A medicalização e a recente farmaceuticalização / Medicalization and the recent pharmaceuticalization

Este artigo buscadiscorrer, por meio de uma revisão narrativa dos descritivos de seus temas centrais, o escopo da já bastante pesquisada medicalização e brevemente contrapô-lo ao da farmaceuticalização, conceito mais recente com o qual guarda alguma justaposição, porém não absoluta. A farmaceuticalização se define como a escolha por um tratamento farmacológico, em detrimento de outros, o que incide diretamente sobre o número de prescrições e vendas farmacológicas e psicofarmacológicas no campo da saúde mental, sobre o qual nos deteremos. A venda psicofarmacológica neste setor vem expressando um aumento exponencial, conforme pesquisas. A farmaceuticalização passou a ser estudada sobretudo por pesquisadores do Ocidente (Estados Unidos e Europa), porém ainda com insuficiente publicação na América Latina e no Brasil

This article seeks to discuss, through a narrative review of its central descriptive-terms, the scope of the already well researched medicalisation, and briefly contrast it with that of pharmaceuticalization, a more recent concept with which it has some juxtaposition, although not absolute. Pharmaceuticalization is defined as the choice of a pharmacological treatment instead of other non-pharmacological ones, what affects the number of pharmacological and psychopharmacological prescriptions and sales in the field of mental health, on which we will focus. Psychopharmacological sales in this sector have been expressing an exponential increase, according to research. Pharmaceuticalization has been studied mainly by western researchers (mostly at the United States and Europe), but with little publication in Latin America and Brazil.

A SUBJETIVIDADE E O PSICOFÁRMACO / Subjectivity and the psychotropic drug

Este estudo teórico pretende, enquanto breve narrativa temática acerca de subjetividade e psicofármaco, abordar de forma crítica a escolha psicofarmacológica. Este tema, que inquieta a muitos há algum tempo, encontra-se em estado agudo: os números atuais são ainda mais alarmantes que antes e seguem crescendo. O fenômeno atualmente chamado de farmaceuticalização (ou farmacologização) ­ ou seja, a escolha por um fármaco em detrimento de outras opções não farmacológicas ­ incide diretamente sobre o consumo psicofarmacológico. Abordaremos o tema com ênfase sobre a subjetividade que busca o medicamento, até mesmo em uma vertente supostamente preventiva, para se evitar a dor psíquica e, em algumas vezes, o trabalho psíquico. Há uma subjetividade não-medicável, que parece se encontrar negada neste estado de coisas.

This theoretical study intends to, as a brief thematic narrative on subjectivity in relation to psychotropic drugs, discuss critically this state of affairs that is the use of psychopharmacological drugs. This subject, long and vastly researched, is in an acute state: the current figures are even more alarming than before. The phenomenon currently called pharmaceuticalization - that is, the choice of a drug instead of a non-pharmacological option - has a direct impact on psychopharmacological consumption. We will approach the theme with emphasis on the subjectivity that seeks medication, even in a supposedly preventive way, to avoid psychic pain and, sometimes, psychic work. There is a subjectivity not passive to medication that seems to be denied in this state of affairs.

Antitumor activity and toxicity of volatile oil from the leaves of Annona leptopetala

Abstract Annona leptopetala (R.E.Fr.) H. Rainer, Annonaceae, is used in folk medicine like antitumor and anti-inflammatory. The aim of this study was to determine chemical composition, toxicity and antitumor activity of A. leptopetala leaves volatile oil. Fresh leaves were hydrodistilled and then the volatile oil chemical composition was assessed by gas chromatography and mass spectrometry. Toxicity was assessed using haemolysis, micronucleus and acute toxicity protocols. Antitumor effects were determined in vitro and in vivo, using sulforhodamine B assay and sarcoma 180 murine tumor model, respectively. Spathulenol was the major component identified (12.56%). The volatile oil showed in vitro antitumor activity mainly in leukemia cell line (K-562), with Total growth inhibit (TGI) (concentration producing TGI) of 0.64 µg/ml. In other hand, the volatile oil <250 µg/ml did not inhibit HaCat non-tumor cell line growth. The concentration that produced 50% haemolysis was 372.8 µg/ml. The 50% lethal dose in mice was approximately 447.2 mg/kg intraperitoneally. Sarcoma 180 tumor growth inhibition rates were 59.29% and 58.77% at 100 and 150 mg/kg intraperitoneally, respectively. The volatile oil presented moderate gastrointestinal toxicity and no genotoxicity was observed at 350 mg/kg. Thus, the volatile oil shows antitumor activity with moderate toxicity.

