Development of a rapid method for the simultaneous determination of aminophylline, doxofylline, bromhexine, and ambroxol by HPLC.

Introduction: Antitussive and expectorant drugs such as aminophylline (APL), doxofylline (DXL), bromhexine hydrochloride (BXH), and ambroxol hydrochloride (AXH), either individually or in combination, are widely used in the prevention and treatment of respiratory diseases. The study aimed to establish a high-performance liquid chromatography (HPLC) method for the simultaneous determination of these four drugs and to investigate their stability in 0.9% sodium chloride injection or 5% glucose injection over 48 hours. Methods: An InertSustain C18 column (150 mm × 4.6 mm, 5 µm) was used. The mobile phase consisted of acetonitrile and 50 mmol·L-1 potassium dihydrogen phosphate solution (pH 4.0) with gradient elution. The flow rate was 0.8 mL·min-1, and the column temperature was maintained at 30°C. The stability of APL, DXL, BXH, and AXH in 0.9% sodium chloride and 5% glucose injections over 48 h was determined using HPLC. Results: APL, DXL, BXH, and AXH showed good linearity within the ranges of 0.01 to 0.20, 0.003-0.06, 0.015-0.30, and 0.016-0.16 mg·mL-1, respectively (r > 0.999). The intraday and interday relative standard deviations were <2%, with recovery rates between 98.4% and 102.2%. The four drugs remained colorless and clear in infusion mixtures. The pH value fluctuated within ±0.3 over 48 hours, and the relative percentage content of the drugs ranged from 95.0% to 105.0%. Conclusion: The established HPLC method is simple, reliable, and stable, allowing for the simultaneous determination of the four antitussive and expectorant drugs. APL, DXL, BXH, and AXH were stable within 48 hours when mixed with 0.9% sodium chloride and 5% glucose injections.

Functional Analysis of Human GBA1 Missense Mutations in Drosophila: Insights into Gaucher Disease Pathogenesis and Phenotypic Consequences.

The human GBA1 gene encodes lysosomal acid ß-glucocerebrosidase, whose activity is deficient in Gaucher disease (GD). In Drosophila, there are two GBA1 orthologs, Gba1a and Gba1b, and Gba1b is the bona fide GCase encoding gene. Several fly lines with different deletions in the Gba1b were studied in the past. However, since most GD-associated GBA1 mutations are point mutations, we created missense mutations homologous to the two most common GD mutations: the mild N370S mutation (D415S in Drosophila) and the severe L444P mutation (L494P in Drosophila), using the CRISPR-Cas9 technology. Flies homozygous for the D415S mutation (dubbed D370S hereafter) presented low GCase activity and substrate accumulation, which led to lysosomal defects, activation of the Unfolded Protein Response (UPR), inflammation/neuroinflammation, and neurodegeneration along with earlier death compared to control flies. Surprisingly, the L494P (called L444P hereafter) flies presented higher GCase activity with fewer lysosomal defects and milder disease in comparison to that presented by the D370S homozygous flies. Treatment with ambroxol had a limited effect on all homozygous fly lines tested. Overall, our results underscore the differences between the fly and human GCase enzymes, as evidenced by the distinct phenotypic outcomes of mutations in flies compared to those observed in human GD patients.

Efficacy and safety of mucolytics in patients with stable chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of mucolytics in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis or exacerbations of COPD have been reported. We conducted a systematic review and meta-analysis of mucolytics in patients with stable COPD. METHODS: Reports from randomized controlled trials to evaluate the efficacy and safety of mucolytics, including ambroxol, bromhexine, carbocisteine, erdosteine, fudosteine, l-methylcysteine, and N-acetylcysteine used in patients with stable COPD were searched for in PubMed, Scopus, Embase, Web of Science, the Cochrane Library, and the Igaku Cyuo Zasshi database. RESULTS: Twenty-three reports with ambroxol, carbocisteine, erdosteine, l-methylcysteine, or N-acetylcysteine were included in the review. Mucolytics significantly reduced the rates of exacerbation and hospitalization, shortened the duration of antibiotic use and exacerbations, prolonged the time to first exacerbation, and had a tendency to reduce the occurrence of two or more exacerbations in patients with stable COPD compared to placebo. Mucolytics did not improve mortality, number of lost workdays, scores on St. George's respiratory questionnaire, forced expiratory volume in 1 s, or forced vital capacity. The safety profile of mucolytics was comparable to that of placebo. CONCLUSIONS: Mucolytics reduce exacerbations and hospitalizations in patients with stable COPD and have a safety profile comparable to that of placebo.

