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1.
J Health Popul Nutr ; 43(1): 132, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39192358

RESUMEN

PURPOSE: To evaluate the therapeutic efficacy of intravenous amoxicillin clavulanate potassium combined with nebulized budesonide and ambroxol hydrochloride in pediatric community-acquired pneumonia (CAP) and its impact across various microbial strains and clinical symptoms. The primary objective of this study is to evaluate the efficacy of intravenous amoxicillin-clavulanate combined with nebulized budesonide and ambroxol hydrochloride in the treatment of pediatric community-acquired pneumonia (CAP), and to analyze their impact on different microbial strains and clinical symptoms. Secondary objectives include assessing the treatment's effect on the improvement of clinical symptoms, hospital stay duration, and the levels of inflammatory markers. DESIGN: Prospective, single-center study. METHODS: Fifty-six children with CAP, aged under 6 years, from Affiliated Maternity and Child Health Care Hospital of Nantong University were included. Patients were treated with conventional therapy and the study medication. Clinical characteristics, microbiological data, symptom improvement, and hospitalization times were analyzed. FINDINGS: Young children, particularly under 1 year, exhibited a higher incidence of multiple microbial infections and severe clinical manifestations. Treatment with budesonide and ambroxol hydrochloride led to significant clinical improvement across all age groups, with notable efficacy against various pathogens. CONCLUSIONS: Nebulized budesonide and ambroxol hydrochloride are effective in treating pediatric CAP, offering a promising therapeutic option, particularly for young children with severe presentations.


Asunto(s)
Ambroxol , Budesonida , Infecciones Comunitarias Adquiridas , Nebulizadores y Vaporizadores , Humanos , Ambroxol/administración & dosificación , Ambroxol/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Femenino , Masculino , Preescolar , Lactante , Estudios Prospectivos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Resultado del Tratamiento , Administración por Inhalación , Combinación Amoxicilina-Clavulanato de Potasio/administración & dosificación , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Niño , Neumonía/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Expectorantes/administración & dosificación , Expectorantes/uso terapéutico , Biomarcadores/sangre , Quimioterapia Combinada , Tiempo de Internación
2.
Clinics (Sao Paulo) ; 79: 100476, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39208656

RESUMEN

OBJECTIVE: This study investigated the effects of N-Acetylcysteine (NAC) combined with Ambroxol Hydrochloride (AH) on clinical symptoms, C-Reactive Protein (CRP), and Procalcitonin (PCT) levels in children with pneumonia. METHODS: A total of 98 children with pneumonia were assigned to the control group and observation group by random number table method. NAC was administered to the observation group and AH was given to the control group. The therapeutic effect was observed, the disappearance time of clinical symptoms and levels of inflammatory factors, lung function parameters, blood gas analysis parameters, and immunoglobulin were measured. The incidence of adverse reactions was statistically analyzed. RESULTS: A higher effective rate was observed in the observation group than in the control group (p < 0.05). Antipyretic time, cough disappearance time, and lung rale disappearance time in the observation group were shorter than those in the control group (p < 0.05). After treatment, CRP and PCT were lower (p < 0.05), FVC, FEV1, and FEV1/FVC were higher, PaCO2 was lower, PaO2 and SaO2 were higher, and IgA, IgG, IgM, and C3 were higher in the observation group than those in the control group (p < 0.05). The incidence of adverse reactions between the two groups was not significantly different (p > 0.05). CONCLUSION: NAC combined with AH is effective in the treatment of pediatric pneumonia by effectively alleviating clinical symptoms, reducing inflammatory factors, and improving lung function and immune function.