Schinus terebinthifolius: phenolic constituents and in vitro antioxidant, antiproliferative and in vivo anti-inflammatory activities

ABSTRACT Schinus terebinthifolius Raddi, Anacardiaceae, native to Brazil, is referred to as "pimento-rosa" and is used to treat inflammatory disease in folk medicine. Studies have reported important pharmacological properties, but these effects have still not been fully exploited. This study reports that the crude extract and isolated compounds of S. terebinthifolius (leaves) have in vitro antioxidant, antiproliferative, and in vivo anti-inflammatory activities. The samples were evaluated for antioxidant activity using 2, 2-diphenyl-1-picrylhydrazyl, β-carotene/linoleic acid and 2,2′-azino-bis-(3-ethylbenzothiazoline)-6-sulphonic acid reagents. The anti-inflammatory effects were assayed against a carrageenan-induced paw oedema model in mice to test doses of 10, 100 and 300 mg/kg at different time points in addition to myeloperoxidase activity analysis. The antiproliferative activity was evaluated using ten human tumour cell lines. Two derivatives of gallic acid and four flavonoids were isolated and exhibited considerable antioxidant activity. The extract and its compounds showed selectivity towards ovarian cancer cells, with growth inhibitory activity values ranging from 1.9 to 6.5 µg/ml. Sample extracts and methyl gallate significantly inhibited carrageenan-induced oedema in the mice paw oedema experimental model. The calculated topological polar surface area for methyl gallate (86.98 Å2) showed good intestinal absorption. The effects reported herein are be related to the presence of flavonoids and the galloyl phenolic derivative content.

Lupeol and its esters: NMR, powder XRD data and in vitro evaluation of cancer cell growth

ABSTRACT The triterpene lupeol (1) and some of its esters are secondary metabolites produced by species of Celastraceae family, which have being associated with cytotoxic activity. We report herein the isolation of 1, the semi-synthesis of eight lupeol esters and the evaluation of their in vitro activity against nine strains of cancer cells. The reaction of carboxylic acids with 1 and DIC/DMAP was used to obtain lupeol stearate (2), lupeol palmitate (3) lupeol miristate (4), and the new esters lupeol laurate (5), lupeol caprate (6), lupeol caprilate (7), lupeol caproate (8) and lupeol 3',4'-dimethoxybenzoate (9), with high yields. Compounds 1-9 were identified using FT-IR, 1H, 13C-NMR, CHN analysis and XRD data and were tested in vitro for proliferation of human cancer cell activity. In these assays, lupeol was inactive (GI50> 250µg/mL) while lupeol esters 2 -4 and 7 - 9 showed a cytostatic effect. The XRD method was a suitable tool to determine the structure of lupeol and its esters in solid state. Compound 3 showed a selective growth inhibition effect on erythromyeloblastoid leukemia (K-562) cells in a concentration-dependent way. Lupeol esters 4 and 9 showed a selective cytostatic effect with low GI50 values representing promising prototypes for the development of new anticancer drugs.