Degradation of ambroxol by UV/chloramine process: Kinetics, degradation pathway, and control of the risk of highly toxic disinfection by-products.

Ambroxol (AMB) is a commonly used bromine-containing organic compound in medical applications and has been frequently found in water environments, which might pose risks of forming brominated disinfection by-products (Br-DBPs) in water treatment systems. The degradation kinetics as well as the degradation mechanism of AMB in the UV/chloramine process were investigated in this study. It was determined that reactive chlorine species (RCS) and the reactive nitrogen species (RNS) were the dominant free radicals for AMB degradation. Debromination occurred mainly in the initial stage of the degradation process, with a debromination rate of 34.5% at 10 min. Four possible degradation pathways of AMB were proposed based on liquid chromatography mass spectrometry (LC-MS) analysis as well as density functional theory (DFT) calculations, meanwhile the ECOSAR model was used to predict the toxicity risk of AMB and its degradation intermediates. Furthermore, after assessing the formation of DBPs during the UV/chloramine pre-oxidation process and conducting a toxicity risk analysis based on the results, it has been verified that this method can effectively remove AMB while reducing the formation potential of DBPs in the water environment. This suggests that the UV/chloramine process shows promise for treating bromine-containing organic compounds in real-world water treatment applications.

Ambroxol hydrochloride spray (Luo Runchang®) in the treatment of acute respiratory infectious diseases: a prospective, multicenter, open label, randomized controlled study.

Purpose: Cough and sputum are the most common clinical symptoms of acute respiratory tract infection. Ambroxol is a mucolytic expectorant commonly used in clinical practice. This study aimed to evaluate the efficacy, safety, and compliance of ambroxol hydrochloride spray (Luo Runchang ®) for the treatment of acute respiratory tract diseases in children. Methods: This was a multicenter, open-labeled, randomized controlled study. The experimental group received ambroxol hydrochloride oral sprays, and the control group received ambroxol hydrochloride oral solutions. The primary endpoint was the change in cough symptom scores from baseline. Secondary endpoints include changes in cough severity score, quality of life, adherence, and adverse events. Results: A total of 154 subjects were randomized and included in the analysis. The mean change of total cough symptom score of the spray group at the end of treatment was -4.7 (1.54) compared to -4.2 (1.62) in the solution group (P = 0.0005). The mean change of cough severity score was -5.7 (2.09) in the spray group compared to -5.2(2.04) in the solution group (P = 0.012). Quality of life scores significantly improved in the spray group (P < 0.0001) compared to the oral solution group. Medication adherence markers were significantly better in the spray group (P < 0.0001). The incidence of adverse events in the experimental group (1.33%) was lower than that in the control group (6.33%), but the difference between the groups was not statistically significant. Conclusion: Ambroxol hydrochloride spray significantly improved cough symptom score, cough severity score, and quality of life score compared to ambroxol hydrochloride oral solution.

The Potential of Ambroxol as a Panacea for Neonatal Diseases: A Scoping Review.

