Blockade of vascular endothelial growth factor receptor 2 inhibits intraplaque haemorrhage by normalization of plaque neovessels.

BACKGROUND: Plaque angiogenesis is associated with atherosclerotic lesion growth, plaque instability and negative clinical outcome. Plaque angiogenesis is a natural occurring process to fulfil the increasing demand of oxygen and nourishment of the vessel wall. However, inadequate formed, immature plaque neovessels are leaky and cause intraplaque haemorrhage. OBJECTIVE: Blockade of VEGFR2 normalizes the unbridled process of plaque neovessel formation and induces maturation of nascent vessels resulting in prevention of intraplaque haemorrhage and influx of inflammatory cells into the plaque and subsequently increases plaque stability. METHODS AND RESULTS: In human carotid and vein graft atherosclerotic lesions, leaky plaque neovessels and intraplaque haemorrhage co-localize with VEGF/VEGFR2 and angiopoietins. Using hypercholesterolaemic ApoE3*Leiden mice that received a donor caval vein interposition in the carotid artery, we demonstrate that atherosclerotic vein graft lesions at t28 are associated with hypoxia, Hif1α and Sdf1 up-regulation. Local VEGF administration results in increased plaque angiogenesis. VEGFR2 blockade in this model results in a significant 44% decrease in intraplaque haemorrhage and 80% less extravasated erythrocytes compared to controls. VEGFR2 blockade in vivo results in a 32% of reduction in vein graft size and more stable lesions with significantly reduced macrophage content (30%), and increased collagen (54%) and smooth muscle cell content (123%). Significant decreased VEGF, angiopoietin-2 and increased Connexin 40 expression levels demonstrate increased plaque neovessel maturation in the vein grafts. VEGFR2 blockade in an aortic ring assay showed increased pericyte coverage of the capillary sprouts. CONCLUSION: Inhibition of intraplaque haemorrhage by controlling neovessels maturation holds promise to improve plaque stability.

Effects of feeding low fishmeal diets with increasing soybean meal levels on growth, gut histology and plasma biochemistry of sea bass.

The aquaculture industry depends upon the development of sustainable protein sources to replace fishmeal (FM) in aquafeeds and the products derived from soybeans are some of the most studied plant feedstuffs. A key area of investigation for continuing to improve modern aquafeeds includes the evaluation of varying proportions and combinations of plant ingredients to identify mixtures that are more efficiently utilized by the fish. This study investigated the effects of increasing soybean meal (SBM) by replacing a mix of plant ingredients in low FM (20%) diets on growth, blood biochemistry profile and gut histology on European sea bass. Five isonitrogenous and isolipidic experimental diets were formulated: four diets containing increasing SBM levels (0, 10, 20 and 30%; 0SBM, 10SBM, 20SBM and 30SBM, respectively) with a low content of FM (20%) and one control diet (0% SBM; 35% FM). Diets containing SBM brought to comparable performance and protein utilization, while 0SBM had negative impact on feed conversion rate and protein utilization. Blood parameters suggested an optimal nutritional status under all feeding treatments, even though slightly decreased values were reported at increasing dietary SBM. Histology examination did not show any changes indicative of soy-induced enteritis. We can conclude that for European sea bass: (i) different blends of plant protein did not affect feed intake despite the 20% FM dietary level; (ii) the inclusion of SBM maintains optimal growth and feed utilization in low FM diets; (iii) blood biochemistry profile showed a good nutritional status under all feeding regimes; (iv) no evidence of soy-induced enteritis was reported in any group fed low FM diets. For formulation of practical diets in on-growing of European sea bass, SBM up to 30% can be successfully incorporated into feeds containing low FM inclusion.

Fatty acid composition of eggs and its relationships to egg and larval viability from domesticated common sole (Solea solea) breeders.

