Allyl-isothiocyanate ameliorates the pre-neoplastic changes induced by the fern Dryopteris nigropalaceae on experimental feeding in Guinea pigs.

Enzootic bovine haematuria, caused by long-term ingestion of ferns, is a chronic disease of hill cattle characterized by neoplastic lesions in the urinary bladder. Objectives of this study were to investigate the toxicity potential of long-term feeding of the fern Dryopteris nigropalaceae and effect of allyl isothiocyanate (AITC) to ameliorate fern toxicity and the associated pathological changes. The LC-MS analysis of the fern showed presence of ptaquiloside (4.5 ±â€¯1.0 µg/g) and pterosin B (39 ±â€¯9.1 µg/g). Groups of animals were fed dried fern powder at the dose of 20% w/w in normal feed and treated with and without AITC at graded doses. Long term feeding of fern induced inflammatory and pre-neoplastic lesions in urinary bladder. The important lesions included cystitis, squamous metaplasia and high-grade dysplasia. Urothelium showed positive immunoreactions for nuclear expression of H-ras and p53. However, no mutation suggestive of neoplastic change was observed on partial mRNA sequences analyses of exon 2 of H-ras and 5 or 7&8 of p53 genes. Strikingly, AITC showed dose-dependent amelioration of pre-neoplastic changes in fern-fed animals. In conclusion, AITC is shown to limit pre-neoplastic changes caused by D. nigropalaceae feeding in guinea pigs.

Elevated blood plasma levels of tissue factor-bearing extracellular vesicles in patients with atrial fibrillation.

BACKGROUND: The risk of thrombus formation in the left atrial appendage (LAA) in patients with atrial fibrillation (AF) may result from blood stasis, local endocardial changes, and/or changed blood composition. Extracellular vesicles (EVs), especially subtypes exposing tissue factor (TF), have procoagulant capacity. We hypothesized that blood concentrations of TF-bearing EVs and other procoagulant biomarkers are elevated in AF patients, particularly in the LAA lumen. METHODS: From 13 AF patients and 12 controls a venous blood sample was drawn prior to cardiac surgery. Intraoperatively, venous blood and blood directly from the LAA was drawn. Plasma levels of EVs, including TF- and cell type specific antigen-bearing EVs, were measured using a protein microarray platform. Plasma levels of TF, von Willebrand factor (vWF), cell free deoxyribonucleic acid (cf-DNA), procoagulant phospholipids (PPLs), and total submicron particles were also evaluated. RESULTS: Significantly higher EV levels, including a several-fold higher median level of TF-bearing EVs were measured in AF patients compared with controls. Median concentrations of TF and vWF were approximately 40% and 30% higher, respectively, in the AF group than in the control group, while no significant differences in levels of cf-DNA, PPLs, or total submicron particles were observed. No significant differences in levels of any of the measured analytes were observed between intraoperative venous and LAA samples. CONCLUSIONS: Increased plasma concentrations of TF in AF patients are accompanied and probably at least partly explained by increased levels of TF-bearing EVs, which may be mechanistically involved in increased thrombogenicity in AF patients.

Survey of ferns and clinico-pathological studies on the field cases of Enzootic bovine haematuria in Himachal Pradesh, a north-western Himalayan state of India.

Enzootic bovine haematuria (EBH) in cattle occurs in upland areas of the world. In India, the disease is present in isolated pockets in the Himalayas and in the Nilgiri Hills. The variation in the disease incidence has been attributed to different environmental conditions and animal rearing practices followed in the different regions. The aim of the study was to conduct field surveys in parts of EBH endemic regions of Himachal Pradesh, a north-western Himalayan state of India. Out of the total 103 plant samples collected, a total of 95 samples were identified as ferns. The major ferns identified included, Onychium japonicum (Thunb.) Kunze, Polystichum piceopaleaceum Tagawa, Dryopteris juxtaposita Christ, Pseudocyclosorus canus (Baker) Holttum and J.W. Grimes, Onychium contiguum C. Hope, Dryopteris nigropaleacea (Fraser-Jenk.), Pteridium aquilinum (L.) Kuhn, Diplazium esculentum (Retz.) Sw., Allantodia maxima (D. Don) Ching, Woodwardia unigemmata (Makino) Nakai, Pteris cretica L., Pteris vittata L., Asplenium trichomanes L., Thelypteris phegopteris (L.) Sloss. ex Rydb, Adiantum venustum D. Don and Paraceterach vestita (Hook.) R.M. Tryon. The concentration of ptaquiloside (PTA) and pterosin B (PtB) in some of the ferns collected from Kullu and Chamba regions ranged from 0 to 358.6 ± 70.5 µg/g and 0 to 652.4 ± 50.0 µg/g, respectively. In addition, field cases of the disease in cattle were also studied in the EBH endemic districts. A total of sixteen cattle urine samples and one urinary bladder of EBH affected cattle were collected. On physical, chemical (benzidine test) and microscopic examination of urine sediment, all the sixteen field samples were found to be positive for erythrocytes and the cases were diagnosed as macrohaematuria. The clinico-pathological studies on the field cases and the presence of PTA and PtB in the ferns indicated that EBH is a prevalent disease and there is an association between chronic fern ingestion and EBH in cattle. On the basis of gross pathology, histopathology and immunohistochemistry (p53 and H-ras nuclear expression in the urothelial cells) of the urinary bladder tissue, the field case was diagnosed as transitional cell adenocarcinoma with chronic lymphocytic cystitis.

