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1.
Cochrane Database Syst Rev ; 7: CD013876, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34291813

RESUMO

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CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies.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.


Assuntos
COVID-19/complicações , Expectorantes/administração & dosagem , Glucocorticoides/administração & dosagem , Descongestionantes Nasais/administração & dosagem , Transtornos do Olfato/tratamento farmacológico , Administração Oral , Ambroxol/administração & dosagem , Betametasona/administração & dosagem , Viés , Humanos , Lavagem Nasal/métodos , Transtornos do Olfato/etiologia , Prednisona/administração & dosagem , Prevalência , Qualidade de Vida , Recuperação de Função Fisiológica , Olfato/efeitos dos fármacos , Fatores de Tempo
2.
Eur J Paediatr Neurol ; 32: 66-72, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33836415

RESUMO

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.


Assuntos
Ambroxol/administração & dosagem , Terapia de Reposição de Enzimas/métodos , Doença de Gaucher/tratamento farmacológico , Prevenção Secundária , Criança , Pré-Escolar , Feminino , Glucosilceramidase/deficiência , Glucosilceramidase/uso terapêutico , Humanos , Lactente , Masculino , Irmãos
3.
J Biol Chem ; 296: 100701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33895135

RESUMO

The acid sphingomyelinase/ceramide system has been shown to be important for cellular infection with at least some viruses, for instance, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Functional inhibition of the acid sphingomyelinase using tricyclic antidepressants prevented infection of epithelial cells, for instance with SARS-CoV-2. The structure of ambroxol, that is, trans-4-[(2,4-dibromanilin-6-yl)-methyamino]-cyclohexanol, a mucolytic drug applied by inhalation, suggests that the drug might inhibit the acid sphingomyelinase and thereby infection with SARS-CoV-2. To test this, we used vesicular stomatitis virus pseudoviral particles presenting SARS-CoV-2 spike protein on their surface (pp-VSV-SARS-CoV-2 spike), a bona fide system for mimicking SARS-CoV-2 entry into cells. Viral uptake and formation of ceramide localization were determined by fluorescence microscopy, activity of the acid sphingomyelinase by consumption of [14C]sphingomyelin and ceramide was quantified by a kinase method. We found that entry of pp-VSV-SARS-CoV-2 spike required activation of acid sphingomyelinase and release of ceramide, events that were all prevented by pretreatment with ambroxol. We also obtained nasal epithelial cells from human volunteers prior to and after inhalation of ambroxol. Inhalation of ambroxol reduced acid sphingomyelinase activity in nasal epithelial cells and prevented pp-VSV-SARS-CoV-2 spike-induced acid sphingomyelinase activation, ceramide release, and entry of pp-VSV-SARS-CoV-2 spike ex vivo. The addition of purified acid sphingomyelinase or C16 ceramide restored entry of pp-VSV-SARS-CoV-2 spike into ambroxol-treated epithelial cells. We propose that ambroxol might be suitable for clinical studies to prevent coronavirus disease 2019.


Assuntos
Ambroxol/farmacologia , Antivirais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Esfingomielina Fosfodiesterase/genética , Vesiculovirus/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Administração por Inalação , Animais , Transporte Biológico , Ceramidas/metabolismo , Chlorocebus aethiops , Reposicionamento de Medicamentos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Células Epiteliais/virologia , Expectorantes , Expressão Gênica , Humanos , Cultura Primária de Células , Vírus Reordenados/efeitos dos fármacos , Vírus Reordenados/fisiologia , SARS-CoV-2/fisiologia , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Esfingomielina Fosfodiesterase/metabolismo , Esfingomielinas/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero , Vesiculovirus/fisiologia
4.
J Immunol Res ; 2021: 8832586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33928172

