Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Antinociceptive and anti-inflammatory effects of Lantana camara L. extract in mice / Efeitos antinociceptivos do extrato de Lantana camara L. em camundongos

ABSTRACT: he Lantana camara L. belongs to the family Verbenaceae, which contains several active compounds in leaves and roots and which are reported to have medicinal and insecticidal properties. Studies of plants within the same family show the existence of anti-inflammatory activity in paw edema induced by carrageenan, serotonin and histamine and analgesic activity in the acetic acid writhing and tail-flick tests. The present study investigated whether the L. camara extract (ACE) also exerts these effects. The ACE toxicity was studied in male mice, and the percentage of mortality recorded 7 days after treatment was assessed. The ACE was evaluated as an antinociceptive agent in the hot plate, tail-flick and acetic acid writhing tests at a nontoxic dose of 1.0 g/Kg. The results showed that 1.5 g/Kg of ACE was not able to cause death, and doses of 3.0 and 4.0 g/Kg caused 50% and 60% death, respectively, in male mice. In all of the antinociceptive tests, 1 g/Kg of ACE markedly reduced responses to pain. Our findings suggest that ACE may have active anti-inflammatory and antinociceptive properties in much smaller doses than toxic.

RESUMO: Lantana camara L. pertence à família Verbenaceae, a qual contem muitos princípios ativos em suas folhas e raízes com propriedade medicinais e inseticidas. Estudos com plantas da mesma família mostram a existência de propriedades antinflamatórias no modelo de edema de pata induzido pela carragenina, serotonina e histamina, além da atividade analgésica nos testes de contorção induzida pelo ácido acético e da retirada da cauda por estímulo térmico. O presente trabalho investigou os efeitos tóxicos e antinociceptivos do extrato de L. camara (ACE) em camundongos. Para tanto, investigou-se a porcentagem de mortes em 7 dias após a administração de diferentes doses do extrato. Avaliou-se também os efeitos antinociceptivos do ACE pelos testes da placa quente, estimulação térmica da cauda e contorções abdominais induzidas pelo ácido acético com a dose não-tóxica [1,0 g/Kg]. Os resultados mostraram que 1,5 g/Kg do ACE não causou mortalidade, enquanto que 3,0 e 4,0 g/Kg promoveram 50 e 60% de mortalidade, respectivamente. Em todos os testes antinociceptivos, a dose de 1,0 g/Kg do ACE reduziu a resposta à dor. Os presentes resultados indicam que o ACE apresenta propriedades antinflamatórias e analgésicas em doses muito menores que a tóxica.

Avaliação de atividade fungitóxica e isolamento de aloaromadendrano - 4α, 10 ß - diol em Hypericum cordatum / Evaluation of the fungitoxic activity and isolation of alloaromadendrene - 4α, 10 ß - diol in Hypericum cordatum

RESUMO Hypericum cordatum é uma espécie do cerrado que foi selecionada em triagem de plantas com atividade fungitóxica. O objetivo do presente trabalho foi isolar e identificar compostos com atividade antifúngica em extratos de folhas em diclorometano. O pó das folhas das plantas foi submetido à extração exaustiva com éter de petróleo e diclorometano. O extrato em diclorometano, e as frações ativas, foram submetidos à fracionamentos biomonitorados em coluna de Sephadex LH-20, respectivamente, com os eluentes clorofórmio:metanol (1:1) e com um gradiente de hexano:diclorometano (1:4); diclorometano:acetona (3:2 e 1:4), metanol, e água. As frações que mostraram atividade foram submetidas à cromatografia em camada delgada preparativa de sílica gel GF254, sendo que o material de maior massa foi analisado em CLAE semipreparativa. A fração ativa foi analisada por RMN de 1H, tendo sido identificado o aloaromadendrano - 4α -10ß - diol como componente principal da fração. Conclui-se, portanto, que este é um dos compostos responsáveis pela atividade fungitóxica de Hypericum cordatum.

