Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in Patients with Chronic Heart Failure.

We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFß, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFß, IL-10, and IL-1α concentrations.

Screening antimycobacterial activity of Baccharis dracunculifolia, Centella asiatica, Lantana camara and Pterodon emarginatus / Atividade anti-micobacteriana de Baccharis dracunculifolia, Centella asiatica, Lantana camara e Pterodon emarginatus

ABSTRACT The permanent investigation of new antimycobacterial drugs is necessary for the eradication programs of tuberculosis and other mycobacterium-related diseases. The aim of the present study is to search for new sources of antimycobacterial drugs using plant materials. In this study, 11 plant materials (extracts, essential oils and some fractions) obtained from 4 species of medicinal plants traditionally used as general therapeutics for different illnesses and specifically as treatment of tuberculosis, were evaluated using the microplate resazurin assay against 2 species of the Mycobacterium tuberculosis Complex and 3 nontuberculous mycobacteria. The results showed the hexane extract and the essential oil from fruits of Pterodonemarginatus (Vogel) as potential sources of antimycobacterial drugs against 4 species of tested mycobacteria. The hexane fraction of methanol extract from leaves of Centella asiatica also presented significant mycobacterial growth inhibition, but against M. chelonae only. In conclusion, it was possible to contribute to the antimycobacterial investigations by presenting three new samples of plants with significant antimicrobial activity against four Mycobacteriumspp and suggest future studies about the antimycobacterial properties of fruits from P. emarginatus.

RESUMO A investigação permanente de novas drogas antimicobacterianas é necessária no programa de erradicação da tuberculose e de outras doenças relacionadas com micobactérias. O objetivo deste estudo foi buscar novas fontes de drogas antimicobacterianas usando material vegetal. Neste estudo, 11 materiais de base vegetal (extratos, óleos essenciais e algumas frações) foram avaliados contra 5 espécies de micobactérias. Estes materiais foram obtidos a partir de 4 espécies de plantas medicinais tradicionalmente utilizadas como terapêutica geral para diferentes doenças e, especificamente, no tratamento de tuberculose (Baccharis dracunculifolia, Centella asiatica, Lantana camara, Pterodon emarginatus). Os ensaios foram realizados em microplacas com resazurina contra duas espécies do Complexo Mycobacteriumtuberculosis e 3 espécies de micobactérias não tuberculosas. Os resultados mostraram o extrato hexânico e o óleo essencial de frutos de P.emarginatus como potenciais fontes para drogas antimicobacterianas contra quatro espécies de micobactérias testadas. A fração hexânica do extrato metanólico das folhas de C. asiatica também apresentou significativa inibição do crescimento de micobactérias apenas contra M.chelonae. Em conclusão, foi possível contribuir para as investigações de antimicobacterianos por apresentar três novas amostras de plantas com atividade antimicrobiana significativa contra quatro Mycobacterium spp e sugerir a realização de estudos futuros sobre as propriedades antimicobacterianas de frutos de P. emarginatus.

Prognostic analysis of patients with operable gastric cancer and tolerability to adjuvant radio-chemo-therapy.

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

[Biological effects of Lamipharen photodynamic therapy].

Biological effects of Lamipharen treatment of sarcoma M-1 was studied in newborn rats and photodynamic therapy in combination with radiation was evaluated.

[Influence of Laminaria japonica and fucus on hemostasis and sarcoma M-1 growth in Wistar rats].

The study was concerned with the effects of brown seaweeds on hemostasis and sarcoma M-1 growth in rats. Laminaria japonica and focus were shown to exert anticoagulant action to inhibit carcinogenesis. They may be used for adjuvant therapy of tumors.

Anti-inflammatory and anti-ulcerogenic properties of Stachytarpheta cayennensis (L.C. Rich) Vahl.

In the present work, the anti-inflammatory and gastroprotective properties of ethanolic extracts of Stachytarpheta cayennesis (L.C. Rich) Vahl (Verbenaceae) were assessed. Chromatographic analysis of the crude ethanolic extract, SC01, revealed high concentrations of the iridoid ipolamiide, whereas the SC02, the second ethanolic extract, presented the arylpropanoid verbacoside as a major constituent. The oral administration of SC01 (100 mg/kg) into Swiss mice failed to inhibit paw oedema and pleural exudation induced by carrageenan and zymosan, whereas SC02 (100 mg/kg, p.o.) inhibited oedema and protein extravasation in all instances. Both extracts inhibited total leukocyte accumulation into the pleural cavity 4 and 24h after the intrathoracic (i.t.) injection of carrageenan, due to the inhibition of neutrophil and mononuclear cell influx, whereas only SC02 was able to inhibit leukocyte mobilization induced by zymosan (100 microg/cavity, i.t.). SC02 inhibited LPS (250 ng/cavity)-induced total leukocyte, neutrophil and eosinophil accumulation in the pleural cavity, whereas SC01 selectively inhibited neutrophil influx. In addition, our data indicates that the extract SC02 presents an important anti-ulcerogenic activity, since it inhibited diclofenac-induced (100 mg/kg, p.o.) gastric ulcera. Overall, these data provide evidence for the anti-inflammatory and gastroprotective properties of Stachytarpheta cayennensis, supporting its use in folk medicine for such purposes.

