Apoptosis Induction in Murine Melanoma (B16F10) Cells by Mannosylerythritol Lipids-B; a Glycolipid Biosurfactant with Antitumoral Activities.

Mannosylerythritol lipids have drawn attention to cosmetic and pharmaceutical industries due to their non-toxicity and excellent biological interactions with human skin, particularly with the deepest epidermal layer. Lamellar liquid crystal structure, formed by MEL-B, is an interesting feature due to its similarity to the stratum corneum molecular arrangement and cell signaling events involved in the deregulation of the cancerous cell membrane. Thus, this work aimed to evaluate the cytotoxicity of commercial mannosylerythritol lipids-B in murine melanoma, fibroblast, and human erythrocytes cells. Cytotoxic effect was more pronounced on the tumor cells from 20 µg/mL, reducing cell viability by 65%, whereas fibroblast and human erythrocytes cells were more resistant to glycolipid treatment. Fluorescence microscopy and flow cytometer proved that mannosylerythritol lipids-B is an apoptosis inducer in tumor cells related to reactive oxygen species generation.

Effects of two diet techniques and delivery mode on weight loss, metabolic profile and food intake of obese adolescents: a fixed diet plan and a calorie-counting diet.

The aim of this study is to compare the weight loss of obese adolescents on two different low-calorie diets: fixed diet plan and calorie-counting diet. This is a randomized clinical study with 66 obese adolescents (body mass index Z score (ZBMI)>+3, 13.7±0.7 years, 60.6% male) with anthropometric, food intake, physical activity, laboratory, body composition and stage of pubertal development data evaluated. There was a reduction in the ZBMI in both groups (P<0.0001), without significant difference between them (P=0.87). There was a significant reduction in insulin, and homeostasis model assessment insulin resistance (HOMA-IR), with no difference between groups. A reduction in total energy intake of the groups was found, with an increase in the proportion of protein and reduction in carbohydrates. In this cohort of severely obese adolescents, fixed diet plan and calorie-counting diet led to a similar reduction of ZBMI, metabolic markers and total energy intake.

Evaluation of the Acute Toxicity, Cytotoxicity, and Genotoxicity of Chresta martii (Asteraceae).

Chresta martii (Asteraceae), found in the Xingó region, northeastern Brazil, is used in the treatment of gastrointestinal (GIT) and liver disorders and malaria. However, there are few studies regarding efficacy and safety of use for this species. Thus, the objective of this study was to determine in vivo acute toxicity and in vitro cytotoxicity of organic extracts of C. martii as well as in vivo genotoxicity of its semipurified fraction. Dried aerial parts of C. martii were extracted using three organic solvents (cyclohexane [ECCm], ethyl acetate [EACm], and ethanol [EECm]), and these extracts were examined for acute toxicity (50-2000 mg/kg ip or po) and cytotoxicity (50 µg/ml) in carcinogenic human cell lines (HL-60, NCIH-292, and MCF-7). The EACm, which showed evidence of toxicity (in vivo and in vitro), was fractionated on a silica column, yielding four fractions (F1-F4). The F1 was utilized for genotoxicity (50 mg/kg ip), by in vivo micronucleus (MN) assay. ECCm showed no indication of acute toxicity or occurrence of death, while the LD50 estimated for the extracts (EACm and EECm) was 500 mg/kg po and 200 mg/kg ip. The EACm (50 µg/ml) inhibited growth of tumor cells HL-60 (96.54%), NCIH-292 (73.43%), and MCF-7 (15%). The F1 fraction induced MN formation in polychromatic erythrocytes of Swiss Webster mice. Organic extracts from C. martii exhibited acute toxicity classified as mild to moderate, in addition to cytotoxicity (in vitro), while the F1 semipurified fraction induced genotoxicity (in vivo).

Study of the Gastroprotective Effect of Extracts and Semipurified Fractions of Chresta martii DC. and Identification of Its Principal Compounds.

Chresta martii (Asteraceae) is a species widely used by the population of the Xingu region of Sergipe, Brazil, in the form of a decoction (aerial parts) for the treatment of gastrointestinal diseases. The study aims to assess the gastroprotective activity of organic extracts and semipurified fractions and identify the principal compounds present in C. martii responsible for such activity. The organic extracts (cyclohexane: ECCm, ethyl acetate: EACm, and ethanol: EECm) were obtained from the dried aerial parts (500 g) of C. martii. For evaluation of the gastroprotective activity of extracts (50, 100, or 200 mg/kg; p.o.), male Swiss Webster mice (25-30 g) were used which had gastric ulcers induced by indomethacin (40 mg/kg, s.c.) or ethanol (0.2 mL/animal; p.o.). Among the extracts evaluated, EACm exhibited significant (P < 0.05) gastroprotective activity in the models used. The fractionation of EACm was performed in a silica gel column 60 eluted with the following compounds: [chloroform-F1 yield (10%)], [chloroform/ethyl acetate (1/1)-F2 yield (6%)], [ethyl acetate-F3 yield (8%)], and [ethyl/methanol acetate (1/1)-F4 yield (5%)]. Of the fractions described above, the F1 (25 mg/kg; p.o.) had greater gastroprotective activity (P < 0.05) than that displayed by ranitidine (80 mg/kg; p.o.) in the ethanol-induced ulcer model. The refractionation of F1 produced 23 subfractions and from these two yellow amorphous compounds were obtained by recrystallization, Rf: 0.46 and 0.31 (ethyl acetate : chloroform 5 : 5). The compounds isolated were characterized by nuclear magnetic resonance spectroscopy ((1)H-NMR and (13)C-NMR) and identified as flavones: chrysoeriol (yield: 0.43%) and 3',4'-dimethoxyluteolin (yield: 0.58%). Conclusion. Flavone 3',4'-dimethoxyluteolin is the principal compound present in the species C. martii and is probably responsible for gastroprotective activity observed in this species.

