Degradable,microporous vascular prosthesis from segmented polyurethane

Small caliber (1.5 mm I. D.) vascular prostheses have been prepared from fractionated segmented polyurethane.The microporous and compliant prosthesis when implanted in the abdominal aorta of the rat, induced the growth of a neo-conduit, with a cellular structure similar to that of the natural artery. The process of growth of the neo-artery was accompanied by a progressive degradation of the prosthesis.Presented in part at the 11th Annual Meeting of the European Society of Artificial Organs, Alpbach-Innsbruck, September 1984.     

Leakage and water exchange characterization of gadofosveset in the myocardium

Purpose

To determine the compartmentalization of the blood pool agent gadofosveset and the effect of its transient binding to albumin on the quantification of steady-state fractional myocardial blood volume (fMBV).

Methods

Myocardial vascular fraction measurements were simulated assuming the limiting cases (slow or fast) of two-compartment water exchange for different contrast agent injection concentrations, binding fractions, bound and free relaxivities, and true cardiac vascular fractions.fMBV was measured in five healthy volunteers (4 males, 1 female, average age 33) at 1.5 T after administration of five injections of gadofosveset. The measurements in the volunteers were retrospectively compared to measurements of fMBV after three serial injections of the ultra-small, paramagnetic iron oxide (USPIO) blood pool agent ferumoxytol in an experimental animal. The true fMBV and exchange rate of water protons in both human and animal data sets was determined by chi square minimization.

Results

Simulations showed an error in the measurement of fMBV due to partial binding of gadofosveset of less than 30%. Measured fMBV values over-estimate simulation predictions, and approach cardiac extracellular volume (22%), which suggests that the intravascular assumption may not be appropriate for the myocardium, although it may apply to more distal perfusion beds. In comparison, fMBV measured with ferumoxytol (5%, with slow water proton exchange across vascular wall) agree with published values of myocardial vascular fraction. Further comparison between myocardium relaxation rates induced by gadofosveset and by other extracellular and intravascular contrast agents showed that gadofosveset behaves like an extracellular contrast agent.

Conclusions

The distribution of the volunteer data indicates that a three-compartment model, with slow water exchange of gadofosveset and water protons between the vascular and interstitial compartments, and fast water exchange between the interstitium and the myocytes, is appropriate. The ferumoxytol measurements indicate that this USPIO is an intravascular contrast agent that can be used to quantify myocardial blood volume, with the appropriate correction for water exchange using a two-compartment water exchange model.     

A Compendium of the Most Promising Synthesized Organic Compounds against Several Fusarium oxysporum Species: Synthesis,Antifungal Activity,and Perspectives

Vascular wilt caused by F. oxysporum (FOX) is one of the main limitations of producing several agricultural products worldwide, causing economic losses between 40% and 100%. Various methods have been developed to control this phytopathogen, such as the cultural, biological, and chemical controls, the latter being the most widely used in the agricultural sector. The treatment of this fungus through systemic fungicides, although practical, brings problems because the agrochemical agents used have shown mutagenic effects on the fungus, increasing the pathogen’s resistance. The design and the synthesis of novel synthetic antifungal agents used against FOX have been broadly studied in recent years. This review article presents a compendium of the synthetic methodologies during the last ten years as promissory, which can be used to afford novel and potential agrochemical agents. The revision is addressed from the structural core of the most active synthetic compounds against FOX. The synthetic methodologies implemented strategies based on cyclo condensation reactions, radical cyclization, electrocyclic closures, and carbon–carbon couplings by metal–organic catalysis. This revision contributes significantly to the organic chemistry, supplying novel alternatives for the use of more effective agrochemical agents against F. oxysporum.     

Insight into the Inhibitory Mechanism of Aryl Formyl Piperidine Derivatives on Monoacylglycerol Lipase through Molecular Dynamics Simulations

Monoacylglycerol lipase (MAGL) can regulate the endocannabinoid system and thus becomes a target of antidepressant drugs. In this paper, molecular docking and molecular dynamics simulations, combined with binding free energy calculation, were employed to investigate the inhibitory mechanism and binding modes of four aryl formyl piperidine derivative inhibitors with different 1-substituents to MAGL. The results showed that in the four systems, the main four regions where the enzyme bound to the inhibitor included around the head aromatic ring, the head carbonyl oxygen, the tail amide bond, and the tail benzene ring. The significant conformational changes in the more flexible lid domain of the enzyme were caused by 1-substituted group differences of inhibitors and resulted in different degrees of flipping in the tail of the inhibitor. The flipping led to a different direction of the tail amide bond and made a greater variation in its interaction with some of the charged residues in the enzyme, which further contributed to a different swing of the tail benzene ring. If the swing is large enough, it can weaken the binding strength of the head carbonyl oxygen to its nearby residues, and even the whole inhibitor with the enzyme so that the inhibition decreases.     