Topical antiinflammatory and analgesic activities of Copaifera duckei dwyer.

The oleoresin of several Copaifera species is used widely in the Amazonian Region mainly as a topical antiinflammatory and healing agent. The topical analgesic and antiinflammatory activities of Copaifera duckei oleoresin, whose terpenoidal chemical composition has been characterized, are now examined. Antiinflammatory activity was evaluated in rats using the carrageenin-induced paw edema and the granuloma tests, and in mice by the croton oil-induced dermatitis test. Analgesic activity was determined in mice using the writhing test method. In the carrageenin-induced edema and granuloma tests the oleoresin in a dose of 1,802 mg/kg inhibited the edema by 18% and granuloma by 42% (p < 0.05), this last result similar to that observed with dexamethasone. Topical doses of 517 mg/kg, 1,035 mg/kg and 1,802 mg/kg produced 52%, 58% and 62% (p < 0.05) reduction of the edema induced by croton oil, respectively, and 48%, 56% and 65% inhibition of the writhing process (p < 0.05). These results suggest that the Copaifera duckei oleoresin has topical antiinflammatory and analgesic activities.

Atividade antimicrobiana dos frutos de Syagrus oleracea e Mauritia vinifera / Antimicrobial activity of Syagrus oleracea and Mauritia vinifera fruits

As espécies pertencentes à família Palmae são muito interessantes do ponto de vista químico e farmacológico. Neste trabalho, foram estudados os frutos de duas espécies da família Palmae, Syagrus oleracea e Mauritia vinifera. Essas palmeiras foram escolhidas por serem espécies brasileiras, abundantes em nosso país, utilizadas popularmente no tratamento de algumas doenças e ainda pouco estudadas. Foram realizados ensaios farmacológicos para avaliação da atividade antimicrobiana dos extratos dos frutos das duas espécies em estudo. Para o teste de atividade antimicrobiana foram utilizadas cepas de bactérias Gram positivas e Gram negativas. A metodologia empregada foi a de Microdiluição em caldo. Foram testados os extratos etanólicos brutos do epicarpo/mesocarpo de S. oleracea e de M. vinifera, o extrato hexânico das amêndoas de S. oleracea, as partições hexânicas e em acetato de etila do epicarpo/mesocarpo de S. oleracea, do epicarpo/mesocarpo e mesocarpo/endocarpo de M. vinifera, na concentração de 100 mg/ml. Os extratos lipofílicos de S. oleracea apresentaram os melhores resultados para essa espécie. Nos testes realizados com M. vinifera, as partições lipofílicas foram as mais inibitórias para a cepa de S. aureus.

Palmae species are very interesting by the chemical and pharmacological points of view. Two species belonging to this family were chosen to initiate the chemical and pharmacological approach of their fruits: Syagrus oleracea (Martius) Beccari and Mauritia vinifera Martius, known in Brazil as Guariroba and Buriti, respectively. Those palm species can be found in several regions of Brazil, especially at the northeast and southeast of the country. They have been used in folk medicine to treat some diseases, however no toxicological and pharmacological studies have been done so far. For the two studied fruits, the antimicrobial activity tests were carried out by broth microdilution methodology. The objective of this work was to contribute for the pharmacological study of palm species, evaluating the antimicrobial activity of the extracts obtained from the fruits of S. oleracea and M. vinifera. The assays evaluated ethanol extracts of the epicarp/mesocarp of S. oleracea and epicarp/mesocarp of M. vinifera; hexane extract of the endosperm of S. oleracea; hexane and ethyl acetate fractions of the epicarp/mesocarp of S. oleracea, epicarp/mesocarp of M. vinifera and mesocarp/endocarp of M. vinifera. The lipophilic extracts of S. oleracea obtained the best results for the species. For M. vinifera, the lipophilic partitions have shown a high inhibitory percentage for S. aureus.