RESUMO

Ion transport modulators are most commonly used to treat various noncommunicable diseases including diabetes and hypertension. They are also known to bind to receptors on various immune cells, but the immunomodulatory properties of most ion transport modulators have not been fully elucidated. We assessed the effects of thirteen FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, omeprazole, pantoprazole, phenytoin, verapamil, drug X, and drug Y on superoxide production, nitric oxide production, and cytokine expression by THP-1-derived macrophages that had been stimulated with ethanol-inactivated Mycobacterium bovis BCG. Ambroxol HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, pantoprazole, phenytoin, verapamil, and drug Y had an inhibitory effect on nitric oxide production, while all the test drugs had an inhibitory effect on superoxide production. Amiloride HCl, diazoxide, digoxin, furosemide, phenytoin, verapamil, drug X, and drug Y enhanced the expression of IL-1ß and TNF-α. Unlike most immunomodulatory compounds currently in clinical use, most of the test drugs inhibited some inflammatory processes while promoting others. Ion pumps and ion channels could therefore serve as targets for more selective immunomodulatory agents which do not cause overt immunosuppression.


Assuntos
Inflamação/tratamento farmacológico , Macrófagos/imunologia , Moduladores de Transporte de Membrana/uso terapêutico , Mycobacterium bovis/imunologia , Ambroxol/uso terapêutico , Células Cultivadas , Humanos , Imunomodulação , Interleucina-1beta/metabolismo , Transporte de Íons , Macrófagos/efeitos dos fármacos , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo
5.
Sci Total Environ ; 780: 146451, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33773343

RESUMO

Ambroxol (AMB) is a drug commonly used for chronic bronchitis prevention. Once released in surface water, this recalcitrant chemical becomes a hazardous pollutant. Here, we investigated the ability of 1% Mn-doped TiO2 (Mn-TiO2) to mineralize AMB by photocatalysis. We studied the morphology, and the physical and electrochemical properties of Mn-TiO2 using X-ray diffraction, Scanning electron microscopy, Transmission electron microscopy, X-ray fluorescence, BET method, UV-visible, and electrochemical study and optimized the AMB degrading experimental conditions through response surface methodology (RSM). Mn-TiO2 at the dose of 0.625 g·L-1 allowed the complete photodegradation of AMB (30 ppm) at pH 7 under UVA light irradiation for 30 min while total mineralization in CO2 (>96%) was achieved after 24 h of irradiation. Mn-TiO2 was 1.6-time more efficient than TiO2 Degussa P25. Product studies were also carried out by liquid chromatography coupled to electrospray high resolution mass spectrometry. Twenty-one photodegradation products were detected and identified. In addition, ionic chromatography analyses revealed the release of Br-, NH4+, and NO3- at respectively 97, 63 and 35% of the total Br, and N initially present in AMB. Finally, the reusability of the photocatalyst was also tested. After four cycles, the almost complete photodegradation of AMB was achieved showing that Mn-TiO2 was highly stable. This work brings new physical characteristics on Mn-TiO2 photocatalyst. Moreover, it is the first study investigating the photocatalytic degradation of recalcitrant AMB drug.


Assuntos
Ambroxol , Poluentes Químicos da Água , Catálise , Projetos de Pesquisa , Titânio , Difração de Raios X
6.
J Virol ; 95(9)2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33608407