Asunto(s)
Acetilcisteína , Ambroxol , Proteína C-Reactiva , Quimioterapia Combinada , Expectorantes , Neumonía , Polipéptido alfa Relacionado con Calcitonina , Humanos , Ambroxol/uso terapéutico , Ambroxol/administración & dosificación , Proteína C-Reactiva/análisis , Acetilcisteína/uso terapéutico , Femenino , Masculino , Polipéptido alfa Relacionado con Calcitonina/sangre , Preescolar , Expectorantes/uso terapéutico , Expectorantes/efectos adversos , Neumonía/tratamiento farmacológico , Niño , Resultado del Tratamiento , Lactante , Análisis de los Gases de la Sangre
3.
Biomater Sci ; 12(18): 4713-4726, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39082607

RESUMEN

Inhalation injuries arising from exposure to toxic gases or smoke in fires or industrial accidents pose grave risks and significant respiratory complications. The limited efficacy of current treatment strategies stems from challenges in delivering therapeutic agents across the mucus barrier to the damaged trachea and bronchus. This research explores the reparative potential and underlying mechanisms of sputum-penetrable magnetic nanoparticles (MNPs) coated with poly(N-isopropylacrylamide) (PNIPAM), combined with polyethylene glycol (PEG), and loaded with ambroxol hydrochloride (AH) (MNPs@PNIPAM-AH@PEG) as an innovative therapeutic approach for inhalation injuries. The PNIPAM coating, a thermo-responsive polymer, aims to enhance targeted drug release under an external stimulus. The PEG component is designed to mitigate hydrophobic repulsion and electrostatic forces, facilitating nanoagent penetration of the mucus barrier-an obstacle in inhalation injury treatment. PEG's hydrophilicity, combined with the magnetically attracted NPs, enables deep penetration through the mucus layer adhering to the mucus epithelium. Thermal effects break the outer thermal shell of MNPs, accelerating drug release, resolving sputum, and reducing inflammation. The results showed improved therapeutic impact by significantly reducing inflammation, enhancing mucociliary clearance, and promoting tissue repair. Moreover, the MNPs@PNIPAM-AH@PEG NPs showed good biocompatibility and biosafety both in vitro and in vivo. This research underscores the potential of MNPs@PNIPAM-AH@PEG NPs as a novel therapeutic strategy for inhalation injuries, paving the way for innovative treatments in emergency medicine and respiratory care.


Asunto(s)
Resinas Acrílicas , Ambroxol , Moco , Polietilenglicoles , Animales , Polietilenglicoles/química , Resinas Acrílicas/química , Moco/metabolismo , Moco/efectos de los fármacos , Ambroxol/química , Ambroxol/administración & dosificación , Ambroxol/farmacología , Ratones , Liberación de Fármacos , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/administración & dosificación , Masculino , Humanos
4.
BMC Neurol ; 24(1): 146, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693511

RESUMEN

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 , Adulto
6.
Comput Math Methods Med ; 2021: 1341644, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34650619

RESUMEN

BACKGROUND: Patients with stable chronic obstructive pulmonary disease (COPD) have been observed to benefit from tiotropium bromide. However, there are few studies of tiotropium bromide on sputum and sputum viscosity. To evaluate the effect of tiotropium bromide on mucus hypersecretion, a randomized, double-blind controlled trial was performed. METHODS: 120 cases of patients with pulmonary function grade II were divided into two groups, which include the treatment group given tiotropium bromide powder inhalation (18 µg, inhalation, QD) and the control group given formoterol fumarate powder inhalation (12 µg, inhalation, BID) plus ambroxol hydrochloride tablets (60 mg, oral, TID). After 3 months of treatment, the pulmonary function and α 1-acid glycoprotein (α 1-AGP) in sputum were detected, and the changes of glycoprotein and Ca2+ content were evaluated by Miller classification. RESULTS: Three patients (2 cases in the treatment group and 1 case in the control group) were dropped due to loss of follow-up, and 117 cases of patients were enrolled in this study. After 3 months of treatment, the sputum character score, α1-acid glycoprotein, Ca2+ content, and lung function of the two groups were significantly improved; group comparison analyses revealed that there was no significant difference in the content of α 1-AGP, Ca2+ in sputum, and lung function between the two groups (P > 0.05), but the improvement of sputum properties was significant (P < 0.05), and the treatment group was better than the control group (t = -2.77; P = 0.007). CONCLUSIONS: Inhaled tiotropium bromide can effectively inhibit the mucus hypersecretion in stable COPD patients, improve the sputum properties and lung function of patients, and improve the quality of life of patients.