Antinociceptive effect of Nidularium procerum: a Bromeliaceae from the Brazilian coastal rain forest.

Nidularium procerum, a common plant of the Brazilian flora, has not yet been studied for its pharmacological properties. We report here that extracts of N. procerum show both analgesic and anti-inflammatory properties. Oral (p.o.) or intraperitoneal (i.p.) administration of an aqueous crude extract from leaves of N. procerum (LAE) inhibited the writhing reaction induced by acetic acid (ED50 value = 0.2 mg/kg body weight, i.p.) in a dose-dependent manner. This analgesic property was confirmed in rats using two different models of bradykinin-induced hyperalgesia; there was 75% inhibition of pain in the modified Hargreaves assay, and 100% inhibition in the classical Hargreaves assay. This potent analgesic effect was not blocked by naloxone, nor was it observed in the hot plate model, indicating that the analgesic effect is not associated with the activation of opioid receptors in the central nervous system. By contrast, we found that LAE (0.02 microg/ml) selectively inhibited prostaglandin E2 production by cyclooxygenase (COX)-2, but not COX-1, which is a plausible mechanism for the analgesic effect. A crude methanol extract from the leaves also showed similar analgesic activity. An identical extract from the roots of N. procerum did not, however, block acetic acid-induced writhes, indicating that the analgesic compounds are concentrated in the leaves. Finally, we found that LAE inhibited an inflammatory reaction induced by lipopolysaccharide in the pleural cavity of mice.

Antileishmanial activity of isolated triterpenoids from Pourouma guianensis.

The inhibiting activity of triterpenoids isolated from the methanolic extract of Pourouma guianensis (Moraceae) leaves is described for promastigotes and intracellular amastigotes of Leishmania amazonensis. Whereas the fractions containing apigenin, friedelin, epi-friedelinol, arjunolic acid, hyptatic acid B, stigmasterol and sitosterol were of no or relatively low inhibitory activity, fractions containing tormentic acid, 2alpha,3beta-dihydroxyursan-12-en-28-oic acid, 2alpha,3beta-dihydroxyolean-12-en-28-oic acid, oleanolic acid and ursolic acid were very potent in inhibiting promastigote growth at 100 microg/ml. Of the eleven isolated compounds, however, only ursolic acid and oleanolic acid showed high activity against intracellular amastigotes (IC50 value = 27 microg/ml and 11 microg/ml, respectively), which was superior to the control drug Glucantime (IC50 value = 83 microg/ml). The antileishmanial activity of oleanolic acid was directed against the parasite and not due to activation of nitric oxide intermediates by macrophages, but this triterpenoid also significantly inhibited the phagocytic capacity of those cells at concentrations above 40 microg/ml, indicating a cytotoxic effect. These results indicate that Pourouma guianensis contains many triterpenoids and some, such as ursolic and oleanolic acids, may serve as lead compounds for new antileishmanial drugs, but chemical modifications may be necessary to avoid unselective cytotoxicity.

[Angioroentgenologic response of rat M-1 sarcoma to low-energy infrared laser irradiation at varying frequency]. / Angiorentgenograficheskie izmeneniia v opukholi M-1 krys v otvet na deistvie nizkointensivnogo infrakrasnogo lazernogo izlucheniia razlichnoi chastoty.

After rats with sarcoma M-1 inoculated in the femur area were exposed to low-energy (0.54 mT1) infra-red laser irradiation, 100Hz, for 10 min, the number of contrast-enhanced vessels of tumor fell sharply as compared with controls. That effect lasted for almost 24 hrs. At 1kHz, the total-sum of diameters of such vessels still increased 24 hrs after the exposure. When at 10kHz, that index decreased, and by day 3 vascular pattern and diameter came back to normal in all experiments.

[Effect of low level infrared laser irradiation on hemostasis (experimental study)]. / Vliianie infrakrasnogo lazernogo izlucheniia nizkoi intensivnosti na sistemu gemostaza.

Roentgenostructural, spectral analyses, functional testing of the hemostatic system in experimental animals demonstrated that infrared low-intensity laser radiation changes functional activity of proteins of the hemostatic system. The effect of the radiation depends on the dose and frequency of the radiation impulses. One of the complications is DIC-syndrome which may develop if the exposure dose on the radiation point in tissues with blocked circulation reaches 9.5 mJ/cm2 and higher.

Immunomodulatory activity of Mollugo verticillata L.

