RESUMEN
Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N-acetylcysteine (NAC) using western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS-SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases.
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Glicerol , Polímeros , Esputo , Compuestos de Sulfhidrilo , Humanos , Glicerol/química , Polímeros/química , Polímeros/farmacología , Esputo/metabolismo , Esputo/química , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/farmacología , Fibrosis Quística/metabolismo , Fibrosis Quística/tratamiento farmacológico , Mucina 5AC/metabolismo , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Enfermedades Pulmonares Obstructivas/metabolismo , Mucina 5B/metabolismo , Sulfatos/química , Sulfatos/farmacología , Expectorantes/farmacología , Expectorantes/química , Moco/metabolismo , Moco/química , Reología , Acetilcisteína/farmacología , Acetilcisteína/química , ViscosidadRESUMEN
The respiratory tract is commonly affected in multisystem disorders. Although many drugs have been developed to target various components of these diseases, there is still a need for effective treatments that can address both respiratory and non-respiratory symptoms. Bromhexine and ambroxol are mucolytic agents with a good safety profile that are widely used to treat respiratory conditions. These compounds seem to present several unresolved questions when carrying out their therapeutic effects, suggesting that they may not merely improve mucociliary clearance. These assumptions have provided the basis for researchers to investigate the specific characteristics of bromhexine and ambroxol. This has led to the emergence of several repositionings for this compound. Accordingly, these compounds have also shown potential benefits in the treatment of various extrapulmonary disorders, including neurological disorders, and inflammatory bowel disease. We gathered findings from relevant studies published in English between 1970 and December 2023 by searching databases including PubMed, Google Scholar, Scopus, Embase, and the Cochrane Library. Our findings revealed that most of the research on extrapulmonary uses has been conducted at the preclinical level. Accordingly, more clinical studies are needed to determine the effectiveness of bromhexine and ambroxol in these conditions. This article provides an overview of the potential extrapulmonary applications of bromhexine and ambroxol and discusses the potential advantages of using these drugs in multisystem disorders.
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Ambroxol , Bromhexina , Expectorantes , Ambroxol/farmacología , Humanos , Bromhexina/farmacología , Expectorantes/farmacología , Expectorantes/uso terapéutico , Animales , Pulmón/efectos de los fármacos , Pulmón/metabolismoAsunto(s)
Acetilcisteína , Humanos , Acetilcisteína/administración & dosificación , Acetilcisteína/uso terapéutico , Moco/metabolismo , Administración Intravenosa , Enfermedades Respiratorias/tratamiento farmacológico , Enfermedades Respiratorias/metabolismo , Expectorantes/administración & dosificación , Expectorantes/uso terapéuticoRESUMEN
INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.
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Bronquiectasia , Expectorantes , Estudios Multicéntricos como Asunto , Calidad de Vida , Tioglicolatos , Tiofenos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Bronquiectasia/tratamiento farmacológico , Progresión de la Enfermedad , Método Doble Ciego , Expectorantes/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tioglicolatos/uso terapéutico , Tiofenos/uso terapéutico , Resultado del TratamientoRESUMEN
Bromhexine and ambroxol are among the mucolytic drugs most widely used to treat acute and chronic respiratory diseases. Entering the municipal wastewater and undergoing transformations during disinfection with active chlorine, these compounds can produce nitrogen- and bromine-containing disinfection by-products (DBPs) that are dangerous for aquatic ecosystems. In the present study, primary and deep degradation products of ambroxol and bromhexine obtained in model aquatic chlorination experiments were studied via the combination of high-performance liquid and gas chromatography with high-resolution mass spectrometry. It was shown that at the initial stages, the reactions of cyclization, hydroxylation, chlorination, electrophilic ipso-substitution of bromine atoms with chlorine, and oxidative N-dealkylation occur. Along with known metabolites, a number of novel primary DBPs were tentatively identified based on their elemental compositions and tandem mass spectra. Deep degradation of bromhexine and ambroxol gives twenty-four identified volatile and semi-volatile compounds of six classes, among which trihalomethanes account for more than 50%. The specific class of bromhexine- and ambroxol-related DBPs are bromine-containing haloanilines. Seven of them, including methoxy derivatives, were first discovered in the present study. One more novel class of DBPs associated with bromhexine and ambroxol is represented by halogenated indazoles formed through dealkylation of the primary transformation products containing pyrazoline or tetrahydropyrimidine cycle in their structure.
