Glucosinolate hydrolysis compounds for weed control

Glucosinolates are allelochemicals present in all Brassica plants. Upon hydrolysis by endogenous enzymes they produce a series of biologically active compounds, such as isothiocyanates and their deriva-tives among others. These compounds have marked fungicidal, nematocidal and herbicidal effects and therefore their use as biodegradable natural products for crop protection has attracted much attention in the last years. A number of these compounds, either individually or in combination, were tested against Sinapis alba and Lollium perenne in Petri dishes bio-assays. C50 values as low as 0.7 and 0.2 mM were obtained. This may open the possibility for using glucosinolate hydrolysis products as herbicides

Prediction model for unsuccessful return to work after hospital-based intervention in low back pain patients

BACKGROUND: Many studies on low back pain (LBP) have identified prognostic factors, but prediction models for use in secondary health care are not available. The purpose of this cohort study, based on a randomised clinical study, was to identify risk factors for unsuccessful return to work (U-RTW) in sick-listed LBP patients with or without radiculopathy and to validate a prediction model for U-RTW. METHODS: 325 sick-listed LBP patients with or without radiculopathy were included in an intervention study and followed for one year. Afterwards, 117 other LBP patients were recruited similarly, included in a validation study and also followed for one year. All patients were subjected to identical procedures and interventions and received a brief intervention by the same rehabilitation doctor and physiotherapist. Half of them received case manager guidance within a multidisciplinary setting. At baseline, they completed a questionnaire and went through a clinical low-back examination. Sciatica was investigated by magnetic resonance imaging (MRI). U-RTW was registered in a national database both initially and at 1-year. RESULTS: Neither initial U-RTW (24.0%) nor one-year U-RTW (38.2%) were statistically significantly different in the two intervention groups nor in patients with and without radiculopathy. Multivariate logistic regression analysis identified two clinical and five psychosocial baseline predictors for one-year U-RTW (primary outcome). The clinical predictors included pain score (back+leg pain) and side-flexion. The five psychosocial predictors included ‘bodily distress’ ‘low expectations of RTW’, ‘blaming the work for pain’, ‘no home ownership’ and ‘drinking alcohol less than once/month’. These predictors were not statistically significantly different in patients with and without radiculopathy, and they also predicted initial U-RTW (secondary outcome). Obesity and older age were only supplementary predictors in patients with radiculopathy. A prediction model was established and tested in the validation study group. The model predicted one-year U-RWT in patients with intermediate and high risk, but only partially in patients with low risk. The model predicted all three risk categories in initial U-RTW. CONCLUSIONS: A prediction model combining baseline clinical and psychosocial risk factors predicted patients with low, intermediate and high risk for unsuccessful return to work, both initially and at 1-year

Prostacyclins have no direct inotropic effect on isolated atrial strips from the normal and pressure-overloaded human right heart

Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostacyclins on right heart function are still not clarified. The aim of this study was to investigate the possible direct inotropic properties of clinical available prostacyclin mimetics in the normal and the pressure-overloaded human right atrium. Trabeculae from the right atrium were collected during surgery from chronic thromboembolic pulmonary hypertension (CTEPH) patients with pressure-overloaded right hearts, undergoing pulmonary thromboendarterectomy (n = 10) and from patients with normal right hearts operated by valve replacement or coronary bypass surgery (n = 9). The trabeculae were placed in an organ bath, continuously paced at 1 Hz. They were subjected to increasing concentrations of iloprost, treprostinil, epoprostenol, or MRE-269, followed by isoprenaline to elicit a reference inotropic response. The force of contraction was measured continuously. The expression of prostanoid receptors was explored through quantitative polymerase chain reaction (qPCR). Iloprost, treprostinil, epoprostenol, or MRE-269 did not alter force of contraction in any of the trabeculae. Isoprenaline showed a direct inotropic response in both trabeculae from the pressure-overloaded right atrium and from the normal right atrium. Control experiments on ventricular trabeculae from the pig failed to show an inotropic response to the prostacyclin mimetics. qPCR demonstrated varying expression of the different prostanoid receptors in the human atrium. In conclusion, prostacyclin mimetics did not increase the force of contraction of human atrial trabeculae from the normal or the pressure-overloaded right heart. These data suggest that prostacyclin mimetics have no direct inotropic effects in the human right atrium

Pulmonary vasodilation in acute pulmonary embolism - a systematic review

Acute pulmonary embolism is the third most common cause of cardiovascular death. Pulmonary embolism increases right ventricular afterload, which causes right ventricular failure, circulatory collapse and death. Most treatments focus on removal of the mechanical obstruction caused by the embolism, but pulmonary vasoconstriction is a significant contributor to the increased right ventricular afterload and is often left untreated. Pulmonary thromboembolism causes mechanical obstruction of the pulmonary vasculature coupled with a complex interaction between humoral factors from the activated platelets, endothelial effects, reflexes and hypoxia to cause pulmonary vasoconstriction that worsens right ventricular afterload. Vasoconstrictors include serotonin, thromboxane, prostaglandins and endothelins, counterbalanced by vasodilators such as nitric oxide and prostacyclins. Exogenous administration of pulmonary vasodilators in acute pulmonary embolism seems attractive but all come with a risk of systemic vasodilation or worsening of pulmonary ventilation-perfusion mismatch. In animal models of acute pulmonary embolism, modulators of the nitric oxide-cyclic guanosine monophosphate-protein kinase G pathway, endothelin pathway and prostaglandin pathway have been investigated. But only a small number of clinical case reports and prospective clinical trials exist. The aim of this review is to give an overview of the causes of pulmonary embolism-induced pulmonary vasoconstriction and of experimental and human investigations of pulmonary vasodilation in acute pulmonary embolism