RESUMO

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infects cells through interaction of its spike protein (SARS2-S) with angiotensin-converting enzyme 2 (ACE2) and activation by proteases, in particular transmembrane protease serine 2 (TMPRSS2). Viruses can also spread through fusion of infected with uninfected cells. We compared the requirements of ACE2 expression, proteolytic activation, and sensitivity to inhibitors for SARS2-S-mediated and SARS-CoV-S (SARS1-S)-mediated cell-cell fusion. SARS2-S-driven fusion was moderately increased by TMPRSS2 and strongly by ACE2, while SARS1-S-driven fusion was strongly increased by TMPRSS2 and less so by ACE2 expression. In contrast to that of SARS1-S, SARS2-S-mediated cell-cell fusion was efficiently activated by batimastat-sensitive metalloproteases. Mutation of the S1/S2 proteolytic cleavage site reduced effector cell-target cell fusion when ACE2 or TMPRSS2 was limiting and rendered SARS2-S-driven cell-cell fusion more dependent on TMPRSS2. When both ACE2 and TMPRSS2 were abundant, initial target cell-effector cell fusion was unaltered compared to that of wild-type (wt) SARS2-S, but syncytia remained smaller. Mutation of the S2 cleavage (S2') site specifically abrogated activation by TMPRSS2 for both cell-cell fusion and SARS2-S-driven pseudoparticle entry but still allowed for activation by metalloproteases for cell-cell fusion and by cathepsins for particle entry. Finally, we found that the TMPRSS2 inhibitor bromhexine, unlike the inhibitor camostat, was unable to reduce TMPRSS2-activated cell-cell fusion by SARS1-S and SARS2-S. Paradoxically, bromhexine enhanced cell-cell fusion in the presence of TMPRSS2, while its metabolite ambroxol exhibited inhibitory activity under some conditions. On Calu-3 lung cells, ambroxol weakly inhibited SARS2-S-driven lentiviral pseudoparticle entry, and both substances exhibited a dose-dependent trend toward weak inhibition of authentic SARS-CoV-2.IMPORTANCE Cell-cell fusion allows viruses to infect neighboring cells without the need to produce free virus and contributes to tissue damage by creating virus-infected syncytia. Our results demonstrate that the S2' cleavage site is essential for activation by TMPRSS2 and unravel important differences between SARS-CoV and SARS-CoV-2, among those, greater dependence of SARS-CoV-2 on ACE2 expression and activation by metalloproteases for cell-cell fusion. Bromhexine, reportedly an inhibitor of TMPRSS2, is currently being tested in clinical trials against coronavirus disease 2019. Our results indicate that bromhexine enhances fusion under some conditions. We therefore caution against the use of bromhexine in high dosages until its effects on SARS-CoV-2 spike activation are better understood. The related compound ambroxol, which similarly to bromhexine is clinically used as an expectorant, did not exhibit activating effects on cell-cell fusion. Both compounds exhibited weak inhibitory activity against SARS-CoV-2 infection at high concentrations, which might be clinically attainable for ambroxol.


Assuntos
COVID-19/metabolismo , Vírus da SARS/metabolismo , SARS-CoV-2/metabolismo , Síndrome Respiratória Aguda Grave/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus , Ambroxol/farmacologia , Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Bromoexina/farmacologia , COVID-19/genética , Linhagem Celular , Humanos , Mutação de Sentido Incorreto , Proteólise/efeitos dos fármacos , Vírus da SARS/genética , SARS-CoV-2/genética , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Síndrome Respiratória Aguda Grave/genética , Glicoproteína da Espícula de Coronavírus/genética
7.
Am J Hematol ; 96(5): 545-551, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33606887

RESUMO

Ambroxol hydrochloride is an oral mucolytic drug available over-the-counter for many years as cough medicine. In 2009 it was identified as a pharmacological chaperone for mutant glucocerebrosidase, albeit in a several-fold higher dose. Unfortunately, there have been no pharma-driven clinical trials to establish its use. Thus, real-world observational data are needed on the safety and efficacy of ambroxol for patients with Gaucher disease (GD) and GBA-Parkinson disease (GBA-PD). Clinicians treating patients with ambroxol for GD and GBA-PD were approached to collaborate in an investigator-initiated registry. Anonymized data were collected, including demographics, GD type, GD-specific therapy (when applicable), adverse events (AEs), and, when available, efficacy data. We report the data of the first 41 patients (25 females) at a median (range) age 17 (1.5-74) from 13 centers; 11 with GD type 1(four diagnosed with PD), 27 with neuronopathic GD (nGD), and three GBA mutation carriers with PD. The median (range) treatment period and maximum dose of ambroxol were 19 (1-76) months and 435 (75-1485) mg/day, respectively. One patient with type 2 GD died of her disease. No other severe AEs were reported. Twelve patients experienced AE, including minor bowel discomfort, cough, allergic reaction, mild proteinuria, dizziness and disease progression. Clinical benefits were reported in 25 patients, including stable or improved neurological status, increased physical activity, and reduced fatigue. Until the approval of specific therapies for nGD and disease-modification for GBA-PD, these preliminary data may be encouraging to physicians and patients who consider an off-label use of ambroxol.


