Coumarin derivative 7-isopentenyloxycoumarin induces in vivo antitumor activity by inhibit angiogenesis via CCL2 chemokine decrease.

Cancer is one of the most urgent problems in medicine. In recent years, cancer is the second leading cause of death globally. In search for more effective and less toxic treatment against cancer, natural products are used as prototypes in the synthesis of new anticancer drugs. The aim of this study was to investigate the in vivo toxicity and the mechanism of antitumor action of 7-isopentenyloxycoumarin (UMB-07), a coumarin derivative with antitumor activity. The toxicity was evaluated in vitro (hemolysis assay), and in vivo (micronucleus and acute toxicity assays). Ehrlich ascites carcinoma model was used to evaluate in vivo antitumor activity of UMB-07 (12.5, 25, or 50 mg/kg, intraperitoneally, i.p.), after 9 days of treatment, as well as toxicity. UMB-07 (2000 µg/mL) induced only 0.8% of hemolysis in peripheral blood erythrocytes of mice. On acute toxicity assay, LD50 (50% lethal dose) was estimated at around 1000 mg/kg (i.p.), and no micronucleated erythrocytes were recorded after UMB-07 (300 mg/kg, i.p.) treatment. UMB-07 (25 and 50 mg/kg) reduced tumor volume and total viable cancer cells. In the mechanism action investigation, no changes were observed on the cell cycle analysis; however, UMB-07 reduced peritumoral microvessels density and CCL2 chemokine levels. In addition, UMB-07 showed weak toxicity on biochemical, hematological, and histological parameters after 9 days of antitumor treatment. The current findings suggest that UMB-07 has low toxicity and exerts antitumor effect by inhibit angiogenesis via CCL2 chemokine decrease.

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.

A new acridine derivative induces cell cycle arrest and antiangiogenic effect on Ehrlich ascites carcinoma model.

BACKGROUND: Acridine derivatives, including amsacrine, have antitumor activity. However, side effects, development of resistance and their low bioavailability, have limited their use. Herein, we described the synthesis, and evaluated the toxicity and antitumor activity of a new amsacrine analogous, the N'-(2-chloro-6-methoxy-acridin-9-yl)-2-cyano-3-(4-dimethylaminophenyl)-acrilohidrazida (ACS-AZ10). METHODS: The compound was obtained in a linear pathway where the ASC-Az intermediate was obtained by coupling of 6,9-dichloro-3-methoxy-acridine and 2-ciany-acethohidrazide followed by condensation with the corresponding aldehyde. The toxicity of ACS-AZ10 was evaluated in mice using acute toxicity and micronucleus assays. Ehrlich ascites carcinoma model was used to investigate the antitumor activity and toxicity of ACS-AZ10 (7.5, 15 or 30mg/kg, i.p.), after nine days of treatment. Cell cycle and angiogenesis were also evaluated. RESULTS: The ASC-AZ10 was obtained with satisfactory yields and its structure was confirmed by spectroscopic and spectrometric techniques. On acute toxicity study, ACS-AZ10 (2000mg/kg, i.p.) induced transient depressant effects on central nervous system. The LD50 was approximately 2500mg/kg. ACS-AZ10 (15 or 30mg/kg) displayed significant antitumor activity considering the tumor weight and volume, cell viability, and total Ehrlich cell count. ACS-AZ10 (7.5mg/kg) induced an increase in sub-G1 peak, suggesting apoptosis. At 15mg/kg ACS-AZ10 induced cell cycle arrest in G2/M phase and a reduction in the percentage of cells in G0/G1 and S phases, suggesting a pre-mitotic blockade. ACS-AZ10 reduced the microvessel density, indicating an antiangiogenic effect. Weak hematological, biochemical and histopathological toxicity were observed. The compound doesn't show genotoxicity in micronucleus assay. CONCLUSIONS: ACS-AZ10 has potent antitumor activity in vivo along with low toxicity.

Essential oil from fruit of Xylopia langsdorffiana: antitumour activity and toxicity.

