Modulatory effect of Byrsonima basiloba extracts on the mutagenicity of certain direct and indirect-acting mutagens in Salmonella typhimurium assays

Byrsonima basiloba A. Juss. species is a native arboreal type from the Brazilian ""cerrado"" (tropical American savanna), and the local population uses it to treat diseases, such as diarrhea and gastric ulcer. It belongs to the Malpighiaceae family, and it is commonly known as ""murici."" Considering the popular use of B. basiloba derivatives and the lack of pharmacological potential studies regarding this vegetal species, the mutagenic and antimutagenic effect of methanol (MeOH) and chloroform extracts were evaluated by the Ames test, using strains TA97a, TA98, TA100, and TA102 of Salmonella typhimurium. No mutagenic activity was observed in any of the extracts. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine, sodium azide, mitomycin C, aflatoxin B(1), benzo[a] pyrene, and hydrogen peroxide. Both the extracts evaluated showed antimutagenic activity, but the highest value of inhibition level (89%) was obtained with the MeOH extract and strain TA100 in the presence of aflatoxin B(1). Phytochemical analysis of the extracts revealed the presence of n-alkanes, lupeol, ursolic and oleanolic acid, (+)-catechin, quercetin- 3-O-alpha-L-arabinopyranoside, gallic acid, methyl gallate, amentoflavone, quercetin, quercetin-3-O-(2 ''-O-galloyl)-beta-D-galactopyranoside, and quercetin-3-O-(2 ''-O-galloyl)-alpha-L-arabinopyranoside.

Inhibitory effect of propolis and bee venom on the mutagenicity of some direct- and indirect-acting mutagens

The antimutagenic effect of ethanolic extract of propolis (EEP) and honeybee (Apis mellifera) venom, both collected in the State of Sb Paulo, Brazil, was assessed by the Salmonella/microsome assay upon direct- and indirect-acting mutagens. EEP had inhibitory effect (in an ascending order) on the mutagenicity power of daunomycin (TA102), benzo(a)pyrene (TA100), and aflatoxin B-1(TA98) and the venom acted against the mutagenicity of 4-nitro-o-phenylenediamine (TA98) and daunomycin (TA102). (C) 1999 Wiley-Liss, Inc.

Modulatory effect of Byrsonima basiloba extracts on the mutagenicity of certain direct and indirect-acting mutagens in Salmonella typhimurium assays

Byrsonima basiloba A. Juss. species is a native arboreal type from the Brazilian cerrado (tropical American savanna), and the local population uses it to treat diseases, such as diarrhea and gastric ulcer. It belongs to the Malpighiaceae family, and it is commonly known as murici. Considering the popular use of B. basiloba derivatives and the lack of pharmacological potential studies regarding this vegetal species, the mutagenic and antimutagenic effect of methanol (MeOH) and chloroform extracts were evaluated by the Ames test, using strains TA97a, TA98, TA100, and TA102 of Salmonella typhimurium. No mutagenic activity was observed in any of the extracts. To evaluate the antimutagenic potential, direct and indirect mutagenic agents were used: 4 nitro-o-phenylenediamine, sodium azide, mitomycin C, aflatoxin B1, benzo[a]pyrene, and hydrogen peroxide. Both the extracts evaluated showed antimutagenic activity, but the highest value of inhibition level (89%) was obtained with the MeOH extract and strain TA100 in the presence of aflatoxin B1. Phytochemical analysis of the extracts revealed the presence of n-alkanes, lupeol, ursolic and oleanolic acid, (+)-catechin, quercetin-3-O-α-L-arabinopyranoside, gallic acid, methyl gallate, amentoflavone, quercetin, quercetin-3-O-(2″-O-galloyl)-β-D- galactopyranoside, and quercetin-3-O-(2″-O-galloyl)-α-L- arabinopyranoside. © 2008 Mary Ann Liebert, Inc.

Differences in the hydroxylation pattern of flavonoids alter their chemoprotective effect against direct- and indirect-acting mutagens

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative Studies of the (Anti) Mutagenicity of Baccharis dracunculifolia and Artepillin C by the Bacterial Reverse Mutation Test

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mutagenicity and antimutagenicity of (-)-hinokinin a trypanosomicidal compound measured by Salmonella microsome and comet assays

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genetic biomonitoring of an urban population exposed to mutagenic airborne pollutants

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estudo do potencial antimutagênico, mutagênico, estrogênico e antibacteriano de flavonoides

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Mutagenicity and chemopreventive activities of Astronium species assessed by Ames test

In the neotropical savannah, Astronium species are used in popular medicine to treat allergies, inflammation, diarrhea and ulcers. Given that natural products are promising starting points for the discovery of novel potentially therapeutic agents, the aim of the present study was to investigate the mutagenic and antimutagenic activities of hydroalcoholic extracts of Astronium spp. The mutagenicity was determined by the Ames test on Salmonella typhimurium strains TA98, TA97a, TA100 and TA102. The antimutagenicity was tested against the direct-acting and indirect-acting mutagens. The results showed that none of the extracts induce any increase in the number of revertants, demonstrating the absence of mutagenic activity. On the other hand, the results on the antimutagenic potential showed a moderate inhibitory effect against NPD and a strong protective effect against B[a]P and AFB1. This study highlights the importance of screening species of Astronium for new medicinal compounds. The promising results obtained open up new avenues for further study and provide a better understanding the mechanisms by which these species act in protecting DNA from damage. However, further pharmacological and toxicological investigations of crude extracts of Astronium spp., as well as of its secondary metabolites, are necessary to determine the mechanism(s) of action to guarantee their safer and more effective application to human health.

