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Braz. j. otorhinolaryngol. (Impr.) ; 86(1): 63-73, Jan.-Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1089372


Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Young Adult , Histamine/blood , Leukotriene D4/blood , Drug Therapy, Combination/methods , Precision Medicine/methods , Rhinitis, Allergic/blood , Quinolines/therapeutic use , Sneezing , RNA, Messenger/genetics , Receptors, Histamine H1/genetics , Nasal Obstruction/drug therapy , Treatment Outcome , Loratadine/therapeutic use , Receptors, Leukotriene/genetics , Anti-Allergic Agents/therapeutic use , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/drug therapy , Mometasone Furoate/therapeutic use , Acetates/therapeutic use , Nasal Mucosa
Chinese Journal of Oncology ; (12): 807-816, 2020.
Article in Chinese | WPRIM | ID: wpr-877492


Anlotinib hydrochloride is the only anti-angiogenic, multi-targeted tyrosine kinase inhibitor, which has been approved for non-small cell lung cancer and small cell lung cancer in China. In order to provide guidance for clinical practitioners to use anlotinib hydrochloride safely and efficiently, the Chinese Association for Clinical Oncologists, the Expert Committee of Vascular Targeted Therapy of Chinese Society of Clincal Oncology and the Cancer Targeted Therapy Professional Committee of China Anti-Cancer Association co-organized experts and integrated multiple evidences of Anlotinib Hydrochloride, from both clinical trial, post-marketed clinical data and the associated experiences of experts accumulated in clinical practice, etc. The present consensus covers the clinical data of anlotinib hydrochloride applied in advanced non-small cell lung cancer and small cell lung cancer, and the safety management recommendations.

Carcinoma, Non-Small-Cell Lung/drug therapy , China , Consensus , Humans , Indoles/therapeutic use , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Quinolines/therapeutic use
Rev. Soc. Bras. Med. Trop ; 53: e20200091, 2020. graf
Article in English | LILACS, ColecionaSUS, SES-SP | ID: biblio-1136875


Abstract INTRODUCTION: The drugs currently available for leishmaniasis treatment have major limitations. METHODS: In vitro and in vivo studies were performed to evaluate the effect of a quinoline derivative, Hydraqui (7-chloro-4-(3-hydroxy-benzilidenehydrazo)quinoline, against Leishmania amazonensis. In silico analyses of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were performed. RESULTS: Hydraqui showed significant in vitro anti-amastigote activity. Also, Hydraqui-treated mice exhibited high efficacy in lesion size (48.3%) and parasitic load (93.8%) reduction, did not cause hepatic and renal toxicity, and showed appropriate ADMET properties. CONCLUSIONS: Hydraqui presents a set of satisfactory criteria for its application as an antileishmanial agent.

Animals , Female , Quinolines/therapeutic use , Leishmania mexicana/drug effects , Leishmaniasis, Cutaneous/drug therapy , Antiprotozoal Agents/therapeutic use , Quinolines/chemistry , Leishmaniasis, Cutaneous/parasitology , Disease Models, Animal , Parasite Load , Mice , Mice, Inbred BALB C
Braz. j. med. biol. res ; 53(7): e9271, 2020. tab, graf
Article in English | LILACS, ColecionaSUS | ID: biblio-1132527


Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

Quinolines/therapeutic use , Asthma/drug therapy , Anti-Asthmatic Agents/therapeutic use , Protective Agents/therapeutic use , Cough/drug therapy , RNA, Long Noncoding/metabolism , Acetates/therapeutic use , Asthma/blood , Cough/blood , Disease Models, Animal , Mice, Inbred BALB C
Rev. Soc. Bras. Med. Trop ; 52: e20180453, 2019. tab, graf
Article in English | LILACS | ID: biblio-1041531


Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.

Humans , Male , Female , Adult , Quinolines/adverse effects , Long QT Syndrome/chemically induced , Malaria, Falciparum/drug therapy , Artemisinins/adverse effects , Antimalarials/adverse effects , Quinolines/therapeutic use , Long QT Syndrome/diagnosis , Retrospective Studies , Artemisinins/therapeutic use , Drug Therapy, Combination , Electrocardiography , Middle Aged , Antimalarials/therapeutic use
Braz. j. med. biol. res ; 49(4): e5031, 2016. tab, graf
Article in English | LILACS | ID: lil-774523


Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research.