CONTEXT: The genus Xylopia L. (Annonaceae) includes aromatic plants that have both nutritional and medicinal uses. Essential oils of Xylopia species have antitumour effects. However, the efficacy of the essential oil from the fruit of Xylopia langsdorffiana St. Hil & Tul. (EOX) has not been examined. OBJECTIVE: EOX was evaluated to determine its chemical composition, antitumour activity and toxicity. MATERIALS AND METHODS: EOX was obtained from fresh fruits of X. langsdorffiana subjected to hydrodistillation, and gas chromatography-mass spectrometry was used to characterize the chemical composition of EOX. The toxicity of EOX was evaluated using haemolysis, acute toxicity and micronucleus assays. The in vitro antitumour activity of EOX was investigated using the sulforhodamine B assay. The sarcoma 180 murine tumour model was used to evaluate the in vivo antitumour activity and toxicity of EOX (50 and 100 mg/kg) after 7 d of treatment. RESULTS: The major components of EOX were α-pinene (34.57%) and limonene (31.75%). The HC50 (concentration producing 50% haemolysis) was 293.6 µg/ml. EOX showed greater selectivity for the leukaemia cell line K562, with total growth inhibition (TGI) (concentration producing TGI) of 1.8 µg/ml, and for multidrug-resistant ovarian tumour cell line NCI/ADR-RES (TGI of 45.4 µg/ml). The LD50 was approximately 351.09 mg/kg. At doses of 50 and 100 mg/kg, EOX inhibited the in vivo growth of sarcoma 180 by 38.67 and 54.32%, respectively. EOX displayed minor hepatic alterations characteristic of acute hepatitis and induced no genotoxicity. CONCLUSION: EOX showed in vitro and in vivo antitumour activity and low toxicity, which warrants further pharmacological studies.

Perfil antropométrico dos idosos residentes em Campina Grande-PB / Anthropometric profile of the elderly residents in Campina Grande-PB, Brazil

O objetivo deste estudo foi descrever o perfil antropométrico dos idosos residentes em Campina Grande - PB. Este estudo é populacional, transversal e domiciliar. Os dados são apresentados sob a forma de média, desvio-padrão e percentil (P5, P10, P25, P50, P75, P90 e P95) do peso, estatura, índice de massa corporal (IMC), perímetro do braço (PB), dobra cutânea tricipital (DCT), circunferência muscular do braço (CMB), perímetro da panturrilha (PP) e perímetro da cintura (PC). Foi realizado o teste t Student para verificar a diferença dos valores médios das variáveis entre os sexos. Foi realizada a análise de variância (ANOVA) para verificar o efeito da idade nas variáveis. Foram avaliados 806 idosos (60 anos ou mais). Os valores médios de todas as variáveis apresentaram diferença estatisticamente significativa entre os sexos. As médias das variáveis peso, estatura, CMB, PP e PC foram significativamente maiores entre os homens, enquanto que as médias de IMC, PB e DCT foram significativamente maiores entre as mulheres. Todas as variáveis apresentaram tendência de declínio entre os grupos etários mais avançados. Os resultados mostram que o padrão antropométrico dos idosos deste estudo segue a tendência de outros estudos, no entanto, os valores diferem. Dessa forma, sugere-se que estes possam ser usados para auxiliar na avaliação antropométrica de idosos.

This study aimed to describe the anthropometric information on elderly people in Campina Grande, PB, Brazil. It is a populational, cross-sectional household-based study. Data were presented as means, standard deviations and percentiles (5th, 10th, 25th, 50th, 75th, 90th and 95th) for weight, stature, body mass index (BMI), mid upper arm circumference (MAC), triceps skinfold thickness (TST), arm muscle circumference (AMC), calf circumference (CC) and waist circumference (WC). The analyses included Student t test to detect differences in mean values of the variable between both sexes. Age impact was investigated by ANOVA. A total of 806 elderly people were interviewed. The mean values of the all variables presented differences statistically significant. The mean values of weight, stature, AMC, CC and WC were higher in men, whereas the mean values of BMI, MAC and TST were higher in women. All variables showed a decrease in average values and percentile (50th) with advanced age. The anthropometric and body composition data of the elderly in the present study showed similar trend of others studies, but with different values. Thereby, such values could be useful in the anthropometric assessment of elderly people.

Accidents caused by Bothrops and Bothropoides in the State of Paraiba: epidemiological and clinical aspects.

INTRODUCTION: Bothrops and Bothropoides snakes cause 70% of the ophidic accidents in Brazil. The species that cause ophidic accidents in State of Paraíba are Bothropoides erythromelas, Bothrops leucurus and Bothropoides neuwiedi. METHODS: This is a prospective and transverse study, following a quantitative approach of accidents involving Bothrops and Bothropoides admitted to the Toxicological Assistance and Information Centers of Campina Grande and João Pessoa (Ceatox-CG and Ceatox-JP), aimed at identifying the epidemiological and clinical profile of such accidents. All of the patients admitted had medical diagnoses and were monitored at Ceatox-CG or Ceatox-JP. RESULTS: The genera Bothrops and Bothropoides caused 91.7% of the ophidic accidents reported. Snake bites were frequent in men (75.1%), rural workers (65.1%), literate individuals (69%) between 11 and 20 years-old (21.7%), and toes the most common area attacked (52.7%). Most (86.6%) patients were admitted within 6 hours after the accident/bite, with a predominance of mild cases (64.6%). The annual occurrence in Paraíba was 5.5 accidents/100,000 inhabitants and lethality was 0.2%. CONCLUSIONS: Positive changes in the profiles of these accidents were verified, such as the non-application of inadequate solutions, including the use of tourniquet, coffee grounds, garlic, suction and/or cutting the bitten area. Moreover, the Itinerant Laboratory project, linked to Paraíba State University in partnership with Ceatox-CG, has contributed positively, providing several cities of the state with information regarding the prevention of accidents involving venomous animals. The local press has also contributed, reporting the educational work developed by the centers.