Does the gastroprotective action of a medicinal plant ensure healing effects? An integrative study of the biological effects of Serjania marginata Casar. (Sapindaceae) in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative Studies of the (Anti) Mutagenicity of Baccharis dracunculifolia and Artepillin C by the Bacterial Reverse Mutation Test

Baccharis dracunculifolia is a plant native from Brazil, commonly known as 'Alecrim-do-campo' and 'Vassoura' and used in alternative medicine for the treatment of inflammation, hepatic disorders and stomach ulcers. Previous studies reported that artepillin C (ArtC, 3-{4-hydroxy-3,5-di(3-methyl-2-butenyl)phenyl}-2(E)-propenoic acid), is the main compound of interest in the leaves. This study was undertaken to assess the mutagenic effect of the ethyl acetate extract of B. dracunculifolia leaves (Bd-EAE: 11.4-182.8 mu g/plate) and ArtC (0.69-10.99 mu g/plate) by the Ames test using Salmonella typhimurium strains TA98, TA97a, TA100 and TA102, and to compare the protective effects of Bd-EAE and ArtC against the mutagenicity of a variety of direct and indirect acting mutagens such as 4-nitro-O-phenylenediamine, sodium azide, mitomycin C, benzo[a]pyrene, aflatoxin B1, 2-aminoanthracene and 2-aminofluorene. The mutagenicity test showed that Bd-EAE and ArtC did not induce an increase in the number of revertant colonies indicating absence of mutagenic activity. ArtC showed a similar antimutagenic effect to that of Bd-EAE in some strains of S. typhimurium, demonstrating that the antimutagenic activity of Bd-EAE can be partially attributed to ArtC. The present results showed that the protective effect of whole plant extracts is due to the combined and synergistic effects of a complex mixture of phytochemicals, the total activity of which may result in health benefits.

Reasons For Brazilian Women To Switch From Different Contraceptives To Long-acting Reversible Contraceptives.

Long-acting reversible contraceptives (LARCs) include the copper-releasing intrauterine device (IUD), the levonorgestrel-releasing intrauterine system (LNG-IUS) and implants. Despite the high contraceptive efficacy of LARCs, their prevalence of use remains low in many countries. The objective of this study was to assess the main reasons for switching from contraceptive methods requiring daily or monthly compliance to LARC methods within a Brazilian cohort. Women of 18-50 years of age using different contraceptives and wishing to switch to a LARC method answered a questionnaire regarding their motivations for switching from their current contraceptive. Continuation rates were evaluated 1 year after method initiation. Sample size was calculated at 1040 women. Clinical performance was evaluated by life table analysis. The cutoff date for analysis was May 23, 2013. Overall, 1167 women were interviewed; however, after 1 year of use, the medical records of only 1154 women were available for review. The main personal reason for switching, as reported by the women, was fear of becoming pregnant while the main medical reasons were nausea and vomiting and unscheduled bleeding. No pregnancies occurred during LARC use, and the main reasons for discontinuation were expulsion (in the case of the IUD and LNG-IUS) and a decision to undergo surgical sterilization (in the case of the etonogestrel-releasing implant). Continuation rate was ~95.0/100 women/year for the three methods. Most women chose a LARC method for its safety and for practical reasons, and after 1 year of use, most women continued with the method.

Estimated Disability-adjusted Life Years Averted By Long-term Provision Of Long Acting Contraceptive Methods In A Brazilian Clinic.

