Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection and treatment of synovial inflammation in murine rheumatoid arthritis.

We have developed a thrombin-sensitive polymeric photosensitizer prodrug (T-PS) to selectively image and eradicate inflammatory lesions in rheumatoid arthritis (RA). Thrombin is a serine protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients. T-PS consists of a polymeric backbone, to which multiple photosensitizer (PS) units are tethered via short thrombin-cleavable peptide linkers. Fluorescence emission and phototoxicity of the prodrug are efficiently quenched due to the interaction of neighboring photosensitizer units. The prodrug is passively delivered to the inflammation site via the enhanced permeability and retention (EPR) effect. Subsequent site-selective proteolytic cleavage of the peptide linkers restores its photoactivity by increasing the mutual distance between PS. Whole animal imaging in murine collagen-induced arthritis, an experimental model of RA revealed a dose-dependent fluorescence increase in arthritic paws after systemic prodrug injection. In addition, administration of T-PS resulted in much higher fluorescence selectivity for arthritic joints as compared to the free PS. Irradiation of the arthritic joints induced light dose dependent phototoxic effects such as apoptosis, vascular damage and local hemorrhage. Long-term observations showed complete regression of the latter. Irradiated non-arthritic tissues or non-irradiated arthritic tissues showed no histological effects after photodynamic therapy with T-PS. This illustrates that T-PS can localize inflammatory lesions with excellent selectivity and induce apoptosis and vascular shut down after irradiation.

On the dual contrast enhancement mechanism in frequency-selective inversion-recovery magnetic resonance angiography (IRON-MRA)

The susceptibility of blood changes after administration of a paramagnetic contrast agent that shortens T(1). Concomitantly, the resonance frequency of the blood vessels shifts in a geometry-dependent way. This frequency change may be exploited for incremental contrast generation by applying a frequency-selective saturation prepulse prior to the imaging sequence. The dual origin of vascular enhancement depending first on off-resonance and second on T(1) lowering was investigated in vitro, together with the geometry dependence of the signal at 3T. First results obtained in an in vivo rabbit model are presented.

Follicular dynamics in zebu cattle

The aim of this study was to investigate the follicular dynamics during estrous cycle in Gir breed (Bos indicus) cows. Follicular growth and atresia during estrous cycle were evaluated using a portable ultrasound device. Luteal activity was evaluated by serum progesterone levels. Cycles with two (6.67%), three (60.00%), four (26.67%) and five (6.67%) follicular waves were observed. There was no difference (P>0.05) in dominant or subordinate follicles growth or atresia rates among follicular waves. The maximum diameter of the ovulatory follicle was higher than the diameter of the other dominant follicles in cycles with four waves, and higher than the diameter of the second dominant follicle in cycles with three waves (P<0.05). There was no difference (P>0.05) in estrous cycle length (21.11±1.76 and 22.25±1.71 days) or progesterone levels during diestrous (4.48±1.45 and 5.08±1.40 ng/mL) between cycles with three or four waves. Follicular dynamics in Gir cattle is characterized by a higher incidence of cycles with three or four waves, associated with a low persistence of the dominant follicle.

Expression of dual angiogenic/neurogenic growth factors in human primary brain tumors.

Brain tumors, benign or malignant, are characterized by a very high degree of vascularization. Recent accumulating evidence suggests that during development the neuronal wiring follows the same routes as the vasculature and that these two systems may share some of the same factors for guidance. Thus, expression of dual angiogenic/neurogenic growth factors was evaluated by in situ hybridization in human primary brain tumors of three different types, i.e., astrocytomas, oligodendrogliomas, and ependymomas, of increasing grades, in relation with the grade and type of the tumor. For this evaluation we selected vascular endothelial growth factor (VEGF-A) and its receptors VEGF-R1 and VEGF-R2 and the neuropilins 1 and 2 (NRP-1 and NRP-2), which have proangiogenic properties, platelet-derived growth factor (PDGF) receptor-beta (PDGF-Rβ), which is required for the functional maturation of blood vessels, the ephrins and their Eph receptors, angiotensinogen (AGT) and thrombospondin-2 (TSP-2), which have potential antiangiogenic properties, and netrin-1 (Net-1), which regulates vascular architecture. We show that the expression of the VEGF-NRP system, PDGF-Rβ, TSP-2, AGT, and Net-1 are differentially regulated, either increased or decreased, in relation with the type and grade of the tumor, whereas regulation of the ephrinB system does not seem to be relevant in these human brain tumors.

Las competencias genéricas en el Grado de Derecho y su evaluación

[spa] El presente estudio versa sobre la evaluación de competencias transversales en el Grado de Derecho a través del uso del portafolio digital. A tal fin son definidos los objetivos a alcanzar, las fases en su aplicación; la selección de las competencias a evaluar, así como una tabla de equivalencias entre actividades y competencias. Dicho portafolio electrónico nos ha permitido hacer el seguimiento, monitorización y evaluación de las competencias de los estudiantes. Se ha escogido deliberadamente llevar a cabo únicamente la evaluación de las competencias genéricas o transversales. La implantación del portafolio se ha hecho como experiencia piloto en un grupo de 90 estudiantes de doble titulación en la Facultad de Derecho de la Universidad de Barcelona.

