Antifungal derivatives from Piper mollicomum and P. lhotzkyanum (Piperaceae)

Bioguided fractionation of the extracts from leaves of Piper mollicomum and Piper lhotzkyanum against the fungi Cladosporium cladosporioides and C. sphaerospermum afforded seven bioactive compounds, four being chromenes: methyl 2,2-dimethyl-2H-chromene-6-carboxylate, methyl 8-hydroxy-2,2-dimethyl-2H-chromene-6-carboxylate, 2-methyl-2-[4'-methyl-3'-pentenyl]-2H-1-benzopyran-6-carboxylic acid, 2,2-dimethyl-2H-chromene-6-carboxylic acid, one a dihydrochalcone: 2',6'-dihydroxy-4'-methoxydihydrochalcone, and two flavanones: 7-methoxy-5,4'-dihydroxy-flavanone and 7,4'-dimethoxy-5-hydroxy-flavanone. The structures of the bioactive isolated derivatives were elucidated by interpretation of their NMR data [¹H and 13C (BBD, DEPT 135º)], and mass spectral data as well as by comparison with data described in the literature.

Amphotericin B associated with triglyceride-rich nanoemulsion: stability studies and in vitro antifungal activity

Amphotericin B (AB) is the standard drug for invasive fungal infection therapy. It has a broad spectrum of activity and it is the best antifungal available against most yeasts and molds. Its therapeutic use, however, is limited by significant side effects, leading to a low therapeutic index when it is used as the traditional formulation (Fungizone®). Due to self-association, AB can form pores in cholesterol-containing membranes. We propose a triglyceride-rich nanoemulsion as a delivery system for AB in low levels of aggregation to reduce the toxicity against host cells.

Antifungal activity against postharvest fungi by extracts from Colombian propolis

The aims of the present study were to evaluate the antifungal properties of Colombian propolis extracts against Colletotrichum gloeosporioides and Botryodiplodia theobromae, and to isolate and identify the main constituents from the active extracts. Therefore, propolis samples were thoroughly extracted with n-hexane/methanol (EPEM), dichloromethane, ethyl acetate, and methanol. Experimental results indicated that mycelial growth of all selected microorganisms was reduced in culture media containing EPEM and dichloromethane fractions. Furthermore, through antifungal bioassay-guided fractionation, three known labdane-type diterpenes: isocupressic acid (1), (+)-agathadiol (2) and epi-13-torulosol (3) were isolated as the main constituents from the active fractions.

Antifungal iridoids, triterpenes and phenol compounds from Alibertia myrciifolia Sprunge Ex. Schum

The new iridoid glucoside 10-O-vanilloyl-geniposidic acid has been isolated from the aerial parts of Alibertia myrciifolia along with hydroxyhopanone, 3α,22-dihydroxyhopane, ursolic acid, luteolin-3´,4´-dimethyl ether, caffeic acid and geniposidic acid. The structures of the isolated compounds were determined by means of mass spectrometry and nuclear magnetic resonance spectral analyses. The antifungal activities of the iridoids 10-O-vanilloyl-geniposidic acid and geniposidic acid were evaluated against the phytopathogenic fungi strains Colletotrichum gloeosporioides, Fusarium solani and Aspergillus niger.

Synthesis and antifungal activity of halogenated aromatic bis-γ-lactones analogous to avenaciolide

Here we describe the total syntheses and characterization by elemental analyses, infrared and NMR spectroscopy of three new compounds analogous to avenaciolide, a bis-γ-lactone isolated from Aspergillus avenaceus that possesses antifungal activity, where the octyl group of the natural product was replaced by aromatic groups containing chlorine and fluorine atoms. The effects of the avenaciolide, the novel compounds and their synthetic precursors on mycelia development and conidia germination of Colletotrichum gloeosporioides and Fusarium solani were evaluated in vitro. The title compounds were almost as active as avenaciolide. The absolute structures of the chlorinated analogs were determined by X-ray diffraction analysis.

