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1.
Mol Pharmacol ; 96(4): 515-525, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31427400

RESUMO

ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modest and variable, prompting the search for complementary interventions. As our previous work identified a positive effect of arginine-dependent nitric oxide signaling on residual F508del-Cftr function in murine intestinal epithelium, we were prompted to determine whether strategies aimed at increasing arginine would enhance F508del-cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in patient-derived airway epithelia. Now, we show that the addition of arginine together with inhibition of intracellular arginase activity increased cytosolic nitric oxide and enhanced the rescue effect of ORKAMBI on F508del-CFTR-mediated chloride conductance at the cell surface of patient-derived bronchial and nasal epithelial cultures. Interestingly, arginine addition plus arginase inhibition also enhanced ORKAMBI-mediated increases in ciliary beat frequency and mucociliary movement, two in vitro CF phenotypes that are downstream of the channel defect. This work suggests that strategies to manipulate the arginine-nitric oxide pathway in combination with CFTR modulators may lead to improved clinical outcomes. SIGNIFICANCE STATEMENT: These proof-of-concept studies highlight the potential to boost the response to cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, lumacaftor and ivacaftor, in patient-derived airway tissues expressing the major CF-causing mutant, F508del-CFTR, by enhancing other regulatory pathways. In this case, we observed enhancement of pharmacologically rescued F508del-CFTR by arginine-dependent, nitric oxide signaling through inhibition of endogenous arginase activity.


Assuntos
Aminofenóis/farmacologia , Aminopiridinas/farmacologia , Arginase/antagonistas & inibidores , Arginina/metabolismo , Benzodioxóis/farmacologia , Fibrose Cística/metabolismo , Óxido Nítrico/metabolismo , Quinolonas/farmacologia , Animais , Brônquios/citologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Células Cultivadas , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Citosol/metabolismo , Combinação de Medicamentos , Humanos , Mucosa Intestinal/metabolismo , Camundongos , Mutação , Nariz/citologia , Nariz/efeitos dos fármacos
2.
Vet Dermatol ; 29(2): 134-e53, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29076573

RESUMO

BACKGROUND: Nasal hyperkeratosis may cause discomfort in dogs by predisposing them to fissures and secondary bacterial infection. Approaches to treatment have been described anecdotally; the effectiveness of such therapies remains unproven. HYPOTHESIS/OBJECTIVES: To investigate the efficacy of a balm containing essential oils and essential fatty acids in dogs with idiopathic nasal hyperkeratosis. ANIMALS: Client-owned dogs with noncomplicated nasal hyperkeratosis. METHODS: The study was conducted as a randomized, double-blind, placebo-controlled clinical trial with parallel group design and two month follow-up period. Dogs received daily topical application of a commercial balm product (group DBB) or placebo (aqueous gelling agent with preservatives, group PB). The main outcome variables were lichenification, dryness, suppleness and extent of lesions. Subjective owner satisfaction index score was a secondary variable. Evaluation was performed on days (D)0, 30 and 60. Response to treatment was assessed as the change from baseline to each examination day for each criterion. RESULTS: Forty eight dogs, principally French (26 of 48) and English (seven of 48) bulldogs, were included and 39 completed the study. No major adverse events were reported. On D60, changes from baseline for lichenification, lesion extent, suppleness and total score were -31.2%, -18.3%, -72.8% and -36.8% in group DBB (23 dogs) and -11.9%, 2.3%, -42.1% and -14% in group PB (16 dogs), respectively. The total score was significantly improved on D60 in group DBB compared to PB (Wilcoxon-Mann-Whitney U-test, P = 0.0016). CONCLUSIONS AND CLINICAL IMPORTANCE: The balm proved safe and helpful in managing canine idiopathic noncomplicated nasal hyperkeratosis.