The Hypericum cordatum is a species of the Brazilian Cerrado that was selected in a screening of plants with fungitoxic activities. The aim of this work was to isolate and identify the compounds with antifungal activity in leaf extracts in dichloromethane. For this end, the powder made from the leaves of the plants was submitted to exhaustive extraction with petroleum ether and dichloromethane. The extract in dichloromethane and the active fractions were submitted to bioassay-guided fractionation in Sephadex LH - 20 column, respectively, with the following eluents chloroform:methanol (1:1) and a gradient of hexane:dichlorometane (1:4); dichloromethane:acetone (3:3 and 1:4), methanol and water. Afterward, the fractions that showed some activity were submitted to preparative thin layer chromatography of silica gel GF254 and the material with the greatest mass was submitted to semi-preparative HPLC. The active fraction obtained was analyzed by 1H NMR, and the main component identified was alloaromadendrene-4α-10ß - diol. We may then conclude that this is one of the compounds responsible for the fungitoxic activity of Hypericum cordatum.

Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model.

BACKGROUND AND PURPOSE: Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice. EXPERIMENTAL APPROACH: Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg(-1) per mice) or dexamethasone (5 mg kg(-1) per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-α, IFN-γ and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry. KEY RESULTS: We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation. CONCLUSIONS AND IMPLICATIONS: These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.

The mystery of the 'resin-of-canuaru': a medicine used by caboclos river-dwellers of the Amazon, Amazonas, Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: 'Resin-of-canuaru' is a medicine utilized by caboclos living in the Amazon Region, Brazil. There is a mystery regarding its origin because the caboclos maintain that this substance is derived only from animal secretions (from a frog called canuaru), whereas the historic literature claims that 'resin-of-canuaru' is derived solely from a plant exudate (resin). Based on our ethnographic studies, we hypothesized that this substance is a combination of both. Because the past reports on this resiniferous material in the literature are based solely on observations, we aimed to present ethnographic, zoological and chemical data to try to elucidate the origin of the 'resin-of-canuaru'. MATERIALS AND METHODS: Ethnographic techniques and methods were applied, including participant observation, the use of field diaries and informal and unstructured interviews. The canuaru frog (Trachycephalus resinifictrix Goeldi, 1907) and 'resin-of-canuaru' were collected for taxonomic identification and chemical analysis, respectively. The resiniferous 'resin-of-canuaru' was extracted using MeOH and then analyzed by silica gel TLC and NMR. RESULTS: Canuaru frogs live in tree cavities and secrete a large amount of substances during spawning, resulting in a resiniferous material. NMR analysis of the MeOH extract of this crude material showed peaks assigned to 3,4-secofriedel-4(23)-en-3-oic acid (putranjuvic acid) and its methyl ester derivative (methyl putranjivate) and to biogenetic precursor of these two compounds (a lactone derivative), which is formed by the oxidation of friedelin. Based on evidence that Protium species accumulate primarily tetracyclic/pentacyclic triterpenoids and that the co-occurrence of the compounds listed above is rarely described in plant species, we suggest that these compounds could be products of the biotransformation of friedelin by the frog. CONCLUSIONS: According to our data, the 'resin-of-canuaru' seems to have both animal and vegetal origins.

The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part I

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

A new potent natural antioxidant mixture provides global protection against oxidative skin cell damage.

Oxidative stress occurs when there is an over production of free radicals and cells are not able to neutralize them by their own antioxidant mechanisms. These excess of free radicals will attack cellular macromolecules leading to cell damage, function impairment or death. Because of that, antioxidant substances have been largely used in products to offer complementary protection. In this study a new mixture of three known antioxidants (cocoa, green tea and alpha-tocopherol) was evaluated and its antioxidant protection was assessed focusing on its capacity to protect main cell macromolecules. Results have shown that it has a high antioxidant capacity by protecting lipids, DNA and proteins against oxidative damage. The antioxidant effect of the mixture on cells was also investigated and it was able to reduce oxidative stress generated by lipopolisacharide in human fibroblasts. Finally, as the mixture has proved to be highly antioxidant, its effect on cell senescence was evaluated, and it was demonstrated that fibroblasts in culture had delayed senescence when treated with these actives on a mixture. All results together provide important data about a new antioxidant mixture that uses a small amount of actives and is able to protect cell against oxidative damages in a global way.

Toxicity of apolar and polar Lantana camara L. crude extracts in mice.

