Anti-Leishmania compounds can be screened using Leishmania spp. expressing red fluorescence (tdTomato).

The main challenges associated with leishmaniasis chemotherapy are drug toxicity, the possible emergence of resistant parasites, and a limited choice of therapeutic agents. Therefore, new drugs and assays to screen and detect novel active compounds against leishmaniasis are urgently needed. We thus validated Leishmania braziliensis (Lb) and Leishmania infantum (Li) that constitutively express the tandem tomato red fluorescent protein (tdTomato) as a model for large-scale screens of anti-Leishmania compounds. Confocal microscopy of Lb and Li::tdTomato revealed red fluorescence distributed throughout the entire parasite, including the flagellum, and flow cytometry confirmed that the parasites emitted intense fluorescence. We evaluated the infectivity of cloned promastigotes and amastigotes constitutively expressing tdTomato, their growth profiles in THP-1 macrophages, and susceptibility to trivalent antimony, amphotericin, and miltefosine in vitro. The phenotypes of mutant and wild-type parasites were similar, indicating that the constitutive expression of tdTomato did not interfere with the evaluated parameters. We applied our validated model to a repositioning strategy and assessed the susceptibility of the parasites to eight commercially available drugs. We also screened 32 natural plant and fungal extracts and 10 pure substances to reveal new active compounds. The infectivity and Glucantime treatment efficacy of BALB/c mice and golden hamsters infected with Lb and Li::tdTomato mutant lines, respectively, were very similar compared to animals infected with wild-type parasites. Standardizing our methodology would offer more rapid, less expensive, and easier assays to screen of compounds against L. braziliensis and L. infantum in vitro and in vivo. Our method could also enhance the discovery of active compounds for treating leishmaniasis.

Diversity, distribution and phytotoxic and anti-Trypanosoma activities of cultivable fungi associated with Magellan sub-Antarctic strait and Maritime Antarctic macroalgae.

We isolated and characterized the community of cultivable fungi associated with marine macroalgae present in the Magellan sub-Antarctic straits and the South Shetland Islands, Maritime Antarctica, and evaluated their production of bioactive metabolites. A total of 201 filamentous fungal isolates were obtained. The genera Antarctomyces, Pseudogymnoascus, Microdochium, Trichoderma, Cladosporium, Penicillium, Neoascochyta, Entomortierella and Linnemannia were associated with Antarctic macroalgae, with Neoascochyta paspali being the most abundant taxon. In contrast, 12 taxa representing Cadophora, Microdochium, Penicillium, Pseudogymnoascus were associated with macroalgae from the Magellan sub-Antarctic, with Penicillium dominating the assemblages. The diversity indices of the fungal communities associated with macroalgae in the two regions were similar. Among 177 fungal extracts assessed for metabolite production, 31 (17.5%) showed strong phytotoxic activity and 17 (9.6%) showed anti-Trypanosoma cruzi activity. Penicillium showed the highest phytotoxic and anti-Trypanosoma activity values. The detection of taxa in common between the polar and cold temperate zones reinforces the need for further investigations of the distribution of species in these distinct ecoregions. The detection of bioactive extracts produced particularly by Penicillium representatives reinforces the potential to obtain active molecules that can be explored as natural products or as sources of bioactive compounds with application in agriculture and biomedicine.

Searching for plant-derived antivirals against dengue virus and Zika virus.