Assuntos
Ácidos Graxos Essenciais/uso terapêutico , Ceratose/veterinária , Nariz/patologia , Óleos Voláteis/uso terapêutico , Animais , Dermatite Atópica/veterinária , Cães , Método Duplo-Cego , Ácidos Graxos Essenciais/administração & dosagem , Ácidos Graxos Essenciais/efeitos adversos , Feminino , Ceratose/tratamento farmacológico , Masculino , Nariz/efeitos dos fármacos , Óleos Voláteis/administração & dosagem , Óleos Voláteis/efeitos adversos , Prurido/veterinária
3.
Nat Prod Res ; 32(24): 2873-2881, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29022380

RESUMO

The current study introduces a new idea of utilising several bio/chemoinformatics tools in comparing two bio-similar natural molecules viz. curcumin and bisdemethoxycurcumin (BDMC) in order to select a potential nose-to-brain remedy for Alzheimer disease. The comparison comprised several bio/chemo informatics tools. It encompassed all levels starting from loading the drug in a certain carrier; PLGA nanoparticles, to the biopharmaceutical level investigating the interaction with mucin and inhibition of P-gp blood-brain barrier efflux pumps. Finally, the therapeutic level was investigated by studying the interaction with pharmacological targets such as amyloid peptide plaques and cyclooxygenase2 enzyme responsible for the inflammatory reactions of the studied disease. The comparison revealed the superiority of curcumin over BDMC. Five new analogues were also hypothesised where diethoxybisdemethoxycurcumin was  recommended as a superior molecule. This work introduced the virtual utilisation of bio/chemo informatics tools as a reliable and economic alternative to the exhausting and resources-consuming wet-lab experimentation.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Biologia Computacional/métodos , Curcumina/análogos & derivados , Curcumina/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Doença de Alzheimer/patologia , Encéfalo/efeitos dos fármacos , Biologia Computacional/normas , Curcumina/farmacologia , Diarileptanoides , Portadores de Fármacos/química , Humanos , Inflamação/tratamento farmacológico , Mucinas/metabolismo , Nariz/efeitos dos fármacos
4.
Hong Kong Med J ; 21(6): 542-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26554271

RESUMO

OBJECTIVES: Pepper (oleoresin capsicum) spray is one of the most common riot-control measures used today. Although not lethal, exposure of pepper spray can cause injury to different organ systems. This review aimed to summarise the major clinicopathological effects of pepper spray in humans. DATA SOURCES: MEDLINE, EMBASE database, and Cochrane Database of Systematic Reviews were used to search for terms associated with the clinicopathological effects of pepper spray in humans and those describing the pathophysiology of capsaicin. A phone interview with two individuals recently exposed to pepper spray was also conducted to establish clinical symptoms. STUDY SELECTION: Major key words used for the MEDLINE search were "pepper spray", "OC spray", "oleoresin capsicum"; and other key words as "riot control agents", "capsaicin", and "capsaicinoid". We then combined the key words "capsaicin" and "capsaicinoid" with the major key words to narrow down the number of articles. A search with other databases including EMBASE and Cochrane Database of Systematic Reviews was also conducted with the above phrases to identify any additional related articles. DATA EXTRACTION: All article searches were confined to human study. The bibliography of articles was screened for additional relevant studies including non-indexed reports, and information from these was also recorded. Non-English articles were included in the search. DATA SYNTHESIS: Fifteen articles were considered relevant. Oleoresin capsicum causes almost instantaneous irritative symptoms to the skin, eyes, and respiratory system. Dermatological effects include a burning sensation, erythema, and hyperalgesia. Ophthalmic effects involve blepharospasm, conjunctivitis, peri-orbital oedema, and corneal pathology. Following inhalation, a stinging or burning sensation can be felt in the nose with sore throat, chest tightness, or dyspnoea. The major pathophysiology is neurogenic inflammation caused by capsaicinoid in the pepper spray. There is no antidote for oleoresin capsicum. Treatment consists of thorough decontamination, symptom-directed supportive measures, and early detection and treatment of systemic toxicity. Decontamination should be carefully carried out to avoid contamination of the surrounding skin and clothing. CONCLUSION: Pepper (oleoresin capsicum) spray is an effective riot-control agent and does not cause life-threatening clinical effects in the majority of exposed individuals. Early decontamination minimises the irritant effects.


Assuntos
Inflamação Neurogênica/induzido quimicamente , Extratos Vegetais/toxicidade , Substâncias para Controle de Distúrbios Civis/toxicidade , Aerossóis , Descontaminação , Dispneia/induzido quimicamente , Oftalmopatias/induzido quimicamente , Humanos , Exposição por Inalação/efeitos adversos , Nariz/efeitos dos fármacos , Faringite/induzido quimicamente , Dermatopatias/induzido quimicamente
5.
PLoS One ; 9(7): e102339, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25058039