Syntheses, characterization and antifungal activity of tris(1,10-phenanthroline)iron(ii) bis(n-r-sulfonyldithiocarbimate)zincate(ii)

Four new compounds with the general formula [Fe(phen)3][Zn(RSO2N=CS2)2], where phen = 1,10-phenanthroline, R = 4-FC6H4 (1), 4-ClC6H4 (2), 4-BrC6H4 (3) and 4-IC6H4 (4), respectively, were obtained by the reaction of the appropriate potassium N-R-sulfonyldithiocarbimate (RSO2N=CS2K2) and tris(1,10-phenanthroline)iron(II) sulfate, with zinc(II) acetate dihydrate in dimethylformamide. The elemental analyses and the IR data were consistent with the formation of the expected complexes salts. The ¹H and 13C NMR spectra showed the signals for the cationic iron(II) complex and dithiocarbimate moieties. The molar conductance data were consistent with the 1:1 cation:anion complexes in 1-4. The antifungal activities of the compounds were tested in vitro against Candida albicans, Candida tropicalis and Colletotrichum gloeosporioides.

MICROESTRUTURA E PROPRIEDADES DE FILMES DE AMIDO-ÁLCOOL POLIVINÍLICO-ALGINATO ADICIONADOS DE ÓLEOS ESSENCIAIS DE COPAÍBA E CAPIM LIMÃO

AbstractFilms obtained by blends between starch and other polymers and films developed with the addition of an oil can show higher water vapor barriers and improved mechanical properties. Films with starch/PVOH/alginate were obtained by adding copaiba and lemongrass essential oils (EOs). Films without oil served as the control. The microstructure, water vapor permeability (PVA), mechanical properties, and antifungal activity were determined for the films. The effects of the addition of the EOs on the properties of the films were dependent of the concentration and type of oil. The films with 0.5% lemongrass EO were similar to the control films. These films showed a 2.02 × 10-12 g s-1Pa m-1 PVA, 11.43 MPa tensile stress, 13.23% elongation, and 247.95 MPa/mm resistance at perforation. The addition of 1% of copaiba EO increased the PVA from 0.5 × 10-12 to 12.1 × 10-12 g s-1 Pa m-1 and the diffusion coefficient from 0.17 × 10-8 to 7.15 × 10-8m2/day. Films with quantities of EOs displayed fissures and micropores; the control films developed micropores with smaller diameters than films with EOs. The addition of EOs did not change the resulting infrared spectrum of the films. The films with oil displayed a diminished development of the Fusarium sp. culture, and the film without EOs did not display notable differences in the development of the culture. The starch/PVOH/alginate films with 0.5% lemongrass EO were the most suited for the development of a packaging active system.

SYNTHESIS AND ANTIFUNGAL ACTIVITY OF PALMITIC ACID-BASED NEOGLYCOLIPIDS RELATED TO PAPULACANDIN D

A series of six new palmitic acid-based neoglycolipids related to Papulacandin D were synthesized in five steps, resulting in good yields, and they were evaluated against Candida spp. All twelve synthetic intermediates were also evaluated. The synthesis involved the initial glycosylation of two phenols (4-hydroxy-3-methoxybenzaldehyde and 3-hydroxybenzaldehyde) via their reaction with peracetylated glucosyl bromide. This was followed by deacetylation with potassium methoxide/metanol solution and the protection of two hydroxyls (C4 and C6 positions) of the saccharide unit as benzilidene acetals (10-11). The next step involved the acylation of the acetal derivatives with palmitic acid, thereby affording a mixture of two isomers mono-acylated at the C2 and C3 positions and a di-acylated product (12-17). After being isolated, each compound was subjected to the removal of the acetal protecting group to yield the papulacandin D analogues 18-23. Three compounds showed low antifungal activity against two species: C. albicans (compounds 7 and 23) and C. tropicalis (compound 17) at 200 µg mL−1.

Natural history of celiac disease-associated antibodies and progression to overt disease in children at increased genetic risk

