Enteric α-synuclein impairs intestinal epithelial barrier through caspase-1-inflammasome signaling in Parkinson's disease before brain pathology.

Bowel inflammation, impaired intestinal epithelial barrier (IEB), and gut dysbiosis could represent early events in Parkinson's disease (PD). This study examined, in a descriptive manner, the correlation among enteric α-synuclein, bowel inflammation, impairments of IEB and alterations of enteric bacteria in a transgenic (Tg) model of PD before brain pathology. Human A53T α-synuclein Tg mice were sacrificed at 3, 6, and 9 months of age to evaluate concomitance of enteric inflammation, IEB impairments, and enteric bacterial metabolite alterations during the early phases of α-synucleinopathy. The molecular mechanisms underlying the interplay between α-synuclein, activation of immune/inflammatory responses and IEB alterations were investigated with in vitro experiments in cell cultures. Tg mice displayed an increase in colonic levels of IL-1ß, TNF, caspase-1 activity and enteric glia activation since 3 months of age. Colonic TLR-2 and zonulin-1 expression were altered in Tg mice as compared with controls. Lipopolysaccharide levels were increased in Tg animals at 3 months, while fecal butyrate and propionate levels were decreased. Co-treatment with lipopolysaccharide and α-synuclein promoted IL-1ß release in the supernatant of THP-1 cells. When applied to Caco-2 cells, the THP-1-derived supernatant decreased zonulin-1 and occludin expression. Such an effect was abrogated when THP-1 cells were incubated with YVAD (caspase-1 inhibitor) or when Caco-2 were incubated with anakinra, while butyrate incubation did not prevent such decrease. Taken together, early enteric α-synuclein accumulation contributes to compromise IEB through the direct activation of canonical caspase-1-dependent inflammasome signaling. These changes could contribute both to bowel symptoms as well as central pathology.

Compact single-shot electro-optic detection system for THz pulses with femtosecond time resolution at MHz repetition rates.

Electro-optical detection has proven to be a valuable technique to study temporal profiles of THz pulses with pulse durations down to femtoseconds. As the Coulomb field around a relativistic electron bunch resembles the current profile, electro-optical detection can be exploited for non-invasive bunch length measurements at accelerators. We have developed a very compact and robust electro-optical detection system based on spectral decoding for single-shot longitudinal bunch profile monitoring at the European X-ray Free Electron Laser (XFEL) for electron bunch lengths down to 200 fs (rms). Apart from the GaP crystal and the corresponding laser optics at the electron beamline, all components are housed in 19 in. chassis for rack mount and remote operation inside the accelerator tunnel. An advanced laser synchronization scheme based on radio-frequency down-conversion has been developed for locking a custom-made Yb-fiber laser to the radio-frequency of the European XFEL accelerator. In order to cope with the high bunch repetition rate of the superconducting accelerator, a novel linear array detector has been employed for spectral measurements of the Yb-fiber laser pulses at frame rates of up to 2.26 MHz. In this paper, we describe all sub-systems of the electro-optical detection system as well as the measurement procedure in detail and discuss the first measurement results of longitudinal bunch profiles of around 400 fs (rms) with an arrival-time jitter of 35 fs (rms).

Effect of different liming levels on the biomass production and essential oil extraction yield of Cunila galioides Benth / Efeito de diferentes níveis de calagem na produção de biomassa e no rendimento de extração de óleo essencial de Cunila galioides Benth

Poejo is an aromatic and medicinal plant native to highland areas of south Brazil, in acid soils with high Al3+ concentration. The main objective of the present work was to evaluate the effect of liming on the extraction yield of essential oil of three chemotypes of poejo (Cunila galioides Benth). For this purpose, the experiments were performed in a greenhouse, using 8-litre pots. The treatments were four dosages of limestone (0, 3.15, 12.5, and 25 g.L-1) and a completely random experimental design was used, with four replications and three chemotypes, set up in a 3 × 4 factorial arrangement. The parameters evaluated were dry weight of aerial parts, essential oil content and chemical composition of essential oil. Results showed that liming affects the biomass production, essential oil yield and chemical composition, with cross interaction verified between chemotype and limestone dosage. For the higher dosage lower biomass production, lower yield of essential oil as well as the lowest content of citral (citral chemotype) and limonene (menthene chemotype) was observed. In the ocimene chemotype, no liming influence was observed on the essential oil yield and on the content of major compounds. The dosage of 3.15 g.L-1 can be considered the best limestone dosage for the production of poejo for the experimental conditions evaluated.