Optimal beef cattle management under agricultural policy reforms in Finland

Selostus: Politiikkamuutosten vaikutus lihanautojen optimaaliseen ruokintaan ja teurastuksen ajoitukseen

Association of bGH and Pit-1 gene variants with milk production traits in dairy Gyr bulls

The objective of this study was to obtain genetic marker information in the Gyr breed by analyzing bGH and Pit-1 gene polymorphisms and to verify their association with milk production traits. One sample including 40 Gyr bulls were genotyped at two bGH gene restriction sites (bGH- AluI and bGH-MspI) and at one restriction site in the Pit-1 gene (Pit-1 HinfI). The bGH-MspI(-) allele was favorable for fat milk percentage. The heterozigous Pit-1 HinfI (+/-) bulls were superior for fat milk production, in relation to homozigous Pit-1 HinfI (+/+). The Pit-1 and bGH genes are strong candidates in the dairy cattle QTL search, and zebuine populations are promising samples for this purpose.

Multi-Purpose ESS/ITS Data Collection Sites, SPR72-00-0003-042, 2014

This document presents the results of a state-of-practice survey of transportation agencies that are installing intelligent transportation sensors (ITS) and other devices along with their environmental sensing stations (ESS) also referred to as roadway weather information system (RWIS) assets.

Imported Cattle Report, September 2014

The Imported Cattle report monthly by the Department of Agricultural.

Imported Cattle Report, October 2014

The Imported Cattle report monthly by the Department of Agricultural.

Imported Cattle Report, November 2014

The Imported Cattle report monthly by the Department of Agricultural.

Imported Cattle Report, December 2014

The Imported Cattle report monthly by the Department of Agricultural.

Modifying effect of dual antiplatelet therapy on incidence of stent thrombosis according to implanted drug-eluting stent type.

AIM: To investigate the putative modifying effect of dual antiplatelet therapy (DAPT) use on the incidence of stent thrombosis at 3 years in patients randomized to Endeavor zotarolimus-eluting stent (E-ZES) or Cypher sirolimus-eluting stent (C-SES). METHODS AND RESULTS: Of 8709 patients in PROTECT, 4357 were randomized to E-ZES and 4352 to C-SES. Aspirin was to be given indefinitely, and clopidogrel/ticlopidine for ≥3 months or up to 12 months after implantation. Main outcome measures were definite or probable stent thrombosis at 3 years. Multivariable Cox regression analysis was applied, with stent type, DAPT, and their interaction as the main outcome determinants. Dual antiplatelet therapy adherence remained the same in the E-ZES and C-SES groups (79.6% at 1 year, 32.8% at 2 years, and 21.6% at 3 years). We observed a statistically significant (P = 0.0052) heterogeneity in treatment effect of stent type in relation to DAPT. In the absence of DAPT, stent thrombosis was lower with E-ZES  vs. C-SES (adjusted hazard ratio 0.38, 95% confidence interval 0.19, 0.75; P = 0.0056). In the presence of DAPT, no difference was found (1.18; 0.79, 1.77; P = 0.43). CONCLUSION: A strong interaction was observed between drug-eluting stent type and DAPT use, most likely prompted by the vascular healing response induced by the implanted DES system. These results suggest that the incidence of stent thrombosis in DES trials should not be evaluated independently of DAPT use, and the optimal duration of DAPT will likely depend upon stent type (Clinicaltrials.gov number NCT00476957).

Larvicidal potential of Sapindus saponaria to control the cattle tick Boophilus microplus

The objective of this study was to evaluate the larvicidal potential of a crude ethanol extract (CEE) of soapberry Sapindus saponaria stem peel on the cattle tick Boophilus microplus. Tick larvae obtained by incubating engorged females, collected from naturally infested cattle, were placed in envelopes of filter paper impregnated with different concentrations of CEE in the test group, and distilled water in the control group. Four repetitions were made with each solution (n>120). Mortality was observed after 48 hours. Lethal concentration values of 1,258 ppm (LC50) and 6,360 ppm (LC99) were obtained.

Inhibition of voltage-gated Na(+) currents in sensory neurones by the sea anemone toxin APETx2.

BACKGROUND AND PURPOSE: APETx2, a toxin from the sea anemone Anthropleura elegantissima, inhibits acid-sensing ion channel 3 (ASIC3)-containing homo- and heterotrimeric channels with IC(50) values < 100 nM and 0.1-2 µM respectively. ASIC3 channels mediate acute acid-induced and inflammatory pain response and APETx2 has been used as a selective pharmacological tool in animal studies. Toxins from sea anemones also modulate voltage-gated Na(+) channel (Na(v) ) function. Here we tested the effects of APETx2 on Na(v) function in sensory neurones.¦EXPERIMENTAL APPROACH: Effects of APETx2 on Na(v) function were studied in rat dorsal root ganglion (DRG) neurones by whole-cell patch clamp.¦KEY RESULTS: APETx2 inhibited the tetrodotoxin (TTX)-resistant Na(v) 1.8 currents of DRG neurones (IC(50) , 2.6 µM). TTX-sensitive currents were less inhibited. The inhibition of Na(v) 1.8 currents was due to a rightward shift in the voltage dependence of activation and a reduction of the maximal macroscopic conductance. The inhibition of Na(v) 1.8 currents by APETx2 was confirmed with cloned channels expressed in Xenopus oocytes. In current-clamp experiments in DRG neurones, the number of action potentials induced by injection of a current ramp was reduced by APETx2.¦CONCLUSIONS AND IMPLICATIONS: APETx2 inhibited Na(v) 1.8 channels, in addition to ASIC3 channels, at concentrations used in in vivo studies. The limited specificity of this toxin should be taken into account when using APETx2 as a pharmacological tool. Its dual action will be an advantage for the use of APETx2 or its derivatives as analgesic drugs.