Ambroxol, a commonly used mucolytic agent, has been extensively studied for its clinical effectiveness in managing respiratory conditions in pediatric and adult patients. The existing body of research on ambroxol demonstrates its safety and efficacy. However, its potential role in preventing and treating neonatal diseases still needs to be explored. This scoping review aims to shed light on the unexplored potential of ambroxol, particularly its applications in perinatal and neonatal care. We aim to offer valuable insights for healthcare professionals, researchers, and academics, thus presenting a positive perspective. Key scientific databases such as Google Scholar, PubMed, Cochrane Library, and Europe PMC were meticulously searched for relevant literature on ambroxol in perinatal and neonatal medicine. Gray literature was also surveyed, and the search encompassed all study designs and languages up to June 2024. Furthermore, citations and reference lists of relevant articles were scrutinized to identify additional pertinent literature. Ambroxol has demonstrated promising effects in preventing and managing respiratory distress syndrome (RDS). It can enter the placental circulation and rapidly build up in human lung tissue to a much greater extent than in plasma. It promotes fetal lung maturation, surfactant production, and alveolar expansion. Numerous studies have demonstrated the efficacy of antenatal and postnatal ambroxol in the prevention and treatment of RDS. Ambroxol has the potential to be administered intravenously or through nebulization, offering the hopeful possibility of reducing the high failure rate typically associated with non-invasive ventilation in extremely preterm infants, instilling a sense of hope and optimism about the potential of ambroxol. It also shows potential in treating bronchopulmonary dysplasia, meconium aspiration syndrome, and neonatal infections. Ambroxol has been observed to assist in the closure of patent ductus arteriosus in preterm infants by inhibiting vasodilator agents such as nitric oxide and exerting vasoconstrictive properties. However, these biological actions may raise concerns regarding the potential induction of pulmonary hypertension and an increased risk of necrotizing enterocolitis. The present scoping review also examines the clinical evidence and the potential of ambroxol in reducing the incidence of intraventricular hemorrhage in preterm infants. Ambroxol may have potential analgesic properties in managing neonatal pain, and as it can penetrate the blood-brain barrier, it suggests potential neuroprotective properties. These properties may encompass the modulation of microglial activation and the antagonistic impact on glutamate receptors. Ambroxol's attributes could contribute to a decreased susceptibility to neurological complications and have demonstrated anticonvulsant effects in preclinical studies. While low-to-moderate-quality evidence indicates potential applications of ambroxol in neonatal care, further research is needed to determine the drug's optimal dosing, timing, and safety profiles in this patient population. We need to investigate ambroxol's potential synergistic effects with antenatal steroids. Exploration is required to assess ambroxol's potential in reducing the high failure rate associated with non-invasive respiratory support for RDS. Lastly, comprehensive studies on the long-term neurodevelopmental outcomes of neonates exposed to ambroxol are essential.

Effects of N-Acetylcysteine combined with Ambroxol Hydrochloride on clinical symptoms, CRP, and PCT in children with pneumonia.

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.

Clinical and preclinical insights into high-dose ambroxol therapy for Gaucher disease type 2 and 3: A comprehensive systematic review.

RATIONALE: Gaucher disease (GD), an autosomal recessive lysosomal storage disease, results from GBA1 variants causing glucocerebrosidase (GCase) deficiency. While enzyme replacement therapy (ERT) helps with systemic symptoms, neurological complications in GD2 and GD3 persist due to the blood-brain-barrier (BBB) limiting ERT efficacy. Ambroxol, a BBB-permeable chaperone, enhances GCase activity. Our review explores high-dose ambroxol's therapeutic potential, both preclinical and clinical, in GD2 and GD3. METHODS: PubMed was searched for studies published before March 2023, including clinical, animal, and in vitro studies focusing on the effect of high-dose ambroxol in GD2 and GD3. A narrative synthesis was performed. RESULTS: Nine in vitro, three animal, and eight clinical studies were included, demonstrating varied responses to ambroxol across diverse outcome measures. In vitro and animal studies demonstrated reduced endoplasmatic reticulum stress due to the relocation of GCase from the ER to the lysosomes. In vitro cell lines exhibited varying degrees of increased GCase activity. Clinical trials observed reduced lyso-GL1 levels in plasma (41-89%) and cerebrospinal fluid (CSF) (26-97%), alongside increased GCase activity in GD3 patients. Ambroxol exhibited varying effects on neurological outcomes and development. No severe adverse events were reported. CONCLUSION: High-dose ambroxol shows promise in managing neurological manifestations in GD3, albeit with uncertainties resulting from genetic heterogeneity and variable response. Further clinical trials, are essential for elucidating dosage-response relationships and refining treatment outcomes and strategies for neuronopathic GD.

Beyond the lungs: Exploring diverse applications of bromhexine and ambroxol.

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.

Molecular mechanisms of the ambroxol action in Gaucher disease and GBA1 mutation-associated Parkinson disease.