Asunto(s)
Moco/efectos de los fármacos , Moco/fisiología , Antagonistas Muscarínicos/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Bromuro de Tiotropio/uso terapéutico , Administración por Inhalación , Ambroxol/administración & dosificación , Calcio/metabolismo , Biología Computacional , Método Doble Ciego , Fumarato de Formoterol/administración & dosificación , Humanos , Antagonistas Muscarínicos/administración & dosificación , Orosomucoide/metabolismo , Ventilación Pulmonar/efectos de los fármacos , Calidad de Vida , Esputo/efectos de los fármacos , Esputo/fisiología , Bromuro de Tiotropio/administración & dosificación
7.
Cochrane Database Syst Rev ; 7: CD013876, 2021 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-34291813

RESUMEN

BACKGROUND: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training). OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.


Asunto(s)
COVID-19/complicaciones , Expectorantes/administración & dosificación , Glucocorticoides/administración & dosificación , Descongestionantes Nasales/administración & dosificación , Trastornos del Olfato/tratamiento farmacológico , Administración Oral , Ambroxol/administración & dosificación , Betametasona/administración & dosificación , Sesgo , Humanos , Lavado Nasal (Proceso)/métodos , Trastornos del Olfato/etiología , Prednisona/administración & dosificación , Prevalencia , Calidad de Vida , Recuperación de la Función , Olfato/efectos de los fármacos , Factores de Tiempo
8.
Eur J Paediatr Neurol ; 32: 66-72, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33836415

RESUMEN

Gaucher disease type 3 (GD3) is a severely debilitating disorder characterized by multisystemic manifestations and neurodegeneration. Enzyme replacement therapy alleviates visceral signs and symptoms but has no effect on neurological features. Ambroxol has been suggested as an enzyme enhancement agent. Some studies have confirmed its effectiveness in preventing the progression of neurological manifestations of neuronopathic Gaucher disease. In this study, we report two GD3 siblings in whom ambroxol combined with enzyme replacement therapy was initiated at different stages of the disease. We demonstrate the enzyme enhancement effect of ambroxol on L444P/H225Q;D409H glucocerebrosidase activity through results of fibroblast studies and long-term clinical outcomes of the two patients. The sibling diagnosed at the age of four-and-a-half years with significant neurological involvement manifested relatively rapid improvement on ambroxol treatment, followed by stabilization of further course. The younger sibling, in whom the treatment was started at seven weeks, displayed attention deficit and low average cognitive functioning at the age of seven years, but did not manifest other neurological symptoms. The difference in neurological outcomes indicates that ambroxol delayed or even halted the evolution of neurological manifestations in the younger sibling. This observation suggests that early initiation of ambroxol treatment may arrest neurological involvement in some GD3 patients.


Asunto(s)
Ambroxol/administración & dosificación , Terapia de Reemplazo Enzimático/métodos , Enfermedad de Gaucher/tratamiento farmacológico , Prevención Secundaria , Niño , Preescolar , Femenino , Glucosilceramidasa/deficiencia , Glucosilceramidasa/uso terapéutico , Humanos , Lactante , Masculino , Hermanos
9.
Comput Math Methods Med ; 2020: 7984565, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33133226

RESUMEN

OBJECTIVE: This paper was aimed at investigating the effects of bronchoalveolar lavage (BAL) with ambroxol hydrochloride (AH) on treating pulmonary infection and on serum proinflammatory cytokines and oxidative stress responses in patients with cerebral infarction (CI). METHODS: One hundred and two patients with cerebral infarction complicated with pulmonary infection (CIPI) who were treated in our hospital were enrolled as research objects, divided into an observation group (52 cases; AH combined with BAL) and a control group (50 cases; single AH) based on therapeutic schemes. They were compared in terms of the therapeutic effect and pre- and posttreatment serum inflammatory cytokines, pulmonary function, and serum indices of oxidative stress. Their adverse reactions during treatment were also recorded and compared. RESULTS: The therapeutic effect in the observation group was remarkably better than that in the control group (P < 0.05). After treatment, the serum inflammatory cytokines, pulmonary function, and serum indices of oxidative stress were remarkably improved in the two groups (P < 0.05), but the improvement was remarkably better in the observation group (P < 0.05). The differences were not significant in intratreatment adverse reactions between the two groups (P > 0.05). CONCLUSION: For CIPI patients, BAL with AH has a better therapeutic effect and higher safety and can control the patients' systemic inflammatory responses and oxidative stress responses, so it is worthy of further promotion in clinical practice.