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Ambroxol , Bromhexina , Expectorantes , Halogenación , Contaminantes Químicos del Agua , Ambroxol/química , Bromhexina/química , Expectorantes/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Cloro/químicaRESUMEN
BACKGROUND: To date, no disease modifying therapies are available for Parkinson's disease (PD). Since PD is the second most prevalent neurodegenerative disorder, there is a high demand for such therapies. Both environmental and genetic risk factors play an important role in the etiology and progression of PD. The most common genetic risk factor for PD is a mutation in the GBA1(GBA)-gene, encoding the lysosomal enzyme glucocerebrosidase (GCase). The mucolytic ambroxol is a repurposed drug, which has shown the property to upregulate GCase activity in-vitro and in-vivo. Ambroxol therefore has the potency to become a disease modifying therapy in PD, which was the reason to design this randomized controlled trial with ambroxol in PD patients. METHODS: This trial is a single-center, double-blind, randomized, placebo-controlled study, including 80 PD patients with a GBA mutation, receiving either ambroxol 1800 mg/day or placebo for 48 weeks. The primary outcome measure is the Unified Parkinson's Disease Rating Scale motor subscore (part III) of the Movement Disorder Society (MDS-UPDRSIII) in the practically defined off-state at 60 weeks (after a 12-week washout period). Secondary outcomes include a 3,4-dihydroxy-6-18F-fluoro-I-phenylalanine ([18F]FDOPA) PET-scan of the brain, Magnetic Resonance Imaging (with resting state f-MRI and Diffusion Tensor Imaging), GCase activity, both intra- and extracellularly, sphingolipid profiles in plasma, Montreal Cognitive Assessment (MoCA), quality of life (QoL) measured by the Parkinson's Disease Questionnaire (PDQ-39) and the Non-Motor Symptom Scale (NMSS) questionnaire. DISCUSSION: Ambroxol up to 1200 mg/day has shown effects on human cerebrospinal fluid endpoints, which supports at least passage of the blood-brain-barrier. The dose titration in this trial up to 1800 mg/day will reveal if this dose level is safe and also effective in modifying the course of the disease. TRIAL REGISTRATION: NCT05830396. Registration date: March 20, 2023.
Asunto(s)
Ambroxol , Glucosilceramidasa , Mutación , Enfermedad de Parkinson , Humanos , Ambroxol/administración & dosificación , Ambroxol/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/diagnóstico por imagen , Glucosilceramidasa/genética , Método Doble Ciego , Masculino , Femenino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Expectorantes/uso terapéutico , Expectorantes/administración & dosificación , AdultoRESUMEN
The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300â mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300â mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.
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Antipiréticos , Antitusígenos , Etanol , Expectorantes , Momordica charantia , Extractos Vegetales , Hojas de la Planta , Animales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Ratones , Antitusígenos/farmacología , Antitusígenos/química , Antitusígenos/aislamiento & purificación , Hojas de la Planta/química , Ratas , Etanol/química , Antipiréticos/farmacología , Antipiréticos/química , Antipiréticos/aislamiento & purificación , Masculino , Momordica charantia/química , Expectorantes/farmacología , Expectorantes/aislamiento & purificación , Expectorantes/química , Tos/tratamiento farmacológico , Ratas Wistar , Relación Dosis-Respuesta a Droga , Saccharomyces cerevisiae/efectos de los fármacos , Fiebre/tratamiento farmacológicoRESUMEN
BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use. METHODS: This was a prospective observational study using data from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) Registry between January 2015 and April 2022. Prespecified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs. RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. The mean age was 67â years (interquartile range 57-74â years, range 18-100â years) and 61% were female. 72% of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the participants and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Participants who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume, compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in participants with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe. CONCLUSIONS: Only a half of people with bronchiectasis in Europe use airway clearance management. Use of and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.
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Bronquiectasia , Sistema de Registros , Humanos , Bronquiectasia/terapia , Bronquiectasia/fisiopatología , Femenino , Persona de Mediana Edad , Masculino , Anciano , Europa (Continente) , Adulto , Estudios Prospectivos , Adolescente , Adulto Joven , Anciano de 80 o más Años , Manejo de la Vía Aérea/métodos , Terapia Respiratoria/métodos , Expectorantes/uso terapéuticoRESUMEN
BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.