BACKGROUND: The worldwide epidemics of diseases as dengue and Zika have triggered an intense effort to repurpose drugs and search for novel antivirals to treat patients as no approved drugs for these diseases are currently available. Our aim was to screen plant-derived extracts to identify and isolate compounds with antiviral properties against dengue virus (DENV) and Zika virus (ZIKV). METHODS: Seven thousand plant extracts were screened in vitro for their antiviral properties against DENV-2 and ZIKV by their viral cytopathic effect reduction followed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, previously validated for this purpose. Selected extracts were submitted to bioactivity-guided fractionation using high- and ultrahigh-pressure liquid chromatography. In parallel, high-resolution mass spectrometric data (MSn) were collected from each fraction, allowing compounds into the active fractions to be tracked in subsequent fractionation procedures. The virucidal activity of extracts and compounds was assessed by using the plaque reduction assay. EC50 and CC50 were determined by dose response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral vs. cytotoxic activity. Purified compounds were used in nuclear magnetic resonance spectroscopy to identify their chemical structures. Two compounds were associated in different proportions and submitted to bioassays against both viruses to investigate possible synergy. In silico prediction of the pharmacokinetic and toxicity (ADMET) properties of the antiviral compounds were calculated using the pkCSM platform. RESULTS: We detected antiviral activity against DENV-2 and ZIKV in 21 extracts obtained from 15 plant species. Hippeastrum (Amaryllidaceae) was the most represented genus, affording seven active extracts. Bioactivity-guided fractionation of several extracts led to the purification of lycorine, pretazettine, narciclasine, and narciclasine-4-O-ß-D-xylopyranoside (NXP). Another 16 compounds were identified in active fractions. Association of lycorine and pretazettine did not improve their antiviral activity against DENV-2 and neither to ZIKV. ADMET prediction suggested that these four compounds may have a good metabolism and no mutagenic toxicity. Predicted oral absorption, distribution, and excretion parameters of lycorine and pretazettine indicate them as candidates to be tested in animal models. CONCLUSIONS: Our results showed that plant extracts, especially those from the Hippeastrum genus, can be a valuable source of antiviral compounds against ZIKV and DENV-2. The majority of compounds identified have never been previously described for their activity against ZIKV and other viruses.

Cognitive Patterns and Conversion in a Representative Sample of Individuals at Risk for Psychosis.

ABSTRACT: Clinical high-risk (CHR) individuals belong to a heterogeneous group, of which only a few will cross the threshold for a clinical diagnosis. Cognitive disturbances are present in CHR subjects and may be indicative of transition. Our study aims to identify such deficits in a representative CHR for psychosis sample. Our sample comprised 92 CHR individuals and 54 controls from a representative cohort of the general population. They were followed up for a mean of 2.5 years, with 15 individuals converting to schizophrenia or other Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnoses. Neurocognitive assessment was performed with the University of Pennsylvania Computerized Neuropsychological Testing, and CHR status was assessed with the Structured Interview for Prodromal Syndromes (SIPS). Baseline scores were entered in a latent profile analysis model. Our study brought forward a four-class model on cognitive performance. One class displayed better performance, whereas the other three performed worse, all compared with controls. The class with lower executive function also had the highest score on disorganized communication (SIPS P5 = 1.36, p < 0.05), although unrelated to conversion. Among the low performers, the class significantly related to conversion (p = 0.023) had the highest score in decreased expression of emotion (SIPS N3 = 0.85, p < 0.05). Our study brings new and relevant data on non-help-seeking CHR individuals and the relationship between cognitive patterns and conversion. We have highlighted a specific cognitive signature, associated with negative symptoms, which represents a stable trait with presumed lower conversion to a psychiatric illness.

Natural Occurring Phenolic Derivatives from Mauritia flexuosa (Buriti) Stems and Their Potential Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus (MRSA).

Mauritia flexuosa Linnaeus filius (buriti or aguage; Arecaceae) is a palm used by traditional medicine in Brazil to treat dysentery and diarrhea. Our group showed that the soluble dichloromethane (CH2 Cl2 ) fraction from EtOH extract from M. flexuosa stems inhibited the growth of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and it is rich in phenolic compounds. This study aimed to isolate new phenolic compounds from CH2 Cl2 fraction from M. flexuosa stems with in vitro antibacterial activity. The crude CH2 Cl2 fraction was fractionated by gel permeation chromatography (GPC) followed by semi-preparative RP-HPLC. The antibacterial activity was evaluated using the broth microdilution method against MSSA (ATCC 29213) and MRSA (clinical isolate 155). All compounds were also tested against Gram-negative (Escherichia coli; ATCC 35218) bacteria and two fungi species (Candida albicans; ATCC 14053 and Trichophyton rubrum; ATCC MYA 4438). The chemical structures of isolated compounds were determined by analysis and comparison with literature data of their NMR and HRMS spectra and optical activity. The chemical investigation yielded seven aromatic compounds, of which four, (2S,15S)-2,15-dimethyl-2,15-dioxa-1,8(1,4)-dibenzenacyclotetradecaphane (1), (2S,5S)-1-(4-hydroxyphenyl)hexane-2,5-diol (3), bruguierol E (4), and buritin (5) were previously unreported and three are known compounds identified as 6-(4'-hydroxyphenyl) hexan-2-one (2), (+)-(2R,3R)-dihydrokaempferol (6), and (+)-(2R)-naringenin (7). Compounds 1 and 7 showed antibacterial activity against MRSA and MSSA with minimum inhibitory concentrations (MICs) of between 62.5 and 31.3 µg/mL, respectively. Our preliminary findings support that CH2 Cl2 fraction from buriti, a typical species of flooded areas of Brazilian savanna, and its aromatic phenolic compounds are active against MSSA and MRSA contributing with understanding about the traditional use of this species.