Asunto(s)
Ambroxol/administración & dosificación , Infarto Cerebral/complicaciones , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/tratamiento farmacológico , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Lavado Broncoalveolar , Estudios de Casos y Controles , Infarto Cerebral/sangre , Biología Computacional , Citocinas/sangre , Expectorantes/administración & dosificación , Femenino , Humanos , Mediadores de Inflamación/sangre , Enfermedades Pulmonares/sangre , Masculino , Malondialdehído/sangre , Conceptos Matemáticos , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacos , Estudios Prospectivos , Infecciones del Sistema Respiratorio/sangre , Superóxido Dismutasa/sangre
10.
Int J Antimicrob Agents ; 56(6): 106192, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33045350

RESUMEN

Knowing the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to bind to the angiotensin-converting enzyme 2 (ACE2) receptor and to enter cells via endocytosis paved the way for repositioning of old drugs as potential treatment of COVID-19, the disease caused by SARS-CoV-2 infection. This paper highlights the potential of azithromycin and ambroxol to treat COVID-19. Azithromycin and ambroxol share lysosomotropic characteristics, i.e. they penetrate and accumulate inside the late endosomes and lysosomes and may possibly interfere with multiplication of the virus inside cells. In addition, both of these drugs have anti-inflammatory effects. Ambroxol has a proven antiviral effect and a unique stimulatory action on the secretion of surfactant by alveolar type II cells, the main target of SARS-CoV-2. Surfactant may form a fundamental defence mechanism against the virus. Involvement of nasal epithelial cells in SARS-CoV-2 entry suggested advantageous use of inhaled drug delivery of these two drugs over the use of systemic administration. Inhaled drug delivery could aid in targeting the drug to the exact site of action with little or no side effects. To conclude, administration of these two drugs using a special drug delivery system provides two kinds of drug targeting: (i) tissue targeting through using an inhaled drug delivery system to achieve high drug concentrations at the respiratory epithelial tissue that overexpress the ACE2 receptor for virus binding; and (ii) cellular targeting of the virus in the acidic vesicles (late endosomes and lysosomes), which represent the fate of endocytic viruses.


Asunto(s)
Ambroxol/administración & dosificación , Azitromicina/administración & dosificación , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2 , Administración por Inhalación , Sistemas de Liberación de Medicamentos , Humanos
11.
Int J Nanomedicine ; 15: 779-793, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32099365