Accidents caused by Bothrops and Bothropoides in the State of Paraiba: epidemiological and clinical aspects / Acidentes causados por serpentes dos gêneros Bothrops e Bothropoides no Estado da Paraíba: aspectos clínicos e epidemiológicos

INTRODUCTION: Bothrops and Bothropoides snakes cause 70 percent of the ophidic accidents in Brazil. The species that cause ophidic accidents in State of Paraíba are Bothropoides erythromelas, Bothrops leucurus and Bothropoides neuwiedi. METHODS: This is a prospective and transverse study, following a quantitative approach of accidents involving Bothrops and Bothropoides admitted to the Toxicological Assistance and Information Centers of Campina Grande and João Pessoa (Ceatox-CG and Ceatox-JP), aimed at identifying the epidemiological and clinical profile of such accidents. All of the patients admitted had medical diagnoses and were monitored at Ceatox-CG or Ceatox-JP. RESULTS: The genera Bothrops and Bothropoides caused 91.7 percent of the ophidic accidents reported. Snake bites were frequent in men (75.1 percent), rural workers (65.1 percent), literate individuals (69 percent) between 11 and 20 years-old (21.7 percent), and toes the most common area attacked (52.7 percent). Most (86.6 percent) patients were admitted within 6 hours after the accident/bite, with a predominance of mild cases (64.6 percent). The annual occurrence in Paraíba was 5.5 accidents/100,000 inhabitants and lethality was 0.2 percent. CONCLUSIONS: Positive changes in the profiles of these accidents were verified, such as the non-application of inadequate solutions, including the use of tourniquet, coffee grounds, garlic, suction and/or cutting the bitten area. Moreover, the Itinerant Laboratory project, linked to Paraíba State University in partnership with Ceatox-CG, has contributed positively, providing several cities of the state with information regarding the prevention of accidents involving venomous animals. The local press has also contributed, reporting the educational work developed by the centers.

INTRODUÇÃO: As serpentes Bothrops e Bothropoides são responsáveis por 70 por cento dos acidentes ofídicos ocorridos no Brasil. As espécies causadoras de acidentes na Paraíba são Bothropoides erythromelas, Bothrops leucurus e Bothropoides neuwiedi. MÉTODOS: Tratou-se de um estudo prospectivo e transversal, com abordagem quantitativa dos acidentes botrópicos e botropóidicos atendidos e registrados pelos Centros de Assistência e Informação Toxicológica de Campina Grande e João Pessoa (Ceatox-CG e Ceatox-JP), com o objetivo de conhecer o perfil epidemiológico e clínico deste agravo. Todos os pacientes atendidos tiveram diagnóstico médico e acompanhamento pelos Ceatox CG e JP. RESULTADOS: Os gêneros Bothrops e Bothropoides foram responsáveis por 91,7 por cento dos acidentes ofídicos notificados. Atingindo frequentemente o sexo masculino (75,1 por cento), trabalhadores rurais (65,1 por cento), alfabetizados (69 por cento) e na faixa etária entre 11 a 20 anos (21,7 por cento), os dedos dos pés foram as regiões anatômicas mais acometidas (52,7 por cento). A maioria (86,6 por cento) dos pacientes foi atendida em até 6 horas após o acidente/picada com predominância de casos leves (64,6 por cento). A incidência anual no estado foi 5,5 acidentes/100.000 habitantes e a letalidade 0,2 por cento. CONCLUSÕES: Verificaram-se mudanças positivas no perfil desses acidentes, como a não utilização de medidas consideradas inadequadas (uso de torniquetes, borra de café, alho, incisão com sucção e outras). Além disso, o projeto Laboratório Itinerante, ligado a Universidade Estadual da Paraíba em parceria com o Ceatox-CG, tem contribuído positivamente, levando a várias cidades do estado informações sobre prevenção e tratamento dos acidentes causados por animais peçonhentos. A imprensa local também tem contribuído, divulgando esse trabalho educativo.