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COVID-19 , Resfriado Común , Faringitis , Humanos , Acetaminofén/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Resfriado Común/tratamiento farmacológico , Resfriado Común/inducido químicamente , Tos , Expectorantes/uso terapéutico , Cefalea/inducido químicamente , Cefalea/tratamiento farmacológico , Medicamentos sin Prescripción/uso terapéutico , Pandemias , Farmacéuticos , Faringitis/inducido químicamente , Faringitis/tratamiento farmacológico , RinorreaRESUMEN
INTRODUCTION: N-acetylcysteine (NAC) is a mucolytic agent with antioxidant properties. Oxidative stress is a key pathogenic mechanism in chronic respiratory conditions such as COPD and chronic bronchitis (CB). In these meta-analyses we investigated the efficacy of NAC in subjects with COPD or CB, the latter being a potential pre-COPD condition (CB/pre-COPD). METHODS: The meta-analyses were conducted according to PRISMA guidelines. Exacerbations were assessed using total number of exacerbations. Improvement in patients' respiratory symptoms and/or patients quality of life (QoL) were measured by validated tools or assessed at the end of the study. RESULTS: Twenty studies were included, of which seven evaluated NAC in patients with symptoms of CB/pre-COPD as entry criterion. NAC treated patients showed a significant reduction of the incidence of exacerbations as compared to placebo both in COPD (IRR=0.76; 95% confidence interval (CI) 0.59-0.99) and CB/pre-COPD (IRR=0.81; 95% CI 0.69-0.95). Sensitivity analyses in studies with duration higher than 5 months, confirmed the overall results. CB/pre-COPD patients treated with NAC were significantly more likely to experience an improvement in symptoms and/or QoL compared to placebo (odds ratio (OR)=3.47; 95% CI 1.92-6.26). A similar trend was observed in the few COPD studies evaluable. Sensitivity analyses showed a significant association of NAC with improvement in symptoms and/or QoL both in CB/pre-COPD and COPD patients. CONCLUSIONS: These findings provide novel data of NAC on the improvement in symptoms and QoL in addition to prevention of exacerbations in COPD and CB/pre-COPD. PROSPERO registry no. CRD42023468154.
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Acetilcisteína , Bronquitis Crónica , Enfermedad Pulmonar Obstructiva Crónica , Calidad de Vida , Humanos , Acetilcisteína/uso terapéutico , Bronquitis Crónica/tratamiento farmacológico , Progresión de la Enfermedad , Expectorantes/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Microbial biofilms, as a hallmark of cystic fibrosis (CF) lung disease and other chronic infections, remain a desirable target for antimicrobial therapy. These biopolymer-based viscoelastic structures protect pathogenic organisms from immune responses and antibiotics. Consequently, treatments directed at disrupting biofilms represent a promising strategy for combating biofilm-associated infections. In CF patients, the viscoelasticity of biofilms is determined mainly by their polymicrobial nature and species-specific traits, such as Pseudomonas aeruginosa filamentous (Pf) bacteriophages. Therefore, we examined the impact of microbicidal ceragenins (CSAs) supported by mucolytic agents-DNase I and poly-aspartic acid (pASP), on the viability and viscoelasticity of mono- and bispecies biofilms formed by Pf-positive and Pf-negative P. aeruginosa strains co-cultured with Staphylococcus aureus or Candida albicans. METHODS: The in vitro antimicrobial activity of ceragenins against P. aeruginosa in mono- and dual-species cultures was assessed by determining minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Inhibition of P. aeruginosa mono- and dual-species biofilms formation by ceragenins alone and in combination with DNase I or poly-aspartic acid (pASP) was estimated by the crystal violet assay. Additionally, the viability of the biofilms was measured by colony-forming unit (CFU) counting. Finally, the biofilms' viscoelastic properties characterized by shear storage (G') and loss moduli (G"), were analyzed with a rotational rheometer. RESULTS: Our results demonstrated that ceragenin CSA-13 inhibits biofilm formation and increases its fluidity regardless of the Pf-profile and species composition; however, the Pf-positive biofilms are characterized by elevated viscosity and elasticity parameters. CONCLUSION: Due to its microbicidal and viscoelasticity-modifying properties, CSA-13 displays therapeutic potential in biofilm-associated infections, especially when combined with mucolytic agents.