RESUMEN

PURPOSE: Cancer chemotherapy effect has been largely limited by cell autophagy and little drug accumulation at the action sites. Herein, we designed an intelligent strategy involving paclitaxel (PTX) polymer micelles in response to biological functions of ambroxol (Ax). The amphiphilic polymers polyethyleneglycol-polylactic acid (PEG-PLA) and Pluronic P105 were selected as nanocarriers to encapsulate PTX to form into lung affinity PEG-PLA/P105/PTX micelles. Ax which can up-regulate the secretion of pulmonary surfactant (PS) and inhibit autophagy was hired to change the microenvironment of the lung, thereby promoting the lung accumulation and increasing cell-killing sensitivity of the micelles. METHODS: The physical and chemical properties of the micelles were characterized including size, morphology, critical micellar concentration (CMC) and in vitro drug release behavior. The therapeutic effects of the combination regimen were characterized both in vitro and in vivo including study on Ax in promoting the secretion of pulmonary surfactant, in vitro cytotoxicity, cellular uptake, Western blotting, in vivo biodistribution, in vivo pharmacokinetics and in vivo antitumor efficacy. RESULTS: The PEG-PLA/P105/PTX micelles showed a particle size of 16.7 ± 0.5 nm, a nearly round shape, small CMC and sustained drug release property. Moreover, the in vitro results indicated that Ax could increase PS and LC3 protein secretion and enhance the cytotoxicity of PEG-PLA/P105/PTX micelles toward A549 cells. The in vivo results indicated that the combination therapeutic regimen could promote the micelles to distribute in lung and enhance the therapeutic effect on lung cancer. CONCLUSION: This multifunctional approach of modulating the tumor microenvironment to enhance drug transportation and cell-killing sensitivity in the action sites might offer a new avenue for effective lung cancer treatment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Portadores de Fármacos/química , Neoplasias Pulmonares/tratamiento farmacológico , Ambroxol/administración & dosificación , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Preparaciones de Acción Retardada/uso terapéutico , Portadores de Fármacos/farmacocinética , Liberación de Fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , Micelas , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Tamaño de la Partícula , Poloxámero/química , Polietilenglicoles/química , Polímeros/química , Ratas Sprague-Dawley , Distribución Tisular
13.
J Hum Genet ; 65(3): 345-349, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31822786

RESUMEN

Gaucher disease (GD) is a lysosomal storage disease caused by the deficiency of glucocerebrosidase characterized by a broad spectrum of clinical manifestations including hepatosplenomegaly, bone infiltration, and cytopenia, and even central nervous system involvement. Bone manifestations are typical of the GD-I and partially responded to mainstay therapy. Ambroxol (ABX), an approved cough-suppressant, was identified as an enzyme-enhancement agent of the residual activity of glucocerebrosidase mutants derived from different misfolding-mutations in the GBA gene. Here, we describe the early beneficial effects of ABX on skeletal and hematological manifestations of a child suffering with progressive GD-I.


Asunto(s)
Ambroxol/administración & dosificación , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedades por Almacenamiento Lisosomal/tratamiento farmacológico , Esqueleto/efectos de los fármacos , Niño , Terapia de Reemplazo Enzimático , Enfermedad de Gaucher/genética , Enfermedad de Gaucher/patología , Glucosilceramidasa/genética , Humanos , Enfermedades por Almacenamiento Lisosomal/genética , Enfermedades por Almacenamiento Lisosomal/fisiopatología , Mutación/genética , Linaje , Esqueleto/anomalías , Esplenomegalia/tratamiento farmacológico , Esplenomegalia/genética
14.
J Med Genet ; 57(2): 124-131, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31649052

RESUMEN

BACKGROUND: Ambroxol (ABX) has been suggested as an augmentative pharmacological agent for neuronopathic Gaucher disease (nGD). This study assessed the long-term safety and efficacy of combined therapy with high-dose ABX and enzyme replacement therapy (ERT) in nGD. METHODS: ABX+ERT therapy was administered for 4.5 years in four patients with nGD. ABX was initiated at a dose of 1.5 mg/kg/day, and the dose was escalated up to 27 mg/kg/day. The target plasma level was 10 µmol/L or less. The changes in glucocerebrosidase activity, biochemical, safety and neurocognitive findings were assessed. RESULTS: Enhanced residual GCcase activity was observed in all patients, as evidenced in both in vitro and in vivo studies. During the first 2 years of study with ABX (up to 21 mg/kg/day), mean seizure frequencies and neurocognitive function worsened. After ABX dosage was increased up to 27 mg/kg/day of ABX, its trough plasma concentration was 3.2-8.8 µmol/L. Drug-to-drug interaction, especially with antiepileptic drug significantly affected the pharmacokinetic parameters of ABX. Importantly, at 27 mg/kg/day of ABX, the seizure frequencies markedly decreased from the baseline, and the neurocognitive function was improved. In addition, Lyso-Gb1, a biomarker for the severity and progression of GD, was normalised in all patients. High-dose ABX was well-tolerated with no severe adverse events. CONCLUSIONS: Long-term treatment with high-dose ABX+ERT was safe and might help to arrest the progression of the neurological manifestations in GD.