Antiproliferative activity, antioxidant capacity and chemical composition of extracts from the leaves and stem of Chresta sphaerocephala

AbstractIn this study, antiproliferative and antioxidant activities of crude extracts (hexane, ethyl acetate and methanol) from leaves and stem of Chresta sphaerocephala DC., Asteraceae, were investigated. Antiproliferative activity was tested in vitro against ten human cancer cells and against VERO (no cancer cell). Antioxidant activities were determined using DPPH and ORAC-FL assays and the total phenolic content was estimated by Folin–Ciocalteu method. Hexane and ethyl acetate extracts (leaves and stem) exhibited antiproliferative activity against cancer cell lines with total growth inhibition (TGI) between 50.40 and 250 µg/ml. For VERO cell, TGI values were >250 µg/ml for all extracts, except to hexane extract of the stem (TGI 80.92 µg/ml). In an initial evaluation, ethyl acetate and methanol extracts (leaves and stem) have shown levels of phenolic compounds between 6.94 and 30.96 mg GAE/kg in Folin–Ciocalteu assay, DPPH free-radical scavenging activity with SC50 in the range of 75.22 and 400 µg/ml and antioxidant capacity between 290.08 and 1088 µmol TE/g of extract in ORAC-FL assay. HPLC-DAD and ESI-MS analysis allowed the identification of flavonoids in the methanol extract from the leaves of C. sphaerocephala. Three steroids and nine triterpenoids were identified in the bioactive hexane extracts using HRGC.

Avaliação das atividades antiproliferativa e antioxidante em frutos de Campomanesia pubescens / Evaluation of antioxidant and antiproliferative activities in fruits of Campomanesia pubescens

A investigação química dos extratos bioativos dos frutos de Campomanesia pubescens (Myrtaceae)resultou no isolamento de duas chalconas. Os compostos isolados foram identificados pelas análises espectroscópicas (1H, 13C e 2D RMN) e, por comparação com os dados descritos na literatura. A capacidade antioxidante dos extratos e frações foi determinada utilizando-se os ensaios de capacidade de absorção de oxigênio radical (ORAC-FL) e de DPPH; e os teores de fenólicos solúveis foram medidos utilizando-seo reagente de Folin-Ciocalteau. Os efeitos antiproliferativos dos extratos e de isolados de chalconas 1 e2 foram determinados in vitro contra as seguintes células cancerosas humanas U251 (glioma), UACC-62 (melanoma), MCF-7 (mama), NC1-ADR/RES (ovário resistente), 786,0 (rim), NCI-H460 (pulmão),PC-3 (próstata), OVCAR-3 (ovário), HT-29 (cólon) e K562 (leucemia), e contra linhagem celular não cancerígena VERO. O extrato hexânico e os compostos isolados de chalconas 1 e 2 demonstraram efeito antiproliferativo potente contra linhagens de células cancerosas com valores de inibição de crescimento total (TGI) menores dos aqueles observados na linhagem celular controle. A atividade mais elevada das chalconas 1 e 2 foi detectada nas células MCF-7, PC-3 e HT-29.

Chemical investigation on the bioactive extracts from fruits of Campomanesia pubescens (Myrtaceae)resulted in the isolation of two chalcones. The isolated compounds were identified by means of spectroscopicanalysis (1H, 13C and 2D NMR), and by comparing with the data reported in the specific literature.Antioxidant capacity of extracts and fractions was determined using the oxygen radical absorbancecapacity (ORAC-FL) and DPPH assays; and the total soluble phenolic contents were measured by usingFolin-Ciocalteau reagent. The anti-proliferative effects of the extracts and of the chalcone isolates 1 and2 were determined in vitro against human cancer cells lineages U251 (glioma), UACC-62 (melanoma),MCF-7 (breast), NC1-ADR/RES (ovarian-resistant), 786.0 (kidney), NCI-H460 (lung), PC-3 (prostate),OVCAR-3 (ovarian), HT-29 (colon) and K562 (leukemia), and against non-cancerous cell line VERO.Hexanic extract and chalcone isolated compounds 1 and 2 showed potent antiproliferative effect againstcancer cell lineages with lower total growth inhibition (TGI) values than those found in control cell line.The highest activity of the chalcones 1 and 2 was observed against the MCF-7, PC-3 and HT-29 cell lines.