Prospective evaluation of immune haemolysis in liver transplantation.

BACKGROUND: Immune haemolysis in liver transplant (LT) can occur due to autoantibodies and alloantibodies. The aim of this study was to evaluate the prevalence and risk factors for immune haemolysis in LT. METHODS: A total of 175 consecutive patients were included. Multiorgan recipients were excluded. Samples, from before LT, seven consecutive days and weekly for 4 weeks, were evaluated for haemolysis and immunohaematological tests. SPSS 24 was used for statistical analysis. RESULTS: Nine patients (5·1%) presented positive antibody screen (AS) before LT, (2·3% clinically significant), more frequent in RhD-negative (P = 0·017). Positive DAT occurred in 53 (30·3%) and was related to high MELD score (P = 0·048), HCV (P = 0·005) and furosemide use (P = 0·001). Positive AS after LT occurred in 22 patients (12·5%), with nine (5·7%) clinically significant antibodies. Positive AS occurred more frequently in RhD negative (P = 0·021) and in those transfused (P = 0·022). Post-transplant positive DAT was associated with piperacillin-tazobactam use (P = 0·021) and minor ABO incompatibility (P = 0·0038). Five patients presented passenger lymphocyte syndrome (PLS), all received liver-graft O, four presented haemolysis, and three were transfused due to PLS. CONCLUSION: Auto- and alloantibodies against red blood cell antigens are frequent in LT, but the frequency of immune haemolysis was only 2·8%. The only risk factor for PLS was minor ABO mismatch.

Fungi in glacial ice of Antarctica: diversity, distribution and bioprospecting of bioactive compounds.

We identified cultivable fungi present in the glacial ice fragments collected in nine sites across Antarctica Peninsula and assessed their abilities to produce bioactive compounds. Three ice fragments with approximately 20 kg were collected, melted and 3 L filtered through of 0.45 µm sterilized membranes, which were placed on the media Sabouraud agar and minimal medium incubated at 10 °C. We collected 66 isolates classified into 27 taxa of 14 genera. Penicillium palitans, Penicillium sp. 1, Thelebolus balaustiformis, Glaciozyma antarctica, Penicillium sp. 7, Rhodotorula mucilaginosa, and Rhodotorula dairenensis had the highest frequencies. The diversity and richness of the fungal community were high with moderate dominance. Penicillium species were present in all samples, with Penicillium chrysogenum showing the broadest distribution. P. chrysogenum, P. palitans, and Penicillium spp. had trypanocidal, leishmanicidal, and herbicidal activities, with P. chrysogenum having the broadest and highest capability. 1H NMR signals revealed the presence of highly functionalized secondary metabolites in the bioactive extracts. Despite extreme environmental conditions, glacial ice harbours a diverse fungal community, including species never before recorded in the Arctic and Antarctica. Among them, Penicillium taxa may represent wild fungal strains with genetic and biochemical pathways that may produce new secondary bioactive metabolites.

Relationship Between Symptomatic Dimensions and Global Functioning of Non-Help-Seeking Individuals at Risk for Psychosis.

This study aims to analyze the relationship between the symptomatic dimensions of psychosis and functioning of individuals at risk for psychosis (ultrahigh risk [UHR]) in a non-help-seeking UHR sample from the general population. The sample is the same as the one used in the Brazilian Subclinical Symptoms and Prodromal Psychosis cohort study. We applied questionnaires of functioning (Global Assessment of Functioning Scale) and symptomatic dimensions (Scale of Prodromal Symptoms). Next, we correlated the symptomatic dimensions with functioning. We found a significant relationship between avolition and uncommon thought content with poor functioning, whereas the remaining symptoms were not as relevant. Poor functioning was most related to avolition, a negative symptom, followed by unusual thought content, a positive symptom.

Thiosemicarbazone of lapachol acts on cell membrane in Paracoccidioides brasiliensis.

Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin American countries. Amphotericin B, sulfonamides, and azoles may be used in the treatment of PCM. However, the high toxicity, prolonged course of treatment, and significant frequency of disease relapse compromise their use. Therefore, there is a need to seek new therapeutic options. We conducted tests with thiosemicarbazone of lapachol (TSC-lap) to determine the antifungal activity and phenotypic effects against several isolates of Paracoccidioides spp. In addition, we evaluated the toxicity against murine macrophages and the ability to enhance phagocytosis. Further, we verified that TSC-lap was active against yeasts but did not show any interaction with the drugs tested. The TSC-lap showed no toxicity at the concentration of 40 µg/ml in macrophages, and at 15.6 µg/ml it could increase the phagocytic index. We observed that this compound induced in vitro ultrastructural changes manifested as withered and broken cells beyond a disorganized cytoplasm with accumulation of granules. We did not observe indications of activity in the cell wall, although membrane damages were noted. We observed alterations in the membrane permeability, culminating in a significant increase in K+ efflux and a gradual loss of the cellular content with increase in the concentration of TSC-lap. In addition, we showed a significant reduction of ergosterol amount in the Pb18 membrane. These data reinforce the possible mechanism of action of this compound to be closely associated with ergosterol biosynthesis and reaffirms the antifungal potential of TSC-lap against Paracoccidioides spp.

Leishmanicidal compounds of Nectria pseudotrichia, an endophytic fungus isolated from the plant Caesalpinia echinata (Brazilwood).

BACKGROUND In a screen of extracts from plants and fungi to detect antileishmanial activity, we found that the ethyl acetate extract of the fungus Nectria pseudotrichia, isolated from the tree Caesalpinia echinata (Brazilwood), is a promising source of bioactive compounds. OBJECTIVES The aims of this study were to isolate and determine the chemical structures of the compounds responsible for the antileishmanial activity of the organic extract from N. pseudotrichia. METHODS Compounds were isolated by chromatographic fractionation using semi-preparative high-performance liquid chromatography, and their chemical structures were determined by analytical and spectral data and by comparison with published data. The antileishmanial activity of the isolated compounds was evaluated in intracellular amastigote forms of Leishmania (Viannia) braziliensis expressing firefly luciferase as reporter gene, and cytotoxicity was determined in Vero and THP-1 mammalian cell lines by MTT assay. FINDINGS Fractionation of the extract yielded seven compounds: 10-acetyl trichoderonic acid A (1), 6'-acetoxy-piliformic acid (2), 5',6'-dehydropiliformic acid (3), piliformic acid (4), hydroheptelidic acid (5), xylaric acid D (6), and cytochalasin D (7). Compounds 1, 2 and 3 are reported here for the first time. Compounds 1, 2, and 5 were more active, with IC50 values of 21.4, 28.3, and 24.8 µM, respectively, and showed low toxicity to Vero and THP-1 cells. MAIN CONCLUSIONS N. pseudotrichia produces secondary metabolites that are more toxic to intracellular amastigote forms of L. (V.) braziliensis than to mammalian cells.

A new insight into purinergic pharmacology: Three fungal species as natural P2X7R antagonists.

P2X7 is a purinergic receptor involved in important physiological functions and pathological processes, such as inflammation, neurodegeneration, and pain. Despite its relevance, there is no selective antagonist useful in the treatment of diseases related to this receptor. In this context, research for a selective, safe, and potent antagonist compound that can be used in clinical therapy has been growing. In this work, we evaluated the potential antagonistic activity of three fungal extracts, namely, Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp., which were discovered in a high-throughput screening campaign to search for new antagonists for P2X7R from natural products. First, the IC50 values of these fungal extracts were determined in J774.G8 (murine macrophage cell line) and U937 (human monocyte cell line) cells through dye uptake assays. The IC50 values of V. victoriae were 2.6 and 0.92 µg/mL, M. australis has IC50 values of 3.8 and 1.5 µg/mL, and Ascomycota sp. showed values of 2.1 and 0.67 µg/mL in J774.G8 and U937 cells, respectively. These extracts also significantly inhibited propidium iodide and Lucifer yellow uptake via P2X7R pore, P2X7R currents in electrophysiology, IL-1ß release, and the production of oxide nitric and reactive oxygen species. The extracts did not cause cytotoxicity within a period of 24 h. The results showed the promising antagonistic activity of these extracts toward P2X7R, thereby indicating that they can be future candidates for phytomedicines with potential clinical applicability.