Assuntos
Ambroxol/uso terapêutico , Doença de Gaucher/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Sistema de Registros , Adolescente , Adulto , Idoso , Ambroxol/efeitos adversos , Ambroxol/farmacologia , Disponibilidade Biológica , Barreira Hematoencefálica , Criança , Pré-Escolar , Terapia Combinada , Terapia de Reposição de Enzimas , Feminino , Glucosilceramidase/deficiência , Glucosilceramidase/genética , Glucosilceramidase/metabolismo , Glucosilceramidase/uso terapêutico , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Doença de Parkinson/genética , Estabilidade Proteica/efeitos dos fármacos , Adulto Jovem
8.
Graefes Arch Clin Exp Ophthalmol ; 259(6): 1529-1538, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33512613

RESUMO

PURPOSE: To investigate if topical administration of ambroxol promotes tear secretion and to compare with Diquas ophthalmic eye drop. METHODS: Two consecutive studies were conducted using sixteen (32 eyes) New Zealand White rabbits. The first study compared the efficacy of ambroxol hydrochloride (0.05%, 0.2%, and 1.0%) on tear and mucin secretion when administered twice daily. Tear secretion was assessed by Schirmer test I and mucin production by conjunctival impression cytology and PAS stain. The second study compared 0.2% ambroxol hydrochloride with Diquas. A human goblet cell line and human conjunctival tissue were used to test the effect of ambroxol hydrochloride on the expression of aquaporin 5 (AQP5) and MUC5AC, using reverse transcriptase-quantitative polymerase chain reaction and immunoblotting. RESULTS: All three concentrations of ambroxol hydrochloride demonstrated significant efficacy on tear stimulation within 2 weeks of treatment and total mucin component appeared increased. When administered topically twice daily, 0.2% ambroxol hydrochloride was more effective in augmenting tear secretion than Diquas. With 24 h of treatment, 5 µM of ambroxol hydrochloride upregulated AQP5 and MU5AC mRNA and MUC5AC protein in a goblet cell line. When tested on preserved human conjunctiva tissue, a trend of increased production of MUC5AC protein was seen (P = 0.26). CONCLUSION: Ambroxol is effective in augmenting tear secretion at the ocular surface in rabbits. With actions desirable of a candidate dry eye drug, further investigation of ambroxol and related compounds is warranted to explore their value toward clinical application.


Assuntos
Ambroxol , Síndromes do Olho Seco , Administração Tópica , Ambroxol/uso terapêutico , Animais , Túnica Conjuntiva , Síndromes do Olho Seco/tratamento farmacológico , Células Caliciformes , Humanos , Mucina-5AC/genética , Soluções Oftálmicas , Coelhos , Lágrimas
9.
J Ethnopharmacol ; 269: 113764, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33383115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ambroxol elevates glucocerebrosidase (GCase) activity and reduces nigrostriatal alpha-synuclein burden to better ameliorate motor function in Parkinson's disease (PD). Polygala tenuifolia is a potential alternative botanical medicine for the treatment of many nonmotor symptoms of PD commonly used in Taiwanese patients. Co-administration of these two medicines pose potential herb-drug interaction. AIM OF THE STUDY: Our hypothesis is that ambroxol and P. tenuifolia may potentially possess herbal drug synergetic effects in the blood and brain. MATERIALS AND METHODS: To investigate this hypothesis, a multiple microdialysis system coupled with validated ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for rat blood and brain samples. Experimental rats were divided into three groups: low-dose and high-dose ambroxol alone (10 mg/kg, i.v. and 30 mg/kg, i.v., respectively) and ambroxol (10 mg/kg, i.v.) pretreated with P. tenuifolia extract (1 g/kg, p.o. for 5 consecutive days). RESULTS: Ambroxol easily penetrated into the brain and reached a maximum concentration in the striatum at approximately 60 min after low- and high-dose treatment. The area under the concentration curve (AUC) ratio increased proportionally at the doses of 10 and 30 mg/kg, which suggested a linear pharmacokinetic manner of ambroxol. The brain penetration of ambroxol was approximately 30-34%, which was defined as the ambroxol AUC blood-to-brain distribution ratio (AUCbrain/AUCblood). The P. tenuifolia extract did not significantly alter the pharmacokinetics of ambroxol in the blood and brain of rats. CONCLUSION: The present study suggests that it is safety without pharmacokinetic interactions for this dosing regimen to use P. tenuifolia extract and ambroxol together.