Atividade antiulcerogênica e mecanismo de ação de alimento fermentado à base de trigo e soja utilizado como alimento funcional / Antiulcer activity and mechanism of action of fermented food based on wheat and soy beans used as functional food

Objetivo: estudar o mecanismo de ação e avaliar a proteção da mucosa do estômago de ratos Wistar pela atividade de um alimento com propriedades funcionais à base de trigo e soja fermentado, a fim de reduzir o processo ulcerativo induzido por etanol. Métodos: nesse estudo foram utilizados os modelos de indução de úlcera por etanol absoluto em ratos Wistar tratadospreviamente com Indometacina (5mg/kg de peso), N-etilmaleimida (10mg/kg de peso) e L-NAME (5mg/kg de peso). No mesmo modelo de indução de úlcera foi realizada a administração de solução salina (10mL/kg de peso) como controle negativo, Carbenoxolona (200mg/kg) como controle positivo e o produto fermentado na dose de 2000mg/kg de peso animal. Resultados: na verificação da atividade antiulcerogênica do fermentado em pó, o Índice de Lesões Ulcerativas (ILU) foi inibido em 29,9%, enquanto a Carbenoxolona utilizada como controle positivo foi capaz de inibir o ILU em 83,7%. No modelo de indução de úlcera por etanol absoluto, com a administração prévia de L-NAME, N-etilmaleimida e da Indometacina, constatou-se que, nos dois primeiros tratamentos, o fermentado apresentou atividade antiulcerogênica de 50,9% e 28,3%, respectivamente e no tratamento com Indometacina, o produto não apresentou atividade antiulcerogênica, o que sugere que seu mecanismo de ação ocorre pela síntese ou redução da degradação de prostaglandinas que são uma das responsáveis pela citoproteção gástrica. Conclusão: com base nos dados obtidos nesse experimento com ratos para avaliação da atividade antiulcerogênica e mecanismo de ação do produto fermentado, concluiu-se que este provavelmente promove a citoproteção gástrica especialmente através dos níveis de prostaglandinas.

Objective: to study the mechanism of action and evaluate the protection of the stomach mucosa of Wistar rats due to the activity of a fermented soy and wheat-based food product with functional properties in order to reduce the ethanol-induced ulcerative process. Methods: in this study, ulcer induction models by absolute ethanol were used in Wistar rats previously treated with Indomethacin (5mg/kg of body weight), N-ethylmaleimide (10mg/kg of body weight), and L-NAME (5mg/kg of body weight). Within the same ulcer induction model, the administration of the following was performed: saline solution (10 mL/kg of body weight) as a negative control, Carbenoxolone (200mg/kg) as a positive control, and the fermented product at a dose of 2,000mg/kg of body weight. Results: when verifying the antiulcerogenic activity of the fermented powder, the Ulcerative Lesion Index (ULI) was inhibited by 29.9%, while the Carbenoxolone used as a positive control was able to inhibit the ULI by 83.7%. In the ulcer induction model by absolute ethanol, with previous administration of L-NAME, N-ethylmaleimide, and Indomethacin, it was verified that with the first two treatments the fermented powder showed 50.9% and 28.3% antiulcerogenic activity, respectively, and no antiulcerogenic activity with the Indomethacin treatment, which suggests that its mechanism of action occurs through the synthesis or degradation reduction of prostaglandins responsible, along with other factors, for the gastric cytoprotection. Conclusion: based on the data from this trial with rats to evaluate the antiulcerogenic activity and mechanism of action of the fermented product, it was concluded that it probably promotes gastric cytoprotection, mainly through prostaglandin levels.