Animals , Male , Mice , Acetates/pharmacology , Anticonvulsants/pharmacology , Leukotriene Antagonists/pharmacology , Quinolines/pharmacology , Seizures/drug therapy , Acetates/therapeutic use , Anticonvulsants/therapeutic use , Blotting, Western , Convulsants , Kindling, Neurologic/drug effects , Leukotriene Antagonists/therapeutic use , Pentylenetetrazole , Phenobarbital/pharmacology , Phenobarbital/therapeutic use , Quinolines/therapeutic use , Receptors, Leukotriene/drug effects , Seizures/chemically induced , Time Factors , Treatment Outcome
Braz. j. med. biol. res ; 49(9): e5388, 2016. tab, graf
Article in English | LILACS | ID: biblio-951696


Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGF-βRI), is the only known TGF-β pathway inhibitor. In the present study, we investigated the effect of galunisertib on taurocholate (TAC)-induced acute pancreatitis (AP) in rats, and the role of TGF-β and NF-κB signaling pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague-Dawley male rats (n=30). The rats (220±50 g) were administered galunisertib intragastrically [75 mg·kg-1·day-1 for 2 days (0 and 24 h)]. Serum IL-1β, IL-6, TNF-α, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were measured by ELISA. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); NF-κBp65 and TGF-β1 proteins, as well as TGF-βRI and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was detected by TUNEL assay. H&E staining was used to evaluate the histopathological alterations of the pancreas. Galunisertib treatment attenuated the severity of AP and decreased the pancreatic histological score. In addition, number of apoptotic cells were significantly increased in the galunisertib-treated group (16.38±2.26) than in the AP group (8.14±1.27) and sham-operated group (1.82±0.73; P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of TGF-βRI and p-Smad2/3 and inhibited NF-κB activation and p65 translocation compared with the sham-operated group. Furthermore, serum IL-1β, IL-6, TNF-α, AMY and LIP levels and tissue MPO activity were significantly decreased in the galunisertib-treated group. Our data demonstrate that galunisertib attenuates the severity of TAC-induced experimental AP in rats by inducing apoptosis in the pancreas, inhibiting the activation of TGF-β signals and NF-κB as well as the secretion of pro-inflammatory cytokines.

Animals , Male , Pancreatitis/drug therapy , Pyrazoles/therapeutic use , Quinolines/therapeutic use , Protein-Serine-Threonine Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Pancreas/drug effects , Pancreas/pathology , Pancreatitis/pathology , Enzyme-Linked Immunosorbent Assay , Blotting, Western , Acute Disease , Interleukin-6/blood , Treatment Outcome , Apoptosis , Peroxidase/analysis , In Situ Nick-End Labeling , Electrophoretic Mobility Shift Assay , Interleukin-1beta/blood , Amylases/blood , Lipase/blood
An. bras. dermatol ; 90(2): 265-267, Mar-Apr/2015. graf
Article in English | LILACS | ID: lil-741067


A sixty-one year old white female was referred to the Dermatology Department to treat an ingrown nail in the inner corner of the left hallux. Examination of the entire nail unit showed the presence of xanthonychia in the outer corner besides thickening and increase in the transverse curvature of the nail plate. Dermoscopy and nuclear magnetic resonance of the free edge of the nail plate detected characteristic signs of onychomatricoma, a diagnosis that was later confirmed by anatomopathological exam.

Humans , Anticholesteremic Agents/therapeutic use , Cholesterol Ester Transfer Proteins/antagonists & inhibitors , Fibric Acids/therapeutic use , Lipoproteins, HDL/blood , Niacin/therapeutic use , Coronary Disease/blood , Coronary Disease/mortality , Coronary Disease/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocardial Infarction/blood , Myocardial Infarction/mortality , Myocardial Infarction/prevention & control , Oxazolidinones/therapeutic use , Quinolines/therapeutic use , Randomized Controlled Trials as Topic , Stroke/blood , Stroke/mortality , Stroke/prevention & control , Sulfhydryl Compounds/therapeutic use
Yonsei Medical Journal ; : 45-52, 2015.
Article in English | WPRIM | ID: wpr-201311


