Effect of tungsten doping on the structural, morphological and bactericidal properties of nanostructured CuO.

Copper oxide (CuO) has been broadly used in different technological and biological applications. However, based on the literature review, there are few reports describing the synthesis of tungsten doped copper oxide and its biological applications, although CuO and W (tungsten) based nanomaterials have been reportedly already synthesized. In this study we synthesized novel CuO and CuO/W (at.1%, 2% and 4%) nanoparticles and explored their tungsten content-dependent bactericide activity. In order to obtain the materials, was used a co-precipitation method which is of low cost. The synthesized materials were characterized by x-ray diffraction (XRD); XRD results indicated that only the sample with at.1% of W presented pure Tenorite phase. Diffuse reflectance spectroscopy (DRS) allowed to obtain the band gap energy values; CuO/W (at.2%) sample exhibited the minimum value of 2.62 eV. Grains sizes ranging from 39.78 to 53.47 nm were established through field emission-scanning electronic microscopy (FE-SEM), and these sizes were confirmed by transmission electron microscopy (TEM). Doping with W also influenced the morphology obtained in all cases. BET (Brunauer, Emmett, Teller) analysis allowed to establish an increase in specific surface area and pore size with W doping. The particle size was determined by dynamic light scattering (DLS). The bactericidal properties were tested using well diffusion method for Escherichia coli and Staphylococcus aureus bacteria. Bactericide response of CuO nanoparticles was improved by the inclusion of W dopant into the CuO structure, leading to an expansion in the inhibition zone for the CuO/W (at.1%) sample; inhibition halo diameters were 1.5 and 12 mm for CuO and CuO/W (at.1%), respectively. Hence, it was possible to infer the remarkable importance of the crystalline phase, morphology, particle size and specific superficial area of the CuO/W (at.1%) nanoparticles in its bactericide performance. WO3 secondary phase affected the bactericide response of the materials obtained at at.2% and at.4% of tungsten content.

Vascularization of the arteriovenous fistula wall and association with maturation outcomes.

BACKGROUND AND OBJECTIVES: The venous vasa vasorum is the mesh of microvessels that provide oxygen and nutrients to the walls of large veins. Whether changes to the vasa vasorum have any effects on human arteriovenous fistula outcomes remains undetermined. In this study, we challenged the hypothesis that inadequate vascularization of the arteriovenous fistula wall is associated with maturation failure. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This case-control pilot study includes pre-access veins and arteriovenous fistula venous samples (i.e. tissue pairs) from 30 patients undergoing two-stage arteriovenous fistula creation (15 matured and 15 failed to mature). Using anti-CD31 immunohistochemistry, we quantified vasa vasorum density and luminal area (vasa vasorum area) in the intima, media, and adventitia of pre-access veins and fistulas. We evaluated the association of pre-existing and postoperative arteriovenous fistula vascularization with maturation failure and with postoperative morphometry. RESULTS: Vascularization of veins and arteriovenous fistulas was predominantly observed in the outer media and adventitia. Only the size of the microvasculature (vasa vasorum area), but not the number of vessels (vasa vasorum density), increased after arteriovenous fistula creation in the adventitia (median vasa vasorum area 1366 µm2/mm2 (interquartile range 495-2582) in veins versus 3077 µm2/mm2 (1812-5323) in arteriovenous fistulas, p < 0.001), while no changes were observed in the intima and media. Postoperative intimal thickness correlated with lower vascularization of the media (r 0.53, p = 0.003 for vasa vasorum density and r 0.37, p = 0.045 for vasa vasorum area). However, there were no significant differences in pre-existing, postoperative, or longitudinal change in vascularization between arteriovenous fistulas with distinct maturation outcomes. CONCLUSION: The lack of change in intimal and medial vascularization after arteriovenous fistula creation argues against higher oxygen demand in the inner walls of the fistula during the vein to arteriovenous fistula transformation. Postoperative intimal hyperplasia in the arteriovenous fistula wall appears to thrive under hypoxic conditions. Vasa vasorum density and area by themselves are not predictive of maturation outcomes.