Untargeted Liquid Chromatography-High-Resolution Mass Spectrometry Metabolomic Investigation Reveals Altered Lipid Content in Leishmania infantum Lacking Lipid Droplet Protein Kinase.

Leishmaniasis is a complex disease caused by different species of Leishmania. To date, no vaccine for humans or ideal therapy has been developed owing to the limited efficacy and toxicity of available drugs, as well as the emergence of resistant strains. Therefore, it is necessary to identify novel therapeutic targets and discover therapeutic options for leishmaniasis. In this study, we evaluated the impact of deleting the lipid droplet protein kinase (LDK) enzyme in Leishmania infantum using an untargeted metabolomics approach performed using liquid chromatography and high-resolution mass spectrometry. LDK is involved in lipid droplet biogenesis in trypanosomatids. Thirty-nine lipid metabolites altered in the stationary and logarithmic growth phases were noted and classified into five classes: (1) sterols, (2) fatty and conjugated acids, (3) ceramides, (4) glycerophosphocholine and its derivatives, and (5) glycerophosphoethanolamine and its derivatives. Our data demonstrated that glycerophosphocholine and its derivatives were the most affected after LDK deletion, suggesting that the absence of this enzyme promotes the remodeling of lipid composition in L. infantum, thus contributing to a better understanding of the function of LDK in this parasite.

Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part I: Aspidosperma nitidum (Benth) used as a remedy to treat fever and malaria in the Amazon.

Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region. Several species of this family are known to possess indole alkaloids and other classes of secondary metabolites, whereas terpenoids, an inositol and the indole alkaloids harmane-3 acid and braznitidumine have been described in A. nitidum . In the present study, extracts from the wood bark, leaves and branches of this species were prepared for assays against malaria parasites and cytotoxicity testing using human hepatoma and normal monkey kidney cells. The wood bark extracts were active against Plasmodium falciparum and showed a low cytotoxicity in vitro, whereas the leaf and branch extracts and the pure alkaloid braznitidumine were inactive. A crude methanol extract was subjected to acid-base fractionation aimed at obtaining alkaloid-rich fractions, which were active at low concentrations against P. falciparum and in mice infected with and sensitive Plasmodium berghei parasites. Our data validate the antimalarial usefulness of A. nitidum wood bark, a remedy that can most likely help to control malaria. However, the molecules responsible for this antimalarial activity have not yet been identified. Considering their high selectivity index, the alkaloid-rich fractions from the plant bark might be useful in the development of new antimalarials.

The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives.

Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.

A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis.

OBJECTIVES: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. METHODS: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. RESULTS: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). CONCLUSION: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Use of a Bayesian Network Model to predict psychiatric illness in individuals with 'at risk mental states' from a general population cohort.

The 'at risk mental state' (ARMS) paradigm has been introduced in psychiatry to study prodromal phases of schizophrenia. With time it was seen that the ARMS state can also precede mental disorders other than schizophrenia, such as depression and anxiety. However, several problems hamper the paradigm's use in preventative medicine, such as varying transition rates across studies, the use of non-naturalistic samples, and the multifactorial nature of psychiatric disorders. To strengthen ARMS predictive power, there is a need for a holistic model incorporating-in an unbiased fashion-the small-effect factors that cause mental disorders. Bayesian networks, a probabilistic graphical model, was used in a populational cohort of 83 ARMS individuals to predict conversion to psychiatric illness. Nine predictors-including state, trait, biological and environmental factors-were inputted. Dopamine receptor 2 polymorphism, high private religiosity, and childhood trauma remained in the final model, which reached an 85.51% (SD = 0.1190) accuracy level in predicting conversion. This is the first time a robust model was produced with Bayesian networks to predict psychiatric illness among at risk individuals from the general population. This could be an important tool to strengthen predictive measures in psychiatry which should be replicated in larger samples to provide the model further learning.

Physicochemical Profile, Antioxidant and Antimicrobial Activities of Honeys Produced in Minas Gerais (Brazil).