PURPOSE: To evaluate the effect of statin treatment on strut coverage after drug-eluting stent (DES) implantation. MATERIALS AND METHODS: In this study, 60 patients were randomly assigned to undergo sirolimus-eluting stent (SES) or biolimus-eluting stent (BES) implantation, after which patients were randomly treated with pitavastatin 2 mg or pravastatin 20 mg for 6 months. The degree of strut coverage was assessed by 6-month follow-up optical coherence tomography, which was performed in 52 DES-implanted patients. RESULTS: The percentages of uncovered struts were 19.4+/-14.7% in pitavastatin-treated patients (n=25) and 19.1+/-15.2% in pravastatin-treated patients (n=27; p=0.927). A lower percentage of uncovered struts was significantly correlated with a lower follow-up low-density lipoprotein (LDL) cholesterol level (r=0.486; p=0.009) and a greater decline of the LDL cholesterol level (r=-0.456; p=0.015) in SES-implanted patients, but not in BES-implanted patients. In SES-implanted patients, the percentage of uncovered struts was significantly lower among those with LDL cholesterol levels of less than 70 mg/dL after 6 months of follow-up (p=0.025), but no significant difference in this variable according to the follow-up LDL cholesterol level was noted among BES-implanted patients (p=0.971). CONCLUSION: Lower follow-up LDL cholesterol levels, especially those less than 70 mg/dL, might have a protective effect against delayed strut coverage after DES implantation. This vascular healing effect of lower LDL cholesterol levels could differ according to the DES type.

Adult , Coronary Angiography , Drug-Eluting Stents , Female , Follow-Up Studies , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Lipoproteins, LDL/blood , Male , Middle Aged , Pravastatin/therapeutic use , Prosthesis Implantation , Quinolines/therapeutic use , Tomography, Optical Coherence , Treatment Outcome
Yonsei Medical Journal ; : 197-202, 2014.
Article in English | WPRIM | ID: wpr-50982


PURPOSE: To compare the epithelial wound healing response of two preservative-free fluoroquinolones, moxifloxacin and levofloxacin, in patients who underwent cataract surgery. MATERIALS AND METHODS: In this prospective, evaluator-masked, randomized clinical trial, 59 eyes of 50 patients who underwent cataract surgery were enrolled. Patients were randomized to receive moxifloxacin 0.5% (n=32 eyes) or levofloxacin 0.5% (n=27 eyes). All patients instilled moxifloxacin or levofloxain four times daily for 1 week prior to surgery and 2 weeks after surgery. The epithelial wound healing status in the corneal incision site was scanned with a raster scan mode of fourier-domain optical coherence tomography (FD-OCT). The number of eyes showing epithelial defect images and average number of corneal epithelial defect cuts per eye were compared between groups. All patients were evaluated on postoperative days 1, 2, 3, and 10. RESULTS: On postoperative days 1, 2, and 3, the number of eyes showing epithelial defects in FD-OCT was not statistically different (all p>0.05). The average number of corneal epithelial defect cuts was also not statistically different between the two groups (all p>0.05). No eyes showed epithelial defects on postoperative day 10 in either group. CONCLUSION: There were no differences on epithelial wound healing comparing these two different fluoroquinolones at the incision site of cataract surgery.

Aged , Aza Compounds/therapeutic use , Cataract Extraction , Cornea/drug effects , Female , Fluoroquinolones/therapeutic use , Humans , Levofloxacin/therapeutic use , Male , Middle Aged , Quinolines/therapeutic use , Tomography, Optical Coherence , Wound Healing/drug effects
Article in English | IMSEAR | ID: sea-157487


Asthma is a chronic relapsing inflammatory disorder characterized by hyper reactive airways, leading to episodic, reversible bronchi constriction, owing to increased responsiveness of the tracheobronchial tree to various stimuli1. Specific objectives of the study to compare the clinical efficacy of oral montelukast with metered dose inhaled steroids. The results of the study suggests that metered dose inhaled steroids are superior than oral montelukast in mild persistent childhood asthma.

Acetates/therapeutic use , Administration, Inhalation , Administration, Oral , Adrenal Cortex Hormones/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Child , Child, Preschool , Drug Combinations , Female , Humans , Male , Quinolines/therapeutic use , Treatment Outcome
Rev. venez. oncol ; 24(4): 272-279, oct.-dic. 2012. tab, graf
Article in Spanish | LILACS | ID: lil-704400