What is the contribution of the provision, at no cost for users, of long acting reversible contraceptive methods (LARC; copper intrauterine device [IUD], the levonorgestrel-releasing intrauterine system [LNG-IUS], contraceptive implants and depot-medroxyprogesterone [DMPA] injection) towards the disability-adjusted life years (DALY) averted through a Brazilian university-based clinic established over 30 years ago. Over the last 10 years of evaluation, provision of LARC methods and DMPA by the clinic are estimated to have contributed to DALY averted by between 37 and 60 maternal deaths, 315-424 child mortalities, 634-853 combined maternal morbidity and mortality and child mortality, and 1056-1412 unsafe abortions averted. LARC methods are associated with a high contraceptive effectiveness when compared with contraceptive methods which need frequent attention; perhaps because LARC methods are independent of individual or couple compliance. However, in general previous studies have evaluated contraceptive methods during clinical studies over a short period of time, or not more than 10 years. Furthermore, information regarding the estimation of the DALY averted is scarce. We reviewed 50 004 medical charts from women who consulted for the first time looking for a contraceptive method over the period from 2 January 1980 through 31 December 2012. Women who consulted at the Department of Obstetrics and Gynaecology, University of Campinas, Brazil were new users and users switching contraceptive, including the copper IUD (n = 13 826), the LNG-IUS (n = 1525), implants (n = 277) and DMPA (n = 9387). Estimation of the DALY averted included maternal morbidity and mortality, child mortality and unsafe abortions averted. We obtained 29 416 contraceptive segments of use including 25 009 contraceptive segments of use from 20 821 new users or switchers to any LARC method or DMPA with at least 1 year of follow-up. The mean (± SD) age of the women at first consultation ranged from 25.3 ± 5.7 (range 12-47) years in the 1980s, to 31.9 ± 7.4 (range 16-50) years in 2010-2011. The most common contraceptive chosen at the first consultation was copper IUD (48.3, 74.5 and 64.7% in the 1980s, 1990s and 2000s, respectively). For an evaluation over 20 years, the cumulative pregnancy rates (SEM) were 0.4 (0.2), 2.8 (2.1), 4.0 (0.4) and 1.3 (0.4) for the LNG-IUS, the implants, copper IUD and DMPA, respectively and cumulative continuation rates (SEM) were 15.1 (3.7), 3.9 (1.4), 14.1 (0.6) and 7.3 (1.7) for the LNG-IUS, implants, copper IUD and DMPA, respectively (P < 0.001). Over the last 10 years of evaluation, the estimation of the contribution of the clinic through the provision of LARC methods and DMPA to DALY averted was 37-60 maternal deaths; between 315 and 424 child mortalities; combined maternal morbidity and mortality and child mortality of between 634 and 853, and 1056-1412 unsafe abortions averted. The main limitations are the number of women who never returned to the clinic (overall 14% among the four methods under evaluation); consequently the pregnancy rate could be different. Other limitations include the analysis of two kinds of copper IUD and two kinds of contraceptive implants as the same IUD or implant, and the low number of users of implants. In addition, the DALY calculation relies on a number of estimates, which may vary in different parts of the world. LARC methods and DMPA are highly effective and women who were well-counselled used these methods for a long time. The benefit of averting maternal morbidity and mortality, child mortality, and unsafe abortions is an example to health policy makers to implement more family planning programmes and to offer contraceptive methods, mainly LARC and DMPA, at no cost or at affordable cost for the underprivileged population. This study received partial financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant # 2012/12810-4 and from the National Research Council (CNPq), grant #573747/2008-3. B.F.B., M.P.G., and V.M.C. were fellows from the scientific initiation programme from FAPESP. Since the year 2001, all the TCu380A IUD were donated by Injeflex, São Paulo, Brazil, and from the year 2006 all the LNG-IUS were donated by the International Contraceptive Access Foundation (ICA), Turku, Finland. Both donations are as unrestricted grants. The authors declare that there are no conflicts of interest associated with this study.

Clinical outcomes of long-acting injectable risperidone in patients with schizophrenia: six-month follow-up from the Electronic Schizophrenia Treatment Adherence Registry in Latin America

Background: Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America. Methods: Data were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S), Personal and Social Performance (PSP), and Global Assessment of Functioning (GAF) scores. Relapse and treatment were also registered. Results: Patients were recruited in Mexico (n = 53), Brazil (n = 11), and Colombia (n = 15). Sixty-five percent (n = 52) were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73) or schizoaffective disorder (n = 6). The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg). The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001). Significant changes were registered on CGI-S, GAF, and PSP scores. Conclusions: RLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization.

Long-acting injectable risperidone in partially adherent and nonadherent patients with schizophrenia

Background: Long-acting injectable antipsychotics may improve medication adherence, thereby improving overall treatment effectiveness. This study aimed to evaluate the effectiveness, safety, and tolerability of risperidone long-acting injection in schizophrenic patients switched from oral antipsychotic medication. Methods: In a 12-month, multicenter, open-label, noncomparative study, symptomatically stable patients on oral antipsychotic medication with poor treatment adherence during the previous 12 months received intramuscular injections of risperidone long-acting injection (25 mg starting dose) every 2 weeks. The primary endpoint was the change in Positive and Negative Syndrome Scale (PANSS) total score. Results: Of the 60 patients who were screened, 53 received at least one injection (safety population), and 51 provided at least one postbaseline assessment. Mean PANSS total scores improved significantly throughout the study and at endpoint. Significant improvements were also observed in Clinical Global Impression of Severity, Personal and Social Performance, and Drug Attitude Inventory scales. Risperidone long-acting injection was safe and well-tolerated. Severity of movement disorders on the Extrapyramidal Symptom Rating Scale was reduced significantly. The most frequently reported adverse events were insomnia (22.6%), increased prolactin (17.0%), and weight gain (13.2%). Conclusion: Risperidone long-acting injection was associated with significant symptomatic improvements in stable patients with schizophrenia following a switch from previous antipsychotic medications.