Asunto(s)
Ambroxol/administración & dosificación , Terapia de Reemplazo Enzimático , Epilepsias Mioclónicas/tratamiento farmacológico , Enfermedad de Gaucher/tratamiento farmacológico , Adolescente , Biomarcadores/sangre , Niño , Relación Dosis-Respuesta a Droga , Epilepsias Mioclónicas/sangre , Epilepsias Mioclónicas/patología , Femenino , Enfermedad de Gaucher/sangre , Enfermedad de Gaucher/patología , Glucosilceramidasa/sangre , Humanos , Masculino
15.
Pak J Pharm Sci ; 32(3 Special): 1409-1413, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31551222

RESUMEN

To observe and analyze the therapeutic efficacy of high-dose ambroxol in the treatment of severe pneumonia, as well as summarize the nursing methods. A total of 180 patients diagnosed with severe pneumonia and treated at our hospital who were enrolled. The patients were divided into a control group and are search group, with 90 patients in each group. Of those, patients in the research group were treated with high-doses ambroxol, while small-dose ambroxol was administered to patients in the control group. The therapeutic efficacy was compared between both groups. Meanwhile, predictive nursing regimens were applied on patients in the research group, while routine nursing care was given to patients in the control group. The nursing satisfaction was compared between both groups. By comparing the pulmonary function indicators, Comparison of procalcitonin (PCT) and C-reactive protein (CRP) results showed that all indicators of the research group were obviously better than those of the control group (p<0.05). The time of infection control, ICU stay and hospital stay of the research group were significantly less than those of the control group (p<0.05). Moreover, the overall nursing satisfaction of the research group was significantly higher than that of the control group (p<0.05).Application of high-dose ambroxol and scientific nursing methods could significantly improve the therapeutic efficacy in the treatment of severe pneumonia and gain favorable nursing satisfaction.


Asunto(s)
Ambroxol/administración & dosificación , Expectorantes/administración & dosificación , Atención de Enfermería , Neumonía/tratamiento farmacológico , Administración Intravenosa , Adulto , Anciano , Ambroxol/uso terapéutico , Proteína C-Reactiva/análisis , Relación Dosis-Respuesta a Droga , Expectorantes/uso terapéutico , Femenino , Humanos , Unidades de Cuidados Intensivos , Pulmón/diagnóstico por imagen , Pulmón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Neumonía/diagnóstico por imagen , Polipéptido alfa Relacionado con Calcitonina/sangre , Resultado del Tratamiento , Adulto Joven
16.
Drug Deliv Transl Res ; 9(5): 997-1007, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31016478

RESUMEN

Resealed erythrocytes (RSE) are potential, site-specific carrier system for drug delivery with prolonged drug release activity. In this study, erythrocytes obtained from Wistar albino rats were loaded with ambroxol hydrochloride (AH) with the focus to convenience the lung targeting possibility of the carrier erythrocytes. AH loading in erythrocytes using preswell dilution technique with glutaraldehyde (GA) as a cross-linking agent was evaluated and validated. Drug-loaded erythrocyte was characterized in terms of in vitro drug release followed by osmotic fragility study which showed amplified drug entrapment efficiency (DEE) and hemoglobin content values as well. In vivo lung fibrosis study, rats were sensitized to egg albumin by intraperitoneal (i.p.) injection and then inhalation in a whole body inhalation chamber. A sign of inflammation, airway sub-mucosal fibrosis, hypertrophy, and hyperplasia was observed. A series of in vivo studies were carried out to describe the effect of AH-loaded RSE including measurement of cytokines in Bronchoalveolar Lavage (BAL) fluid and histopathology study. AH showed a stepwise reduced level of cytokines in BAL at a different time interval after being injected of AH-loaded RSE. Furthermore, in vivo lung distribution experiments were performed for optimized formulation, and degree of distribution of the drugs inside the targeted organ was found to be satisfactory.