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Antiinfecciosos , Fibrosis Quística , Infecciones por Pseudomonas , Esteroides , Humanos , Pseudomonas aeruginosa , Ácido Aspártico , Expectorantes , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Biopelículas , Desoxirribonucleasa I , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Little research has been completed on the correlation between cystic fibrosis (CF) modulator therapy and its effect on respiratory cultures in CF patients. This study evaluated the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory colonization with Pseudomonas aeruginosa. METHODS: This single center, IRB approved, retrospective chart review compared patient data two years immediately prior to ETI initiation with patient data two years post-initiation from January 2017-December 2022. Patients were included in the study if they were at least 18 years old with a diagnosis of CF and had at least one month of ETI dispensed, at least one sputum culture obtained, and were currently on ETI. Those who had not been seen since ETI initiation or received a bilateral lung transplant were excluded. The primary outcome was rate of patients with respiratory colonization post-ETI. Colonization was defined as two or more positive P. aeruginosa cultures in a 12-month period. Decolonization was defined as three consecutive negative P. aeruginosa cultures after previous colonization. Key secondary outcomes included average time to discontinuation of mucolytic therapy and relative risk of pulmonary exacerbation. RESULTS: A significant reduction (p<0.001) in colonization with P. aeruginosa was observed with 49 patients in the pre-ETI group compared to 25 in the post-ETI group meeting the definition of colonization (n=79). Average time to discontinuation of mucolytic therapy was 14 months (p=0.002). Relative risk of pulmonary exacerbation was 4.80 (p<0.001). CONCLUSIONS: ETI use resulted in reduced colonization with P. aeruginosa, discontinuation of mucolytic therapy, and decreased frequency of pulmonary exacerbation.
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Aminofenoles , Benzodioxoles , Fibrosis Quística , Indoles , Pirazoles , Piridinas , Pirrolidinas , Quinolonas , Adulto , Humanos , Adolescente , Fibrosis Quística/tratamiento farmacológico , Expectorantes , Estudios Retrospectivos , MutaciónRESUMEN
The development of effective strategies against multidrug-resistant (MDR) pathogens is an urgent need in modern medicine. Nanoantibiotics (nABs) offer a new hope in countering the surge of MDR-pathogens. The aim of the current study was to evaluate the antibacterial activity of two attractive nABs, TiO2 NPs and ZnO NPs, and their performance in improving the antimicrobial activity of defined antibiotics (amoxicillin-clavulanic acid, amox-clav) against MDR-pathogens. The nABs were synthesized using a green method. The physicochemical characteristics of the synthesized nanoparticles were determined using standard methods. The results showed the formation of pure anatase TiO2 NPs and hexagonal ZnO NPs with an average particle size of 38.65 nm and 57.87 nm, respectively. The values of zeta potential indicated the high stability of the samples. At 8 mg/mL, both nABs exhibited 100 % antioxidant activity, while ZnO showed significantly higher activity at lower concentrations. The antibiofilm assay showed that both nABs could inhibit the formation of biofilms of Acinetobacter baumannii 80 and Escherichia coli 27G (MDR-isolates). However, ZnO NPs showed superior antibiofilm activity (100 %) against E. coli 27G. The MIC values were determined to be 8 (1), 2 (2), and 4 (4) mg/mL for amox-clav, TiO2 NPs, and ZnO NPs against A. baumannii 80 (E. coli 27G), respectively. The results showed that both nABs had synergistically enhanced antibacterial performance in combination with amox-clav. Specifically, an 8-fold reduction in MIC values of antibiotics was observed when they were combined with nABs. These findings highlight the potential of TiO2 NPs and ZnO NPs as effective nanoantibiotics against MDR-pathogens. The synergistic effect observed when combining nABs with antibiotics suggests a promising approach for combating antibiotic resistance. Further research and development in this area could lead to the development of more effective treatment strategies against MDR infections.