Prevalence of hepatitis C virus (HCV) infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil.

Hepatitis C virus (HCV) infection has been identified as the major cause of chronic liver disease among patients on chronic hemodialysis (HD), despite the important reduction in risks obtained by testing candidate blood donors for anti-HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross-sectional study was performed to estimate the prevalence of HCV infection and genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV seroprevalence was determined by ELISA in 1243 HD patients from all ten different dialysis centers of the city. HCV infection was confirmed by RT-PCR and genotyping was performed by restriction fragment length polymorphism. Anti-HCV seroprevalence among HD patients was 10.5% (95% CI: 8.8-12.3) (Murex anti-HCV, Abbott Murex, Chicago, IL, USA). Blood samples for qualitative HCV detection and genotyping were collected from 125/130 seropositive HD patients (96.2%). HCV-RNA was detected in 92/125 (73.6%) of the anti-HCV-positive patients. HCV genotype 1 (77.9%) was the most prevalent, followed by genotype 3 (10.5%) and genotype 2 (4.6%). Mixed infections of genotypes 1 and 3 were found in 7.0% of the total number of patients. The present results indicate a significant decrease in anti-HCV prevalence from 23.8% detected in a study carried out in 1994 to 10.5% in the present study. The HCV genotype distribution was closely similar to that observed in other hemodialysis populations in Brazil, in local candidate blood donors and in other groups at risk of transfusion-transmitted infection.

Prevalence of hepatitis C virus (HCV) infection and HCV genotypes of hemodialysis patients in Salvador, Northeastern Brazil

Hepatitis C virus (HCV) infection has been identified as the major cause of chronic liver disease among patients on chronic hemodialysis (HD), despite the important reduction in risks obtained by testing candidate blood donors for anti-HCV antibodies and the use of recombinant erythropoietin to treat anemia. A cross-sectional study was performed to estimate the prevalence of HCV infection and genotypes among HD patients in Salvador, Northeastern Brazil. Anti-HCV seroprevalence was determined by ELISA in 1243 HD patients from all ten different dialysis centers of the city. HCV infection was confirmed by RT-PCR and genotyping was performed by restriction fragment length polymorphism. Anti-HCV seroprevalence among HD patients was 10.5 percent (95 percent CI: 8.8-12.3) (Murex anti-HCV, Abbott Murex, Chicago, IL, USA). Blood samples for qualitative HCV detection and genotyping were collected from 125/130 seropositive HD patients (96.2 percent). HCV-RNA was detected in 92/125 (73.6 percent) of the anti-HCV-positive patients. HCV genotype 1 (77.9 percent) was the most prevalent, followed by genotype 3 (10.5 percent) and genotype 2 (4.6 percent). Mixed infections of genotypes 1 and 3 were found in 7.0 percent of the total number of patients. The present results indicate a significant decrease in anti-HCV prevalence from 23.8 percent detected in a study carried out in 1994 to 10.5 percent in the present study. The HCV genotype distribution was closely similar to that observed in other hemodialysis populations in Brazil, in local candidate blood donors and in other groups at risk of transfusion-transmitted infection.

Gene therapeutic approaches to induction and maintenance of tolerance.

Tolerance induction would be an ideal way to treat autoimmune diseases, especially if achievable in primed individuals. Moreover, specific tolerance would preclude the need for immunosuppressive treatment with its side effects. In this review, we will revisit the historical concepts of tolerance, and introduce a novel approach to tolerance via gene therapy. Our model system is based on the tolerogenicity of IgG carriers and B-cell antigen presentation. Results with this model demonstrate that it is simple and effective even in primed recipients, and has proven efficacy in three autoimmune models. We discuss the mechanisms of tolerance with fusion IgG's and analyze how our model of gene therapy approached can be utilized to fit in the future treatment of autoimmune conditions.

