Resumo Introdução: Estudos que avaliaram o manejo do refluxo laringofaríngeo por otorrinolaringologistas mostraram uma importante heterogeneidade em relação à definição, diagnóstico e tratamento, o que leva a discrepâncias no tratamento do paciente. Faltam informações sobre o conhecimento e as práticas atuais dos otorrinolaringologistas brasileiros sobre o refluxo laringofaríngeo. Objetivo: Investigar as tendências no manejo da doença do refluxo laringofaríngeo entre os otorrinolaringologistas brasileiros. Método: O questionário foi enviado por e-mail aos membros da Associação Brasileira de Otorrinolaringologia-Cirurgia de Cabeça e Pescoço. Esta pesquisa foi inicialmente conduzida pelo LPR Study Group of Young Otolaryngologists da International Federation of Otolaryngological Societies. Resultados: De acordo com os respondentes da pesquisa, a prevalência de refluxo laringofaríngeo foi estimada em 26,8% dos pacientes consultados e os sintomas mais comuns foram sensação de globus, pigarro, tosse e refluxo de ácido estomacal. Obstrução nasal, disfunção da trompa de Eustáquio, otite média aguda e crônica, nódulos nas pregas vocais e hemorragia foram considerados como não associados ao refluxo laringofaríngeo pela maioria dos respondentes. Cerca de 2/3 dos otorrinolaringologistas brasileiros basearam o diagnóstico de refluxo laringofaríngeo na avaliação dos sintomas e achados e na resposta positiva a testes terapêuticos empíricos. Inibidores de bomba de prótons uma ou duas vezes ao dia foi o esquema terapêutico mais usado. Somente 21,4% dos otorrinolaringologistas brasileiros já ouviram falar sobre refluxo laringofaríngeo não ácido e misto e o conhecimento sobre a utilidade do monitoramento de pH por impedância intraluminal multicanal foi mínimo; 30,5% dos respondentes não se consideraram tão bem informados sobre o refluxo laringofaríngeo. Conclusão: Embora os sintomas relacionados ao refluxo laringofaríngeo e as principais abordagens diagnósticas e terapêuticas referidas pelos otorrinolaringologistas brasileiros sejam consistentes com a literatura, a pesquisa identificou algumas limitações, como o conhecimento insuficiente do papel do refluxo laringofaríngeo em diversas condições otorrinolaringológicas e da possibilidade de refluxo não ácido ou misto em casos refratários. Estudos futuros são necessários para estabelecer recomendações internacionais para o manejo de doença do refluxo laringofaríngeo.

Abstract Introduction: Studies assessing the management of laryngopharyngeal reflux by otolaryngologists have reported an important heterogeneity regarding the definition, diagnosis, and treatment, which leads to discrepancies in the management of the patient. Information about the current knowledge and practices of Brazilian otolaryngologists in laryngopharyngeal reflux is lacking. Objective: To investigate the trends in management of laryngopharyngeal reflux disease among Brazilian otolaryngologists. Methods: A survey was sent by email to the members of the Brazilian Association of Otolaryngology-Head Neck Surgery. This survey has initially been conducted by the laryngopharyngeal reflux study group of young otolaryngologists of the International Federation of Otolaryngological Societies. Results: According to the survey responders, the prevalence of laryngopharyngeal reflux was estimated to be 26.8% of patients consulting in otolaryngology and the most common symptoms were globus sensation, throat clearing, cough and stomach acid reflux. Nasal obstruction, Eustachian tube dysfunction, acute and chronic otitis media, vocal fold nodules and hemorrhage were considered not associated with laryngopharyngeal reflux by the majority of responders. About 2/3 of Brazilian otolaryngologists based the diagnosis of laryngopharyngeal reflux on the assessment of both symptoms and findings and a positive response to empiric therapeutic trials. Proton pump inhibitor utilized once or twice daily, was the most commonly used therapeutic scheme. Only 21.4% of Brazilian otolaryngologists have heard about nonacid and mixed laryngopharyngeal reflux and the awareness about the usefulness of multichannel intraluminal impedance pH monitoring (MII-pH) was minimal; 30.5% of responders did not consider themselves as well-informed about laryngopharyngeal reflux. Conclusion: Although the laryngopharyngeal reflux-related symptoms, main diagnostic and treatment approaches referred by Brazilian otolaryngologists are consistent with the literature, the survey identified some limitations, such as the insufficient awareness of the role of laryngopharyngeal reflux in many otolaryngological conditions and of the possibility of non-acid or mixed reflux in refractory cases. Future studies are needed to establish international recommendations for the management of laryngopharyngeal reflux disease.