RESUMO

H2N2 Influenza A caused the Asian flu pandemic in 1957, circulated for more than 10 years and disappeared from the human population after 1968. Given that people born after 1968 are naïve to H2N2, that the virus still circulates in wild birds and that this influenza subtype has a proven pandemic track record, H2N2 is regarded as a potential pandemic threat. To prepare for an H2N2 pandemic, here we developed and tested in mice and ferrets two live attenuated influenza vaccines based on the haemagglutinins of the two different H2N2 lineages that circulated at the end of the cycle, using the well characterized A/Leningrad/134/17/57 (H2N2) master donor virus as the backbone. The vaccine strains containing the HA and NA of A/California/1/66 (clade 1) or A/Tokyo/3/67 (clade 2) showed a temperature sensitive and cold adapted phenotype and a reduced reproduction that was limited to the respiratory tract of mice, suggesting that the vaccines may be safe for use in humans. Both vaccine strains induced haemagglutination inhibition titers in mice. Vaccination abolished virus replication in the nose and lung and protected mice from weight loss after homologous and heterologous challenge with the respective donor wild type strains. In ferrets, the live attenuated vaccines induced high virus neutralizing, haemagglutination and neuraminidase inhibition titers, however; the vaccine based on the A/California/1/66 wt virus induced higher homologous and better cross-reactive antibody responses than the A/Tokyo/3/67 based vaccine. In line with this observation, was the higher virus reduction observed in the throat and nose of ferrets vaccinated with this vaccine after challenge with either of the wild type donor viruses. Moreover, both vaccines clearly reduced the infection-induced rhinitis observed in placebo-vaccinated ferrets. The results favor the vaccine based on the A/California/1/66 isolate, which will be evaluated in a clinical study.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vírus da Influenza A Subtipo H2N2/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Pandemias/prevenção & controle , Vírus Reordenados/imunologia , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Furões , Expressão Gênica , Hemaglutininas Virais/genética , Hemaglutininas Virais/imunologia , Humanos , Imunização , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/genética , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos CBA , Neuraminidase/genética , Neuraminidase/imunologia , Nariz/efeitos dos fármacos , Nariz/imunologia , Nariz/virologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vírus Reordenados/genética , Vacinas Atenuadas , Replicação Viral
6.
PLoS One ; 9(6): e98671, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24910991

RESUMO

BACKGROUND: Smokers have increased susceptibility and altered innate host defense responses to influenza virus infection. Broccoli sprouts are a source of the Nrf2 activating agentsulforaphane, and short term ingestion of broccoli sprout homogenates (BSH) has been shown to reduce nasal inflammatory responses to oxidant pollutants. OBJECTIVES: Assess the effects of BSH on nasal cytokines, virus replication, and Nrf2-dependent enzyme expression in smokers and nonsmokers. METHODS: We conducted a randomized, double-blind, placebo-controlled trial comparing the effects of BSH on serially sampled nasal lavage fluid (NLF) cytokines, viral sequence quantity, and Nrf2-dependent enzyme expression in NLF cells and biopsied epithelium. Healthy young adult smokers and nonsmokers ingested BSH or placebo (alfalfa sprout homogenate) for 4 days, designated Days -1, 0, 1, 2. On Day 0 they received standard vaccine dose of live attenuated influenza virus (LAIV) intranasally. Nasal lavage fluids and nasal biopsies were collected serially to assess response to LAIV. RESULTS: In area under curve analyses, post-LAIV IL-6 responses (P = 0.03) and influenza sequences (P = 0.01) were significantly reduced in NLF from BSH-treated smokers, while NAD(P)H: quinoneoxidoreductasein NLF cells was significantly increased. In nonsmokers, a similar trend for reduction in virus quantity with BSH did not reach statistical significance. CONCLUSIONS: In smokers, short term ingestion of broccoli sprout homogenates appears to significantly reduce some virus-induced markers of inflammation, as well as reducing virus quantity. Nutritional antioxidant interventions have promise as a safe, low-cost strategy for reducing influenza risk among smokers and other at risk populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT01269723.