Background: Celiac disease is a lifelong, gluten-sensitive, autoimmune-mediated chronic enteropathy, tightly associated with risk alleles at the HLA class II genes. Aims: This study was carried out as a part of the population-based Type 1 Diabetes Prediction and Prevention (DIPP) Project. The first aim was to study the natural history of celiac disease-associated antibodies before the diagnosis of celiac disease was made. The second aim was to describe when and in which order celiac disease-associated and type 1 diabetes-associated antibodies appeared in children with genetic risk for both diseases. Subjects and Methods: Antibodies against tissue transglutaminase (TGA) and other celiac disease-associated antibodies were measured in serum samples collected at 3- to 12-month intervals of children at genetic risk for celiac disease who participated in the DIPP project. Celiac disease was confirmed by duodenal biopsy. Type 1 diabetes-associated antibodies were measured in all samples that had been collected. Overt disease was diagnosed according to World Health Organization criteria. Follow-up continued until a diagnosis of type 1 diabetes or until the end of a defined follow-up period. Results: TGA appeared in children at genetic risk for celiac disease only after the first year of life, but anti-gliadin antibodies often emerged significantly earlier, at age 6 months. The data show that spontaneous disappearance of celiac disease-associated antibodies, transient or persisting, is a common phenomenon, at least in prepubertal children. In children with genetic susceptibility to type 1 diabetes and celiac disease, celiac disease-associated antibodies usually develop earlier than the type 1 diabetes-associated antibodies. Conclusions: The transient nature of celiac disease-associated antibodies emphasizes the significance of establishing seropositivity repeatedly in screening detected celiac disease before gastroscopy and duodenal biopsy are considered and emphasized the importance of duodenal biopsy for diagnosing celiac disease.

Towards increased productivity and quality in software development using agile, lean and collaborative approaches

Dagens programvaruindustri står inför alltmer komplicerade utmaningar i en värld där programvara är nästan allstädes närvarande i våra dagliga liv. Konsumenten vill ha produkter som är pålitliga, innovativa och rika i funktionalitet, men samtidigt också förmånliga. Utmaningen för oss inom IT-industrin är att skapa mer komplexa, innovativa lösningar till en lägre kostnad. Detta är en av orsakerna till att processförbättring som forskningsområde inte har minskat i betydelse. IT-proffs ställer sig frågan: “Hur håller vi våra löften till våra kunder, samtidigt som vi minimerar vår risk och ökar vår kvalitet och produktivitet?” Inom processförbättringsområdet finns det olika tillvägagångssätt. Traditionella processförbättringsmetoder för programvara som CMMI och SPICE fokuserar på kvalitets- och riskaspekten hos förbättringsprocessen. Mer lättviktiga metoder som t.ex. lättrörliga metoder (agile methods) och Lean-metoder fokuserar på att hålla löften och förbättra produktiviteten genom att minimera slöseri inom utvecklingsprocessen. Forskningen som presenteras i denna avhandling utfördes med ett specifikt mål framför ögonen: att förbättra kostnadseffektiviteten i arbetsmetoderna utan att kompromissa med kvaliteten. Den utmaningen attackerades från tre olika vinklar. För det första förbättras arbetsmetoderna genom att man introducerar lättrörliga metoder. För det andra bibehålls kvaliteten genom att man använder mätmetoder på produktnivå. För det tredje förbättras kunskapsspridningen inom stora företag genom metoder som sätter samarbete i centrum. Rörelsen bakom lättrörliga arbetsmetoder växte fram under 90-talet som en reaktion på de orealistiska krav som den tidigare förhärskande vattenfallsmetoden ställde på IT-branschen. Programutveckling är en kreativ process och skiljer sig från annan industri i det att den största delen av det dagliga arbetet går ut på att skapa något nytt som inte har funnits tidigare. Varje programutvecklare måste vara expert på sitt område och använder en stor del av sin arbetsdag till att skapa lösningar på problem som hon aldrig tidigare har löst. Trots att detta har varit ett välkänt faktum redan i många decennier, styrs ändå många programvaruprojekt som om de vore produktionslinjer i fabriker. Ett av målen för rörelsen bakom lättrörliga metoder är att lyfta fram just denna diskrepans mellan programutvecklingens innersta natur och sättet på vilket programvaruprojekt styrs. Lättrörliga arbetsmetoder har visat sig fungera väl i de sammanhang de skapades för, dvs. små, samlokaliserade team som jobbar i nära samarbete med en engagerad kund. I andra sammanhang, och speciellt i stora, geografiskt utspridda företag, är det mera utmanande att införa lättrörliga metoder. Vi har nalkats utmaningen genom att införa lättrörliga metoder med hjälp av pilotprojekt. Detta har två klara fördelar. För det första kan man inkrementellt samla kunskap om metoderna och deras samverkan med sammanhanget i fråga. På så sätt kan man lättare utveckla och anpassa metoderna till de specifika krav som sammanhanget ställer. För det andra kan man lättare överbrygga motstånd mot förändring genom att introducera kulturella förändringar varsamt och genom att målgruppen får direkt förstahandskontakt med de nya metoderna. Relevanta mätmetoder för produkter kan hjälpa programvaruutvecklingsteam att förbättra sina arbetsmetoder. När det gäller team som jobbar med lättrörliga och Lean-metoder kan en bra uppsättning mätmetoder vara avgörande för beslutsfattandet när man prioriterar listan över uppgifter som ska göras. Vårt fokus har legat på att stöda lättrörliga och Lean-team med interna produktmätmetoder för beslutsstöd gällande så kallad omfaktorering, dvs. kontinuerlig kvalitetsförbättring av programmets kod och design. Det kan vara svårt att ta ett beslut att omfaktorera, speciellt för lättrörliga och Lean-team, eftersom de förväntas kunna rättfärdiga sina prioriteter i termer av affärsvärde. Vi föreslår ett sätt att mäta designkvaliteten hos system som har utvecklats med hjälp av det så kallade modelldrivna paradigmet. Vi konstruerar även ett sätt att integrera denna mätmetod i lättrörliga och Lean-arbetsmetoder. En viktig del av alla processförbättringsinitiativ är att sprida kunskap om den nya programvaruprocessen. Detta gäller oavsett hurdan process man försöker introducera – vare sig processen är plandriven eller lättrörlig. Vi föreslår att metoder som baserar sig på samarbete när processen skapas och vidareutvecklas är ett bra sätt att stöda kunskapsspridning på. Vi ger en översikt över författarverktyg för processer på marknaden med det förslaget i åtanke.

