Luiz Carlos da Cunha

Antitumoral and antiangiogenic activity of Synadenium umbellatum Pax

AIM OF THE STUDY Synadenium umbellatum Pax (SU), a plant used in the Midwestern region of Brazil, was tested for its antitumor and antiangiogenic activities in vitro, using K-562 and Ehrlich ascites tumor (EAT) cells, and in vivo, using the EAT-bearing model. MATERIALS AND METHODS The viability of tumor cells was evaluated by MTT and trypan blue exclusion assays, after incubation with the ethanolic extract of SU (EESU) (0.15-20mg/mL) or equivalent concentrations of its partitioned fractions (chloroformic, hexanic, and methanolic). In vivo studies were performed in EAT-bearing mice treated intraperitoneally with 5, 10, and 25mg/kg of the EESU or equivalent doses of the fractions for 10 days. The methotrexate (1.5mg/kg), for 10 days, was used as control. RESULTS SU and fractions, except the methanolic, decreased the viability of the cells in a concentration-dependent manner. In vivo results showed a significant dose-dependent antitumoral efficacy of SU against EAT growth. The best results in prolonging life span were produced by 25mg/kg of EESU. In these animals, the levels of vascular endothelial growth factor were markedly decreased after the treatment. CONCLUSIONS The data presented herein could open interesting perspectives for further research of SU as a candidate anticancer agent.

Synadenium umbellatum: citotoxicidade e danos ao DNA de células da medula óssea de camundongos

No presente estudo investigamos o potencial citotoxico e mutagenico, in vitro e in vivo, respectivamente, do extrato etanolico de Synadenium umbellatum (EESU) sobre celulas da medula ossea de camundongos. A citotoxicidade in vitro foi avaliada por meio da exposicao de celulas da medula ossea de animais normais a diferentes concentracoes (40-0,312 mg/mL) do EESU, por 12, 24 ou 48 h, utilizando os testes de reducao do MTT e o de exclusao do azul de tripano. O ensaio de micronucleo foi realizado para investigar potenciais efeitos mutagenicos do EESU (10, 25 ou 50 mg/kg/dia) sobre a medula ossea de camundongos. Os animais foram expostos a uma unica dose, por via oral, e 24 h apos a exposicao, sacrificados para realizacao do estudo (n=5/grupo). Os resultados obtidos demonstraram que o EESU possui potencial efeito citotoxico e mutagenico, de forma dose-dependente, sobre as celulas da medula ossea de camundongos, in vitro e in vivo, respectivamente. Maiores estudos sao necessarios para expandir o conhecimento acerca do potencial toxicologico/farmacologico do EESU.

Antinociceptive and antiinflammatory activities of grandisin extracted from Virola surinamensis

The antinociceptive and antiinflammatory properties of the neolignan, grandisin, isolated from Virola surinamensis (Myristicaceae) were investigated. Grandisin (GRA) is present in several plant species from Brazil used in popular medicine for the treatment of disorders such as colic, inflammation, rheumatism, dyspepsia and liver dysfunction. These studies demonstrated that GRA is able to inhibit the acetic acid‐induced writhing in mice dose‐dependently, and that this effect is not caused by motor incoordination or sedation due to depressant effect in the CNS. Through the formalin test the antiinflammatory activity of GRA was characterized, this substance reduced the time licking the paw by 60.5% (only in the second phase (inflammatory pain). This activity was also verified by the oil‐induced ear oedema test, where GRA 10.0 mg/kg reduced the oedema by 36.4%. The results suggest that GRA has antinociceptive effects arising from antiinflammatory activity. Copyright

Avaliação da toxicidade aguda e subaguda, em ratos, do extrato etanólico das folhas e do látex de Synadenium umbellatum Pax.

