Exploring colorant production by amazonian filamentous fungi: Stability and applications.

The aim of this study was to investigate the production, stability and applicability of colorants produced by filamentous fungi isolated from soil samples from the Amazon. Initially, the isolates were evaluated in a screening for the production of colorants. The influences of cultivation and nutritional conditions on the production of colorants by fungal isolates were investigated. The colorants produced by selected fungal isolates were chemically characterized using the Liquid Chromatography-Mass Spectrometry technique. The antimicrobial and cytotoxic activities, stability evaluation and applicability of the colorants were investigated. As results, we observed that the isolates Penicillium sclerotiorum P3SO224, Clonostachys rosea P2SO329 and Penicillium gravinicasei P3SO332 stood out since they produced the most intense colorants. Compounds produced by Penicillium sclerotiorum P3SO224 and Clonostachys rosea P2SO329 were identified as sclerotiorin and penicillic acid. The colorant fraction (EtOAc) produced by these species has antimicrobial activity, stability at temperature and at different pHs, stability when exposure to light and UV, and when exposed to different concentrations of salts, as well as being nontoxic and having the ability to dye fabrics and be used as a pigment in creams and soap. Considering the results found in this study, it was concluded that fungi from the soil in the Amazon have the potential to produce colorants with applications in the textile and pharmaceutical industries.

Evidence of altitudinal gradient modifying genomic and chemical diversity in populations of Lychnophora pinaster Mart.

Lychnophora pinaster Mart. (Asteraceae) is endemic to the Brazilian Cerrado. It is distributed along the altitudinal gradient of the mountainous ranges of the state of Minas Gerais. This study aimed to evaluate the influence of altitude on the genetic diversity of L. pinaster populations and the effects of altitude and climatic factors on essential oil chemical composition. Essential oils from L. pinaster populations from the north (North 01, North 02, and North 03, 700-859 m) and the Metropolitan region of Belo Horizonte (MhBH 01 and MrBH 02, 1366-1498 m) were analyzed. SNP markers from L. pinaster in these regions and Campos das Vertentes (CV 01, CV 02, and CV 03, 1055-1292 m) were also analyzed. The main compounds in essential oils were 14-hydroxy-α-humulene (North 01 and North 03), cedr-8(15)-en-9-α-ol (North 02), 14-acetoxy-α-humulene (MrBH 01), and 4-oxo-15-nor-eudesman-11-ene (MrBH 02). Hierarchical cluster and heatmap analyses showed that the North and MrBH populations included five different groups, indicating the chemical composition of essential oils is distinct in each population. Furthermore, principal component analysis showed that higher altitudes (1366 m and 1498 m) in the MrBH influence the chemical composition of essential oils, and climatic factors determine the chemical composition in North region. The genetic diversity showed that most alleles are in Hardy-Weinberg equilibrium and imply high genetic variation and genetic polymorphisms between populations. Furthermore, the results of Mantel tests (R = 0.3861517; p = 0.04709529; R = 0.9423121; p = 0.02739726) also showed that higher altitude (>1360 m) shapes the genetic diversity at the MrBH. The genetic structure showed that higher altitudes (>1360 m) contribute to the structure of the MrBH populations, but not to North and CV populations. Therefore, the altitudinal ranges of Minas Gerais mountainous ranges determine the higher genetic and chemical diversity of L. pinaster populations.

Responses of wheat (Triticum aestivum) and turnip (Brassica rapa) to the combined exposure of carbaryl and ultraviolet radiation.

The increase of ultraviolet (UV) radiation reaching the Earth's surface as a result of increased ozone layer depletion has affected crop production systems and, in combination with pesticides used in agricultural activities, can lead to greater risks to the environment. The impact of UV radiation and carbaryl singly and in combination on Triticum aestivum (wheat) and Brassica rapa (turnip) was studied. The combined exposure was analyzed using the MixTox tool and was based on the conceptual model of independent action, where possible deviations to synergism or antagonism and dose-ratio or dose-level response pattern were also considered. Compared with the control, carbaryl and UV radiation individually led to reductions in growth, fresh and dry weight, and water content for both species. Combined treatment of UV and carbaryl was more deleterious compared with single exposure. For T. aestivum length, no interaction between the 2 stressors was found (independent action), and a dose-level deviation was the best description for the weight parameters. For B. rapa, dose-ratio deviations from the conceptual model were found when length and dry weight were analyzed, and a higher than expected effect on the fresh weight (synergism) occurred with combined exposure.