El cáncer es una enfermedad multifactorial caracterizada por anormalidad en el crecimiento celular provocado por factores ambientales y múltiples cambios en la expresión de los genes. El cáncer de mama representa una de las enfermedades que más afecta a la población femenina mundial. Actualmente, se ha mostrado un auge en las investigaciones sobre compuestos extraídos de diversas plantas y origen sintético con posibles agentes antitumorales, entre los que se pueden nombrar los derivados sintéticos de quinolinas. Realizado estudio del grupo sintético indeno (2,1-c) quinolinas y sus efectos citotóxicos sobre líneas de cáncer de mama SKBr3 yMCF-7. La evaluación de la actividad citotóxica de estos compuestos fue determinada a través del método del MTT, se calcularon los valores de concentración inhibitoria, los índices de selectividad y combinaciones con taxanos. Los resultados obtenidos muestran una alta selectividad de los compuestos sintéticos y natural evaluados hacia las líneas celulares MCF-7 y SKBr3 con respecto a las células control (fibroblastos dérmicos humanos); además de una interacción de tipo potenciación en la combinación de un derivado quinolínico y la drogataxano. Con todo esto se puede inferir que solo ciertos compuestos que tuvieron modificaciones químicas realizadas sobre el compuesto patrón del grupo sintético indeno (2,1-c) quinolinas mostraron una inhibición sobre la viabilidad celular sobre las líneas tumorales SKBr3 y MCF-7, conforme aumenta la dosis de los compuestos, además de evidenciar la efectividad de compuestos derivados de quinolinas como moléculas con características antineoplásicas

The cancer is a multifactorial disease characterized by abnormal cell growth caused by environmental factors and for multiple changes in the gene expression. The breast cancer is a disease that affects the female population in worldwide. Currently, there is shown an increment in the research on compounds that we extracted from various plants and synthetic origin with potential antitumor agents, among which can be namedthe synthetic derivatives of the quinolines. A study was performed on an group of synthetic indeno (2,1-c) quinolines and their cytotoxic effects on breast cancer cell lines SKBR3 and MCF-7 was performed. The evaluation of the cytotoxic activity of these compounds was determined through the MTT method; we were calculated inhibitory concentration values, the rates of selectivity and the drug combinations with taxanes. The results show a high selectivity of the natural and the synthetic compounds evaluated towards the cell lines MCF-7 and SKBR3 cells with respect to control (dermal fibroblasts human), besides an enhancement type interaction in the combination of a drug derivative and the quinolinic taxanes. With all this we can infer that only certain compounds had chemical modifications performed on the composite pattern of synthetic group indeno (2, 1-c) quinolines showed an inhibition on cell viability on tumor cell lines SKBR3 and MCF-7, with increasing dose of the compounds, also showing the effectiveness of compounds derived from the quinolines as molecules with the antineoplastic properties and his characteristics

Female , Antibody-Dependent Cell Cytotoxicity , Breast Neoplasms/prevention & control , Breast Neoplasms/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Drug Therapy/methods , Quinolines/therapeutic use , Vaccines, Synthetic/therapeutic use , Drug Screening Assays, Antitumor/methods , Cell Line, Tumor , Cell Line, Tumor/pathology , Medical Oncology
Indian J Ophthalmol ; 2012 Mar; 60(2): 134-136
Article in English | IMSEAR | ID: sea-138808


We report a case of unilateral conjunctival ulcer due to Stenotrophomonas maltophilia infection in an immunocompetent individual. A 44-year-old male presented with complaints of pain and yellowish discharge in the right eye for one week. Patient underwent complete ophthalmic evaluation and relevant laboratory investigations. Anterior segment examination revealed localized conjunctival and episcleral congestion with conjunctival ulceration on the bulbar conjunctiva in the right eye. Gram's stain revealed gram-negative bacilli. Culture and sensitivity revealed S. maltophilia and responded well to topical moxifloxacin with systemic co-trimoxazole therapy.

Adult , Anti-Infective Agents/therapeutic use , Aza Compounds/therapeutic use , Conjunctivitis/drug therapy , Conjunctivitis/microbiology , Conjunctivitis/pathology , Gram-Negative Bacterial Infections/complications , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/pathology , Humans , Male , Quinolines/therapeutic use , Stenotrophomonas maltophilia/isolation & purification , Ulcer/drug therapy , Ulcer/microbiology , Ulcer/microbiology
Rev. bras. reumatol ; 52(1): 30-32, jan.-fev. 2012. tab
Article in Portuguese | LILACS | ID: lil-611468