Assuntos
Ambroxol/farmacocinética , Encéfalo/metabolismo , Corpo Estriado/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Transtornos Parkinsonianos/tratamento farmacológico , Polygala/química , Ambroxol/metabolismo , Ambroxol/uso terapêutico , Animais , Área Sob a Curva , Análise Química do Sangue , Barreira Hematoencefálica , Encéfalo/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Interações Ervas-Drogas , Masculino , Microdiálise/métodos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
10.
Eur Rev Med Pharmacol Sci ; 24(22): 11971-11976, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33275274

RESUMO

OBJECTIVE: This paper presents a newborn (G2P2, gestational age of 39+6 weeks, birth weight of 3,200 g, with normal fetal amniotic fluid) with suspected coronavirus disease 2019 (COVID-19) admitted to our hospital on February 10, 2020, at the birth age of 16 hours and 34 minutes. The Apgar scores at 1 and 5 min were 9 and 10 points, respectively. PATIENTS AND METHODS: The mother of the newborn was exposed to a patient with COVID-19 five days before delivery. The newborn had nausea and vomiting after birth, with feeding intolerance, and full enteral feeding was given on the 6th day after birth. The newborn was in good general condition during the period of hospitalization. RESULTS: The two 2019-nCoV nucleic acid tests of the newborn were negative on the 5th and 7th days after birth. On the 1st and 8th days after birth, typical pulmonary lesions were detected in the newborn by chest CT. Our study supports that chest imaging examination should be actively performed in the newborn even with a negative 2019-nCoV nucleic acid test in cases where a pregnant woman is exposed to a patient with COVID-19 or is confirmed with 2019-nCoV infection. CONCLUSIONS: For newborns with typical pulmonary lesions, strict quarantine measures are suggested if the possibility of COVID-19 cannot be excluded.


Assuntos
Teste de Ácido Nucleico para COVID-19 , COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Exposição Materna , Náusea/fisiopatologia , Complicações Infecciosas na Gravidez/diagnóstico , Tomografia Computadorizada por Raios X , Vômito/fisiopatologia , Ambroxol , Antibacterianos/uso terapêutico , Ácido Ascórbico/uso terapêutico , Aleitamento Materno , Proteína C-Reativa/metabolismo , COVID-19/metabolismo , COVID-19/fisiopatologia , COVID-19/terapia , Expectorantes/uso terapêutico , Feminino , Humanos , Recém-Nascido , Masculino , Nutrição Parenteral , Gravidez , Proteína Amiloide A Sérica/metabolismo , Vitaminas/uso terapêutico
11.
BMC Complement Med Ther ; 20(1): 380, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33357221