Honeys can be classified as polyfloral or monofloral and have been extensively studied due to an increased interest in their consumption. There is concern with the correct identification of their flowering, the use of analyses that guarantee their physicochemical quality and the quantification of some compounds such as phenolics, to determine their antioxidant and antimicrobial action. This study aims at botanical identification, physicochemical analyses, and the determination of total polyphenols, chromatographic profile and antiradical and antimicrobial activity of honey from different regions of Minas Gerais. Seven different samples were analyzed for the presence of pollen, and color determination. The physicochemical analyses performed were total acidity, moisture, HMF, reducing sugar, and apparent sucrose. The compound profile was determined by UHPLC/MS, the determination of total phenolics and antiradical activity (DPPH method) were performed by spectrophotometry, and minimum inhibitory and bacterial concentrations were determined for cariogenic bacteria. All honey samples met the quality standards required by international legislation, twenty compounds were detected as the main ones, the polyfloral honey was the only honey that inhibited all of the bacteria tested. Sample M6 (Coffee) was the one with the highest amount of total polyphenols, while the lowest was M4 (Cipó-uva). Regarding the antioxidant activity, M5 (Velame) had the best result and M4 (Cipó-uva) was the one that least inhibited oxidation. Of the polyfloral honeys, there was not as high a concentration of phenolic compounds as in the others. Coffee, Aroeira, Velame and Polyfloral have the best anti-radical actions. Betônica, Aroeira, Cipó-uva and Pequi inhibited only some bacteria. The best bacterial inhibition results are from Polyfloral.

Antifungal activity of trichothecenes from Fusarium sp. against clinical isolates of Paracoccidioides brasiliensis.

Paracoccidioidomycosis (PCM), a human mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis, is a serious public health problem in several countries of Latin America. In our search we found that the crude extract of the endophytic fungus UFMGCB 551 was able to inhibit several clinical strains of P. brasiliensis, and was also active in the bioautographic assay against Cladosporium sphaerospermum. The endophytic fungus UFMGCB 551 was isolated from the plant Piptadenia adiantoides J.F. Macbr (Fabaceae). The fungus was identified as Fusarium sp. based on its macro- and micro-morphology, and on the sequence of the internally transcribed spacer regions (ITS) of its rRNA gene. The chromatographic fractionation of the fungal extract was guided by the bioautographic assay to afford three known trichothecene mycotoxins: T2-toxin (1) and a mixture of 8-n-butyrylneosolaniol (2) and 8-isobutyrylsolaniol (3). The minimal inhibitory concentrations (MIC) of the these compounds against eleven clinical strains of P. brasiliensis were evaluated and found to be in the range between 75 and 640 nmol l(-1) for 1 and 160-640 nmol l(-1) for the mixture of 2 and 3.

Gray Matter Volume in Elderly adults With ADHD: Associations of Symptoms and Comorbidities With Brain Structures.

Objective: To investigate total and selected region-of-interest-based gray matter volume (GMV) in older adults with ADHD. Method: Twenty-five elderly (≥65 years old) patients with ADHD and 34 healthy controls underwent 1.5-T magnetic resonance imaging (MRI). We used voxel-based morphometry to compare GMV between groups and performed a correlation analysis with ADHD symptoms and comorbidities. Results: Findings revealed a smaller total GMV in males with ADHD and a smaller GMV in the right medial frontal orbital area extending toward the medial frontal superior, the frontal superior, and the subgenual anterior cingulate cortex (ACC) besides correlations between inattentiveness and ACC (bilaterally) and left cerebellum, hyperactivity/impulsivity and the left frontal inferior orbital, depression and caudate (bilaterally), and the right inferior parietal lobule. Conclusion: Neural correlates in regions related to attention, executive control, and affective processing suggest that impairments in frontostriatal and frontoparietal-cerebellar areas observed in adults with ADHD persist into old age.

Trypanocidal Trixikingolides From Trixis Vauthieri.

Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi. Only two drugs are available, with the drawback of low rate of cure in the chronic phase of the disease and undesirable side effects. These facts highlight the need to find new compounds for Chagas disease chemotherapy. We describe the isolation and identification of an inseparable mixture of two new trixikingolides from Trixis vauthieri, a plant from family Asteraceae, which present outstanding in vitro trypanocidal activity, with IC50 value of 0.053 µM against the intracellular trypomastigotes and amastigotes forms of T. cruzi infecting L929 cells. The IC50 of the mixture against the host cells is 68 times higher and about 70 times more potent than benznidazole, the reference drug used as control at the experiments. The next step, which depends on obtaining larger quantities of the mixture, is to test it on mice infected with T. cruzi.