Transcriptomics of Human Arteriovenous Fistula Failure: Genes Associated With Nonmaturation.

RATIONALE & OBJECTIVE: Improving arteriovenous fistula (AVF) outcomes requires better understanding of the biology underlying maturation or failure. Our current knowledge of maturation relies on extrapolation from other vascular pathologies, which does not incorporate unique aspects of AVF remodeling. This study compares the RNA expression of pre-access (native) veins and AVFs with distinct maturation outcomes. STUDY DESIGN: Case-control study. SETTING & PARTICIPANTS: 64 patients undergoing 2-stage AVF surgeries at a single center. 19 native veins and 19 AVF samples were analyzed using RNA sequencing (RNA-seq). 58 native veins were studied using real-time polymerase chain reaction; 45, using immunohistochemistry; and 19, using Western blot analysis. PREDICTOR: RNA expression in native veins and AVFs. OUTCOME: Anatomic nonmaturation, defined as an AVF that never achieved an internal diameter ≥ 6mm. ANALYTICAL APPROACH: Pre-access native veins and AVF samples were obtained from patients undergoing 2-stage AVF creation. Veins that subsequently matured or failed after access creation were analyzed using RNA-seq to search for genes associated with maturation failure. Genes associated with nonmaturation were confirmed using real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. In addition, the association between pre-access gene expression and postoperative morphology was evaluated. RNA-seq was also performed on AVFs to search for transcriptional differences between AVFs that matured and those that failed at the time of transposition. RESULTS: Pro-inflammatory genes (CSF3R, FPR1, S100A8, S100A9, and VNN2) were upregulated in pre-access veins that failed (false discovery rate < 0.05), and their expression colocalized to smooth muscle cells. Expression of S100A8 and S100A9 correlated with postoperative intimal hyperplasia and the product of medial fibrosis and intimal hyperplasia (r=0.32-0.38; P < 0.05). AVFs that matured or failed were transcriptionally similar at the time of transposition. LIMITATIONS: Small sample size, analysis of only upper-arm veins and transposed fistulas. CONCLUSIONS: Increased expression of proinflammatory genes in pre-access veins appears to be associated with greater risk for AVF nonmaturation.

Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous Fistulas.

The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; P=0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population's median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.

Similar degree of intimal hyperplasia in surgically detected stenotic and nonstenotic arteriovenous fistula segments: a preliminary report.

BACKGROUND: Intimal hyperplasia has been historically associated with improper venous remodeling and stenosis after creation of an arteriovenous fistula. Recently, however, we showed that intimal hyperplasia by itself does not explain the failure of maturation of 2-stage arteriovenous fistulas. We seek to evaluate whether intimal hyperplasia plays a role in the development of focal stenosis of an arteriovenous fistula. METHODS: This study compares intimal hyperplasia lesions in stenotic and nearby nonstenotic segments collected from the same arteriovenous fistula. Focal areas of stenosis were detected in the operating room in patients (n= 14) undergoing the second-stage vein transposition procedure. The entire vein was inspected, and areas of stenosis were visually located with the aid of manual palpation and hemodynamic changes in the vein peripheral and central to the narrowing. Stenotic and nonstenotic segments were documented by photography before tissue collection (14 tissue pairs). Intimal area and thickness, intima-media thickness, and intima to media area ratio were measured in hematoxylin and eosin stained cross-sections followed by pairwise statistical comparisons. RESULTS: The intimal area in stenotic and nonstenotic segments ranged from 1.25 to 11.61 mm2 and 1.29 to 5.81 mm2, respectively. There was no significant difference between these 2 groups (P=.26). Maximal intimal thickness (P=.22), maximal intima-media thickness (P=.13), and intima to media area ratio (P=.73) were also similar between both types of segments. CONCLUSION: This preliminary study indicates that postoperative intimal hyperplasia by itself is not associated with the development of focal venous stenosis in 2-stage fistulas.