O poejo é uma espécie aromática e medicinal, autóctone do sul do Brasil, encontrada em regiões de campos nativos de altitude, onde os solos se caracterizam por apresentar elevada acidez e altas concentrações de Al3+. O presente trabalho objetivou avaliar o efeito da calagem na produção de biomassa e de óleo essencial de três quimiotipos (QT) de poejo (Cunila galioides Benth.). O experimento foi conduzido em casa de vegetação utilizando-se recipientes com capacidade de oito litros. Os tratamentos consistiram de quatro dosagens de calcário dolomítico (0; 3,15; 12,5; 25 g.L-1 de substrato) e o delineamento experimental foi completamente casualisado, utilizando-se três quimiotipos de poejo (citral, menteno e ocimeno), quatro tratamentos e quatro repetições, em esquema fatorial 3 × 4. Foram avaliados o peso de matéria seca da parte aérea das plantas, o teor de óleo essencial e a composição química dos componentes majoritários presentes no óleo. Os resultados mostraram efeito da calagem na produção de biomassa, no teor e na composição química do óleo, ocorrendo efeito de interação entre quimiotipo e dosagem de calcário. Na maior dosagem, observou-se a menor produção de biomassa média, o teor de óleo essencial foi significativamente menor, assim como os componentes citral (QT-citral) e limoneno (QT-menteno). Para o quimiotipo ocimeno, as dosagens de calcário não influenciaram o teor e os componentes majoritários do óleo essencial, mas prejudicaram a produção de biomassa em doses elevadas. A calagem com 3,15 g.L-1 de substrato, elevando o pH para 5,0, pode ser considerada a melhor dosagem de calcário e a mais adequada faixa de pH para a produção de poejo, nas condições experimentais avaliadas.

Effect of different liming levels on the biomass production and essential oil extraction yield of Cunila galioides Benth.

Poejo is an aromatic and medicinal plant native to highland areas of south Brazil, in acid soils with high Al3+ concentration. The main objective of the present work was to evaluate the effect of liming on the extraction yield of essential oil of three chemotypes of poejo (Cunila galioides Benth). For this purpose, the experiments were performed in a greenhouse, using 8-litre pots. The treatments were four dosages of limestone (0, 3.15, 12.5, and 25 g.L(-1)) and a completely random experimental design was used, with four replications and three chemotypes, set up in a 3 × 4 factorial arrangement. The parameters evaluated were dry weight of aerial parts, essential oil content and chemical composition of essential oil. Results showed that liming affects the biomass production, essential oil yield and chemical composition, with cross interaction verified between chemotype and limestone dosage. For the higher dosage lower biomass production, lower yield of essential oil as well as the lowest content of citral (citral chemotype) and limonene (menthene chemotype) was observed. In the ocimene chemotype, no liming influence was observed on the essential oil yield and on the content of major compounds. The dosage of 3.15 g.L(-1) can be considered the best limestone dosage for the production of poejo for the experimental conditions evaluated.

Morphological characterisation and agronomical parameters of different species of Salvia sp. (Lamiaceae).

The aim of this work is to assess the morphological characteristics and parameters of biomass production, such as fresh and dry matter weight (FMW and DMW, g/plant), yield of dry matter (YDM) in terms of ton/ha, essential oil content (EOC, mL/100 g) and yield of essential oils (YEO) expressed as L/ha of the following plants Salvia verbenaca, Salvia argentea, Salvia lavandulifolia, Salvia pratensis, Salvia sclarea, Salvia triloba and Salvia officinalis. Except for Salvia argentea (S2) all other species have adapted to the south Brazilian climate conditions, with morphological differences among the species evaluated. In terms of DMW and YDM, S. officinalis was found to be the most productive species with 445.83 g/plant and 11.14 ton/ha. The higher essential oil content and yield was observed for S. officinalis, affording 1.99 mL/100 g and 221.74 L/ha, respectively. Chemical characterisation of the essential oils obtained from hydrodistillation was performed through GC and GC/MSD analyses, which revealed for most of the species studied, α e ß-thujone, camphor and 1,8-cineole as major compounds, apart from S. sclarea, for which linalool, linalyl acetate and α-terpineol were the major components.