Assuntos
Brassica/química , Vacinas contra Influenza/imunologia , Nariz/efeitos dos fármacos , Orthomyxoviridae/imunologia , Extratos Vegetais/farmacologia , Brotos de Planta/química , Fumar , Adulto , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Masculino , NAD(P)H Desidrogenase (Quinona)/genética , Líquido da Lavagem Nasal/imunologia , Nariz/imunologia , Nariz/patologia , Vacinas Atenuadas/imunologia
7.
Phytomedicine ; 21(6): 824-9, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24613102

RESUMO

The fruits of Xanthium strumarium L. (Asteraceae) have been used extensively in China for treatment of various diseases such as allergic rhinitis (AR), tympanitis, urticaria and arthritis or ozena. This study was designed to systemically investigate the effects of the caffeoylxanthiazonoside (CXT) isolated from fruits of X. strumarium on AR in rodent animals. Animals were orally administered with CXT. Anti-allergic activity of CXT was evaluated by passive cutaneous anaphylaxis test (PCA); acetic acid-induced writhing tests were used to evaluate the analgesic effects of CXT; acetic acid-induced vascular permeability tests were performed to evaluate anti-inflammatory effect of CXT. Then, the model AR in rats was established to evaluate the effects of CXT on AR with the following tests: the sneezing and nasal scratching frequencies, IgE level in serum, and histopathological examinations. Our results demonstrated that CXT had favorable anti-allergic, anti-inflammatory and analgesic effects. Additionally, we found that CXT was helpful to ameliorate the nasal symptoms and to down-regulate IgE levels in AR rats. Thus, we suggested that CXT can be treated as a candidate for treating AR.


Assuntos
Analgésicos/uso terapêutico , Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Rinite Alérgica/tratamento farmacológico , Xanthium/química , Ácido Acético , Analgésicos/farmacologia , Animais , Antialérgicos/isolamento & purificação , Antialérgicos/farmacologia , Anti-Inflamatórios/farmacologia , Ácidos Cafeicos/isolamento & purificação , Ácidos Cafeicos/farmacologia , Modelos Animais de Doenças , Regulação para Baixo , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Frutas/química , Imunoglobulina E/sangue , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Camundongos Endogâmicos ICR , Nariz/efeitos dos fármacos , Dor/induzido quimicamente , Dor/tratamento farmacológico , Ratos Sprague-Dawley , Rinite Alérgica/sangue , Rinite Alérgica/complicações , Rinite Alérgica/patologia , Espirro/efeitos dos fármacos
8.
Toxicol Pathol ; 42(5): 830-43, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23960164

RESUMO

Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program's Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use.


Assuntos
Ginkgo biloba/toxicidade , Fígado/efeitos dos fármacos , Nariz/efeitos dos fármacos , Extratos Vegetais/toxicidade , Glândula Tireoide/efeitos dos fármacos , Animais , Testes de Carcinogenicidade , Carcinógenos/toxicidade , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Ginkgo biloba/química , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Nariz/patologia , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Ratos Endogâmicos F344 , Glândula Tireoide/patologia
9.
Food Funct ; 5(1): 35-41, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24287881

RESUMO

The generation of oxidative stress by ambient air pollution particles contributes to the development of allergic sensitization and asthma, as demonstrated by intranasal challenge with well-characterized diesel exhaust particle (DEP) suspensions in humans. This effect is due to the presence of redox active organic chemicals in DEP, and can be suppressed by antioxidants and inducers of phase II enzymes in animals. In this communication, we determined whether the administration of a standardized broccoli sprout extract (BSE), which contains a reproducible amount of the sulforaphane (SFN) precursor, glucoraphanin, could be used to suppress the nasal inflammatory response in human subjects challenged with 300 µg of an aqueous DEP suspension (equivalent to daily PM exposure levels on a Los Angeles freeway). SFN is capable of inducing an antioxidant and phase II response via activation of the nuclear transcription factor (erythroid-derived 2)-like 2 (Nrf2). Previous studies have shown that 70-90% SFN delivered by BSE is absorbed, metabolized, and excreted in humans. An initial intranasal challenge with DEP in 29 human subjects was used to characterize the magnitude of the inflammatory response. Following a 4 week washout, a BSE that delivers a reproducible and standardized dose of 100 µmol SFN in mango juice was administered daily for four days. The nasal DEP challenge was repeated and lavage fluid collected to perform white blood cell (WBC) counts. The average nasal WBC increased by 66% over the initial screening levels and by 85% over the control levels 24 hours after DEP exposure. However, total cell counts decreased by 54% when DEP challenge was preceded by daily BSE administration for 4 days (p < 0.001). Since the SFN dose in these studies is equivalent to the consumption of 100-200 g broccoli, our study demonstrates the potential preventive and therapeutic potential of broccoli or broccoli sprouts rich in glucoraphanin for reducing the impact of particulate pollution on allergic disease and asthma.