OBJETIVO: Avaliar a ação do medicamento inibidor do receptor de leucotrieno CysLT1 (montelucaste) nas alterações vasculares das mãos em pacientes com fenômeno de Raynaud. MÉTODOS: Foram selecionadas pacientes com fenômeno de Raynaud secundário à doença inflamatória do tecido conjuntivo, excluindo tabagismo, hipertensão arterial e diabetes mellitus. As pacientes mantiveram a medicação prévia e iniciaram o uso de montelucaste 10 mg/dia por 60 dias. Foi realizada capilaroscopia periungueal dos dedos das mãos antes do uso da medicação e após 30 e 60 dias. A análise estatística foi feita por meio de porcentagem, média, desvio-padrão e teste exato de Fisher, com intervalo de confiança de 95 por cento. RESULTADOS: Foram estudadas cinco pacientes mulheres, brancas, com fenômeno de Raynaud secundário a doenças do tecido conjuntivo, das quais três apresentavam esclerodermia e duas apresentavam doença mista do tecido conjuntivo. A média de idade foi de 42,4 ± 12,4 anos, e a média de tempo de doença foi de 9,6 ± 4,8 anos. As pacientes estavam em uso de até 20 mg/dia de prednisona (pacientes com doença mista do tecido conjuntivo), nifedipina, pentoxifilina. As medicações foram mantidas. Após o uso de inibidor de receptor de leucotrieno por dois meses, o controle com capilaroscopia ungueal demonstrou diminuição do edema e da palidez e normalização do número, tamanho e distribuição dos capilares. CONCLUSÃO: O uso do montelucaste modificou as alterações capilares observadas na capilaroscopia periungueal de pacientes com fenômeno de Raynaud.

OBJECTIVE: To assess the effect of the leukotriene receptor inhibitor (montelukast) on vascular alterations in fingers of patients with Raynaud's phenomenon. METHODS: Patients with Raynaud's phenomenon of the hands secondary to inflammatory connective tissue disease were selected, and those with the following characteristics were excluded: smokers, arterial hypertension, and diabetes mellitus. All patients maintained their previous medications and started the use of montelukast, 10 mg/day, for 60 days. Naifold capillaroscopy of fingers was performed before the use of medication and after 30 and 60 days. Statistical analysis was performed with percentage, media, standard deviation, Fisher exact test, with 95 percent of confidence interval. RESULTS: The study assessed five Caucasian, female patients with Raynaud's phenomenon secondary to inflammatory connective tissue disease (three with scleroderma and two with mixed connective tissue disease), aged 42.4 ± 11.5 years, and with 9.6 ± 4.8 years of disease duration. Patients were on nifedipine and pentoxifylline, and those with mixed connective tissue disease were also on prednisone. The medications were maintained. After using montelukast for two months, nailfold capillaroscopy showed a reduction in edema and pallor, and normalization of capillary number, size, and distribution. CONCLUSION: The use of montelukast modified the capillary abnormalities observed on nailfold capillaroscopy of patients with Raynaud's phenomenon.

Adult , Female , Humans , Acetates/therapeutic use , Leukotriene Antagonists/therapeutic use , Microscopic Angioscopy , Quinolines/therapeutic use , Raynaud Disease/diagnosis , Raynaud Disease/drug therapy , Receptors, Leukotriene/drug effects , Prospective Studies
Rev. Inst. Med. Trop. Säo Paulo ; 53(5): 291-294, Sept.-Oct. 2011. ilus, tab
Article in English | LILACS | ID: lil-602366


The majority of infections caused by R. equi occur in hosts with some degree of cell-mediated immunodeficiency. Immunocompetent individuals are infrequently affected and usually present with localized disease. Infections of the skin or related structures are uncommon and are usually related to environmental contamination. The microbiology laboratory plays a key role in the identification of the organism since it may be mistaken for common skin flora. We describe a 31 year-old woman without medical problems who presented nine weeks after breast reduction with right breast cellulitis and purulent drainage from the surgical wound. She underwent incision and drainage, and cultures of the wound yielded Rhodococcus equi. The patient completed six weeks of antimicrobial therapy with moxifloxacin and rifampin with complete resolution.

La mayoría de las infecciones causadas por Rhodococcus equi ocurren en huéspedes con algún grado de inmunodeficiencia celular. Los individuos inmunocompetentes son afectados con baja frecuencia y suelen presentarse con enfermedad localizada. Las infecciones de la piel o partes blandas son poco frecuentes y están usualmente relacionadas con contaminación ambiental. El laboratorio de microbiología juega un papel clave en la identificación del organismo, ya que este puede confundirse con flora normal de la piel. Se describe una mujer de 31 años sin problemas médicos que consultó nueve semanas después de haber sido sometida a cirugía de reducción mamaria, con celulitis del seno derecho y drenaje purulento de la herida quirúrgica. Se practicó incisión y drenaje quirúrgico y los cultivos de la herida demostraron R. equi. La paciente recibió seis semanas de tratamiento antimicrobiano con moxifloxacina y rifampicina demostrando resolución completa.