Carbaryl toxicity prediction to soil organisms under high and low temperature regimes.

Many studies on risk assessment of pesticides on non-target organisms have been performed based on standardized protocols that reflect conditions in temperate climates. However, the responses of organisms to chemical compounds may differ according to latitude and thus predicting the toxicity of chemicals at different temperatures is an important factor to consider in risk assessment. The toxic effects of the pesticide carbaryl were evaluated at different temperature regimes, which are indicative of temperate and tropical climates and are relevant to climate change predictions or seasonal temperature fluctuations. Four standard organisms were used (Folsomia candida, Eisenia andrei; Triticum aestivum and Brassica rapa) and the effects were assessed using synergistic ratios, calculated from EC/LC50 values. When possible, the MIXTOX tool was used based on the reference model of independent action (IA) and possible deviations. A decrease on carbaryl toxicity at higher temperatures was found in F. candida reproduction, but when the mixtox tool was used no interactions between these stressors (Independent Action) was observed, so an additive response was suggested. Synergistic ratios showed a tendency to synergism at high temperatures for E. andrei and B. rapa and antagonism at low temperatures for both species. T. aestivum showed to be less affected than expected (antagonism), when exposed to both low and high temperatures. The results showed that temperature may increase the deleterious effects of carbaryl to non-target organisms, which is important considering both seasonal and latitude related differences, as well as the global climate change context.

Safety and immunovirologic outcomes with maraviroc combination regimens in patients with a history of past treatment failures and virologic resistance in Brazil: an open-label, multicenter phase 3b study.

Maraviroc is a first-in-class chemokine coreceptor type-5 (CCR5) antagonist with demonstrated immunovirologic activity in treatment-experienced (TE) patients with CCR5 (R5)-tropic HIV-1; however, experience in regimens containing newer antiretroviral agents is limited. The primary objective of this 96-week open-label, noncomparative, multicenter Phase 3b study (NCT00478231) was to assess the safety of maraviroc in combination with optimized background therapy (OBT), which could include recently introduced agents such as darunavir and raltegravir in TE patients in Brazil with R5 HIV-1 and limited therapeutic options. Immunovirologic activity was a secondary endpoint. Of 638 patients screened, 206 were treated and 125 completed the study. Approximately 70% were male; the mean age was 43.2 years. Most patients (65.0%) received an OBT combination of protease inhibitor plus nucleoside reverse transcriptase inhibitor. Adverse event (AE) and treatment-related AE incidence was 91.3% and 36.9%, respectively. The most common AEs were diarrhea, nasopharyngitis, and headache. Serious AEs and treatment-related serious AEs occurred in 16.5% and 4.4% of patients. Only eight patients (3.9%) discontinued due to AEs. Few AIDS-defining events were observed (4.9%). The proportion of patients with viral load <400 copies/ml increased from 2.4% at baseline to 43.9% at week 8, remaining >40% until week 48. At the end of treatment, 26.7% of patients had a viral load <400 copies/ml. Median CD4(+) cell count increased throughout the study; the mean change from baseline to end of treatment was 174.1 cells/µl. In conclusion, maraviroc, combined with different agents from multiple classes, was well tolerated in highly TE patients. Maraviroc plus OBT was associated with an immunovirologic response in this population.

Combined effects of soil moisture and carbaryl to earthworms and plants: simulation of flood and drought scenarios.

Studying tolerance limits in organisms exposed to climatic variations is key to understanding effects on behaviour and physiology. The presence of pollutants may influence these tolerance limits, by altering the toxicity or bioavailability of the chemical. In this work, the plant species Brassica rapa and Triticum aestivum and the earthworm Eisenia andrei were exposed to different levels of soil moisture and carbaryl, as natural and chemical stressors, respectively. Both stress factors were tested individually, as well as in combination. Acute and chronic tests were performed and results were discussed in order to evaluate the responses of organisms to the combination of stressors. When possible, data was fitted to widely employed models for describing chemical mixture responses. Synergistic interactions were observed in earthworms exposed to carbaryl and drought conditions, while antagonistic interactions were more representative for plants, especially in relation to biomass loss under flood-simulation conditions.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial.

