Ultrastructural alterations in capillaries of the diabetic hypertensive rat retina: protective effects of ACE inhibition

Aims/hypothesis: The ACE inhibitor cilazapril was administered to diabetic hypertensive rats to evaluate its ability to influence the development of retinal capillary alterations. Methods: Normotensive (strain: Wistar Kyoto) and genetically hypertensive (strain: spontaneously hypertensive) rats were rendered diabetic by intravenous injections of streptozotocin. Half of the diabetic animals received cilazapril with their daily food. At 20 weeks of diabetes, endothelial cells, pericytes and extracellular matrix were assessed by ultrastructural morphometry. Each experimental group consisted of seven animals. Results: Cilazapril normalised systolic arterial pressure in diabetic hypertensive rats (137±2mmHg compared with 188±16mmHg in non-medicated diabetic hypertensive rats, p<0.001). The number of endothelial intercellular junctions was reduced in untreated diabetic hypertensive rats (0.15±0.05, p<0.02, vs 0.47±0.20 in non-diabetic normotensive rats). In diabetic hypertensive animals treated with cilazapril, this loss was attenuated (0.32±0.16, p<0.05). The significant thickening of the basement membrane observed in the diabetic normotensive (132.8±19.4nm) and diabetic hypertensive (150.3±20.2nm) groups was decreased by cilazapril in the diabetic hypertensive group (116.7±11.0nm, p<0.01), but was unaffected in the normotensive (131.9±17.3nm) group. No protective effect of the drug was observed in either group on pericytes. Conclusions/interpretation: Long-term administration of an effective antihypertensive therapy normalises endothelial alterations and basement membrane thickness in diabetic hypertensive conditions, and thus may account for the well-known improvement of the blood-retinal barrier observed during antihypertensive treatmen

Uav Photogrammetry: Block Triangulation Comparisons

UAVs systems represent a flexible technology able to collect a big amount of high resolution information, both for metric and interpretation uses. In the frame of experimental tests carried out at Dept. ICA of Politecnico di Milano to validate vector-sensor systems and to assess metric accuracies of images acquired by UAVs, a block of photos taken by a fixed wing system is triangulated with several software. The test field is a rural area included in an Italian Park ("Parco Adda Nord"), useful to study flight and imagery performances on buildings, roads, cultivated and uncultivated vegetation. The UAV SenseFly, equipped with a camera Canon Ixus 220HS, flew autonomously over the area at a height of 130 m yielding a block of 49 images divided in 5 strips. Sixteen pre-signalized Ground Control Points, surveyed in the area through GPS (NRTK survey), allowed the referencing of the block and accuracy analyses. Approximate values for exterior orientation parameters (positions and attitudes) were recorded by the flight control system. The block was processed with several software: Erdas-LPS, EyeDEA (Univ. of Parma), Agisoft Photoscan, Pix4UAV, in assisted or automatic way. Results comparisons are given in terms of differences among digital surface models, differences in orientation parameters and accuracies, when available. Moreover, image and ground point coordinates obtained by the various software were independently used as initial values in a comparative adjustment made by scientific in-house software, which can apply constraints to evaluate the effectiveness of different methods of point extraction and accuracies on ground check points

A " high 4 He/ 3 He " mantle material detected under the East Pacific Rise (15°4′N)

International audienceWe investigate in details helium isotope data reported in Mougel et al. (2014) for 14 basaltic samples collected on the East Pacific Rise by submersible (15°4′N) where the ridge interacts with the Mathematician seamounts. Samples locations are separated by only few hundred meters across a 15 km along-axis profile. The data reveal a strong geochemical variability that has never been observed at such high spatial resolution for helium isotope compositions. Moreover, they reveal an unusually high 4 He/ 3 He mantle component also characterized by unradiogenic lead, atypical in oceanic basalts. He-Pb systematics suggests a mixture between a nonradiogenic lead and radiogenic helium pyroxenitic component, recycled from the deep continental lithosphere and the ambient peridotitic mantle. The He isotope difference between these two end-members can be interpreted as a time evolution of two distinct mantle sources after a slight (U + Th)/ 3 He fractionation, likely due to some ancient degassing during the formation of deep continental pyroxenites

Trans-Dimensional Geoacoustic Inversion of Wind-Driven Ambient Noise

This letter applies trans-dimensional Bayesian geoacoustic inversion to quantify the uncertainty due to model selection when inverting bottom-loss data derived from wind-driven ambient-noise measurements. A partition model is used to represent the seabed, in which the number of layers, their thicknesses, and acoustic parameters are unknowns to be determined from the data. Exploration of the parameter space is implemented using the Metropolis–Hastings algorithm with parallel tempering, whereas jumps between parameterizations are controlled by a reversible-jump Markov chain Monte Carlo algorithm. Sediment uncertainty profiles from inversion of simulated and experimental data are presented