Adult , Female , Humans , Actinomycetales Infections/diagnosis , Mammaplasty/adverse effects , Rhodococcus equi/isolation & purification , Actinomycetales Infections/drug therapy , Anti-Infective Agents/therapeutic use , Aza Compounds/therapeutic use , Immunocompetence , Quinolines/therapeutic use , Rifampin/therapeutic use
Medicina (B.Aires) ; 71(4): 343-349, July-Aug. 2011. ilus, tab
Article in English | LILACS | ID: lil-633875


Eosinophil is considered to be a main protagonist in asthma; however, often discordances between clinical manifestations and response to treatment are observed. We aimed to determine the occurrence of neutrophil predominance in asthma and to identify its characteristics on the basis of clinical-functional features, induced sputum cellular pattern and soluble molecules, to guide the appropriated anti-inflammatory therapy. A total of 41 patients were included in randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid-naïve and non-smokers. An induced sputum sample was obtained under basal conditions, a second one after treatment with budesonide (400 µg b.i.d.) or montelukast (10 mg/d) for six weeks, and a final one after a 4-week washout period. By cytospin we evaluated eosinophil (EP) or neutrophil predominance (NP), and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability (PEFV) was measured. A total of 23/41 patients corresponded to EP and 18/41 patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP than with EP. No difference was found for CC16. Montelukast reduced the predominant cell in both subsets, whereas budesonide only reduced eosinophils in EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the total treated-samples in each subset, CC16 level increased significantly in EP. In conclusion: a NP subset of asthmatic patients was identified. These patients show a lower bronchial lability; the leukotriene pathway is involved which responds to anti-leukotriene treatment. This phenotype shows a poor recovery of CC16 level after treatment.

El eosinófilo es considerado la célula protagonista principal en el asma; sin embargo, a menudo se observan discordancias entre las manifestaciones clínicas y la respuesta de los pacientes al tratamiento. Nos propusimos determinar la ocurrencia de predominio de neutrófilos en el asma e identificar las características clínico-funcionales, el patrón celular y las moléculas solubles del esputo inducido, para guiar el tratamiento apropiado anti-inflamatorio. Se incluyeron 41 pacientes: 21 a 40 años de edad, con asma estable leve a grave, no tratados con esteroides tópicos ni sistémicos y no fumadores. Se obtuvo una muestra de esputo inducido en condiciones basales, una segunda muestra después del tratamiento al azar con budesonida (400 µg dos veces al día) o el montelukast (10 mg/d) durante seis semanas, y una final después de un período de lavado de 4 semanas. En el frotis por citocentrifugado se evaluó el predominio de eosinófilos (EP) o neutrófilos (NP), y en el sobrenadante se determinó LTE4, y CC16. Se midió la variabilidad del flujo espiratorio máximo (PEFV). Un total de 23/41 pacientes correspondieron al EP y 18/41 pacientes con NP. El PEFV fue mayor en el EP que en NP. LTE4 fue mayor en NP que en EP. No se encontraron diferencias de los niveles de CC16 en ambos grupos. Montelukast redujo la célula predominante en ambos subgrupos, mientras que budesonida sólo redujo los eosinófilos en EP. Tanto budesonida como montelukast redujeron PEFV en EP, pero no en NP. El nivel de CC16 aumentó significativamente en el EP luego del tratamiento antiinflamatorio. En conclusión: se identificó un subgrupo de asmáticos NP que presentan una menor labilidad bronquial, la vía de los leucotrienos parece estar involucrada y responde al tratamiento anti-leucotrienos. Este fenotipo muestra una escasa recuperación del nivel de CC16 posterior al tratamiento.

Adult , Female , Humans , Male , Young Adult , Anti-Asthmatic Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Eosinophils/cytology , Neutrophils/cytology , Sputum/cytology , Acetates/therapeutic use , Asthma/pathology , Asthma/physiopathology , Budesonide/therapeutic use , Cell Count , Drug Therapy, Combination , Eosinophils/drug effects , Neutrophils/drug effects , Quinolines/therapeutic use , Severity of Illness Index , Single-Blind Method , Uteroglobin/physiology
Invest. clín ; 52(1): 15-22, mar. 2011. ilus
Article in English | LILACS | ID: lil-630916