Screening the mutagenic activities of commonly used antiparasite drugs by the simultest, a simplified Salmonella/microsome plate incorporation assay

As atividades mutagenicas de 16 drogas com acao anti-parasitaria foram avaliadas pelo Simultest em ensaios qualitativos (spot testes) e quantitativos (incorporacao em placa) com uma mistura das linhagens indicadoras de Salmonella typhimurium TA97, TA98, TA100 e TA102. Quatro drogas anti-doenca de Chagas (nifurtimox, benzonidazol, CL 64,855 e MK 436) e duas drogas anti-amebiase (metronidazol e tinidazol) deram resultados positivos em testes qualitativos e a incorporacao de fracao microssomal de figado de rato nao alterou os resultados. Curvas comparadas de efeito da dose da atividade mutagenica do metronidazol, benzonidazol e CL 64,855 detectadas oelo Simultest e linhagens indicadoras individuais demonstraram que as duas abordagens possuem sensibilidades semelhantes. Os resultados corroboram a validade do Simultest como uma versao simplificada, rapida e economica do teste de Ames no rastreamento preliminar de drogas potencialmente mutagenicas

Screening the mutagenic activities of commonly used antiparasite drugs by the Simultest, a simplified Salmonella/microsome plate incorporation assay.

The mutagenic activities of 16 anti-parasite drugs were screened by the Simultest in both qualitative (spot test) and quantitative (plate incorporation) assays with a Salmonella typhimurium pool composed by the indicator strains TA97, TA98, TA100 and TA102. Four anti Chagas' disease drugs (nifurtimox, benznidazole, CL 64,855, and MK 436) and two anti-amebae drugs (metronidazole and tinidazole) gave positive results in qualitative tests and incorporation of rat liver microsomes did not alter the results. Comparative dose response curves of the mutagenic activities of CL 64,855, metronidazole and benznidazole obtained by the simultest and by individual Salmonella indicator strains demonstrated that both approaches have similar sensitivities. The results corroborate the validity of the Simultest, as a simplified, fast and economic version of the Ames test in preliminary screening of potential mutagenic drugs.

[Bacteriologic and serologic studies of an outbreak of plague in the State of Paraíba, Brazil]. / Estudos bacteriológicos e sorológicos de um surto de peste no Estado da Paraíba, Brasil.

During a plaque outbreak in the Borborema Plateau focus (Paraiba), bacteriological and serological studies were carried out in material from 452 patients (48 positives), 1,938 rodents and other small mammals (75 positives), 4,756 dogs (141 positives) and 2,047 cats (57 positives) obtained from 41 counties (out of which, 21 produced positive samples). Twenty Yersinia pestis strains isolated from material from 3 patients and 17 rodents, displayed biochemical reactions, virulence factors, antibiotic susceptibility and animal experimental pathogenicity similar to those observed in strains previously isolated. According to our findings this recent plague outbreak did not exhibit different factors from those observed during prior outbreaks in other plague foci in the northeast of Brazil.

Evaluation of genotoxic activity in the blood and urine of guinea pigs treated with nifurtimox and benznidazole.

1. The mutagenicity of serum and urine from guinea pigs treated with a single oral dose (500 mg/kg) of benznidazole and nifurtimox was assayed using the Salmonella/plate incorporation test with strain TA 100 and a nitroreductase-deficient derivative, TA 100NR. 2. The urine and blood of animals treated with nifurtimox were not mutagenic for either tester strain. 3. The urine and blood of animals receiving benznidazole were mutagenic to the TA 100 but not to the TA 100NR strain. Similar results were obtained with nitrofurantoin-treated animals. Maximum mutagenicity values were obtained in serum and urine of treated animals 90 min and 24 h after administration, respectively. 4. Mutagenicity induced by benznidazole in the serum and urine of treated animals was not altered when assayed in anaerobic environments. 5. These results indicate that benznidazole and nifurtimox are not metabolized by the mammalian host into stable mutagenic derivatives detectable by the Ames test. Based on these data, we suggest that the potential cancer risk to patients treated with these drugs is small but should be further evaluated.

Evaluation of genotoxic activity in the blood and urine of guinea pigs treated with nifurtimox and benznidazole

1. The mutagenicity of serum and urine from fuinea pigs treated with a single oral dose (500 mg/Kg) of benznidazole and nifurtimox was assayed using the Salmonella/plate incorporation test with strain TA100 and a nitroreductase-deficient derivative, TA100NR. 2. The urine and blood of animals treated with nifurtimox were not mutagenic for either tester strain. 3. The urine and blood of animals receiving benznidazole were mutagenic to the TA100 but not to the TA100NR strain. Similar results were obtained with nitrofurantoin-treated animals. Maximum mutagenicity values were obtained in serum and urine of treated animals 90 min and 24 h after administration, respectively. 4. Mutagenicity induced by benznidazole in the serum and urine of treated animals was not altered when assayed in anaerobic environments. 5. These results indicate that benznidazole and nifurtimox are not metabolized by the mammalian host into stable mutagenic derivatives detectable by the Ames test. Based on these data, we suggest that the potential cancer risk to patients treated with these drugs is small but should be further evaluated

Schistosoma mansoni: structural damage after treatment with oxamniquine.

The effects of a single dose (100 mg/kg-body weight of mouse) of oxamniquine on the worm's tegument and paranchyma in relation to the process of immunological granulomatous reaction of the host's liver are described under light and electron microscopy (EM). The lesions caused by the drug are sequentially and simultaneously described in form of swelling, surface bulble and disruption with erosions. Ulceration in the tubercules with loss of spines is often more extensive and severe in male worms and concentration of host's mononuclear cells is observed. The possible role of host's immune response is discussed.