Impact of anticoagulation regimen prior to revascularization in patients with non-ST-segment elevation acute coronary syndromes: The ACUITY trial.

AIM: To evaluate the impact of antithrombotic regimens during the medical phase of treatment among 13,819 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) treated with an early invasive strategy in the acute catheterization and urgent intervention triage strategy (ACUITY) trial. METHODS AND RESULTS: Endpoints included composite major adverse cardiac events (MACE), major bleeding, and net adverse clinical events (NACE; MACE or major bleeding). The median (interquartile range) duration of antithrombin use in the medical only treatment phase was 6.5 (1.8-22.5) hours. MACE, major bleeding, and NACE during the medical only phase occurred in 63 (0.5%), 117 (0.9%), and 178 (1.3%) patients, respectively. MACE rates in the medical-treatment-only phase were not significantly different between the four randomized medical regimens used (heparin alone, bivalirudin alone, heparin plus a glycoprotein IIb/IIIa inhibitor [GPI], and bivalirudin plus GPI) (Ptrend = 0.65). The lowest rates of major bleeding and NACE during the medical treatment phase occurred in patients treated with bivalirudin alone (Ptrend = 0.0006 and Ptrend = 0.0004, respectively). CONCLUSIONS: In patients with NSTE-ACS undergoing an early invasive strategy, treatment with bivalirudin alone significantly reduced major bleeding and improved net clinical outcomes during the upstream medical management phase with comparable rates of MACE. © 2015 Wiley Periodicals, Inc.

Dietary intake of total marine n-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid and docosapentaenoic acid and the risk of acute coronary syndrome - a cohort study.

Dietary intake of marine n-3 PUFA has been negatively associated with the risk of CHD among subjects with known CHD, whereas an effect in healthy subjects is less documented. We assessed the hypothesis that dietary intake of marine n-3 PUFA is negatively associated with the risk of acute coronary syndrome (ACS) in healthy subjects. In the Danish Diet, Cancer and Health cohort study, 57 053 participants were enrolled. Dietary intake of total n-3 PUFA, including EPA, docosapentaenoic acid (DPA) and DHA, was assessed. During a mean follow-up period of 7.6 years, we identified all cases (n 1150) from this cohort with an incident ACS diagnosis in the Danish National Patient Registry or the Cause of Death Registry. Diagnoses were verified through medical record review. In Cox proportional hazard models, we adjusted for established risk factors for CHD. Men in the four highest quintiles of n-3 PUFA intake (>0.39 g n-3 PUFA per d) had a lower incidence of ACS compared with men in the lowest quintile. The hazard ratio was 0.83 (95 % CI 0.67, 1.03) when we compared men in the second lowest and lowest quintile of n-3 PUFA intake. Higher intake of n-3 PUFA did not strengthen this association. Associations for EPA, DPA and DHA were all negative, but less consistent. No convincing associations were found among women. In conclusion, we found borderline significant negative associations between the intake of marine n-3 PUFA and ACS among healthy men.

Randomized trial comparing endovenous laser ablation of the great saphenous vein with high ligation and stripping in patients with varicose veins: short-term results.