Core-shell fibrous vascular grafts with the nitric oxide releasing property

Small-diameter vascular grafts with the nitric oxide(NO) releasing property were designed and prepared.Diazeniumdiolated N,N'-dibutyl-1,6-hexanediamine(DBHD/N2O2) was first synthesized as the NO donor and doped into the biocompatible polymer poly(ε-caprolactone)(PCL).The fibrous vascular grafts were fabricated by electrospinning.Despite the reduced platelet adhesion observed on the NO releasing grafts,the cytotoxicity and burst release were apparent,especially at a higher loading level of the NO donor.In or...     

Dynamics and Correlates of Microscopic Changes in Affect

How are momentary microscopic assessments of behavioral dynamics related to traditional macroscopic, static measures? The present study used the computerized “mouse paradigm” to assess near-instantaneous changes in affect over a short time. Dynamic indices were computed from approximately 1400 measurements from the last 2.5 minutes of a 3-minute assessment. Subjects monitored and reported emotional states by moving a cursor along a dimension from “Sadder” to “Happier.” They also completed self-report measures: Scales 2 (Depression) and 9 (Mania) of the MMPI-2, the Positive and Negative Affect Scale, and the Wisconsin scales of Physical Anhedonia and Hypomanic traits. The instantaneous data yielded a summary measure of mean affect, as well as indices of variability. Complexity indices were derived and examined. Mean affect ratings correlated in expected directions with the paper and pencil measures. There was evidence for low-dimensional chaos in short-term affect dynamics. As hypothesized, greater complexity was associated with Pleasant Affect and Hypomania but was negatively correlated with Anhedonia.     

慢性舒张性心力衰竭患者动脉僵硬度影响因素分析

目的探讨慢性舒张性心力衰竭患者动脉僵硬度的影响因素.方法选取慢性舒张性心力衰竭患者354例,测量身高、体重、血压,计算BMI,采集空腹静脉血分析血脂、血糖、血浆B型脑钠肽(BNP)等指标,超声心动图检查各项指标,采用动脉硬化检测仪测量CAVI,分析CAVI与各临床特征的相关性.结果单因素相关分析结果显示,CAVI与年龄、收缩压、BNP呈明显正相关(r=0.3664、0.1193、0.2591,P<0.05或0.01),与BMI、E/A呈显著负相关(r=0.2040、0.1759,均P<0.01);多元逐步回归分析显示,高龄、女性、吸烟史、BMI、BNP、E/A是CAVI的独立影响因素(β=0.0443、0.2617、-0.0675、0.3904、0.4939、-0.7899,P<0.05或0.01),且E/A比值作用最强(P<0.05).结论老龄、女性、吸烟、BMI、BNP、E/A是影响慢性舒张性心力衰竭患者动脉僵硬度的主要危险因素.     

Collagen‐Reinforced Electrospun Silk Fibroin Tubular Construct as Small Calibre Vascular Graft

None of the replacements proposed in the literature for small‐calibre blood vessels (SCBV) fully satisfies the stringent requirements that these grafts have to fulfil. Here, an electrospun silk fibroin tubular construct is hybridized with type I collagen gel to produce a biomimetic SCBV graft with physiologically relevant compliance and burst pressure and optimal cytocompatibility. The hybridization of the two polymers results in the formation of a nanofibrillar hydrated matrix, where the collagen gel enhances the mechanical properties of the SF tubular construct and improves the early response of the material to in vitro cell adhesion and proliferation.

     

Characterization of a Water-Dispersed Biodegradable Polyurethane-Silk Composite Sponge Using 13C Solid-State Nuclear Magnetic Resonance as Coating Material for Silk Vascular Grafts with Small Diameters

Recently, Bombyx mori silk fibroin (SF) has been shown to be a suitable material for vascular prostheses for small arteries. In this study, we developed a softer SF graft by coating water-dispersed biodegradable polyurethane (PU) based on polycaprolactone and an SF composite sponge on the knitted SF vascular graft. Three kinds of ¹³C solid-state nuclear magnetic resonance (NMR), namely carbon-13 (¹³C) cross-polarization/magic angle spinning (MAS), ¹³C dipolar decoupled MAS, and ¹³C refocused insensitive nuclei enhanced by polarization transfer (r-INEPT) NMR, were used to characterize the PU-SF coating sponge. Especially the ¹³C r-INEPT NMR spectrum of water-dispersed biodegradable PU showed that both main components of the non-crystalline domain of PU and amorphous domain of SF were highly mobile in the hydrated state. Then, the small-diameter SF artificial vascular grafts coated with this sponge were evaluated through implantation experiments with rats. The implanted PU-SF-coated SF grafts showed a high patency rate. It was confirmed that the inside of the SF grafts was covered with vascular endothelial cells 4 weeks after implantation. These results showed that the water-dispersed biodegradable PU-SF-coated SF graft created in this study could be a strong candidate for small-diameter artificial vascular graft.