Assuntos
Poluentes Atmosféricos/imunologia , Brassica/química , Hipersensibilidade/tratamento farmacológico , Isotiocianatos/administração & dosagem , Nariz/imunologia , Extratos Vegetais/administração & dosagem , Emissões de Veículos/análise , Adulto , Feminino , Humanos , Hipersensibilidade/genética , Hipersensibilidade/imunologia , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/imunologia , Nariz/efeitos dos fármacos , Sulfóxidos
10.
Toxicol Pathol ; 38(7): 1070-84, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20884815

RESUMO

The toxicity of green tea extract (GTE) was evaluated in 14-week gavage studies in male and female F344/NTac rats and B6C3F1 mice at doses up to 1,000 mg/kg. In the rats, no treatment-related mortality was noted. In the mice, treatment-related mortality occurred in male and female mice in the 1,000 mg/kg dose groups. The cause of early deaths was likely related to liver necrosis. Treatment-related histopathological changes were seen in both species in the liver, nose, mesenteric lymph nodes, and thymus. In addition, in mice, changes were seen in the Peyer's patches, spleen, and mandibular lymph nodes. The no adverse effect level (NOAEL) for the liver in both species was 500 mg/kg. In the nose of rats, the NOAEL in males was 62.5 mg/kg, and in females no NOAEL was found. No NOAEL was found in the nose of female or male mice. The changes in the liver and nose were considered primary toxic effects of GTE, while the changes in other organs were considered to be secondary effects. The nose and liver are organs with high metabolic enzyme activity. The increased susceptibility of the nose and liver suggests a role for GTE metabolites in toxicity induction.


Assuntos
Camellia sinensis/química , Extratos Vegetais/toxicidade , Chá/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Longevidade/efeitos dos fármacos , Tecido Linfoide/efeitos dos fármacos , Tecido Linfoide/patologia , Masculino , Camundongos , Camundongos Endogâmicos , Nível de Efeito Adverso não Observado , Nariz/efeitos dos fármacos , Nariz/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Testes de Toxicidade
11.
Int J Toxicol ; 29(5): 467-78, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20884857

RESUMO

Ketorolac tromethamine is a potent analgesic and moderately effective anti-inflammatory drug approved for treatment of moderately severe acute pain as an intravenous/intramuscular injectable solution and an oral tablet. ROXRO PHARMA, Inc has developed an intranasal formulation, SPRIX, that delivers the drug with a similar pharmacokinetic profile to that obtained with intramuscular administration. Local tolerance and systemic toxicology studies were performed in rats and rabbits and showed that intranasal administration of SPRIX exhibits toxicity similar to that of other routes of administration and does not result in any adverse effects on the nasal passage and upper and lower respiratory system.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/toxicidade , Cetorolaco de Trometamina/administração & dosagem , Cetorolaco de Trometamina/toxicidade , Administração Intranasal , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Química Farmacêutica , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Cetorolaco de Trometamina/sangue , Cetorolaco de Trometamina/farmacocinética , Masculino , Nariz/efeitos dos fármacos , Nariz/patologia , Coelhos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade
12.
Am J Chin Med ; 38(4): 661-73, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20626052

RESUMO

The aim of this study is pursue the effect of herbal point-patch treatment on allergic rhinitis patients by investigation of the changes of serum total IgE (T-IgE) and eosinophile cationic protein (ECP) levels and through assessment of the results of SF-36 and rhinitis severity questionnaires. A prospective, randomized, single-blind, parallel, controlled study was used. Forty- three eligible participants were selected from outpatients of the Dept. of Ear, Nose, and Throat and Chinese medicine clinic, and 33 eligible participants completed the treatment satisfactorily. Participants used a Chinese herbal point-patch or a placebo patch once a week, for three hours at a time, after being randomly assigned to a control or an experimental group. Each treatment course was three weeks in duration, and each participant underwent two courses of treatment. Before and after each course, participants evaluated the effectiveness of the treatment by completing a questionnaire, and blood samples were collected for T-IgE and ECP analysis. The data revealed that the acupoint herbal patch is a valuable treatment for allergic rhinitis, especially in the symptoms of sneezing, running and itchy nose. The results of the SF-36 indicate a distinct improvement in GH (general health) and VT (vitality) in patients treated with acupoint herbal patches. This study supports the belief that the acupoint herbal patch is an effective treatment for allergic rhinitis and can significantly improve general health, social life and vitality in quality of life.