Increased oxidative stress markers may be a promising indicator of risk for primary ovarian insufficiency: a cross-sectional case control study

PURPOSE: The aim of this study was to evaluate serum levels of inducible nitric oxide synthase (INOS), myeloperoxidase (MPO), total antioxidant status (TAS), and total oxidative status (TOS) in women with primary ovarian insufficiency (POI) and to compare them with healthy fertile women. We also examined the possible risk factors associated with POI.METHODS: This cross-sectional case control study was conducted in Zekai Tahir Burak Women's Health Education and Research Hospital. The study population consisted of 44 women with POI (study group) and 36 healthy fertile women (control group). In all patients, serum levels of INOS, MPO, TAS, and TOS were determined. INOS and MPO levels were measured by enzyme-linked immunosorbent assay whereas colorimetric method was used for evaluating TAS and TOS levels. Age, body mass index (BMI), obstetric history, smoking status, family history, comorbidities, sonographic findings, complete blood count values, C-reactive protein and baseline hormone levels were also analyzed. Student's t-test or Mann-Whitney U test was used to compare continuous variables between the groups; categorical data were evaluated by using Pearson χ2 or Fisher exact test, when appropriate. Binary logistic regression method was used to identify risk factors for POI.RESULTS: We found significantly elevated levels of INOS (234.1±749.5 versus133.8±143.0; p=0.005), MPO (3,438.7±1,228.6 versus 2,481.9±1,230.1; p=0.001), and TOS (4.3±1.4 versus 3.6±1.4; p=0.02) in the sera of the study group when compared to the BMI-age matched control group. However, difference in serum levels of TAS were not significant between the 2 groups (1.7±0.2 versus 1.6±0.2; p=0.15). Logistic regression method demonstrated that BMI <25 kg/m2, nulliparity, family history of POI, smoking, and elevated serum levels of INOS, MPO, and TOS were independent risk factors for POI.CONCLUSION: We found an increase in INOS, MPO, and TOS in women with POI. These serum markers may be promising in early diagnosis of POI. Further large-scale studies are required to determine whether oxidative stress markers have a role in diagnosing POI.

Loss of Ovarian Function Results in Increased Loss of Skeletal Muscle in Arthritic Rats