Non-steroidal anti-inflammatory drugs (NSAIDS) are the first line of therapy in acute gouty arthritis. NSAIDs inhibit the cyclooxygenase pathway, but not the lipooxygenase activity and can have many adverse effects and thus have a limited effect on the control of inflammation in this disease. In this work we studied the effect of montelukast on the cellular inflammatory infiltrate in a model of murine arthritis induced by sodium monourate crystals (SMU), using a subcutaneous air cavity (air pouch) in BALB/c mice. Seven groups of BALB/c mice (n = 4) were distributed into five experimental groups and two inflammatory control groups, a positive and a negative one. Previous to SMU exposure, the experimental groups received montelukast (1 and 0.01 mg/Kg/w) and/or indomethacine (2.5 mg/Kg/w), followed by administration of SMU in the air pouch. The total and differential counts of inflammatory cells were analyzed after 2, 6, 12 and 24 hours. Montelukast, significantly reduced the total number of cells (p<0.05), with a predominant impact on polymorphonuclear over mononuclear cells, especially after 12 hours of the medication. The montelukast/indometacine combination showed an additive effect. Our data show that montelukast has an anti-inflammatory effect in the model of gouty arthritis. Consequently, anti-leukotrienes could represent a new and effective therapy, either isolated or combined with conventional therapy of gouty arthritis.

En artritis gotosa aguda las drogas antiinflamatorias no esteroideas son la primera línea terapéutica. Este tratamiento no es satisfactorio porque inhibe la ciclooxigenasa sin modificar la actividad de la lipooxigenasa, y puede acompañarse de numerosos efectos adversos. Investigamos el efecto de montelukast sobre el infiltrado celular inflamatorio en un modelo de artritis múrida inducida por cristales de monourato de sodio (MUS) en el modelo experimental de la bolsa de aire (air pouch). Siete grupos de ratones BALB/c (n = 4) fueron distribuidos en cinco grupos experimentales y dos grupos controles inflamatorios: positivo y negativo. Los grupos experimentales recibieron, montelukast (1 y 0,01 mg/Kg/p) y/o indometacina (2,5 mg/Kg/p) por vía oral, previo a la administración de MUS en la bolsa del aire. El conteo absoluto y diferencial de las células inflamatorias fue analizado después de 2, 6, 12 y 24 horas de tratamiento. El tratamiento con montelukast redujo significativamente el número total de células presentes en el infiltrado inflamatorio (p < 0,05), con un efecto mayor sobre polimorfonucleares que sobre las células mononucleares, y con un máximo efecto a las 12 horas después de la administración del medicamento. La combinación montelukast/indometacina mostró un efecto aditivo. Los resultados demuestran que montelukast tiene un efecto antiinflamatorio en el modelo de la artritis gotosa. Por lo tanto, los anti-leucotrienos podrían representar una nueva y eficaz terapia, aislada o en combinación con la terapéutica convencional, para la artritis gotosa.

Animals , Male , Mice , Acetates/therapeutic use , Arthritis, Gouty/drug therapy , Leukotriene Antagonists/therapeutic use , Quinolines/therapeutic use , Uric Acid/toxicity , Acetates/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Gouty/chemically induced , Arthritis, Gouty/prevention & control , Cell Migration Assays, Leukocyte , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Drug Synergism , Indomethacin/administration & dosage , Indomethacin/therapeutic use , Inflammation/chemically induced , Inflammation/drug therapy , Leukocytes, Mononuclear/drug effects , Leukotriene Antagonists/administration & dosage , Mice, Inbred BALB C , Neutrophils/drug effects , Premedication , Quinolines/administration & dosage
Arq. bras. endocrinol. metab ; 54(9): 777-784, dez. 2010. ilus, tab
Article in Portuguese | LILACS | ID: lil-578357


Estudos epidemiológicos mostram relação inversa entre níveis plasmáticos de HDL-colesterol (HDL-C) e incidência de doença cardiovascular (DCV). O papel antiaterogênico da HDL é atribuído às suas atividades anti-inflamatória, antitrombótica e antioxidante, além de sua participação no transporte reverso de colesterol (TRC), processo pelo qual a HDL remove colesterol dos tecidos periféricos, incluindo macrófagos da íntima arterial, e o transporta para o fígado para ser excretado pela bile. Com base nesses fatos, o HDL-C tornou-se alvo atrativo para a prevenção da DCV. No entanto, o fracasso do torcetrapib, droga que aumenta substancialmente os níveis de HDL-C, em prevenir DCV, além do conhecimento gerado por estudos de modelos animais e doenças monogênicas que afetam a concentração de HDL-C, tem suscitado questionamentos sobre o papel antiaterogênico da HDL. Esta revisão tem como objetivo abordar aspectos atuais do conhecimento da HDL, baseando-se nessas recentes controvérsias.