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 +/- 19.8) were administered IVA (500 mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500 mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study--EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1%) completed the study. At the end of treatment, 95.2% (CI95: 88.9% - 100%) reported cure or clinical improvement; at the end of the study, that figure was 88.9% (CI95: 74.1% - 91.7%). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40%), and 8 reported presumed eradication (53.3%). At end of study evaluation, 9 patients showed pathogen eradication (50%), and 7 showed presumed eradication (38.89%). Therefore, negative cultures were obtained from 93.3% of the patients at EOT, and from 88.9% at the end of the study. One patient (6.67% of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11%) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3% of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin associated to ceftriaxone and followed by oral azithromycin proved to be efficacious and well-tolerated in the treatment of Brazilian inpatients with CAP.

Intravenous azithromycin plus ceftriaxone followed by oral azithromycin for the treatment of inpatients with community-acquired pneumonia: an open-label, non-comparative multicenter trial

Community-Acquired Pneumonia (CAP) is a major public health problem. In Brazil it has been estimated that 2,000,000 people are affected by CAP every year. Of those, 780,000 are admitted to hospital, and 30,000 have death as the outcome. This is an open-label, non-comparative study with the purpose of evaluating efficacy, safety, and tolerability levels of IV azithromycin (IVA) and IV ceftriaxone (IVC), followed by oral azithromycin (OA) for the treatment of inpatients with mild to severe CAP. Eighty-six patients (mean age 56.6 ± 19.8) were administered IVA (500mg/day) and IVC (1g/day) for 2 to 5 days, followed by AO (500mg/day) to complete a total of 10 days. At the end of treatment (EOT) and after 30 days (End of Study - EOS) the medication was evaluated clinically, microbiologically and for tolerability levels. Out of the total 86-patient population, 62 (72.1 percent) completed the study. At the end of treatment, 95.2 percent (CI95: 88.9 percent - 100 percent) reported cure or clinical improvement; at the end of the study, that figure was 88.9 percent (CI95: 74.1 percent - 91.7 percent). Out of the 86 patients enrolled in the study, 15 were microbiologically evaluable for bacteriological response. Of those, 6 reported pathogen eradication at the end of therapy (40 percent), and 8 reported presumed eradication (53.3 percent). At end of study evaluation, 9 patients showed pathogen eradication (50 percent), and 7 showed presumed eradication (38.89 percent). Therefore, negative cultures were obtained from 93.3 percent of the patients at EOT, and from 88.9 percent at the end of the study. One patient (6.67 percent of patient population) reported presumed microbiological resistance. At study end, 2 patients (11.11 percent) still reported undetermined culture. Uncontrollable vomiting and worsening pneumonia condition were reported by 2.3 percent of patients. Discussion and Conclusion Treatment based on the administration of IV azithromycin...

Mother-to-Infant transmission of hepatitis C virus (HCV) in Brazil.

Sixty-one women with anti-HCV antibodies, detected by a third-generation enzyme immunoassay (EIA3), were prospectively recruited for investigation of vertical HCV transmission during child-birth, at the University Hospital of the Catholic University of Campinas, Brazil, between January 1994 and July 1998. Six of the women presented coinfection with the human immunodeficiency virus type 1 (HIV-1). All of the 72 children born in this period were followed at least until they were 18 months of age. Analyses of anti-HCV, HCV RNA, and alanine aminotransferase were performed in a minimum of two blood samples during follow-up. One (2.4 per cent; 95 per cent CI, 2.2-7) of the 42 children born to HCV viremic mothers was both anti-HCV and HCV RNA-positive, with altered ALT levels. Passively transferred maternal anti-HCV antibodies became undetectable within 9-12 months. None of the nine infants born to HIV-1 infected mothers were infected either by HIV or HCV. Thus, the mother-infant HCV transmission rate is low and seems to be associated with maternal HCV RNA positivity.