RESUMO

BACKGROUND: Rhinoviruses and influenza viruses cause millions of acute respiratory infections annually. Symptoms of mild acute respiratory infections are commonly treated with over-the-counter products like ambroxol, bromhexine, and N-acetyl cysteine, as well as of thyme and pelargonium extracts today. Because the direct antiviral activity of these over-the-counter products has not been studied in a systematic way, the current study aimed to compare their inhibitory effect against rhinovirus and influenza virus replication in an in vitro setting. METHODS: The cytotoxicity of ambroxol, bromhexine, and N-acetyl cysteine, as well as of thyme and pelargonium extracts was analyzed in Madin Darby canine kidney (MDCK) and HeLa Ohio cells. The antiviral effect of these over-the-counter products was compared by analyzing the dose-dependent inhibition (i) of rhinovirus A2- and B14-induced cytopathic effect in HeLa Ohio cells and (ii) of influenza virus A/Hong Kong/68 (subtype H3N2)- and A/Jena/8178/09 (subtype H1N1, pandemic)-induced cytopathic effect in MDCK cells at non-cytotoxic concentrations. To get insights into the mechanism of action of pelargonium extract against influenza virus, we performed time-of-addition assays as well as hemagglutination and neuraminidase inhibition assays. RESULTS: N-acetyl cysteine, thyme and pelargonium extract showed no or only marginal cytotoxicity in MDCK and HeLa Ohio cells in the tested concentration range. The 50% cytotoxic concentration of ambroxol and bromhexine was 51.85 and 61.24 µM, respectively. No anti-rhinoviral activity was detected at non-cytotoxic concentrations in this in vitro study setting. Ambroxol, bromhexine, and N-acetyl cysteine inhibited the influenza virus-induced cytopathic effect in MDCK cells no or less than 50%. In contrast, a dose-dependent anti-influenza virus activity of thyme and pelargonium extracts was demonstrated. The time-of addition assays revealed an inhibition of early and late steps of influenza virus replication by pelargonium extract whereas zanamivir acted on late steps only. The proven block of viral neuraminidase activity might explain the inhibition of influenza virus replication when added after viral adsorption. CONCLUSION: The study results indicate a distinct inhibition of influenza A virus replication by thyme and pelargonium extract which might contribute to the beneficial effects of these plant extracts on acute respiratory infections symptoms.


Assuntos
Vírus da Influenza A/efeitos dos fármacos , Pelargonium , Extratos Vegetais/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Rhinovirus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Acetilcisteína , Ambroxol , Animais , Bromoexina , Cães , Células HeLa , Humanos , Células Madin Darby de Rim Canino , Testes de Sensibilidade Microbiana , Fitoterapia , Extratos Vegetais/farmacologia , Thymus (Planta) , Testes de Toxicidade
12.
Comput Math Methods Med ; 2020: 7984565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133226

RESUMO

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.


Assuntos
Ambroxol/administração & dosagem , Infarto Cerebral/complicações , Pneumopatias/complicações , Pneumopatias/tratamento farmacológico , Infecções Respiratórias/complicações , Infecções Respiratórias/tratamento farmacológico , Lavagem Broncoalveolar , Estudos de Casos e Controles , Infarto Cerebral/sangue , Biologia Computacional , Citocinas/sangue , Expectorantes/administração & dosagem , Feminino , Humanos , Mediadores da Inflamação/sangue , Pneumopatias/sangue , Masculino , Malondialdeído/sangue , Conceitos Matemáticos , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Infecções Respiratórias/sangue , Superóxido Dismutase/sangue
13.
Biomed Pharmacother ; 132: 110890, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33080465