Asunto(s)
Ambroxol/administración & dosificación , Portadores de Fármacos/administración & dosificación , Eritrocitos , Enfermedades Pulmonares/tratamiento farmacológico , Albúminas , Ambroxol/química , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/inmunología , Portadores de Fármacos/química , Liberación de Fármacos , Fibrosis , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/patología , Masculino , Fragilidad Osmótica , Ratas Wistar
17.
Expert Opin Drug Metab Toxicol ; 15(3): 213-218, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30721101

RESUMEN

INTRODUCTION: Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to optimize therapy using existing agents are also attractive. Ambroxol induces lung autophagy at human-relevant doses and improves lung levels of several approved antibiotics. Areas covered: This review discusses preclinical and clinical studies of the effects of ambroxol (and its prodrug precursor bromhexine) co-treatment upon levels of antibiotics in lung tissue, sputum, and bronchoalveolar lavage fluid. Expert opinion: Ambroxol co-treatment is associated with significant increases in lung tissue and airway surface fluid levels of a range of antibiotics including beta lactams, glycopeptides, macrolides, nitrofurans, and rifamycins. In most cases, the increased levels are only modest and are insufficient to overcome high-level resistance against that same antibiotic class, and so co-treatment with ambroxol is unlikely to alter clinical outcomes. Additionally, for most antibiotics there is no evidence that outcomes in non-resistant disease are improved by higher drug levels, and there is limited efficacy of co-treatment of antibiotics with ambroxol for most pathogens. The two cases where ambroxol may improve therapy are rifampin-sensitive tuberculosis and non-tuberculous mycobacterial infection, and vancomycin sensitive methicillin resistant Staphylococcus aureus pneumonia.


Asunto(s)
Ambroxol/farmacología , Antibacterianos/farmacocinética , Bromhexina/farmacología , Ambroxol/administración & dosificación , Animales , Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Bromhexina/administración & dosificación , Farmacorresistencia Bacteriana , Expectorantes/administración & dosificación , Expectorantes/farmacología , Humanos , Pulmón/metabolismo , Enfermedades Pulmonares/tratamiento farmacológico , Distribución Tisular
18.
Headache ; 59(3): 418-429, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30653673

RESUMEN

BACKGROUND: Trigeminal neuralgia is difficult to treat and shows upregulation of sodium channels. The expectorant ambroxol acts as a strong local anesthetic, about 40 times stronger than lidocaine. It preferentially inhibits the channel subtype Nav 1.8, expressed especially in nociceptive C-fibers. It seemed reasonable to try ambroxol for the treatment with neuropathic facial pain unresponsive to other standard options. MATERIAL AND METHODS: Medical records of patients suffering from classical trigeminal neuralgia (n = 5) and successful pain reduction following topical ambroxol 20% cream in addition to standard treatment are reported. RESULTS: All patients reported pain attacks with pain intensity between 4 and 10 NRS (numeric pain scale). In all cases they could be triggered, 3 patients reported additional spontaneous pain. Attacks were reduced in all 5 patients. Pain reduction achieved following ambroxol 20% cream was 2-8 points (NRS) earliest within 15-30 minutes and lasted for 4-6 hours mostly. This was reproducible in all cases; in one case pain was eliminated after 1 week. No patient reported side effects or skin changes; oral medication was reduced in 2 patients. CONCLUSION: For the first time, a clinically significant pain relief following topical ambroxol 20% cream in patients with trigeminal neuralgia is reported. In view of the positive side effect profile, topical ambroxol for patients with such a highly impaired quality of life should be investigated further as a matter of urgency.


Asunto(s)
Ambroxol/administración & dosificación , Ambroxol/química , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Neuralgia del Trigémino/diagnóstico , Neuralgia del Trigémino/tratamiento farmacológico , Administración Tópica , Adulto , Anciano , Composición de Medicamentos , Expectorantes/administración & dosificación , Expectorantes/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
19.
Heart Lung ; 48(2): 141-147, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30409442