Inotropic Effects of Prostacyclins on the Right Ventricle Are Abolished in Isolated Rat Hearts With Right-Ventricular Hypertrophy and Failure

BACKGROUND: Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right-ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertrophy and failure. METHODS: Wistar rats were subjected to pulmonary trunk banding to induce compensated RV hypertrophy (n = 32) or manifest RV failure (n = 32). Rats without banding served as healthy controls (n = 30). The hearts were excised and perfused in a Langendorff system and subjected to iloprost, treprostinil, epoprostenol, or MRE-269 in increasing concentrations. The effect on RV function was evaluated using a balloon-tipped catheter inserted into the right ventricle. RESULTS: In control hearts, iloprost, treprostinil, and MRE-269 improved RV function. The effect was, however, absent in hearts with RV hypertrophy and failure. Treprostinil and MRE-269 even impaired RV function in hearts with manifest RV failure. CONCLUSIONS: Iloprost, treprostinil, and MRE-269 improved RV function in the healthy rat heart. RV hypertrophy abolished the positive inotropic effect, and in the failing right ventricle, MRE-269 and treprostinil impaired RV function. This may be related to changes in prostanoid receptor expression and reduced coronary flow reserve in the hypertrophic and failing right ventricle

Putative Biomarkers for Acute Pulmonary Embolism in Exhaled Breath Condensate

Current diagnostic markers for pulmonary embolism (PE) are unspecific. We investigated the proteome of the exhaled breath condensate (EBC) in a porcine model of acute PE in order to identify putative diagnostic markers for PE. EBC was collected at baseline and after the induction of autologous intermediate-risk PE in 14 pigs, plus four negative control pigs. The protein profiles of the EBC were analyzed using label-free quantitative nano liquid chromatography–tandem mass spectrometry. A total of 897 proteins were identified in the EBCs from the pigs. Alterations were found in the levels of 145 different proteins after PE compared with the baseline and negative controls: albumin was among the most upregulated proteins, with 14-fold higher levels 2.5 h after PE (p-value: 0.02). The levels of 49 other proteins were between 1.3- and 17.1-fold higher after PE. The levels of 95 proteins were lower after PE. Neutrophil gelatinase-associated lipocalin (fold change 0.3, p-value < 0.01) was among the most reduced proteins 2.5 h after PE. A prediction model based on penalized regression identified five proteins including albumin and neutrophil gelatinase-associated lipocalin. The model was capable of discriminating baseline samples from EBC samples collected 2.5 h after PE correctly in 22 out of 27 samples. In conclusion, the EBC from pigs with acute PE contained several putative diagnostic markers of PE

Wave Intensity Analysis Provides Novel Insights Into Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar. CONCLUSIONS: Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases

Mechanisms, predictors, and evolution of severe peri-device leaks with two different left atrial appendage occluders.

AIMS Incomplete left atrial appendage occlusion (LAAO) due to peri-device leak (PDL) is a limitation of the therapy. The Amulet IDE trial is the largest randomized head-to-head trial comparing the Amulet and Watchman 2.5 LAAO devices with fundamentally different designs. The predictors and mechanistic factors impacting differences in PDLs within the Amulet IDE trial are assessed in the current analysis. METHODS AND RESULTS An independent core lab analysed all images for the presence or absence of severe PDL (>5 mm). The incidence, mechanistic factors, predictors using propensity score-matched controls, and evolution of severe PDLs through 18 months were assessed. Of the 1878 patients randomized in the trial, the Amulet occluder had significantly fewer severe PDLs than the Watchman device at 45 days (1.1 vs. 3.2%, P < 0.001) and 12 months (0.1 vs. 1.1%, P < 0.001). Off-axis deployment or missed lobes were leading mechanistic PDL factors in each device group. Larger left atrial appendage (LAA) dimensions including orifice diameter, landing zone diameter, and depth predicted severe PDL with the Watchman device, with no significant anatomical limitations noted with the Amulet occluder. Procedural and device implant predictors were found with the Amulet occluder attributed to the learning curve with the device. A majority of Watchman device severe PDLs did not resolve over time through 18 months. CONCLUSION The dual-occlusive Amplatzer Amulet LAA occluder provided improved LAA closure compared with the Watchman 2.5 device. Predictors and temporal observations of severe PDLs were identified in the Amulet IDE trial. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov Unique identifier NCT02879448