RESUMO

BACKGROUND: Ambroxol hydrochloride is being used in respiratory diseases as a broncholytic therapy. Beta-Glucosylceramide (GC) is a naturally occurring glycosphingolipid that exerts an immune protective effect. The aim of the present study was to determine the synergistic immunomodulatory effect between these two compounds. METHODS: Immune-mediated hepatitis was induced in the mice by administration of Con A. Mice were treated with either Ambroxol or GC alone or with the combination of both. Mice were followed for their effect on the liver injury, cytokine profile, and the immune system. RESULTS: Coadministration of Ambroxol and GC significantly alleviated the liver injury induced by ConA, as demonstrated by the decreased liver enzymes. The combined treatment had a statistically significant synergistic effect on the suppression of intrahepatic CD8+CD25+, an increase in the CD4/CD8 lymphocyte ratio and in the CD8+ intrahepatic lymphocyte trapping, as well as on change of serum in the IL4 levels. The beneficial effect was associated with the promotion of regulatory T lymphocytes subsets, and with a trend for a pro-inflammatory to an anti-inflammatory cytokine shift. CONCLUSIONS: Coadministration of Ambroxol with GC exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage. Considering the high safety profile of both agents, the combination may become a novel immunomodulatory non-immunosuppressive therapeutic agent. SIGNIFICANCE STATEMENT: Coadministration of Ambroxol with glucocerebroside exerted a synergistic immunoprotective effect in a model of immune-mediated acute liver damage.


Assuntos
Ambroxol/farmacologia , Anti-Inflamatórios/farmacologia , Glucosilceramidas/farmacologia , Hepatite/prevenção & controle , Fatores Imunológicos/farmacologia , Fígado/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Animais , Concanavalina A , Citocinas/sangue , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Hepatite/sangue , Hepatite/imunologia , Mediadores da Inflamação/sangue , Fígado/imunologia , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Linfócitos T/imunologia , Linfócitos T/metabolismo
14.
Int J Antimicrob Agents ; 56(6): 106192, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33045350

RESUMO

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.


Assuntos
Ambroxol/administração & dosagem , Azitromicina/administração & dosagem , COVID-19/tratamento farmacológico , SARS-CoV-2 , Administração por Inalação , Sistemas de Liberação de Medicamentos , Humanos
15.
Wiad Lek ; 73(4): 773-776, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32731714

RESUMO

OBJECTIVE: The aim of the study is to increase the effectiveness of the treatment of exacerbation of COPD group B GOLD II with the use of combined therapy of the combined drug PulmoBRIZ containing two components - ambroxol and acetylcysteine and the course of halotherapy. PATIENTS AND METHODS: Materials and methods: We observed 60 patients with COPD B, GOLD II. They were divided into two groups: the first - the main (n=30) - patients receiving basic therapy, mucolytic therapy - a combination of Ambroxol and acetylcysteine - 200/30 to 1 tabl. 2 times a day, number 7 days and, from the 3rd day - sessions of halotherapy 1 time per day № 10. The second group, the control group (n=30), followed only basic therapy, did not take mucolytics and halotherapy sessions. RESULTS: Results: Patients receiving therapy with the combination of ambroxol and acetylcysteine and halotherapy sessions experienced a significant increase in FEV1 by 8.3% (p <0.05); the Tiffon index was 7.2% (p<0.05), reactive anxiety levels (RA) and manifestations of autonomic dysfunction decreased, whereas in patients in the control group these indicators did not improve significantly. CONCLUSION: Conclusions: The proposed complex therapy of COPD patients with the inclusion of the combined drug ambroxol and acetylcysteine and halotherapy sessions contributes to the improvement of the quality of life of patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Ambroxol , Expectorantes , Humanos , Qualidade de Vida
16.
Eur J Pharmacol ; 884: 173446, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32739173

RESUMO

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. While it is primarily characterized by the death of upper and lower motor neurons, there is a significant metabolic component involved in the progression of the disease. Two-thirds of ALS patients have metabolic alterations that are associated with the severity of symptoms. In ALS, as in other neurodegenerative diseases, the metabolism of glycosphingolipids, a class of complex lipids, is strongly dysregulated. We therefore assume that this pathway constitutes an interesting avenue for therapeutic approaches. We have shown that the glucosylceramide degrading enzyme, glucocerebrosidase (GBA) 2 is abnormally increased in the spinal cord of the SOD1G86R mouse model of ALS. Ambroxol, a chaperone molecule that inhibits GBA2, has been shown to have beneficial effects by slowing the development of the disease in SOD1G86R mice. Currently used in clinical trials for Parkinson's and Gaucher disease, ambroxol could be considered as a promising therapeutic treatment for ALS.