The use of medicinal plants has been being very significant in the last years, being the use encouraged by WHO. Synadenium umbellatum Pax, Euphorbiacea (popularly known as cola-note, cancerola, miraculous) has the latex used empirically as anti-cancerous and anti-inflammatory. For there being toxic species in this family and aiming at the safety in the use of vegetable extracts, such study evaluated the pre-clinical toxicity of the latex and of the ethanolic extract of the leaves (EEL) of S. umbellatum, administrated by oral route, in Wistar female rats. The study followed OECDs Guidelines for test of acute toxicity (Guideline 423) and for subacute toxicity (Guideline 407). In the acute toxicity of latex and EEL, behavioral and physiological alterations were not observed neither animals death in the dose level of 2,000 mg/kg. However, the latex caused congestion and leukocytes infiltration of the kidneys, liver and lungs, effects not observed with EEL. In the subacute toxicity, dose levels of 50, 100 and 200 mg/kg of EEL did not produced significant dose-dependent alterations in the lab results and no physiologic, macroscopic and hystopathological alterations. EEL of S. umbellatum is practically poisonless in acute exposure; already the latex can cause hystological damages. The chronic use of S. umbellatum needs more specific studies.

Chemoselective and Regiospecific Formylation of 1-Phenyl-1H-pyrazoles Through the Duff Reaction

Abstract The synthesis of formylated 1-phenyl-1H-pyrazole derivatives under the Duff reaction conditions is reported. Our results indicate that 1-phenyl-1H-pyrazole systems containing electron-withdrawing and electron-donating substituents at the phenyl moiety react under the Duff reaction conditions to furnish formylated derivatives in good yields. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT

Healing activity of laser InGaAlP (660nm) in rats

PURPOSE To evaluate the effect the healing activity of diode laser Indium Gallium Aluminum Phosphorus (InGaAlP) ë660nm on healing of surgical wounds in rats. METHODS Fifty-four female Wistar rats were used, divided into three groups (n=18) and subdivided into three subgroups (n=6) to be studied in 5, 10 and 15(th) days after surgical procedures. The wound was induced in the dorsal-cervical using punch. The lesions were irradiated on alternate days with InGaAlP laser, the energy densities of 3J/cm(2) (L3) or 6J/cm(2) (L6). The control group received no irradiation. At 5, 10 and 15(th) days after surgery the animals were euthanized and the repair area was removed and histological sections were stained with hematoxylin-eosin and picrossírius. We evaluated macroscopic and histological lesions in the times cited, as well as morphometric analysis of angiogenesis and collagen content. RESULTS The wound healing activity InGaAlP laser was evidenced by increased angiogenesis group L3 and L6 in relation to control group (CG) at the 5(th) day (p=0.0001) and decreased polymorphonuclear infiltrate and hemorrhage (p=0.045 and p=0.07 respectively) in the groups L3 and L6 in relation to control group (GC). On the 10 and 15(th) days was also observed in groups treated with laser L3 and L6 stimulation was pronounced fibroplasia (p=0.0003 and p=0.034 respectively) when compared with the control group (CG). CONCLUSION The InGaAlP laser acted positively on the healing of skin wounds in rats.

Antinociceptive and Anti-Inflammatory Activities of the Ethanolic Extract from Synadenium umbellatum Pax. (Euphorbiaceae) Leaves and Its Fractions

Synadenium umbellatum Pax., popularly known in Brazil as “cola-nota,” “avelós,” “cancerola,” and “milagrosa”, is a plant species used in folk medicine for the treatment of inflammation, pain, and several diseases. This study aimed to investigate the antinociceptive and anti-inflammatory activities of the ethanolic extract from Synadenium umbellatum Pax. leaves (EES) and its hexane (HF), chloroform (CF), and methanol/water (MF) fractions using the acetic acid-induced abdominal writhing test, formalin-induced paw licking test, tail flick test, croton oil-induced ear edema test, and carrageenan-induced peritonitis test. EES and MF reduced the number of acetic acid-induced abdominal writhes, while CF and HF did not. EES effect on acetic acid-induced abdominal writhing was reversed with a pretreatment with naloxone. EES reduced licking time in both phases of the formalin-induced paw licking test, but did not prolong the latency in the tail flick test. These results show that EES presented antinociceptive activity, probably involving the opioid system, anti-inflammatory activity in the croton oil-induced ear edema test, and leukocyte migration into the intraperitoneal cavity. MF also presented anti-inflammatory activity in the croton oil-induced ear edema test. In conclusion, EES and MF have antinociceptive activity involving the opioid system and anti-inflammatory activity.