The cytotoxicity of a hexanic fraction produced from the ethanolic crude extract, obtained from Jatropha ribifolia (Pohl) Baill, Euphorbiaceae, roots was evaluated against ten human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460,786-O, UACC-62, K-562, U251) compared with doxorrubicine as positive control. Compounds jatrophone and cyperenoic acid were isolated from the hexanic extract and characterized by spectroscopic techniques (NMR of ¹H, 13C and IR). The in vitro antiproliferative activity of jatrophone showed selectivity in a concentration dependent way with Total Inhibition growth of: glioma 0.57 µg mL-1 (U251), breast cancer 9.2 µg mL-1 (MCF-7), adriamycin-resistant ovarian cancer 0.96 µg mL-1 (NCI-ADR/RES), kidney 4.2 µg mL-1 (786-0), prostate cancer 8.4 µg mL-1 (PC-3), colon cancer 16.1 µg mL-1 (HT29) and leukemia 0.21 µg mL-1 (K-562).

A practical and didactic sequence of experiments was proposed to illustrate the stereochemistry concept, optically active compounds, resolution of racemates, and use of the NMR technique, including 2D-COSY for identification of organic compounds, on a laboratory course for undergraduate students. The sequence was: extractions of racemic ibuprofen and chiral naproxen from commercial tablets; syntheses of diastereoisomeric amides reacting chiral (S)-(-)-α-methylbenzylamine with (±)-ibuprofen; separation and determination of absolute configuration of amides by ¹H NMR spectroscopy and GC analysis, and hydrolysis of amides to obtain (+)- and (-)-ibuprofen.

Ipomoea imperati (Vahl) Griseb., Convolvulaceae, is used in traditional medicine for the treatment of inflammation, swelling and wounds, as well as to treat pains and stomach problems. This work evaluates the anti-oxidative activity by ESR (Electron Spin Resonance spectroscopy) and the preventive and curative actions of I. imperati in gastric ulcer animal model. Ipomoea imperati (200 mg/kg, p.o.) prevented the formation of gastric lesions in 78% (p<0.05) when compared with the negative control tween 80. Lanzoprazole, prevented in 85% the gastric lesions formation induced by ethanol (p<0.05). Therefore, the oral administration of I. imperati one hour before the ulcerogenic agent prevented the ulcer formation, conserving the citoprotection characteristics of the gastric mucosa and assuring the integrity of gastric glands and gastric fossets. The healing activity of I. imperati (200 mg/kg, p.o.) evaluated in chronic ulcer experiments induced by the acetic acid, was 72% (p<0.05). The positive control, ranitidine, healed 78% of the gastric lesions (p<0.05). The histological analysis confirmed the recovery of the mucosal layer and the muscle mucosal layer harmed by the acetic acid. Experiments in vitro with DPPH (2.2-diphenyl-1-picrylhydrazyl) of anti-oxidative activity demonstrated that I. imperati presents an IC50 of 0.73±0.01 mg/mL.

A espécie vegetal Ipomoea imperati (Vahl) Griseb., Convolvulaceae, é usada popularmente para tratar inflamação, inchaço e feridas, bem como para tratar dor após o parto e dor estomacal. A administração do extrato etanólico e das frações lipídica e aquosa de I. imperati(300, 100 e 200 mg/kg) inibiu significativamente as contrações abdominais em camundongo induzidas por ácido acético, aumentou o tempo de sono evocado por pentobarbital sódico e mostrou significativa atividade inibitória sobre o edema de pata de camundongo induzido por formalina. As mesmas doses de I. imperati(300, 100 e 200 mg/kg) também elevou a latência de todos os tempos observados no teste da placa quente. O pré-tratamento de animais com naloxona (5 mg/kg, i.p) sugere a participação do sistema opioide no efeito anti-nociceptivo de Ipomoea imperati.

Ipomoea imperati (Vahl) Griseb., Convolvulaceae, is used in folk medicine for the treatment of inflammation, swelling and wounds, as well as to treat pains after childbirth and for stomach problems. Administration of ethanol extract, lipid and aqueous fraction of I. imperati(300, 100 and 200 mg/kg) significantly inhibited the abdominal constriction in mice induced by acetic acid; increased the sleeping time evoked by pentobarbital sodium and showed a significant activity by inhibiting formalin-induced paw edema in mice. The same dose of I. imperatialso raised the pain of mice in the hot-plate test and increased the latency at all observation times. The pre-treatment of the animals with naloxone (5 mg/kg, i.p.) suggested the participation of the opioid system in the antinociceptive effect of Ipomoea imperati.