Chemical composition and cytotoxic activity of the essential oil from the leaves of Casearia lasiophylla

The essential oil obtained by hydrodistillation from fresh leaves of Casearia lasiophylla Eichler, Salicaceae, was analyzed by gas capillary (GC/FID and GC/MS). The cytotoxicity of the leaves essential oil was tested in vitro againstU251 (glioma), UACC-62 (melanoma), MCF-7 (breast), NC1-ADR/RES (ovarian-resistant), NCI-H460 (lung), PC03 (prostate), OVCAR-3 (ovarian), HT-29 (colon) and K562 (leukemia) human cancer cells and against VERO (no cancer cell). The yield of oil was 0.02 percent. Fifty two compounds were identified, representing 87.1 percent of the total of the oil. The main components were identified as germacrene D (18.6 percent), β-caryophyllene (14.7 percent), δ-cadinene (6.2 percent), and α-cadinol (5.4 percent). The oil exhibited antiproliferative activity against all cell lines (TGI<100 µg/mL), with exception of NCI-H460 cell line (TGI 191.31 µg/mL). The highest activity was observed against UACC-62 (TGI 7.30 µg/mL), and K562 (TGI 7.56 µg/mL) cell lines. The observed activity could be related to high content of germacrene D and β-caryophyllene, compounds known as cytotoxic.

Antiproliferative activity, isolation and identification of active compound from Gaylussacia brasiliensis

Gaylussacia brasiliensis (Spreng.) Meissn., Ericaceae, is used in folk medicine for treatment of several inflammatory processes and as healing agent. The scope of this work was to evaluate the in vitro antiproliferative activity of crude dichloromethane extract (CHD) and to identify the compound(s) responsible for this activity. CHD was evaluated and showed a concentration dependent inhibition on all cells lines. Therefore CHD was submitted to several classical columns chromatography providing the most active fraction (FC), inhibiting all cells line at 25 µg/mL. FC was further fractionated affording isolated compound 2β, 3β-dihydroxy-urs-12-ene-28-oic acid , identified on basis of 2D-NMR experiments and showed concentration-dependent activity and selectivity for kidney and breast cell lines.

Atividade antiproliferativa dos extratos e da fração orgânica obtidos das folhas de Virola sebifera Aubl. (Myristicaceae) / Antiproliferative activity of extracts and fractions from Virola sebifera Aubl. leaves (Myristicaceae)

As cascas de Virola sebifera (Myristicaceae) são utilizadas por populações indígenas amazônicas em preparações alucinógenas, nas quais foram encontrados alcalóides como a dimetiltriptamina e seus derivados. Considerando a enorme importância dos alcalóides isolados de plantas na terapêutica do câncer e a presença desses compostos em espécies de Virola, o presente trabalho teve por objetivo o estudo da atividade antiproliferativa em cultura de células tumorais humanas de extratos e da fração orgânica, obtidos das folhas de Virola sebifera. O extrato bruto diclorometânico (EBD) foi considerado o mais ativo, com seletividade principalmente para a linhagem de pulmão (NCI-460) - IC50: 4,46 µg/mL e para a fração orgânica (FO) obtida por extração ácido-base - IC50; 6,91 µg/mL. A atividade observada possivelmente pode ser atribuída a alcalóides ou compostos nitrogenados que foram evidenciados pelo corante Dragendorff. Assim, a purificação da FO será necessária a fim de comprovar a presença de compostos nitrogenados, através de isolamento e determinação estrutural, bem como a participação desses compostos na atividade antiproliferativa observada.

Barks of Virola sebifera (Myristicaceae) used by Amazonian Indian communities in hallucinogenic snuff preparations have yielded dimethyltryptamine and derivatives. Considering the importance of the alkaloids isolated from plants for the development of chemotherapy, and the presence of these compounds in several Virola species, the scope of this work was to evaluate the antiproliferative activity of the extracts and the organic fraction from Virola sebifera leaves. The crude dichloromethane extract was the most active with selectivity for lung line (NCI-460) - IC50: 4.46 µg/mL, as well as the organic fraction (OF) - IC50: 6.91 µg/mL. The observed activity could probably be attributed to alkaloids or nitrogen compounds that were evidenced by the Dragendorff reagent. However, the future purification of OF will be necessary to prove the presence of alkaloids and their role in the antiproliferative activity in human cells as well as isolating and identifying these compounds.