Glucocerebrosidase (GCase), encoded by the GBA1 gene, is one of the lysosomal enzymes responsible for hydrolyzing the glycosphingolipids. Deficiency in GCase activity (in patients with two defective alleles of GBA1) leads to glucosylceramide storage in lysosomes which in turn results in the development of the Gaucher diseases, a lysosomal storage disorder, while a heterozygous state may be correlated with the GBA1 mutation-associated Parkinson disease. One of the proposed forms of therapy for these two conditions is the use of pharmacological chaperones which work by facilitating the achievement of the correct conformation of abnormally folded enzymes. Several compounds with chaperone activities against GCase have already been tested, one of which turned out to be ambroxol. Studies conducted on the action of this compound have indeed indicated its effectiveness in increasing GCase levels and activity. However, some data have begun to question its activity as a chaperone against certain GCase variants. Then, a number of articles appeared pointing to other mechanisms of action of ambroxol, which may also contribute to the improvement of patients' condition. This paper summarizes the biological mechanisms of action of ambroxol in Gaucher disease and GBA1 mutation-associated Parkinson disease, focused on its activity as a chaperone, modulator of ERAD pathways, inducer of autophagy, and pain reliever in cellular and animal models as well as in patients. The effects of these activities on the reduction of disease markers and symptoms in patients are also discussed. Consideration of all the properties of ambroxol can help in the appropriate choice of therapy and the determination of the effective drug dose.

Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2.

Objective: Our aim was to compare the costs and efficacy of ambroxol in combination with imiglucerase with the costs and efficacy of imiglucerase only in the treatment of Gaucher disease type 2 (GD2) in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. Methods: The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was 6 years. The main outcomes of the study were quality-adjusted life years gained with ambroxol + imiglucerase and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Markov chain model. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Results: Treatment with ambroxol in combination with imiglucerase was cost-effective when compared with imiglucerase only and was associated with positive values of net monetary benefit regardless of the onset of the disease. Such beneficial result for ambroxol and imiglucerase combination is primarily driven by the low cost of ambroxol and its considerable clinical effectiveness in slowing the progression of neural complications of GD2. Conclusion: If ambroxol and imiglucerase are used in combination for the treatment of GD2, it is more cost-effective than using imiglucerase alone.

Mucolytic Drugs Ambroxol and Bromhexine: Transformation under Aqueous Chlorination Conditions.

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.

Study protocol of the GRoningen early-PD Ambroxol treatment (GREAT) trial: a randomized, double-blind, placebo-controlled, single center trial with ambroxol in Parkinson patients with a GBA mutation.

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.

Rapid and long-lasting efficacy of high-dose ambroxol therapy for neuronopathic Gaucher disease: A case report and literature review.

Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, ß-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.

The use of Ambroxol for the treatment of Gaucher disease: A systematic review.

Gaucher disease (GD) is a heterogeneous condition requiring tailored treatment approaches. The aim of this systematic review was to synthesise and evaluate current evidence pertaining to the use of Ambroxol for the treatment of GD. Published and unpublished literature databases, conference proceedings and the reference lists of included studies were searched until 23 November 2023. A narrative synthesis was performed. Database search and risk of bias assessment were performed independently by two reviewers. Twenty-one studies (182 patients) were included. The evidence was low in quality. Variable responses to Ambroxol were observed. Response rates were 36% and 55% in two studies reporting on type 1 GD. One study found a 22% response rate in type 2 GD, whereas another study found 29% of patients with type 3 GD reported neurological improvements. No severe adverse events were reported in the literature, with mild and reversible side effects reported. Varying response rates are to be expected (29%-100%) when treating neurological manifestations. Varying degrees of symptomatic improvement for the treatment of GD were noted in the literature. Multidisciplinary team input and clinical judgement are advised to provide personalized treatment of this complex and multi-faceted condition.

Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies.

Gaucher disease (GD) is mainly caused by glucocerebrosidase (GCase) enzyme deficiency due to genetic variations in the GBA1 gene leading to the toxic accumulation of sphingolipids in various organs, which causes symptoms such as anemia, thrombocytopenia, hepatosplenomegaly, and neurological manifestations. GD is clinically classified into the non-neuronopathic type 1, and the acute and chronic neuronopathic forms, types 2 and 3, respectively. In addition to the current approved GD medications, the repurposing of Ambroxol (ABX) has emerged as a prospective enzyme enhancement therapy option showing its potential to enhance mutated GCase activity and reduce glucosylceramide accumulation in GD-affected tissues of different GBA1 genotypes. The variability in response to ABX varies across different variants, highlighting the diversity in patients' therapeutic outcomes. Its oral availability and safety profile make it an attractive option, particularly for patients with neurological manifestations. Clinical trials are essential to explore further ABX's potential as a therapeutic medication for GD to encourage pharmaceutical companies' investment in its development. This review highlights the potential of ABX as a pharmacological chaperone therapy for GD and stresses the importance of addressing response variability in clinical studies to improve the management of this rare and complex disorder.