Survey on the use of psychotropic drugs by twelve military police units in the municipalities of Goiânia and Aparecida de Goiânia, state of Goiás, Brazil

OBJECTIVE To determine the prevalence of psychotropic drug use among military police officers in the state of Goiás, Brazil. METHOD Study carried out at twelve military police units located in the municipalities of Goiânia and Aparecida de Goiânia between March to October 2008. Volunteers (n=221) were interviewed about drug use using a questionnaire especially designed by the Centro Brasileiro de Informações sobre Drogas Psicotrópicas (CEBRID). Descriptive statistics was used to determine the prevalence of licit and illicit drug use in the study sample. RESULTS The frequency of use was divided into: 1) lifetime use: tobacco-39.9%, alcohol-87.8%, cannabis-8.1%, cocaine-1.8%, stimulants-7.2%, solvents-10.0%, sedatives, anxiolytics, antidepressants-6.8%, LSD-0.5%, Bentyl®-0.5%, anabolic steroids-5.4%; 2) use in the previous year: tobacco-15.4%, alcohol-72.9%, stimulants-6.3%, solvents-0.5%, sedatives, anxiolytics, antidepressants-3.7%; 3) use in the previous 30 days: tobacco-14.5%, alcohol-57.5%, stimulants-5.0%, solvents-0.5, sedatives, anxiolytics, antidepressants-3.7%. CONCLUSION The high prevalence rate of psychotropic drug use found amoung military police officers in two cities of the state of Goiás in Brazil can be considered an important factor with potential influence on job activities.

Anti-inflammatory and anti-nociceptive effects of Pterodon emarginatus stem bark alcohol extract.

The tail flick, the acetic acid writhing, the croton oil-induced mouse ear edema, and carrageenan-induced peritonitis tests were used to study the anti-inflammatory effects of the alcohol extract from Pterodon emarginatus Vogel. (Leguminosae/Fabaceae) stem bark. The alcohol extract caused inhibition of acetic acid-induced abdominal writhing, reducing the number of leukocytes (x 107) per mL of peritoneal wash and ear edema formation. The results suggest that Pterodon emarginatus stem bark contains compounds with analgesic and anti-inflammatory actions.

Avaliação da toxicidade aguda e da atividade cicatrizante dos extratos etanólicos das folhas e raízes da Memora nodosa (Silva Manso) Miers (Bignoniaceae)

Memora nodosa (Silva Manso) Miers e uma especie da flora do Cerrado cujas folhas e caules sao utilizados popularmente no tratamento de feridas e ulceras externas, enquanto as raizes sao empregadas para dores abdominais e no tratamento da sarna. O objetivo desse trabalho foi avaliar a toxicidade aguda dos extratos etanolicos das folhas e raizes nas doses de 2000 e 5000 mg kg-1 em ratos e camundongos e a atividade cicatrizante das solucoes aquosas contendo 2% desses extratos em feridas cutâneas em ratos. A contracao das bordas das feridas foi avaliada por analises histologicas e morfometricas apos 4, 7 e 14 dias de tratamento e por reacao imunohistoquimica apos 7 dias de tratamento. Os extratos etanolicos das folhas e raizes nao apresentaram toxicidade na dose de 2000 mg kg-1 para ratos e camundongos e na dose de 5000 mg kg-1 para ratos. Nos camundongos, a dose de 5000 mg kg-1 dos extratos das folhas e raizes provocou alteracoes histologicas no figado. Nao foram observadas diferencas significativas na contracao das feridas entre os grupos tratados com os extratos das folhas e das raizes e o controle apos 4 e 7 dias de tratamento. Apos 14 dias de tratamento, 50% dos animais tratados com o extrato das raizes apresentaram reepitelizacao total das feridas e reconstrucao parcial dos anexos. A alantoina, isolada do extrato etanolico da raiz, pode ser considerada como um dos metabolitos secundarios responsaveis pela aceleracao da reepitelizacao.