Efeito de um hidrolisado de proteínas de soro de leite e de seus peptídeos na proteção de lesões ulcerativas da mucosa gástrica de ratos / Effects of a whey protein concentrate and it's peptides in the protection of ulcerative lesions at rat gastric mucosa

OBJETIVO: Avaliar a atividade do hidrolisado das proteínas de soro de leite bovino e uma fração de peptídeos de baixo peso molecular (peso molecular <1kDa), na proteção do epitélio da mucosa do estômago de ratos Wistar adultos contra o processo ulcerativo, induzidos por três diferentes agentes. MÉTODOS: Nesse estudo foram utilizados os modelos de indução de úlcera pelo antiinflamatório indometacina (30mg/kg de peso), por etanol absoluto (1ml/animal) e por estresse causado por imobilização e frio (4ºC/2h) em ratos Wistar adultos. RESULTADO: O hidrolisado protéico de soro de leite foi obtido por tratamento com pancreatina, ao grau de hidrólise de 20 por cento, e fracionado em membrana de fluxo tangencial com faixa de corte de 1kDa, para obtenção de uma fração contendo peptídeos de baixo peso molecular denominada peptídeos do hidrolisado protéico de soro (<1kDa). A administração aguda do hidrolisado protéico de soro, de acordo com o modelo etanol, resultou em 65,5 por cento de redução dos índices de lesões ulcerativas, sendo obtida 77,4 por cento de inibição em dose dupla. CONCLUSAO: O efeito citoprotetor dos peptídeos de baixo peso molecular foi mais elevado para o modelo de indução por antiinflamatório, em relação ao hidrolisado integral, tanto em dose única como em dupla (53,1 por cento e 71,6 por cento de redução dos índices de lesões ulcerativas, respectivamente). Não foi constatada atividade protetora em modelos de úlcera induzidos por estresse.

Efeitos da administração aguda e subcrônica da Luehea divaricata Martus et Zuccarini / Effects of acute and subchronic administration of Luehea divaricata Martus et Zuccarini

As cascas de Luehea divaricata Martus et Zuccarini (Tiliaceae) são usadas na medicina popular como antinflamatório e como anti-rumático. O objetivo deste trabalho foi determinar o efeito toxicológico subcrônico do extrato bruto hidroalcoólico (70 por cento) (CHE) em ratos, pela via oral e intraperitonial.

Regulaçäo e modulaçäo da secreçäo gástrica / Regulation and modulation of gastric secretion

O aumento da secreçäo de ácido clorídrico, assim como alteraçöes da integridade da mucosa e dos fatores de citoproteçäo gástrica podem contribuir para a patogênese multifatorial da úlcera péptica. Atualmente, o tratamento desta doença é geralmente baseado na inibiçäo da secreçäo ácida gástrica por bloqueadores do receptor H2 da histamina ou por inibiçäo da bomba protônica ou, ainda, pelo uso de antimuscarínicos. O uso de medicamentos citoprotetores ficou restrito à carbenoxolona e ao misoprostol, que possuem diversas contra-indicaçöes. Portanto, a pesquisa de agentes citoprotetores pode dar origem a drogas coadjuvantes ou mesmo a alternativas para o tratamento com anti-secretores.

Avaliaçäo farmacológica do extrato fluido de Cochlospermum regium (Mart. et Schr.) Pilger / Plarmacological evaluation of the fluid extract of Cochlospermum regium (Mart. et Schr.) Pilger

O extrato fluido de algodäozinho-do-campo - Cochlospermum regium (Mart. et Schr.) Pilger foi avaliado farmacológicamente, realizando-se testes de toxicidade aguda, determinaçäo da DL50 em camundongos e testes de atividade anti-edematogênica e anti-ulcerogênica deste extrato liofilizado.

Cardiac glycosides isolated from the Indian-snuff, Maquira sclerophylla Ducke

The hydroalcoholic extract of the powdered bark of the Indian-snuff Maquira sclerophylla Ducke was purified by column chromatography in silica-gel and the major cardenolide isolated from preparative TLC was identified by 1H-NMR, 1 2 C-NMR and IR analyses. The spectra showed that the active substance has strophanthidin as aglicone.