This article describes the evaluation of immunomodulatory activity of Mollugo verticillata L. (Molluginaceae), a weed plant common in warm and/or wet regions of the American continent. Nitric oxide (NO) release was evaluated in mice peritoneal cell cultures treated in vivo using the ethanolic extract of M. verticillata with and without BCG. The plant extract showed immunostimulatory activity when peritoneal cells were stimulated in vitro with BCG antigen only. However, mice peritoneal cells treated with M. verticillata plus BCG showed a drastic reduction in NO production when they received the additional stimulus in vitro with BCG. Ethanolic extracts of M. verticillata could directly increase NO release by peritoneal cells, but suppress the immune response of these cells when treated with BCG antigen and Mycobacterium tuberculosis whole antigen (TB). Preliminary phytochemical tests allowed the detection of quercetin and triterpenoid glycosides in the ethanolic extract of M. verticillata, and those compounds are probably responsible for the effect of this plant material on the immune system.

[Resonance response of cell-tissue structures to impulse frequency of infrared laser radiation of low intensity (experimental study)]. / Rezonansnyi otvet kletochno-tkanevykh struktur na chastotu impul'sov infrakrasnogo lazernogo izlucheniia nizkoi intensivnosti (éksperimental'noe issledovanie).

A morphological evaluation of the results of transcutaneous radiation of male mice with infra-red impulse laser beam for 10 min (10,100, 1000, 10,000 Hz) 5 min, 3 and 24 hours after the procedure has confirmed the existence of "resonance" frequencies for different types of endocrine cells and has shown that the response depends not only on the dose of infrared low-intensity laser radiation. Thus, account for resonance frequencies is one of perspective approaches to optimization of laser therapy which may raise effectiveness and safety of laser exposure.

Photosensitization and mutation induced in Escherichia coli and Saccharomyces cerevisiae strains by dorstenin, a psoralen analog isolated from Dorstenia bahiensis.

Dorstenin, 5-[3-(4,5-dihydro-5,5-dimethyl-4-oxo-2-furanyl)-butoxy]-7H-furo[3, 2-g] benzopyran-7-one, is a psoralen analog recently isolated from Dorstenia species (Moraceae). In order to characterize its biological activity, its photosensitizing and mutational properties were measured in wild-type E. coli and S. cerevisiae and also in strains carrying mutations which affect DNA repair. Compared to the high activities of psoralen and bergapten, dorstenin showed lower genotoxic effect.

Effect of leaf essential oil from Piper solmsianum C.DC. in mice behaviour.

The essential oil from Piper solmsianum leaves and its major compound (sarisan) were tested to verify their influences upon mice behaviour. The essential oil was obtained by hydrodistillation in a modified Clevenger extractor and analysed by GC/ MS. This analysis revealed in the oil the presence of monoterpenes, sesquiterpenes and of arylpropanoids. The compound sarisan, a myristicin analogue, was isolated from the oil to perform the pharmacological tests. Emulsions of the oil and of sarisan (5.0 and 10.0% v/v) were used in the tests. Pentobarbital (30 mg/ kg s.c.) or diazepam (2.5 mg/ kg s.c.) were tested as standard drugs to verify depressant or anxiolytic effects, respectively. Both essential oil and sarisan showed to have exciting and depressant effects in the tested animals.

Chrysobalanus icaco L. extract for antiangiogenic potential observation.

Angiogenesis is an important process in several physiological situations and it is also implicated in the development of some diseases such as diabetes and cancer. This study investigated the antiangiogenic potential of Chrysobalanus icaco methanol extract in the chicken embrionary tissue. Clinical trials for cancer treatment using drugs based on this mechanism are already in progress. Chorioallantoic membrane model (CAM) of chicken embryos, with C. icaco methanol extract in plastic diskes was used. The results showed an average of 44% angiogenesis inhibition in CAM areas with the plant extract compared to the controls. The data indicate that C. icaco methanol extract reduce the formation of new blood vessels in chicken chorioallantoic membrane.

Molluscicidal constituents of Marsypianthes chamaedrys.

Marsypianthes chamaedrys is a common herb that occurs in the North and Northeast regions of Brazil. Phytochemical studies showed this plant to be rich in triterpenoids. The hexane extract of M. chamaedrys yielded, after chromatographic separations, two mixtures: the first containing monohydroxylated-compounds (alpha-amyrin, beta-amyrin, lupeol and germanicol) and the second, dihydroxylated compounds (chamaedrydiol, castanopsol, 2alpha-hydroxylupeol and epigermanidiol). Molluscicidal tests were performed for the crude hexane extract and for mixtures I and II. Mixture II showed high activity.