The study of lipids and fatty acids (FAs) has been used in the assessment of egg quality because their composition can influence the fertilization rate, hatching, survival and growth of marine fish larvae. For these reasons, the lipid content (TL) and fatty acid composition of common sole (Solea solea) eggs were measured and correlated to egg and larval viability parameters throughout an entire reproductive season. Seventeen batches of fertile eggs obtained from natural spawning of captive breeders were characterized for the TL, FA profile, hatching rate (HR) and survival rate of larvae (SR) at 0-6 days post-hatching (dph). The egg FA composition reflected the composition of the feed supplied to the broodstock during summer and autumn (before and during vitellogenesis) rather than that supplied during the spawning season. In general, the egg FA profile showed minimal differences among the early-, mid- and late-spawning periods (possibly due to the change of the diet and/or water temperature) indicating that it is possible to obtain a similar egg quality in terms of egg FA profile over 2 months of spawning. Saturated FAs and monounsaturated FAs (MUFA) were positively correlated with HR, while TL, 22 : 6n-3 (DHA), 20 : 4n-6 (ARA), polyunsaturated FAs of the (n-3) series (n-3 PUFA) and polyunsaturated FAs of the (n-6) series were negatively correlated (p ≤ 0.05). MUFA, 20 : 5n-3 (EPA), n-6/n-3 were positively correlated with SR, while DHA, n-3 PUFA, DHA/EPA were negatively correlated (p ≤ 0.05). In conclusion, the feed supplied before and during vitellogenesis has a major role in determining the egg FA profile in common sole. The relationships found between TL and FAs with egg and larval viability parameters differ from many other farmed marine fish species, which may suggest the need for a specific broodstock feed for this species.

Mechanical adaptability of a sponge extracellular matrix: Evidence for cellular control of mesohyl stiffness in Chondrosia reniformis Nardo.

The marine sponge Chondrosia reniformis Nardo consists largely of a collagenous tissue, the mesohyl, which confers a cartilaginous consistency on the whole animal. This investigation was prompted by the incidental observation that, despite a paucity of potentially contractile elements in the mesohyl, intact C. reniformis stiffen noticeably when touched. By measuring the deflection under gravity of beam-shaped tissue samples, it was demonstrated that the flexural stiffness of the mesohyl is altered by treatments that influence cellular activities, including [Ca2+] manipulation, inorganic and organic calcium channel-blockers and cell membrane disrupters, and that it is also sensitive to extracts of C. reniformis tissue that have been repeatedly frozen then thawed. Since the membrane disrupters and tissue extracts cause marked stiffening of mesohyl samples, it is hypothesised that cells in the mesohyl store a stiffening factor and that the physiologically controlled release of this factor is responsible for the touch-induced stiffening of intact animals.

Hepatic iron overload in patients with chronic viral hepatitis: role of HFE gene mutations.

Mild to moderate hepatic iron overload is frequent in patients with chronic viral hepatitis (CH). We evaluated the role of hemochromatosis (HFE) gene mutations and other acquired factors in the development of iron overload in these patients. We studied 110 patients with chronic B or C viral hepatitis (31 women, 79 men), including 20 with cirrhosis, and 139 controls. Hepatic iron was evaluated by semiquantitative analysis in all the patients, and hepatic iron concentration (HIC) was determined in 97 of them (26 women, 71 men). C282Y and H63D mutations were sought in all the subjects by a polymerase chain reaction-restriction assay. The frequency of HFE genotypes and alleles did not differ in patients and controls. No relation was detected between hepatic iron stores and HFE gene mutations in women. In men, all C282Y heterozygotes had iron overload, and the H63D mutation was significantly more frequent in patients with more marked hepatic siderosis than in those with mild or no siderosis (P = .0039) and in controls (P = .0008). Heavy alcohol intake and hepatic cirrhosis were also associated with increased hepatic iron stores in the men. In the 71 men in whom HIC was measured, multiple regression analysis showed that this variable was related independently only to alcohol intake and HFE gene mutations. We suggest that in patients with CH, iron accumulates in the liver as the result of an interplay between genetic and acquired factors, and that increased liver iron stores may influence progression toward liver fibrosis.

Fully automatic quantitative analysis of alpha-radiation spectral data using a minicomputer.

Fully automatic computer programs for the analysis of alpha-spectroscopy data have been developed and installed on a PDP-11/45 minicomputer at the Eastern Environmental Radiation Facility (EERF) of the U.S. Environmental Protection Agency (EPA) in Montgomery, AL. The programs presently in use evaluate the activities of the U, Pu and Am nuclides of interest to EERF. A mathematical enhancement of the spectra processed makes reliable determination of nuclide gross counts possible without the human interaction previously necessary at the laboratory. A number of safeguards that attempt to detect conditions (anomalous chemistry, etc.) which may cause invalid analyses are provided in the programs.

Effect of excitation and emission wavelength on the fluorescence lifetimes of chlorophyll a.

The effect of excitation and emission wavelengths on fluorescence decay times of Chlorophyll a were measured in four solutions (C approximately 10(-5) mol X 1(-1] and in polymethyl methacrylate films. The decay times observed were corrected with respect to self-absorption and re-emission effects. The fluorescence decay times of Chlorophyll a was found to depend on both the excitation and the emission wavelengths.