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).

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.

The effect of timing of vincristine administration during a course of fractionated radiotherapy in a mouse carcinoma.

It has been previously shown that the uptake of 3H-vincristine by the NT carcinoma tumour in CBA mice can vary by a factor of 3 during a course of fractionated radiotherapy (2 Gy day-1, 5 day week-1, for 5 weeks). Here the effect of therapeutic doses of vincristine given at times of either maximum or minimum uptake has been investigated. The results show that whereas vincristine alone has a dose-related effect on this tumour, when given in combination with fractionated radiation it is only effective if administered during the first few fractions. It does not seem to matter whether it is given at times of maximum or minimum uptake. It is concluded that vincristine either exacerbates the radiation-induced vascular damage so that drug extravasation is reduced or that it causes a shift in the time of appearance of the peaks and troughs of uptake. The possibility that radiation-induced resistance to vincristine may have played a part in the results is also discussed.

A clinicopathological study of liver disease in haemophiliacs.

Chronic liver disease is not often reported in patients with haemophilia. Although a high incidence of abnormal liver function tests has been reported, the clinical significance of these findings and their relation to chronic liver disease cannot be established without a liver biopsy. The results of this procedure, carried out in 11 patients with severe haemophilia A and B, in whom SGOT had been persistently raised for three years, are reported. Five patients had chronic active hepatitis, four had chronic persistent hepatitis, one had cirrhosis, and one alcoholic hepatitis. No haemorrhagic complication followed the biopsy procedure, which was carried out in patients given prophylactic clotting factor concentrates. These results suggest that duration of abnormal liver function tests is likely to represent liver disease in haemophiliacs, and that biopsy should be considered to establish the diagnosis and plan a suitable therapeutic programme.

ROC analysis of benefit and limitation in radiotherapy for cancer of the oral cavity.

The ROC analysis of optimalization of radiation treatment of cancer of the oral cavity was carried out. Material of 210 patients with squamous cell carcinoma (SCC) of the oral cavity was included into the study. Based on dose-response curves for tumor and late mucosal reactions, iso-utility curves and optimal k values were estimated. Optimal k values decreased from 0.792 to 0.584 with extension of overall treatment time from 35 to 49 days. It may suggest that the planning of additional dose to compensate tumor clonogens repopulation during prolonged treatment time does not improve therapeutic gain in radiotherapy for cancer of the oral cavity. The ROC is a useful model to estimate optimal radiation treatment for a given tumor because it is independent of any arbitrary consensus or theoretical assumption.

False aneurysm of the internal mammary artery.

Iatrogenic false aneurysm of a branch of the internal mammary artery after sternal wire closure is a very rare occurrence. We describe a case which appeared in a 62 year old woman operated upon for mitral valve replacement and diagnosed after Digital Subtraction Angiography.

Therapeutic embolization of bronchial artery: a successful treatment in 209 cases of relapse hemoptysis.

Still today bronchial artery embolization (BAE) is an important procedure in the management of hemoptysis, as an alternative to, or in association with, surgical or medical therapy. From 1974 to 1990, BAE was performed in 209 patients who suffered from hemoptysis with different etiopathogeneses and severity. Bronchiectasis were the most frequent indication (46%) followed by tuberculosis (31%), cystic fibrosis (16%), lung cancer (4%), and aspergillosis (3%). BAEs were performed by means of polyvinyl alcohol particles and absorbable gelatin sponge. In a few cases complete occlusion of the main truncus of particularly large bronchial arteries was obtained by use of Gianturco steel coin (5 mm o) technique. In the last seven years, together with the traditional angiographic techniques, selective digital angiography (SDA) was performed, above all in preliminary control phases, to evaluate occlusion during embolization. SDA reduced catheterization time and the mean quantity of contrast administered, decreasing side effects; 98% of hemoptysis was controlled in the first twenty-four hours, the other 2% in the following forty eight hours; 16% relapses occurred within the first year; 27 patients needed reembolization (15 patients twice, 11 patients three times, 1 patient five times). No complications were seen. If diagnosis, therapeutic indications, operative technique, and equipment selection are adequate, BAE has a high reliability in patients affected by relapsing hemoptysis, which is difficult to resolve.

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.

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.

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.

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.