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Antiinfecciosos , Fármacos Dermatológicos , Nanopartículas del Metal , Óxido de Zinc , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Óxido de Zinc/farmacología , Óxido de Zinc/química , Escherichia coli , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Fármacos Dermatológicos/farmacología , Vitaminas , Expectorantes , Pruebas de Sensibilidad Microbiana , Nanopartículas del Metal/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea bulbifera L. (Rhizoma Dioscoreae Bulbiferae; RDB) is commonly used as an expectorant and cough suppressant herb but is accompanied by severe hepatotoxicity. Using the juice of auxiliary herbs (such as Glycyrrhiza uralensis Fisch. (Glycyrrhizae Radix et Rhizoma; GRR) juice) in concocting poisonous Chinese medicine is a conventional method to reduce toxicity or increase effects. Our previous study found that concoction with GRR juice provided a detoxifying effect against the major toxic hepatotoxicity induced by RDB, but the principle for the detoxification of the concoction is unknown to date. AIM OF THE STUDY: The principle of concoction was investigated by using the processing excipient GRR juice to reduce the major toxic hepatotoxicity of RDB, and the efficacy of RDB as an expectorant and cough suppressant was enhanced. MATERIALS AND METHODS: In this study, common factors (RDB:GRR ratio, concocted temperature, and concocted time) in the concoction process were used for the preparation of each RDB concocted with GRR juice by using an orthogonal experimental design. We measured the content of the main toxic compound diosbulbin B (DB) and serum biochemical indicators and performed pathological analysis in liver tissues of mice to determine the best detoxification process of RDB concocted with GRR juice. On this basis, the biological mechanisms of target organs were detected by Western blot and enzyme-linked immunosorbent assay at the inflammation and apoptosis levels. Further, the effects of RDB on expectorant and cough suppressant with GRR juice were evaluated by the conventional tests of phenol red expectorant and concentrated ammonia-induced cough. Lastly, the major compounds in the GRR juice introduced to RDB concoction were determined. RESULTS: RDB concocted with GRR juice significantly alleviated DB content, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase levels, and improved liver pathological damages. The best detoxification process was achieved by using an RDB:GRR ratio of 100:20 at 120 °C for 20 min. Further, RDB concocted with GRR juice down-regulated the protein levels of nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX-2), and Bcl-2 related X protein (Bax) in the liver and enhanced the expectorant and cough suppressant effects of RDB. Finally, liquiritin (LQ) and glycyrrhizic acid (GA) in the GRR juice were introduced to the RDB concoction. CONCLUSION: Concoction with GRR juice not only effectively reduced the major toxic hepatotoxicity of RDB but also enhanced its main efficacy as an expectorant and cough suppressant, and that the rationale for the detoxification and/or potentiation of RDB was related to the reduction in the content of the main hepatotoxic compound, DB, the introduction of the hepatoprotective active compounds, LQ and GA, in the auxiliary GRR juice, as well as the inhibition of NF-κB/COX-2/Bax signaling-mediated inflammation and apoptosis.
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Antitusígenos , Enfermedad Hepática Inducida por Sustancias y Drogas , Dioscorea , Medicamentos Herbarios Chinos , Glycyrrhiza uralensis , Glycyrrhiza , Ratones , Animales , Glycyrrhiza uralensis/química , Expectorantes , Antitusígenos/farmacología , Excipientes , Dioscorea/química , FN-kappa B , Ciclooxigenasa 2 , Proteína X Asociada a bcl-2 , Medicamentos Herbarios Chinos/análisis , Glycyrrhiza/química , InflamaciónRESUMEN
No disponible
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Humanos , Ciencias de la Salud , Expectorantes/análisis , Expectorantes/farmacología , Expectorantes/normas , Broncodilatadores/normasRESUMEN
La colonoscopia es el patrón oro para el diagnóstico de lesiones epiteliales colorrectales y su eficiencia está íntimamente relacionada con la calidad de la exploración. Lograr una adecuada limpieza colónica es un factor fundamental para alcanzar los estándares de calidad recomendados. Actualmente, hasta el 30% de los pacientes a los que se realiza una colonoscopia ambulatoria presentan una calidad deficiente. Por ello, en los últimos años numerosos estudios han diseñado estrategias para optimizar la limpieza colónica mejorando la adherencia y la tolerancia de la solución de limpieza colónica o la eficacia de esta. La identificación de factores predictores de una limpieza colónica inadecuada ha propiciado el desarrollo de estrategias de preparación individualizadas con resultados prometedores. En este artículo se revisan los estudios que evaluaron los factores asociados a una limpieza colónica deficiente, así como las estrategias diseñadas para optimizar la limpieza colónica en pacientes con elevada probabilidad de una limpieza colónica inadecuada