Boron-nitrogen-doped nanographenes: a synthetic tale from borazine precursors

In this paper we report a comprehensive account of our synthetic efforts to prepare borazino-doped hexabenzocoronenes using the Friedel-Crafts-type electrophilic aromatic substitution. We showed that hexafluoro-functionalized aryl-borazines, bearing an ortho fluoride leaving group on each N- and B-aryl rings, could lead to cascade-type electrophilic aromatic substitution events in the stepwise C-C bond formation giving higher yields of borazinocoronenes than those obtained with borazine precursors bearing fluoride leaving groups at the ortho positions of the B-aryl substituents. It is with this pathway that an unprecedented boroxadizine-doped PAH featuring a gulf-type periphery could be isolated, and its structure proved through single crystal X-ray diffraction analysis. Mechanistic studies on the stepwise Friedel-Crafts-type cyclisation suggest that the mechanism of the planarization reaction proceeds through extension of the π system. To appraise the doping effect of the boroxadizine unit on the optoelectronic properties of topology-equivalent molecular graphenes, the all-carbon and pyrylium PAH analogues, all featuring a gulf-type periphery, were also prepared. As already shown for the borazino-doped hexabenzocoronene, the replacement of the central benzene ring by its B3N2O congener widens the HOMO-LUMO gap and it dramatically enhances the fluorescence quantum yield

ANTIDIARRHOEAL ACTIVITY OF AN ETHANOL EXTRACT OF THE STEM BARK OF PILIOSTIGMA RETICULATUM (CAESALPINIACEAE) IN RATS

Piliostigma reticulatum (Caesalpiniaceae) is used in Africa as a traditional medicine for the treatment of many diseases, such as malaria, tuberculosis and diarrhoea. We investigated the antidiarrhoeal properties of a crude ethanol extract from the stem bark of Piliostigma reticulatum (EEPR) in Wistar albino rats to substantiate its traditional use and to determine its phytochemical constituents. The antidiarrhoeal activity of the plant extract was evaluated in a castor oil-induced diarrhoea model in rats and compared with loperamide. The effect of the extract on gastrointestinal motility was also determined by the oral administration of charcoal meal and castor oil-induced intestinal fluid accumulation (enteropooling). EEPR showed remarkable dose-dependent antidiarrhoeal activity evidenced by a reduction of defecation frequency and change in consistency. Extracts at 250, 500 and 1000 mg/kg body weight significantly reduced diarrhoeal faeces. EEPR also significantly inhibited gastrointestinal motility and castor oil-induced enteropooling at 500 and 1000 mg/kg, similar to the inhibition obtained in control rats treated by atropine. Phytochemical screening revealed the presence of tannins, flavonoids, polyphenols and reducing sugars in the stem bark of P. reticulatum. No mortality or visible signs of general weakness were observed in the rats following administration of the crude extract in doses up to 6000 mg/kg body weight in an acute toxicity study. Our results show that the stem bark of P. reticulatum possesses antidiarrhoeal activity and strongly suggest that its use in traditional medicine practice could be justified

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: A Phase III study

BACKGROUND. The noninferiority of a 6-week dosing schedule of lanreotide Auto-gel (Lan ATG) at a dose of 120 mg compared with a 3-week dosing schedule of lanreotide microparticles (Lan MP) at a dose of 60 mg was investigated in patients with neuroendocrine tumors (NET). METHODS. Patients who had sporadic, well differentiated NET with a low grade of malignancy were recruited for this open-label, Phase 111, multicenter trial. Patients were randomized to receive either 3 deep subcutaneous injections of Lan ATG (120 mg, every 6 weeks) or 6 intramuscular injections of Lan MP (60 mg, every 3 weeks). Tumor markers, tumor size, and symptoms were assessed between baseline and Week 18. Success was classified as a response that ranged from disappearance to an increase &lt; 25% in tumor marker, tumor size, or symptom frequency. RESULTS. Sixty patients were randomized, and 46 patients completed the study. Both for tumor markers and for tumor size, Lan ATG was not inferior to Lan MP (55% and 59% of patients responded on tumor markers, respectively; 68% and 66% of patients responded on tumor size, respectively). There were too few symptomatic patients to compare carcinoid symptoms. Both treatments were tolerated well, and no safety concerns were identified. CONCLUSIONS. Lan ATG at a dose of 120 mg every 6 weeks was as effective for controlling NET as Lan MP at a dose of 60 mg every 3 weeks

Pervasive melt percolation reactions in ultra-depleted refractory harzburgites at the Mid-Atlantic Ridge, 15° 20′N : ODP Hole 1274A

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 153 (2007): 303-319, doi:10.1007/s00410-006-0148-6.ODP Leg 209 Site 1274 mantle peridotites are highly refractory in terms of lack of residual clinopyroxene, olivine Mg# (up to 0.92) and spinel Cr# (~0.5), suggesting high degree of partial melting (>20%). Detailed studies of their microstructures show that they have extensively reacted with a pervading intergranular melt prior to cooling in the lithosphere, leading to crystallization of olivine, clinopyroxene and spinel at the expense of orthopyroxene. The least reacted harzburgites are too rich in orthopyroxene to be simple residues of low-pressure (spinel field) partial melting. Cu-rich sulfides that precipitated with the clinopyroxenes indicate that the intergranular melt was generated by no more than 12% melting of a MORB mantle or by more extensive melting of a clinopyroxene-rich lithology. Rare olivine-rich lherzolitic domains, characterized by relics of coarse clinopyroxenes intergrown with magmatic sulfides, support the second interpretation. Further, coarse and intergranular clinopyroxenes are highly depleted in REE, Zr and Ti. A two-stage partial melting/melt-rock reaction history is proposed, in which initial mantle underwent depletion and refertilization after an earlier high pressure (garnet field) melting event before upwelling and remelting beneath the present-day ridge. The ultra-depleted compositions were acquired through melt re-equilibration with residual harzburgites.Funding for this research was provided by Centre National de la Recherche Scientifique-Institut National des Sciences de l’Univers (Programme Dynamique et Evolution de la Terre Interne)