Objective We studied the effects of loss of ovarian function (ovariectomy) onmuscle mass of gastrocnemius and themRNA levels of IGF-1, atrogin-1, MuRF-1, andmyostatin in an experimental model of rheumatoid arthritis in rats. Methods We randomly allocated 24 female Wistar rats (9 weeks, 195.3±17.4 grams) into four groups: control (CT-Sham; n = 6); rheumatoid arthritis (RA; n = 6); ovariectomy without rheumatoid arthritis (OV; n = 6); ovariectomy with rheumatoid arthritis (RAOV; n = 6). We performed the ovariectomy (OV and RAOV) or Sham (CTSham or RA) procedures at the same time, fifteen days before the rheumatoid arthritis induction. The RA and RAOV groups were immunized and then were injected with Met- BSA in the tibiotarsal joint. After 15 days of intra-articular injections the animals were euthanized. We evaluated the external manifestations of rheumatoid arthritis (perimeter joint) as well as animal weight, and food intake throughout the study. We also analyzed the cross-sectional areas (CSA) of gastrocnemius muscle fibers in 200 fibers (H&E method). In the gastrocnemius muscle, we analyzed mRNA expression by quantitative real time PCR followed by the Livak method (ΔΔCT). Results The rheumatoid arthritis induced reduction in CSA of gastrocnemius muscle fibers. The RAOV group showed a lower CSA of gastrocnemius muscle fibers compared to RA and CT-Sham groups. Skeletal muscle IGF-1 mRNA increased in arthritics and ovariectomized rats. The increased IGF-1 mRNA was higher in OV groups than in the RA and RAOV groups. Antrogin-1 mRNA also increased in the gastrocnemius muscle of arthritic and ovariectomized rats. However, the increased atrogin-1 mRNA was higher in RAOV groups than in the RA and OV groups. Gastrocnemius muscle MuRF-1 mRNA increased in the OVand RAOVgroups, but not in the RA and Shamgroups. However, the RAOV group showed higher MuRF-1 mRNA than the OV group. The myostatin gene expression was similar in all groups. Conclusion Loss of ovarian function results in increased loss of skeletal musclerelated ubiquitin ligases atrogin-1 and MuRF-1 in arthritic rats.

Increased expression of Interleukin-6 related to nephritis in chickens challenged with an Avian infectious bronchitis virus variant

A Brazilian field isolate (IBV/Brazil/PR05) of avian infectious bronchitis virus (IBV), associated with development of nephritis in chickens, was previously genotyped as IBV variant after S1 gene sequencing. The aim of this study was to evaluate the levels of IL-6 in kidneys and trachea of birds vaccinated and challenged with IBV/Brazil/PR05 strain, correlating these results with scores of microscopic lesions, specific IBV antigen detection and viral load. The up-regulation of IL-6 and the increased levels of viral load on renal and tracheal samples were significantly correlated with scores of microscopic lesions. Reduced levels of viral load were detected in kidneys of birds previously vaccinated and challenged, compared to non-vaccinated challenged group, although markedly microscopic lesions were observed for both groups. The expression of IL-6, present both in the kidney and in the tracheas, was dependent on the load of the virus present in the tissue, and the development of lesions was related with IL-6 present in the tissues. These data suggest that variant IBV/Brazil/PR05 can induce the expression of proinflammatory cytokines in a manner correlated with viral load and increased IL-6 is involved in the tissue with the influx of inflammatory cells and subsequent nephritis. This may contribute with a model to the development of immunosuppressive agents of IL-6 to prevent acute inflammatory processes against infection with IBV and perhaps other coronaviruses, as well as contribute to the understanding of the immunopathogenesis of IBV nephropatogenic strains.

Chemical composition, acetylcholinesterase inhibitory and antifungal activities of Pera glabrata (Schott) Baill. (Euphorbiaceae)

Pera glabrata (Schott) Baill. was selected for this study after showing a preliminary positive result in a screening of Atlantic Forest plant species in the search for acetylcholinesterase inhibitors and antifungal compounds. The bioassays were conducted with crude ethanol extract of the leaves using direct bioautography method for acetylcholinesterase and antifungal activities. This extract was partitioned with hexane, chloroform and ethyl acetate solvents. The active chloroform fraction was submitted to silica gel chromatography column affording 12 groups. Caffeine, an alkaloid, which showed detection limits of 0.1 and 1.0 µg for anticholinesterasic and antifungal activities, respectively, was isolated from group nine. After microplate analyses, only groups four, nine, 10, 11 and 12 showed acetylcholinesterase inhibitory activity of 40% or higher. The group 12 was purified by preparative layer chromatography affording four sub-fractions. Two sub-fractions from this group were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. The first sub-fraction showed anticholinesterasic activity and contained two major compounds: 9-hydroxy-4-megastigmen-3-one (84%) and caffeine (6%). The second sub-fraction presented five major compounds identified as 9-hydroxy-4-megastigmen-3-one, isololiolide, (-) loliolide, palmitic acid and lupeol and did not show activity.