RESUMEN

BACKGROUND AND OBJECTIVES: Inhaled mucoactive agents are used to enhance airway clearance, however efficacy and safety are unclear in adults with acute respiratory conditions. METHODS: We systematically reviewed randomized controlled trials assessing respiratory function; safety; length of stay (LOS); mucus; radiology; and oxygenation. RESULTS: No adverse events were reported for dornase alfa (n = 63), N-acetylcysteine (NAC, n = 50), ambroxol (n = 140), hypertonic saline (n = 33), heparin (n = 384), mannitol (n = 20) or isotonic saline. During invasive ventilation, NAC, dornase alfa and saline had no effect on mucus. Postoperatively, mucus characteristics improved with NAC (n = 10). Ambroxol lowered LOS (mean difference 4 days) and halved complications following lung carcinoma resection (n = 140). Heparin improved ventilator-free days (n = 130, mean difference 3.9-4.6) and intensive care LOS (n = 223, 3.2 days), but not ventilator-acquired pneumonia. CONCLUSION: Dornase alfa, hypertonic saline and NAC were ineffective for atelectasis/mucus plugging while intubated. More data are required to support using NAC, ambroxol and heparin during acute illness.


Asunto(s)
Expectorantes/administración & dosificación , Enfermedades Pulmonares/tratamiento farmacológico , Depuración Mucociliar/efectos de los fármacos , Enfermedad Aguda , Administración por Inhalación , Adulto , Ambroxol/administración & dosificación , Desoxirribonucleasa I/administración & dosificación , Humanos , Enfermedades Pulmonares/metabolismo , Manitol/administración & dosificación , Proteínas Recombinantes/administración & dosificación
20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 50(5): 840-844, 2018 Oct 18.
Artículo en Chino | MEDLINE | ID: mdl-30337745

RESUMEN

OBJECTIVE: To study the clinical effect of the oxygen drive aerosol in halation with budesonide and ambroxol in the prevention of adult post-thoracotomy pneumonia. METHODS: This was a randomized, open and parallel controlled trial. We chose 80 cases of patients in the department of thoracic surgery in the First Affiliated Hospital of Xi'an Jiaotong University which fitted our criteria as the research object. The selected patients were randomly divided into the active group and the control group, and the active group underwent oxygen drive aerosol inhalation (2 mg budesonide combined 60 mg ambroxol) for 3 days before operation, and the control group without preoperative aerosol inhalation, and their postoperative therapy was the same. RESULTS: The baseline data showed that the differences in sex, age, disease and smoking were not statistically significant between the two groups, P>0.05. The results of blood gas analysis before 12 hours of operation suggested that, the PaO2and PaCO2values of the active group were (88.40±9.40) mmHg and (38.30±6.10) mmHg; The PaO2and PaCO2 values of the control group were (85.09±7.18) mmHg and (41.21±3.15) mmHg. And the two groups' P values were 0.029 and 0.011, with statistical differences. There were 3 patients who developed postoperative pneumonia out of 40 patients in the active group, the incidence was 7.50%, but the incidence of control group was 25.00%. The P value was 0.034, with statistical differences. We also analyzed the influence of different diseases and surgical methods on postoperative pneumonia, and the results showed that in the active group and the control group, the incidence of postoperative pneumonia in the patients with esophageal cancer was lower than that in lung cancer patients, and there was a statistically significant difference (P<0.05). In the active group, the numbers of pulmonary deed resection, lobectomy and pulmonary sleeve resection were 2, 21 and 1 cases respectively, and the corresponding numbers in the control group were 2, 21 and 2. Among the two groups, the incidence of postoperative pneumonia in the patients with different surgical methods of lung cancer was statistically significant (P<0.05). CONCLUSION: If we implement respiratory preparation with budesonide plus ambroxol inhalation for 3 days before operation, we can greatly reduce the incidence of postoperative pneumonia?


Asunto(s)
Ambroxol , Broncodilatadores , Budesonida , Neumonía , Toracotomía , Adulto , Aerosoles , Ambroxol/administración & dosificación , Broncodilatadores/administración & dosificación , Budesonida/administración & dosificación , Quimioterapia Combinada , Humanos , Oxígeno , Neumonía/etiología , Neumonía/prevención & control , Toracotomía/efectos adversos
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