BACKGROUND: Endovenous laser (EVL) ablation of the great saphenous vein (GSV) is thought to minimize postoperative morbidity and reduce work loss compared with high ligation and stripping (HL/S). However, the procedures have not previously been compared in a randomized trial with parallel groups where both treatments were performed in tumescent anesthesia on an out-patient basis. METHODS: Patients with varicose veins due to GSV insufficiency were randomized to either EVL (980 nm) or HL/S in tumescent anesthesia. Miniphlebectomies were also performed. Patients were examined preoperatively and at 12 days, and 1, 3, and 6 months postoperatively. Sick leave, time to normal physical activity, pain score, use of analgesics, Aberdeen score, Medical Outcomes Study Short Form-36 quality-of-life score, Venous Clinical Severity Score (VCSS), and complication rates were investigated. The total cost of the procedures, including lost wages and equipment, was calculated. Cost calculations were based on the standard fee for HL/S with the addition of laser equipment and the standard salary and productivity level in Denmark. RESULTS: A follow-up of 6 months was achieved in 121 patients (137 legs). The groups were well matched for patient and GSV characteristics. Two HL/S procedures failed, and three GSVs recanalized in the EVL group. The groups experienced similar improvement in quality-of-life scores and VCSS score at 3 months. Only one patient in the HL/S group had a major complication, a wound infection that was treated successfully with antibiotics. The HL/S and EVL groups did not differ in mean time to resume normal physical activity (7.7 vs 6.9 calendar days) and work (7.6 vs 7.0 calendar days). Postoperative pain and bruising was higher in the HL/S group, but no difference in the use of analgesics was recorded. The total cost of the procedures, including lost wages, was euro 3084 ($3948 US) in the HL/S and euro 3396 ($4347 US) in the EVL group. CONCLUSIONS: This study suggests that the short-term efficacy and safety of EVL and HL/S are similar. Except for slightly increased postoperative pain and bruising in the HL/S group, no differences were found between the two treatment modalities. The treatments were equally safe and efficient in eliminating GSV reflux, alleviating symptoms and signs of GSV varicosities, and improving quality of life. Long-term outcomes, particularly with respect to recurrence rates, shall be investigated in future studies, including the continuation of the present.

Microbial degradation and impact of Bracken toxin ptaquiloside on microbial communities in soil.

The carcinogenic and toxic ptaquiloside (PTA) is a major secondary metabolite in Bracken fern (Pteridium aquilinum (L.) Kuhn) and was hypothesized to influence microbial communities in soil below Bracken stands. Soil and Bracken tissue were sampled at field sites in Denmark (DK) and New Zealand (NZ). PTA contents of 2.1 +/- 0.5 mg g(-1) and 37.0 +/- 8.7 mg g(-1) tissue were measured in Bracken fronds from DK and NZ, respectively. In the two soils the PTA levels were similar (0-5 microg g(-1) soil); a decrease with depth could be discerned in the deeper B and C horizons of the DK soil (weak acid sandy Spodosol), but not in the NZ soil (weak acid loamy Entisol). In the DK soil PTA turnover was predominantly due to microbial degradation (biodegradation); chemical hydrolysis was occurring mainly in the uppermost A horizon where pH was very low (3.4). Microbial activity (basal respiration) and growth ([3H]leucine incorporation assay) increased after PTA exposure, indicating that the Bracken toxin served as a C substrate for the organotrophic microorganisms. On the other hand, there was no apparent impact of PTA on community size as measured by substrate-induced respiration or composition as indicated by community-level physiological profiles. Our results demonstrate that PTA stimulates microbial activity and that microorganisms play a predominant role for rapid PTA degradation in Bracken-impacted soils.

Bivalirudin for patients with acute coronary syndromes.

BACKGROUND: Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. METHODS: We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. RESULTS: Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P=0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P=0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). CONCLUSIONS: In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158 [ClinicalTrials.gov].).

Occurrence of the carcinogenic Bracken constituent ptaquiloside in fronds, topsoils and organic soil layers in Denmark.

Bracken (Pteridium aquilinum (L.) Kuhn) is a common fern found on all continents except Antarctica. It is under suspicion of causing cancer among people who utilizes it as food. The main carcinogenic compound is thought to be the water-soluble compound ptaquiloside. Ptaquiloside-uptake may occur not only through food, but also via drinking water as ptaquiloside might leach from plant material. The purpose of the study was to identify environmental parameters that correlate with the ptaquiloside-content in fronds, and to quantify the amount of ptaquiloside in the soil environment. The ptaquiloside-content in fronds, Oi/Oe-, and Oa/A-horizons was quantified at end of the growth season at 20 sites in Denmark. The fronds had ptaquiloside-contents between 108 and 3795 microgg(-1). The Oi/Oe-horizons had contents between 0.09 and 7.70 microgg(-1), while Oa/A-horizons had contents between 0.01 and 0.09 microgg(-1). The ptaquiloside-content in the standing biomass, which could be transferred to the soil by the end of the growing season, ranged between 10 and 260 mgm(-2), with nine sites having ptaquiloside loads over 100 mgm(-2). The carbon-content in the O-horizon, the precipitation, the amount of Bracken-litter, the turnover rate and the size of Bracken-stands determined the ptaquiloside-content in the soil materials while the content in fronds was found to be a function of the frond-height and the light-exposure in the ecosystem.