factors for the occurrence of ADRs, 16 attributes were examined, and none of them were found to be significant. Efficacy was evaluated in 881 patients. The median time (95% CI) to fever resolution was 37.0 (33.0-39.0) h in type A virus (785 patients), 45.0 (34.0-56.0) h in type B virus (95 patients), and 22.0 h (1 patient) in the mixed type. This was similar to the time to fever resolution in the clinical trials. CONCLUSION: The results of this surveillance verified that there are no noticeable problems with the safety or efficacy of laninamivir for children under the age of 5 infected with the influenza A and B viruses.


Assuntos
Influenza Humana , Neuraminidase , Administração por Inalação , Antivirais/efeitos adversos , Criança , Guanidinas/uso terapêutico , Humanos , Influenza Humana/tratamento farmacológico , Vigilância de Produtos Comercializados , Piranos/uso terapêutico , Ácidos Siálicos/uso terapêutico , Zanamivir/efeitos adversos
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