Effects of N-Acetylcysteine combined with Ambroxol Hydrochloride on clinical symptoms, CRP, and PCT in children with pneumonia

Abstract 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.

Meta-analysis of the efficacy of budesonide and ambroxol hydrochloride inhalation in children with pneumonia and their effects on inflammatory response.

Childhood pneumonia, often caused by acute upper respiratory tract infections or bronchitis, is one of the leading causes of mortality in children. Nebulized inhalation, as a low-risk treatment method, has garnered significant attention. However, its effectiveness and safety remain controversial. In this study, a systematic review of relevant literature on the use of budesonide (BUD) and ambroxol hydrochloride (AMB) inhalation in the treatment of childhood pneumonia was conducted, and a total of 10 articles were included. The meta-analysis revealed an odds ratio (OR) of 1.61 and an I2 value of 0.00 % for the effectiveness of combined BUD and AMB inhalation therapy in children with pneumonia, indicating no heterogeneity among the studies in terms of effectiveness. The OR values for BUD or AMB inhalation in alleviating cough, lung auscultation abnormalities, respiratory distress, body temperature, and cyanosis of the lips in children with pneumonia all favored the combined BUD therapy, showing significant relief of the aforementioned symptoms. However, due to variations in drug dosage and administration methods, high heterogeneity was observed. This study suggested that combined BUD and AMB inhalation therapy has better efficacy in treating childhood pneumonia, and BUD combined with AMB inhalation is more effective in alleviating symptoms such as cough, lung auscultation abnormalities, respiratory distress, normalizing body temperature, and reducing cyanosis of the lips. Nevertheless, further validation is required due to the limited sample size and substantial heterogeneity in the included studies. To sum up, this study provides the first analysis of the efficacy and inflammatory response of BUD and AMB inhalation in children with pneumonia. Future research should aim to verify and clarify these findings, considering the limitations of the existing studies in terms of sample size and heterogeneity.

Characterization of Ambroxol and Its Hydrochloride Salt Crystals by Bromine K-Edge X-Ray Absorption Near-Edge Structure Spectroscopy and X-Ray Crystal Structure Analysis.

Polymorphic crystals of ambroxol, forms I and II, and form A ambroxol hydrochloride crystals were characterized with bromine K-edge X-ray absorption near-edge structure (XANES) spectroscopy and single-crystal X-ray structure analysis. The XANES spectra had unique shapes depending on the crystal forms. Refined single-crystal structures revealed different interatomic interactions around bromine atoms, such as C-H…Br and N-H…Br hydrogen bonds, Br…O halogen bonds, and N-H…π interactions. Differences in these weak interactions could affect the electronic states of the bromines, resulting in differences in the XANES spectra. The results demonstrated that weak non-conventional interatomic interactions could alter the shape of XANES spectra. Hence, the spectra could be used for evaluating polymorphs of active pharmaceutical ingredients.

Structural and dynamics insights into the GBA variants associated with Parkinson's disease.

The GBA1 gene encodes for the lysosomal enzyme glucocerebrosidase (GCase), which maintains glycosphingolipid homeostasis and regulates the autophagy process. Genomic variants of GBA1 are associated with Goucher disease; however, several heterozygous variants of GBA (E326K, T369M, N370S, L444P) are frequent high-risk factors for Parkinson's disease (PD). The underlying mechanism of these variants has been revealed through functional and patient-centered research, but the structural and dynamical aspects of these variants have not yet been thoroughly investigated. In the current study, we used a thorough computational method to pinpoint the structural changes that GBA underwent because of genomic variants and drug binding mechanisms. According to our findings, PD-linked nsSNP variants of GBA showed structural variation and abnormal dynamics when compared to wild-typ. The docking analysis demonstrated that the mutants E326K, N370S, and L444P have higher binding affinities for Ambroxol. Root means square deviation (RMSD), Root mean square fluctuation analysis (RMSF), and MM-GBSA analysis confirmed that the Ambroxol are more stable in the binding site of N370S and L444P, and that their binding affinities are stronger as compared to the wild-type and T369M variants of GBA. The evaluation of hydrogen bonds and the calculation of the free binding energy provided additional evidence in favor of this conclusion. When docked with Ambroxol, GBA demonstrated an increase in binding affinity and catalytic activity. Understanding the therapeutic efficacy and potential against the aforementioned changes in the GBA will be beneficial in order to use more efficient methods for developing novel drugs.Communicated by Ramaswamy H. Sarma.