Assuntos
Pontos de Acupuntura , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Cutânea , Adolescente , Adulto , Criança , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Proteína Catiônica de Eosinófilo/sangue , Feminino , Humanos , Imunoglobulina E/sangue , Magnoliopsida , Masculino , Mucosa Nasal/efeitos dos fármacos , Nariz/efeitos dos fármacos , Qualidade de Vida , Rinite Alérgica Perene/complicações , Rinite Alérgica Perene/imunologia , Rinite Alérgica Sazonal/complicações , Rinite Alérgica Sazonal/imunologia , Método Simples-Cego , Espirro/efeitos dos fármacos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
13.
Immunopharmacol Immunotoxicol ; 31(4): 688-93, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19874242

RESUMO

We studied the effect of Brazilian propolis on sneezing and nasal rubbing in experimental allergic rhinitis of mice. A single administration of propolis caused no significant effect on both antigen-induced nasal rubbing and sneezing at a dose of 1000 mg/kg, but a significant inhibition was observed after repeated administration for 2 weeks at this dose. Propolis caused no significant inhibitory effect on the production of total IgE level after repeated administration of 1000 mg/kg. The drug also caused no significant inhibition of histamine-induced nasal rubbing and sneezing at a dose of 1000 mg/kg. On the other hand, propolis significantly inhibited histamine release from rat mast cells induced by antigen and compound 48/80 at a concentration of more than 10 microg/ml. These results clearly demonstrated that propolis may be effective in the relief of symptoms of allergic rhinitis through inhibition of histamine release.


Assuntos
Alérgenos/administração & dosagem , Nariz/efeitos dos fármacos , Nariz/imunologia , Própole/uso terapêutico , Prurido/prevenção & controle , Rinite Alérgica Perene/prevenção & controle , Espirro/efeitos dos fármacos , Alérgenos/imunologia , Animais , Brasil , Histamina/administração & dosagem , Histamina/imunologia , Imunoglobulina E/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Própole/farmacologia , Prurido/imunologia , Ratos , Rinite Alérgica Perene/imunologia , Espirro/imunologia
14.
Zhongguo Zhong Yao Za Zhi ; 33(3): 259-61, 2008 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-18536460

RESUMO

OBJECTIVE: To evaluate the influence of borneol on nasal absorption enhancement of ligustrazine. METHOD: The rats were randomly divided into 3 groups: Xiongbing nasal spray group (group A), Chuanxiong nasal spray group (group B) and Xiongbing group by decoction intragastric administration (group C). All the rats were decapitated at several time points after administration. The whole brains of rats were taken to homogenate and detected the concentrations of ligustrazine. RESULT: Compared with group B and C, group A has its characteristics: quick absorption, quick distribution and quick excretion of ligustrazine. CONCLUSION: Nasal administration is a quick-acting way for ischemic cerebral vessel insufficientia. Borneol promoted nasal absorption of ligustrazine into brain.


Assuntos
Canfanos/farmacologia , Mucosa Nasal/metabolismo , Nariz/efeitos dos fármacos , Pirazinas/administração & dosagem , Pirazinas/farmacocinética , Animais , Transporte Biológico/efeitos dos fármacos , Vias de Administração de Medicamentos , Feminino , Cinética , Masculino , Ratos , Ratos Sprague-Dawley
15.
Biol Pharm Bull ; 28(2): 238-41, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15684476

RESUMO

We studied the effect of Lo Han Kuo (Siraitia grosvenori Swingle) on histamine-induced nasal rubbing and compound 48/80-induced skin scratching behavior in ICR mice. An extract and glycoside (a complex of sweet components) of Lo Han Kuo were used in the study. Both the extract and glycoside caused no significant effect on nasal rubbing or scratching behavior, even at a dose of 1000 mg/kg when administered in a single dose. However, the effect of Lo Han Kuo became clear after repeated administration, and 300 and 1000 mg/kg of both extract and glycoside significantly inhibited nasal rubbing and skin scratching behavior after consecutive treatment for 4 weeks. Both the extract and glycoside inhibited the histamine release induced by compound 48/80 at concentrations of 300 and 1000 microg/ml. From these results, it is assumed that the inhibition of nasal rubbing and skin scratching behavior induced by Lo Han Kuo occurs through a mast cell-dependent mechanism.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Nariz/efeitos dos fármacos , Prurido/tratamento farmacológico , Animais , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Frutas , Histamina/toxicidade , Liberação de Histamina/efeitos dos fármacos , Liberação de Histamina/fisiologia , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Mucosa Nasal/metabolismo , Prurido/induzido quimicamente , Ratos
16.
Curr Allergy Asthma Rep ; 3(3): 210-4, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12662469