Variable effect of P2Y12 inhibition on platelet thrombus volume in flowing blood.

BACKGROUND AND OBJECTIVES: Patients treated with percutaneous coronary intervention receive aspirin and P2Y12 ADP receptor inhibitors to reduce thrombotic complications. The choice of methodology for monitoring the effects of treatment and assessing its efficacy is still a topic of debate. We evaluated how decreased P2Y12 function influences platelet aggregate (thrombus) size measured ex vivo. METHODS AND RESULTS: We used confocal videomicroscopy to measure in real time the volume of platelet thrombi forming upon blood perfusion over fibrillar collagen type I at a wall shear rate of 1500 s(-1). The average volume was significantly smaller in 31 patients receiving aspirin and clopidogrel (19) or ticlopidine (12) than in 21 controls, but individual values were above the lower limit of the normal distribution, albeit mostly within the lower quartile, in 61.3% of cases. Disaggregation of platelet thrombi at later perfusion times occurred frequently in the patients. Vasodilator-stimulated phosphoprotein phosphorylation, reflecting P2Y12 inhibition, was also decreased in the patient group, and only 22.6% of individual values were above the lower normal limit. We found no correlation between volume of thrombus formed on collagen fibrils and level of P2Y12 inhibition, suggesting that additional and individually variable factors can influence the inhibitory effect of treatment on platelet function. CONCLUSIONS: Measurements of platelet thrombus formation in flowing blood reflects the consequences of antiplatelet therapy in a manner that is not proportional to P2Y12 inhibition. Combining the results of the two assays may improve the assessment of thrombotic risk.

Venous thromboembolism during pregnancy, postpartum or during contraceptive use.

Venous thromboembolism (VTE) is a leading cause of maternal death during pregnancy or postpartum, and in women using hormonal contraceptives. However, important issues concerning its natural history and therapy remain unsolved, and most of the protocols for treatment of VTE in this patient population are based on data extrapolated from other populations. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic, acute VTE. We examined the clinical characteristics and three-month outcome of all enrolled women with pregnancy, postpartum or using hormonal contraceptives. As of December 2008, 173 pregnant women, 135 postpartum, and 798 contraceptive users were enrolled. Of these, 438 (40%) presented with pulmonary embolism (PE) and 668 with deep-vein thrombosis (DVT). Most women with acute PE had dyspnea (72%) or chest pain (75%), but only 2.0% had hypoxaemia. During the three-month study period, five women (0.45%; 95% CI: 0.17-1.00) died (3 had fatal PE), 13 (1.18%; 95% CI: 0.66-1.95) had VTE recurrences, and seven (0.63%; 95% CI: 0.28-1.25) major bleeding. Two of the three women with fatal PE died during the first few hours after arriving at the emergency ward, with no time to start any therapy. The outcome of pregnant or postpartum women with VTE is similar to that in contraceptive users, even though the treatment is different. The non-specific nature of PE signs may have caused some delay in PE diagnosis.

Common genetic markers and prediction of recurrent events after ischemic stroke in young adults.

BACKGROUND: Scarce information is available on the usefulness of new prediction markers for identifying young ischemic stroke patients at highest risk of recurrence. METHODS: The predictive effect of traditional risk factors as well as of the 20210A variant of prothrombin gene, the 1691A variant of factor V gene, and the TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR) gene on the risk of recurrence was investigated in a hospital-based cohort study of 511 ischemic stroke patients younger than 45 years followed up for a mean of 43.4 months. Outcome measures were fatal/nonfatal myocardial infarction, ischemic stroke, or TIA. Risk prediction was assessed with the use of the concordance c (c index), and the Net Reclassification Improvement (NRI). RESULTS: The risk of recurrence increased with increasing number of traditional factors (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.57-3.35 for subjects with 1 factor: HR 5.25, 95% CI 2.45-11.2 for subjects with 2), as well as with that of predisposing genotypes (HR 1.96, 95% CI 1.33-2.89 for subjects carrying 1 at-risk genotype; HR 3.83, 95% CI 1.76-8.34 for those carrying 2). The c statistics increased significantly when the genotypes were included into a model with traditional risk factors (0.696 vs 0.635, test z = 2.41). The NRI was also significant (NRI = 0.172, test z = 2.17). CONCLUSIONS: Addition of common genetic variants to traditional risk factors may be an effective method for discriminating young stroke patients at different risk of future ischemic events.