Lantana camara L, widely used in folk medicine, presents toxicity for farm animals. The acute poisoning effects of the apolar and polar L. camara L. extracts in mice were done. The percentage of death during 7 days after treatment, the acute signs of toxicity as well as the general activity observed in open field were assessed. The extracts were administered by i.p. route at 1.5, 3.0 and 5.0 g/kg. Animals were evaluated during the first 2 h after the treatments to assess the acute signs of toxicity and daily observations were done for the presence of death. In the end of the experiment, at day 7, or immediately after death the animals had their organs removed, weighted and observed for macroscopic alterations. (1)H NMR and TLC analysis suggest the presence of triterpenoids in the apolar phase but not in the polar phase. Results showed also that both extracts produced similar percentage of death, mainly after 2 days of treatment; only the apolar extract presented a dose-dependent increased lethality. At necropsy, mice treated by both apolar and polar extracts were severely icteric, dehydrated and constipated, with hepatosis, showed congested heart and lung, and nephrosis; no skin lesions were shown. The main signs of toxicity revealed a decreased spontaneous general activity. In addition, it was observed a decreased duration of locomotion and animal rearing parallel to an increased immobility in the open field. The similarity of the signs related to the acute toxicity for both apolar and polar extracts suggested that the extracts have some of the active toxic principles in common. Data from open field behavior and spontaneous signs of toxicity suggest that the toxic principles have depressive properties on central nervous system.

Evaluation of Components of Partial Resistance to Oat Crown Rust Using Digital Image Analysis.

Digital image analysis is an objective and nondestructive method potentially capable of providing accurate and precise estimates of disease resistance components. This study was conducted to quantify components of partial resistance to crown rust through the analysis of sequential digital images of inoculated leaves of adult oat plants, and to compare components found in two sources of resistance unrelated genetically. Uredinium density, relative infection frequency, latent period, days to first pustule appearance, uredinium size, and disease progress rates were assessed on three oat lines (RS-line 3W-C2R-9-3b, MN-841801, Starter) in two greenhouse experiments. Resistant lines had fewer and smaller uredinia, and these appeared later than in the susceptible check. Relative infection frequency, latent period, and uredinium size were equally important components in the expression of the partial resistance to crown rust, and the two sources of resistance could not be differentiated by any of the variables studied. The analysis of sequential digital images of diseased leaves produced precise estimates of partial resistance components and disease progress rates.

Terpenes from leaves of Guarea macrophylla (Meliaceae).

The dichloromethane extract from the leaves of Guarea macrophylla (Meliaceae) was submitted to adsorption chromatography. Guai-6-en-10beta-ol, isopimara-7,15-dien-2alpha-ol and cycloarta-23,25-dien-3-one were isolated and identified by spectroscopic data, mainly by 1H and 13C NMR analyses; eight other known terpenoids were also isolated.

The transpuboperineal approach for repair of traumatic strictures of the posterior urethra in children.

Strictures of the posterior urethra resulting from pelvic fractures in children pose a formidable challenge due to the limitations of perineal exposure. With the transpubic approach, direct access to the involved anatomy is obtained. This technique, combined with perineal mobilization of the distal urethra, allows the performance of a tension-free anastomosis. The use of an omental pedicle wrap graft seems to add safety to the procedure. It is particularly suited for long strictures and after failure of the transperineal approaches. The results reported in the literature are remarkably good. There are no reports of orthopedic sequelae in children. Sexual potency and continence do not seem to be adversely affected. We present two cases successfully operated upon by this technique.

Variables epidemiológicas de pacientes con linfomas no hodgkinianos en el Instituto Nacional de Oncología y Radiobiología, 1970 - 1982 / Epidemiologic variables of patients presenting non-hodgkin's lymphomas at the National Institute of Oncology and Radiology during 1970 -1982 period