RESUMO

Menthol, in lozenges, nasal sprays, vapo-rubs, inhalers, and cough syrups, is widely used as a treatment for rhinitis that is associated with acute upper respiratory tract infection and allergy. Menthol as a plant extract has been used in traditional medicine in Asia for the treatment of respiratory diseases for hundreds of years, but it was only introduced to the West as a medicine at the end of the 19th century. With the recent discovery of a menthol receptor on the sensory nerves that modulate the cool sensation, menthol has graduated from the realms of herbal medicine into the field of molecular pharmacology. This review concerns the physiologic and pharmacologic mechanisms that underlie the widespread use of menthol as a treatment for the relief of nasal congestion associated with rhinitis and its effects on the drive to breathe and symptomatic relief of dyspnea.


Assuntos
Dispneia/tratamento farmacológico , Mentol/farmacologia , Nariz/efeitos dos fármacos , Sensação/efeitos dos fármacos , Humanos , Mentol/uso terapêutico , Nariz/fisiologia , Relação Estrutura-Atividade
17.
Am J Rhinol ; 13(5): 391-9, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10582118

RESUMO

We studied the pharmacological actions of combined histamine H1/H3 receptor blockade on the increase in nasal airway resistance (NAR) and decrease in nasal cavity volume produced by nasal exposure to compound 48/80, a mast cell degranulator. In the anesthetized cat compound 48/80 (1%) produced a maximum increase in NAR of 9.1 +/- 0.7 cmH20.L/minute. The increase in NAR in animals pretreated with a combination of the H1 antagonist, chlorpheniramine (CTM; 0.8 mg/kg i.v.) and increasing doses of the H3 antagonist, thioperamide (THIO; 1.0, 3.0, and 10.0 mg/kg i.v.) were 6.1 +/- 2.1, 4.2 +/- 1.0 and 2.2 +/- 0.7 cmH20.L/minute, respectively. A second H3 antagonist, clobenpropit (CLOB; 0.03, 0.3, and 1.0 mg/kg i.v.) combined with CTM (0.8 mg/kg i.v.) also inhibited the nasal effects of compound 48/80. When the nonsedating H1 antihistamine, loratadine (3.0 mg/kg i.v.), was substituted for CTM, it also reduced nasal congestion when given in combination with THIO (10 mg/kg i.v.). In contrast, treatment with CTM (1.0 mg/kg i.v.) and the H2 antagonist, ranitidine (RAN; 1.0 mg/kg i.v.) were without activity. Loratadine, CTM, CLOB, RAN, or THIO administered alone were inactive. The alpha-adrenergic agonist, phenylpropanolamine (PPA; 1.0 mg/kg i.v.) demonstrated decongestant effects, but in contrast to H1/H3 blockade, PPA produced a significant hypertensive effect. Using acoustic rhinometry (AcR) we found that combined i.v. CTM (1.0 mg/kg) and THIO (10 mg/kg) and combined oral CTM (10 mg/kg) and THIO (30 mg/kg) blocked the decrease in nasal cavity volume produced by intranasal compound 48/80 (1%, 50 microL). We conclude that combined H1/H3 histamine receptor blockade enhances the efficacy of an H1 antagonist by conferring decongestant activity to the H1 antihistamine. We propose that the decongestant activity of combined H1/H3 blockade may provide a novel approach for the treatment of allergic nasal congestion without the hypertensive liability of current therapies.