Use of palmae wax hydrocarbon fractions as chemotaxonomical markers in Butia and Syagrus.

The wax hydrocarbon fractions of native Butia and Syagrus species collected from Palms in different regions of the of Rio Grande do Sul state (Brazil) and in Rocha (Uruguay) were analyzed to evaluate their potential as chemotaxonomic markers. The wax was extracted with chloroform and the resulting wax was fractionated by preparative TLC. The hydrocarbon fractions were analyzed by GC-MS. Statistical analyses were completed with the Statistica 5.0 program. The total crude wax yields averaged 0.31% w.w-1 dried leaves for Butia samples and 0.28% for Syagrus samples. The linear hydrocarbons represented on average 15% of the total waxes in the case of Butia samples and 13.7% in Syagrus samples. Hentriacontane and triacontane were the main components of all samples. The comparison of the means showed significant differences among Butia and Syagrus samples, and amongst Butia samples collected in different localities. In the case of the Syagrus collections no consistent groupings could be made. In the case of Butia samples the formation of three groupings could be observed, which were consistent with the species described for their geographical distribution. These results are discussed in the paper.

Use of palmae wax hydrocarbon fractions as chemotaxonomical markers in Butia and Syagrus / Uso de frações de hidrocarbonetos de palmeiras como marcadores quimiotaxonômicos em Butia e Syagrus

The wax hydrocarbon fractions of native Butia and Syagrus species collected from Palms in different regions of the of Rio Grande do Sul state (Brazil) and in Rocha (Uruguay) were analyzed to evaluate their potential as chemotaxonomic markers. The wax was extracted with chloroform and the resulting wax was fractionated by preparative TLC. The hydrocarbon fractions were analyzed by GC-MS. Statistical analyses were completed with the Statistica 5.0 program. The total crude wax yields averaged 0.31% w.w–1 dried leaves for Butia samples and 0.28% for Syagrus samples. The linear hydrocarbons represented on average 15% of the total waxes in the case of Butia samples and 13.7% in Syagrus samples. Hentriacontane and triacontane were the main components of all samples. The comparison of the means showed significant differences among Butia and Syagrus samples, and amongst Butia samples collected in different localities. In the case of the Syagrus collections no consistent groupings could be made. In the case of Butia samples the formation of three groupings could be observed, which were consistent with the species described for their geographical distribution. These results are discussed in the paper.

Frações de hidrocarbonetos das ceras de espécies nativas de Butia e Syagrus coletadas de palmeiras em diferentes regiões do Rio Grande do Sul (Brasil) e em Rocha (Uruguai) foram analisadas para avaliar o seu potencial como marcadores quiomiotaxonômicos. As ceras foram extraídas com clorofórmio e fracionadas por TLC preparativo. As frações de hidrocarbonetos foram analisadas por CG-EM. As análises estatísticas foram realizadas com auxílio do programa Statistica 5.0. O rendimento total de cera das folhas secas foi de 0,31% g.g–1 para as amostras de Butia e de 0,28% para Syagrus. Os hidrocarbonetos lineares representaram em média 15 e 13% do total das ceras para Butia e Syagrus, respectivamente. Hentriacontano e triacontano foram os compostos majoritários em todas as amostras. A comparação de médias mostrou diferenças significativas entre as amostras de Butia e Syagrus e entre as amostras de Butia coletadas em diferentes localidades. As amostras de Syagrus não formaram agrupamentos relacionados com os locais de coleta. Já no caso de Butia, três agrupamentos puderam ser observados e são consistentes com a distribuição geográfica desta espécie. Estes resultados são discutidos no trabalho.