Assuntos
Ambroxol/farmacologia , Esclerose Amiotrófica Lateral/tratamento farmacológico , Reposicionamento de Medicamentos , Inibidores Enzimáticos/farmacologia , Degeneração Neural , Fármacos Neuroprotetores/farmacologia , Medula Espinal/efeitos dos fármacos , beta-Glucosidase/antagonistas & inibidores , Esclerose Amiotrófica Lateral/enzimologia , Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Glucosilceramidase/antagonistas & inibidores , Glucosilceramidase/metabolismo , Humanos , Mutação , Medula Espinal/enzimologia , Medula Espinal/patologia , Superóxido Dismutase-1/genética , beta-Glucosidase/metabolismo
17.
J Med Virol ; 92(10): 2238-2242, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32484990

RESUMO

A healthy patient presented to Klinikum Altmühlfranken Weißenburg Hospital, Germany, with two morning attacks of painful muscle spasm in the left upper and lower limbs, without altered consciousness. Full examinations, radiological imaging, electroencephalography, lumbar puncture, and autoimmune profile were either normal or not consistent with patient's complaint. Subsequent epileptic episodes were observed on admission day and the following days; thus, the patient was diagnosed with focal epilepsy. The patient started to develop a fever and severe cough on day 4, and SARS-coronavirus-2 was confirmed through a nasopharyngeal swap. She received anticonvulsants and symptomatic treatments and completely recovered. This report emphasizes the potential nervous system involvement in severe acute respiratory syndrome-coronavirus-2 pathogenesis.


Assuntos
COVID-19/complicações , Epilepsias Parciais/complicações , SARS-CoV-2/patogenicidade , Acetaminofen/uso terapêutico , Acetilcisteína/uso terapêutico , Idoso , Ambroxol/uso terapêutico , Anticonvulsivantes/uso terapêutico , COVID-19/diagnóstico por imagem , COVID-19/tratamento farmacológico , COVID-19/virologia , Tosse/diagnóstico , Tosse/fisiopatologia , Dipirona/uso terapêutico , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/virologia , Feminino , Febre/diagnóstico , Febre/fisiopatologia , Humanos , Nasofaringe/virologia , Radiografia Abdominal , Resultado do Tratamento
18.
Med Hypotheses ; 144: 110020, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32590326

RESUMO

Pulmonary surfactant is considered to be one of the soaps. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the other enveloped viruses become very weak against surfactant. The SARS virus binds to angiotensin-converting enzyme (ACE2) receptor and causes pneumonia. In the lung, the ACE2 receptor sits on the top of lung cells known as alveolar epithelial type II (AE2) cells. These cells play an important role in producing surfactant. Pulmonary surfactant is believed to regulate the alveolar surface tension in mammalian lungs. To our knowledge, AE2 cells are believed to act as immunoregulatory cells; however, pulmonary surfactant itself has not been believed to act as a defender against the enveloped viruses. This study hypothesises that pulmonary surfactant may be a strong defender of enveloped viruses. Therefore, old coronaviruses merely cause pneumonia. On the contrary, new SARS-CoV-2 can suppress the production of surfactant that binds to the ACE2 of AE2 cells. The coronavirus can survive in the lung tissue because of the exhaustion of pulmonary surfactant.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/prevenção & controle , COVID-19/fisiopatologia , Pneumonia Viral/fisiopatologia , Surfactantes Pulmonares/uso terapêutico , SARS-CoV-2 , Ambroxol/uso terapêutico , Bromoexina/uso terapêutico , COVID-19/tratamento farmacológico , Ensaios Clínicos como Assunto , Cristalografia por Raios X , Humanos , Modelos Teóricos , Fagocitose , Pregnenodionas/uso terapêutico , Alvéolos Pulmonares/metabolismo , Tensão Superficial , Tensoativos
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