Colonoscopy is the gold standard procedure for detecting neoplastic lesions of the colon and its efficiency is closely linked to the quality of the procedure. Adequate bowel preparation is a crucial factor in achieving the recommended quality indicators, but poor preparation has been reported in up to 30% of outpatients referred for colonoscopy. Consequently, over recent years, a number of studies have developed strategies to optimise bowel cleansing by improving adherence and tolerance to and the efficacy of the bowel preparation. Moreover, the identification of risk factors for inadequate bowel cleansing has led to tailored bowel preparation strategies being designed, with promising results. We aimed to review studies that assessed risk factors for inadequate bowel preparation and strategies to optimise bowel cleansing in patients at high risk of having poor preparation
Asunto(s)
Humanos , Catárticos/administración & dosificación , Colonoscopía/métodos , Factores de Riesgo , Dietética/métodos , Diuréticos Osmóticos/clasificación , Cuidados Preoperatorios/métodos , Sociedades Médicas/normas , Garantía de la Calidad de Atención de Salud/normas , Calidad de la Atención de Salud , Expectorantes , ColectomíaRESUMEN
Objective: There is controversy regarding the effectiveness of chest physiotherapy to solve airway obstruction problems experienced by children younger than five years of age with pneumonia. The aim of this study was to determine the effectiveness of chest physiotherapy and nebulization on the respiratory status of these children. Method: This study was quasi-experimental with a pre- and post-test nonequivalent control group design. Thirty-four respondents selected by consecutive sampling were divided into two groups: one that received nebulization and one that received nebulization with chest physiotherapy. The independent t-test was used to analyze the effect of chest physiotherapy and nebulization on the respiratory status of children younger than age five with pneumonia. Results: There was a significant mean difference in heart rate, respiratory rate, and oxygen saturation between the control and intervention group (p=0.000). Despite the correlation between age and heart rate, other characteristics (nutritional status, exclusive breast-feeding, vaccination, the length of illness, and the content of nebulization medication) had no effect on heart rate, respiratory rate, and oxygen saturation. Conclusions: The combination of nebulization and chest physiotherapy is more effective than nebulization only. It is important to reconsider the combination of nebulization and chest physiotherapy to overcome airway obstruction problems
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Asunto(s)
Humanos , Niño , Broncodilatadores/administración & dosificación , Modalidades de Fisioterapia , Neumonía/terapia , Expectorantes/administración & dosificación , Nebulizadores y Vaporizadores , Terapia Combinada/métodos , Obstrucción de las Vías Aéreas/terapia , Ejercicios RespiratoriosRESUMEN
La enfermedad pulmonar obstructiva crónica (EPOC) presenta una gran heterogeneidad clínica, por lo que su tratamiento se debe individualizar según el nivel de riesgo y el fenotipo. La Guía española de la EPOC (GesEPOC) estableció por primera vez en 2012 unas pautas de tratamiento farmacológico basadas en fenotipos clínicos. Estas pautas han sido adoptadas posteriormente por otras normativas nacionales, y han sido respaldadas por nuevas evidencias publicadas desde entonces. En esta actualización 2017 se ha sustituido la clasificación de gravedad inicial por una clasificación de riesgo mucho más sencilla (bajo o alto riesgo), basándose en la función pulmonar, el grado de disnea y la historia de agudizaciones, y se recomienda la determinación del fenotipo clínico únicamente en pacientes de alto riesgo. Se mantienen los mismos fenotipos clínicos: no agudizador, EPOC-asma (ACO), agudizador con enfisema y agudizador con bronquitis crónica. La base del tratamiento farmacológico de la EPOC es la broncodilatación, y también es el único tratamiento recomendado en pacientes de bajo riesgo. En los pacientes con alto riesgo se añadirán diversos fármacos a los broncodilatadores según el fenotipo clínico. GesEPOC supone una aproximación al tratamiento de la EPOC más individualizado según las características clínicas de los pacientes y su nivel de riesgo o de complejidad.(AU)
The clinical presentation of chronic obstructive pulmonary disease (COPD) varies widely, so treatment must be tailored according to the level of risk and phenotype. In 2012, the Spanish COPD Guidelines (GesEPOC) first established pharmacological treatment regimens based on clinical phenotypes. These regimens were subsequently adopted by other national guidelines, and since then, have been backed up by new evidence. In this 2017 update, the original severity classification has been replaced by a much simpler risk classification (low or high risk), on the basis of lung function, dyspnea grade, and history of exacerbations, while determination of clinical phenotype is recommended only in high-risk patients. The same clinical phenotypes have been maintained: non-exacerbator, asthma-COPD overlap (ACO), exacerbator with emphysema, and exacerbator with bronchitis. Pharmacological treatment of COPD is based on bronchodilators, the only treatment recommended in low-risk patients. High-risk patients will receive different drugs in addition to bronchodilators, depending on their clinical phenotype. GesEPOC reflects a more individualized approach to COPD treatment, according to patient clinical characteristics and level of risk or complexity.(AU)