A randomized controlled trial to evaluate short-term treatment with eosin vs. topical steroids in psoriasis.

BACKGROUND: The therapeutic effects of some histological staining agents on psoriasis have been reported in the past. One of these agents is eosin, which is still currently used in routine treatment, although it has never been formally tested in a randomized controlled trial. Aim. To compare treatment with eosin in patients with moderate to severe psoriasis vs. short-course topical steroid, a well-defined, evidence-based treatment. METHODS: A randomized trial was designed and conducted. The Skindex-29 and General Health Questionnaire (GHQ)-12 questionnaires, and Psoriasis Activity and Disease Index (PASI) were used before treatment in 43 patients. Five days after treatment, PASI was measured again. RESULTS: Five days after treatment, a significant mean reduction of PASI was observed in both groups: 6.8 (95% CI 5.5-8) for eosin, and 5.2 (3.2-7.1) for steroids. The difference between the two groups was not significant (P = 0.161). CONCLUSIONS: Eosin has a short-term effect similar to topical steroids. The low cost of eosin treatment and its limited collateral effects suggest that eosin could be an effective steroid-sparing agent in the initial phase of psoriasis treatment.

Análise de taninos totais em plantas aromáticas e medicinais cultivadas no Nordeste do Rio Grande do Sul / Determination of tannin total content in aromatic and medicinal plants cultivated in Northern Rio Grande do Sul State, Brazil

Os taninos são componentes polifenólicos encontrados em plantas, alimentos e bebidas, sendo utilizados como fonte de matéria-prima para várias indústrias, como por exemplo a farmacêutica e a alimentícia, no curtimento do couro, na produção de borrachas, no tratamento de água em barragens, entre outras. Em vista da importância deste grupo de compostos, algumas plantas aromáticas e medicinais cultivadas no Núcleo Agronômico do Instituto de Biotecnologia da Universidade de Caxias dos Sul foram avaliadas quanto ao teor de taninos totais: Angelica archangelica , Cinnamomun camphora var. linaloolifera fugita , Cymbopogon citratus, Lavandula dentata , Lippia alba, Rosmarinus officinalis e Thymus vulgaris, e esses foram comparados com o teor de taninos totais da Acacia mearnsii (acácia negra), planta utilizada para a extração de taninos. O processo de extração empregado foi a maceração com metanol e a quantificação foi realizada por espectrofotometria, utilizando-se o reagente de Folin Denis. A partir da curva de calibração ( por cento equivalente ao ácido tânico) foram obtidos os teores de taninos totais, que variaram de 0,01 por cento para Cymbopogom citratus a 18,9 por cento para Lippia alba.

Tannins are polyphenolic compounds present in plants which are also found in foods and beverages. They are specially used by pharmaceutical, food, leather and rubber industries, and also for water treatment. Considering the significance of this group of compounds, several of aromatic and medicinal plants cultivated in Northern Rio Grande do Sul State, Brazil, were tested for their total tannin content. Angelica archangelica , Cinnamomun camphora var. linaloolifera fugita , Cymbopogon citratus, Lavandula dentata , Lippia alba, Rosmarinus officinalis and Thymus vulgaris were analysed and compared with Acacia mearnsii (black wattle) which is industrially used for tannin extraction. The extraction procedure was made by macerating the plants in methanol, and the quantification was done using Folin Denis reagent and spectrophotometry. By using a calibration curve ( percent tannic acid equivalent) the total tannin contents range from 0.01 percent ( Cymbopogom citratus ) to 18.9 percent ( Lippia alba ).

Ocular alterations in alopecia areata.

PURPOSE: To determine the ocular alterations occurring in alopecia areata with regard to the lens and fundus. METHODS: Seventy-five patients with alopecia areata were examined. Seventy healthy control patients unaffected by skin, ocular or systemic disorders were also studied. RESULTS: Symptomless punctate lens opacities were found in 38 (51%) patients, whereas only 2 (3%) control patients had similar lens changes. Fundus alterations were found in 31 (41%) cases of alopecia areata and in only 16 (23%) controls. CONCLUSIONS: These ocular alterations and their prevalence are reported and some theories regarding the possible aetiopathogenetic mechanisms are discussed.