Epidemiological studies demonstrate an inverse correlation between plasma HDL-cholesterol (HDL-C) concentration and incidence of cardiovascular disease (CVD). The antiatherogenic role of HDL has been attributed to its anti-inflammatory, antithrombotic and antioxidant properties, besides its participation in the reverse cholesterol transport (RCT), whereby cholesterol from peripheral tissues (including macrophages of the arterial intima) is delivered to the liver for excretion in bile. Due to these actions, HDL-C has evolved as an attractive target for prevention of CVD. However, the failure of torcetrapib, drug that substantially increases HDL-C levels, in preventing CVD and data from studies with animal models and with carriers of monogenic disorders affecting HDL-C levels in humans provide conflicting data about HDL being antiatherogenic. This review addresses the current state of knowledge regarding HDL based on these recent controversies.

Humans , Anticholesteremic Agents/therapeutic use , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/metabolism , Quinolines/therapeutic use , Biological Transport , Cardiovascular Diseases/blood , Cholesterol, HDL/drug effects , Yin-Yang
Rev. méd. Chile ; 137(5): 666-671, mayo 2009. ilus
Article in Spanish | LILACS | ID: lil-521869


Eosinophilic esophagitis in adults (EE) is a disease of unknown cause, characterized by symptoms such as reflux and dysphagia that traditionally do not respond to antacid treatment. It affects mostly young men with a strong personal or familial history of a topy asthma and allergies. We repot three male patients aged 10, 14 and 15years, all with symptoms of dysphagia, two of them with chest pain caused by spasm of the esophagus, with heterogeneous endoscopic findings which included from leucoplakia to stenosis that needed endoscopic dilatation. All of them had abnormal findings in immunity studies (prick test or IgE levels). They received treatment based on diet measures, acid suppression and leukotriene inhibitors, with satisfactory clinical, endoscopic and histological response. EE should be suspected in children and adults with esophageal symptoms and personal or family history of allergy and asthma.

Adolescent , Child , Humans , Male , Eosinophilia/pathology , Esophagitis/pathology , Acetates/therapeutic use , Esophagoscopy , Eosinophilia/drug therapy , Esophagitis/drug therapy , Omeprazole/therapeutic use , Quinolines/therapeutic use , /therapeutic use
Arq. bras. oftalmol ; 72(2): 261-263, mar.-abr. 2009. ilus
Article in Portuguese | LILACS | ID: lil-513903


Relatamos um caso de conjuntivite ocasionada por Achromobacter xylosoxidans em paciente imunocompetente usuária de lentes de contato rígidas. A bactéria foi isolada da solução utilizada para a desinfecção das lentes bem como do raspado conjuntival. A. xylosoxidans tem sido descrita em infecções oportunistas em pacientes imunodeprimidos, contudo pode ser confundida com outros bacilos gram-negativos, principalmente Pseudomonas aeruginosa, isoladas de infecções oculares em pacientes imunocompetentes. Devido ao reduzido perfil de sensibilidade aos antimicrobianos demonstrado pelo A. xylosoxidans, torna-se importante a identificação deste agente etiológico em quadros de conjuntivite.

We report here a case of conjunctivitis in an immunocompetent patient due to Achromobacter xylosoxidans, which was associated with the use of rigid contact lenses. The bacteria were isolated from the scraped conjunctival swab as well as from the lens cleaning fluid. A. xylosoxidans is an opportunistic pathogen, especially in immunocompromised patients; however, in isolates of ocular infections, from immunocompetent patients, it may be confused with other gram-negative organisms, particularly Pseudomonas aeruginosa. Due to an increased resistance against different antimicrobial agents, A. xylosoxidans must be fully identified and differentiated from other gram-negative isolates from ocular infections.

Female , Humans , Young Adult , Achromobacter denitrificans/isolation & purification , Conjunctivitis, Bacterial/microbiology , Contact Lenses/microbiology , Gram-Negative Bacterial Infections/microbiology , Anti-Infective Agents/therapeutic use , Aza Compounds/therapeutic use , Conjunctivitis, Bacterial/diagnosis , Conjunctivitis, Bacterial/drug therapy , Contact Lenses/adverse effects , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Immunocompetence , Quinolines/therapeutic use , Young Adult