Se estudian las variables epidemiológicas de pacientes inscriptos en el INOR entre los años 1970 a 1982 con diagnóstico de linfoma no hodgkin. Se analiza sexo, edad, histopatología, etapa clínica y presencia de síntomas y se correlacionan las variables entre si. Predominó el sexo masculino en todas las edades, excepto entre 50 y 69 años. La ausencia de síntomas generales se evidenció en el grupo. El linfoma linfocítico bién diferenciado predominó el tipo mixto y el linfoma histiocítico, con 76 y 69

respectivamente (significativo en el 95

). La etapa I se vió más frecuente en pacientes mayores de 50 años; la etapa III entre 30 a 69 años; y la etapa IV en menor proporción en mayores de 70 años (p<0,01). Las variables nodulares fueron más frecuentes en etapas I y II y las difusas en las etapas IV (p<0,01)

Variables epidemiológicas de pacientes con linfomas no hodgkinianos en el Instituto Nacional de Oncología y Radiobiología, 1970 - 1982 / Epidemiologic variables of patients presenting non-hodgkin's lymphomas at the National Institute of Oncology and Radiology during 1970 -1982 period

Se estudian las variables epidemiológicas de pacientes inscriptos en el INOR entre los años 1970 a 1982 con diagnóstico de linfoma no hodgkin. Se analiza sexo, edad, histopatología, etapa clínica y presencia de síntomas y se correlacionan las variables entre si. Predominó el sexo masculino en todas las edades, excepto entre 50 y 69 años. La ausencia de síntomas generales se evidenció en el grupo. El linfoma linfocítico bién diferenciado predominó el tipo mixto y el linfoma histiocítico, con 76 y 69 % respectivamente (significativo en el 95 %). La etapa I se vió más frecuente en pacientes mayores de 50 años; la etapa III entre 30 a 69 años; y la etapa IV en menor proporción en mayores de 70 años (p<0,01). Las variables nodulares fueron más frecuentes en etapas I y II y las difusas en las etapas IV (p<0,01)

Field evaluation of an enzyme immunoassay for detection of asymptomatic patients in a hydatid control program.

In South America programs to control hydatidosis caused by Echinococcus granulosus include the active search for asymptomatic patients through population surveys for the detection of antibodies against arc 5 antigens using the double diffusion arc 5 test (DD5). Though simple to perform and highly specific, DD5 is not practical for population studies due to the time lapse between testing and receiving results. This work evaluates the application of an enzyme immunoassay to screen sera for subsequent processing using DD5. The efficiency of an enzyme immunoassay screening/DD5 confirmation scheme vs. DD5 alone was compared within the framework of a control program. A total of 5,839 sera from residents of endemic areas was processed and 47 hydatid patients were detected by both schemes. The proposed enzyme immunoassay identified all sera having antibody activity against arc 5 antigens detectable by DD5 and ruled out 95.3% of sera which tested by DD5 would have produced negative results.

Cáncer de Colon: Lesiones Asociadas

Se analizan las lesiones neoplásicas asociadas a Cáncer del Colon en 100 pacientes tratados por esta enfermedad en el Hospital Marcelino Freyre de la ciudad de Rosario (Argentina); demostrándose en 91 piezas resecadas, 24 pólipos de diferentes variedades histológicas. Se enfatiza en la necesidad de demostrar dichas lesiones previamente a la cirugía o mediante colonoscopia intraoperatoria

Determinaciones de dispersión y dilución en el Río Paraná de las Palmas (Vuelta de Hinojo) con aplicación de trazadores radiactivos

Mediante la inyección en la corriente hídrica de dos trazadores radiactivos (I-131, de alta vida media y del In-113 m. de baja vida media) en forma puntual, se midió el desplazamiento de la nube radiactiva, a través de una embarcación acondicionada para tal fin. Se describe la técnica y el equipo empleado, remarcando los inconvenientes que ocasiona la aplicación de sustancias radiactivas, la operación del sistema y la detección-ubicación del trazador, ante las variaciones del régimen delrío. El caso estudiado ofrece dos particularidades: la influencia de las mareas en la dispersión y dilución de los contaminantes (y trazadores); y la ocurrencia de efectos zonales, como consecuencia de la formación de barreras de mezcla, que provocan cambios en la magnitud y dirección del escurrimiento, con factores de dilución extremos. Sin embargo, se concluye que esta técnica aplicada a grandes ríos, con el fin de obtener valores cuantitativos resulta imprácticable, debido a las altas cantidades de trazadores requerida, la elevada actividad del material radiactivo y, por ende, la imposibilidad de su manipuleo