Assuntos
Clorfeniramina/uso terapêutico , Modelos Animais de Doenças , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Descongestionantes Nasais/uso terapêutico , Obstrução Nasal/tratamento farmacológico , Piperidinas/uso terapêutico , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Gatos , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Liberação de Histamina/efeitos dos fármacos , Masculino , Cavidade Nasal/efeitos dos fármacos , Cavidade Nasal/patologia , Obstrução Nasal/induzido quimicamente , Obstrução Nasal/fisiopatologia , Nariz/efeitos dos fármacos , Nariz/fisiopatologia , p-Metoxi-N-metilfenetilamina
18.
J Allergy Clin Immunol ; 99(1 Pt 1): 58-64, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9003212

RESUMO

Nitric oxide (NO) is produced in large amounts in the noses of normal individuals. We have measured NO by chemiluminescence in the noses and exhaled air of subjects with symptomatic allergic rhinitis, some of whom had concomitant asthma, during the pollen season and compared this with values measured in normal subjects and in patients treated with nasal and/or inhaled glucocorticoids. We found that nasal levels of NO were significantly (p < 0.001) elevated in patients with untreated rhinitis (1527 +/- 87 ppb, n = 12) compared with normal individuals (996 +/- 39 ppb, n = 46) or subjects treated with nasal steroids (681 +/- 34 ppb, n = 10), whereas exhaled NO in patients with untreated rhinitis was similar to that in normal subjects (10 +/- 2 ppb vs 7 +/- 0.6 ppb, respectively). In five subjects who were nasally challenged with allergen, there was a significant decrease in nasal NO 1 hour after challenge, and this was significantly correlated with increased rhinitis symptoms. In patients with rhinitis and concomitant asthma, nasal NO was also significantly elevated (1441 +/- 76 ppb, n = 16) but not when they were treated with nasal or inhaled steroids; whereas exhaled NO was elevated in untreated patients and in patients treated with nasal, but not inhaled, steroids. Our data suggest that the increase in exhaled NO in patients with allergic rhinitis is likely to be due to increased local production, caused by long-term exposure to allergen, which is suppressed by locally administered steroids. Measurement of nasal NO may be useful to study the inflammatory response in rhinitis and its response to antiinflammatory treatments.


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Asma/metabolismo , Mucosa Nasal/metabolismo , Óxido Nítrico/metabolismo , Rinite Alérgica Sazonal/tratamento farmacológico , Rinite Alérgica Sazonal/metabolismo , Administração por Inalação , Administração Tópica , Adulto , Alérgenos/imunologia , Alérgenos/farmacologia , Feminino , Glucocorticoides , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/metabolismo , Nariz/efeitos dos fármacos , Pólen/imunologia
19.
Eur Arch Otorhinolaryngol ; 254 Suppl 1: S82-4, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9065635

RESUMO

Acoustic rhinometry (AR) was used for objective measurements of nasal cavity dimensions in conjunction with a 100-mm horizontal visual analogue scale (VAS) for simultaneous subjective assessments of nasal sensations of airflow. Studies were conducted on 45 patients with perennial allergic rhinitis before, during and after a 2-week period of treatment with oral emedastine difumarate, azelastine hydrochloride, and xiao qing long tang (a homeopathic decongestant), as well as intranasal fluticasone propionate aqueous nasal spray. During the treatment period, there was a significant increase in the right and left minimum cross-sectional areas (MCA) of the nose and/or nasal cavity volumes (NCV) in all groups. The average increase in MCA ranged from 21-39% after 1 week of treatment and 16-39% after 2 weeks, whereas that in the NCV ranged from 16-24% and 19-24%, respectively. Post-treatment measurements were not significantly different from the corresponding pre-treatment ones. These findings were in close agreement with that obtained with VAS, demonstrating that AR can be used to validate the application of VAS in the evaluation of nasal airflow during medical therapy.


Assuntos
Cavidade Nasal/efeitos dos fármacos , Obstrução Nasal/tratamento farmacológico , Rinite Alérgica Perene/tratamento farmacológico , Acústica , Administração Intranasal , Administração Oral , Adulto , Androstadienos/administração & dosagem , Androstadienos/uso terapêutico , Antialérgicos/administração & dosagem , Antialérgicos/uso terapêutico , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Estudos de Avaliação como Assunto , Feminino , Fluticasona , Seguimentos , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Homeopatia , Humanos , Imidazóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nafazolina/uso terapêutico , Cavidade Nasal/patologia , Descongestionantes Nasais/administração & dosagem , Descongestionantes Nasais/uso terapêutico , Obstrução Nasal/patologia , Nariz/efeitos dos fármacos , Nariz/patologia , Ftalazinas/administração & dosagem , Ftalazinas/uso terapêutico , Ventilação Pulmonar/efeitos dos fármacos , Reprodutibilidade dos Testes , Rinite Alérgica Perene/patologia
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