Um novo ent-dinorlabdano (-)-13(R)-14,15-dinorlabd-8(17)-eno-3,13-diol foi isolado a partir do óleo de copaíba comercial juntamente com dois outros dinorditerpenos conhecidos. A configuração absoluta destes dinorditerpenos foi determinada pela primeira vez através de síntese partindo do ácido (-)-3-hidróxi-copalico isolado do mesmo óleo.

A novel ent-dinorlabdane (-)-13(R)-14,15-dinorlabd-8(17)-ene-3,13-diol was isolated from commercial copaiba oil along with two known dinorlabdanes. The absolute configuration of these dinorditerpenes was established for the first time through synthesis starting from known (-)-3-hydroxycopalic acid, which was also isolated from the same oleoresin.

As configurações absolutas de dois diterpenos butenolidos naturais foram confirmadas através da síntese do ent-16-hidroxicleroda-4(18),13-dien-15,16-olida (2) e ent-cleroda-4(18),13-dien-15,16-olida (3), enantiômeros de produtos naturais, a partir do ácido (+)-hardwickiico (1).

The absolute configurations of two natural diterpene butenolides were confirmed through the synthesis of ent-16-hydroxycleroda-4(18),13-dien-15,16-olide (2) and ent-cleroda-4(18),13-dien-15,16-olide (3), enantiomers of the natural products, starting from (+)-hardwickiic acid (1).

Neste trabalho descrevemos as reações de transformações químicas do anel C do ácido abiético (1a) com o objetivo de gerar novos síntons quirais. A partir do intermediário ceto-aldeído 9, obtido através da reação de ozonólise do abietato de metila (1b), foram sintetizados derivados bicíclicos tais como 14, 15 e 16 e um novo diterpeno tetracíclico 4. Foram também sintetizados, a partir 17, novos derivados contendo esqueleto abeo-abietano[6,6,5] tais como 19 e 20.

Chemical transformations of the C-ring abietic acid (1a) for the preparation of some new chiral synthons are described. From the intermediate keto-aldehyde 9, readily available from 1b through the ozonide 2, the new tetracyclic diterpene 4 was synthesized. Additionally, from 13 and 17, previously prepared from 2, the bicyclic compounds 14, 15 and 16 and the derivatives containing the abeo-abietane[6,6,5] framework 19 and 20 were also synthesized.

A synthesis of artificial sweetener dulcin starting from nitrobenzene was elaborated for undergraduate organic laboratory course. Paracetamol and phenacetin, both physiologically active analgesic compounds, were also prepared as intermediates. Besides a large scope of discussion subjects related with organic synthesis, interesting lectures about analgesics and sweeteners may also be performed in this project. The advantage of this project is the adaptability according to the conditions offered by the course, i.e., convenience and/or availability of time and reagents.

Da casca do tronco de Hymenaea courbaril var. altissima (Ducke) foi isolado um novo ent-clerodano na forma de éster metílico, após esterificação com diazometano, o (-)-(5R,8S,9S,10R)-clerod-3-en-15-oato de metila. Foram isolados também dois ent-labdanos conhecidos: o (-)-copalato de metila e (-)-eperuato de metila. Do extrato AcOEt do epicarpo foi isolado, após esterificação com diazometano, o (-)-zanzibarato de metila. As estruturas dos compostos foram elucidadas com base na análise de dados espectroscópicos.

A new ent-clerodane and two known ent-labdanes were isolated from the barks of Hymenaea courbaril var. altissima (Ducke). The new diterpene was identified, after esterification with diazomethane, as methyl (-)-(5R,8S,9S,10R)-clerod-3-en-15-oate and known diterpenes were identified as methyl (-)-copalate and methyl (-)-eperuate. From the EtOAc extract of seed pods a known methyl (-)-zanzibarate was isolated. The structures of isolated compounds were elucidated based on spectroscopic studies.

A ozonólise do éster metílico do anidrido maleopimárico na presença de tetracianoetileno produziu um epóxido e um ozonídeo, e a ozonólise do fumaropimarato de trimetila, seguida por tratamento com Me2S, forneceu um epóxido, um dieno, um ceto-ácido e um produto de oxidação alílica. Alguns dos compostos obtidos apresentaram atividade antibacteriana contra Staphylococcus aureus, Bacilllus subtilis e Micrococcus luteus.

Ozonolysis of maleopimaric anhydride methyl ester in the presence of tetracyanoethylene led to an epoxide and an ozonide. Ozonolysis of the trimethyl fumaropimarate, followed by treatment with Me2S, led to an epoxide, a diene, a keto-acid and an allylic oxidation product. Some of the compounds obtained were active against Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus.