Hemodialysis vascular access can develop venous neointimal hyperplasia (VNH) causing stenosis. Recent clinical and experimental data has demonstrated that there is increased expression of a ...disintegrin and metalloproteinase thrombospondin motifs-1 (ADAMTS-1) at site of VNH. The experiments outlined in the present paper were designed to test the hypothesis that targeting of the adventitia of the outflow vein of murine arteriovenous fistula (AVF) using a small hairpin RNA that inhibits ADAMTS-1 expression (LV-shRNA-ADAMTS-1) at the time of fistula creation will decrease VNH. At early time points, ADAMTS-1 expression was significantly decreased associated with a reduction in vascular endothelial growth factor-A (VEGF-A) and matrix metalloproteinase-9 (MMP-9) (LV-shRNA-ADAMTS-1 transduced vessels vs. controls). These changes in gene and protein expression resulted in favorable vascular remodeling with a significant increase in mean lumen vessel area, decrease in media/adventitia area, with a significant increase in TUNEL staining accompanied with a decrease in cellular proliferation accompanied with a reduction in CD68 staining. Collectively, these results demonstrate that ADAMTS-1 transduced vessels of the outflow vein of AVF have positive vascular remodeling.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The presence of marine debris has been reported recently in several oceans basins; there is very little information available for Mexican Pacific coasts, however. This research examined the ...composition, possible sources, distribution, and density of Floating Marine Debris (FMD) during nine research surveys conducted during 2010–2012 in the Mexican Central Pacific (MCP). Of 1820 floating objects recorded, 80% were plastic items. Sources of FMD were determined using key objects, which indicated that the most were related to the presence of the industrial harbor and of a growing fishing industry in the study area. Densities were relatively high, ranging from 40 to 2440objects/km2; the highest densities were recorded in autumn. FMD were distributed near coastal regions, mainly in Jalisco, influenced by river outflow and surface currents. Our results seem to follow worldwide trends and highlight the need for further studies on potential ecological impacts within coastal waters of the MCP.
•Results from nine research surveys conducted to look for FMD in MCP waters.•Approximately 80% of all items were plastics.•The main FMD source was ocean-based, and was attributed to fishing/commercial harbor activities.•FMD densities ranged between 40 2,440 objects/km2, being highest in autumn and in the coastal area, mainly in Jalisco state.•This research represents the baseline for future studies of FMD in MCP waters.
Venous neointimal hyperplasia (VNH) causes hemodialysis vascular access failure. Here we tested whether VNH formation occurs in part due to local vessel hypoxia caused by surgical trauma to the vasa ...vasorum of the outflow vein at the time of arteriovenous fistula placement. Selective targeting of the adventitia of the outflow vein at the time of fistula creation was performed using a lentivirus-delivered small-hairpin RNA that inhibits VEGF-A expression. This resulted in significant increase in mean lumen vessel area, decreased media/adventitia area, and decreased constrictive remodeling with a significant increase in apoptosis (increase in caspase 3 activity and TUNEL staining) accompanied with decreased cellular proliferation and hypoxia-inducible factor-1α at the outflow vein. There was significant decrease in cells staining positive for α-smooth muscle actin (a myofibroblast marker) and VEGFR-1 expression with a decrease in MMP-2 and MMP-9. These results were confirmed in animals that were treated with humanized monoclonal antibody to VEGF-A with similar results. Since hypoxia can cause fibroblast to differentiate into myofibroblasts, we silenced VEGF-A gene expression in fibroblasts and subjected them to hypoxia. This decreased myofibroblast production, cellular proliferation, cell invasion, MMP-2 activity, and increased caspase 3. Thus, VEGF-A reduction at the time of arteriovenous fistula placement results in increased positive vascular remodeling.
The renin–angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and ...cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE–Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling.
The Mexican Central Pacific (MCP) has complex oceanographic dynamics, with a well-defined seasonal pattern and influence of interannual sea surface temperature anomalies. The present study ...investigated the relationship between the distribution/abundance of spotted dolphins and the environmental conditions in the MCP. Dolphin sighting data were collected during January 2010–December 2015; distance to coast, sea surface temperature, and chlorophyll a (Chla) were obtained for each sighting location through georeferenced maps and satellite images. A total of 746 spotted dolphin sightings were obtained with a survey effort of 31,695 km. Spotted dolphins in the MCP showed a predominantly coastal distribution regardless of environmental conditions. Significant differences were detected concerning regional seasonal variation, with higher mean sighting rate during the stratified periods and higher density/abundance estimates during the mixed periods. Spotted dolphins showed preference for warmer conditions, with higher mean sighting rate, abundance, and distance to coast during the neutral and warm interannual periods. During the coolest conditions (cold periods), mean sighting rate and abundance decreased and spotted dolphins were located closer to the coast, where Chla concentration increased. These results suggest that changes in the distribution/abundance of these dolphins could be associated with habitat quality related to tropical (El Niño/Southern Oscillation) and extratropical (The Blob) oceanographic phenomena, which could be modulating their foraging activities.
Beaked whales from the family Ziphiidae are some of the least frequently observed animals on the planet. These cetaceans are deep divers with remarkable physiological and behavioral capabilities, ...allowing them to access ecological niches at depths exceeding 1,000 m, where they endure radical changes in pressure, temperature, and light. Fatal stranding events involving several beaked whale species have been associated with Navy mid-frequency active sonar use. These events have been of public interest, prompting management actions, litigation, and research during recent decades. Stranding events of single individuals, however, are the most common, and they may be associated with natural factors or anthropogenic activities. During the monitoring program, 11 beaked whale sightings were registered. Ten of them were observed during the coastal--oceanic surveys, whereas the 11th sighting was seen during one coastal survey.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To determine if adventitial transplantation of human adipose tissue-derived mesenchymal stem cells (MSCs) to the outflow vein of B6.Cg-Foxn1(nu)/J mice with arteriovenous fistula (AVF) at the time of ...creation would reduce monocyte chemoattractant protein-1 (Mcp-1) gene expression and venous neointimal hyperplasia. The second aim was to track transplanted zirconium 89 ((89)Zr)-labeled MSCs serially with positron emission tomography (PET) for 21 days.
All animal experiments were performed according to protocols approved by the institutional animal care and use committee. Fifty B6.Cg-Foxn1(nu)/J mice were used to accomplish the study aims. Green fluorescent protein was used to stably label 2.5 × 10(5) MSCs, which were injected into the adventitia of the outflow vein at the time of AVF creation in the MSC group. Eleven mice died after AVF placement. Animals were sacrificed on day 7 after AVF placement for real-time polymerase chain reaction (n = 6 for MSC and control groups) and histomorphometric (n = 6 for MSC and control groups) analyses and on day 21 for histomorphometric analysis only (n = 6 for MSC and control groups). In a separate group of experiments (n = 3), animals with transplanted (89)Zr-labeled MSCs were serially imaged with PET for 3 weeks. Multiple comparisons were performed with two-way analysis of variance, followed by the Student t test with post hoc Bonferroni correction.
In vessels with transplanted MSCs compared with control vessels, there was a significant decrease in Mcp-1 gene expression (day 7: mean reduction, 62%; P = .029), with a significant increase in the mean lumen vessel area (day 7: mean increase, 176% P = .013; day 21: mean increase, 415% P = .011). Moreover, this was accompanied by a significant decrease in Ki-67 index (proliferation on day 7: mean reduction, 81% P = .0003; proliferation on day 21: mean reduction, 60%, P = .016). Prolonged retention of MSCs at the adventitia was evidenced by serial PET images of (89)Zr-labeled cells.
Adventitial transplantation of MSCs decreases Mcp-1 gene expression, accompanied by a reduction in venous neointimal hyperplasia.
•Inter-state natural gas infrastructure investment across socioeconomic context.•Existing pipeline capacity is insufficient to satisfy future demand for natural gas.•Geographic distribution of ...investments within the U.S. is heterogeneous.•Risks of under-utilization of pipeline capacity in a low-carbon future economy.
Changes in the natural gas market have spawned the need for pipeline infrastructure planning. Previous studies have analyzed natural gas infrastructure development largely independent of the interactions of the natural gas sector with the broader economy. However, natural gas infrastructure development is strongly influenced by broader domestic and international socioeconomic conditions. We couple a global Human-Earth system model with state-level detail in the United States (GCAM-USA) that provides the broader socioeconomic context for natural gas supply and demand with a natural gas infrastructure investment model (NANGAM) to examine inter-state natural gas pipeline infrastructure development in the U.S. under a range of socioeconomic scenarios. Here we show that existing pipeline infrastructure in the U.S. is insufficient to satisfy the increasing demand for natural gas and investments in pipeline capacity will be required. However, the geographic distribution of investments within the U.S. is heterogeneous and depends on the capacity of existing infrastructure as well as the magnitude of increase in demand. Our results also illustrate the risks of under-utilization of pipeline capacity, in particular, under a scenario characterized by long-term systemic transitions toward a low-carbon economy. More broadly, our study highlights the value of integrated approaches to facilitate informed decision-making.
Dimethyl sulfoxide (DMSO), a widely utilized solvent in the medical industry, has been associated with various adverse effects, even at low concentrations, including damage to mitochondrial ...integrity, altered membrane potentials, caspase activation, and apoptosis. Notably, therapeutic molecules for central nervous system treatments, such as embolic agents or some chemotherapy drugs that are dissolved in DMSO, have been associated with hydrocephalus as a secondary complication. Our study investigated the potential adverse effects of DMSO on the brain, specifically focusing on the development of hydrocephalus and the effect on astrocytes.
Varied concentrations of DMSO were intraventricularly injected into 3-day-old mice, and astrocyte cultures were exposed to similar concentrations of DMSO. After 14 days of injection, magnetic resonance imaging (MRI) was employed to quantify the brain ventricular volumes in mice. Immunofluorescence analysis was conducted to delineate DMSO-dependent effects in the brain. Additionally, astrocyte cultures were utilized to assess astrocyte viability and the effects of cellular apoptosis.
Our findings revealed a dose-dependent induction of ventriculomegaly in mice with 2%, 10%, and 100% DMSO injections (p < 0.001). The ciliated cells of the ventricles were also proportionally affected by DMSO concentration (p < 0.0001). Furthermore, cultured astrocytes exhibited increased apoptosis after DMSO exposure (p < 0.001).
Our study establishes that intraventricular administration of DMSO induces hydrocephalus in a dose-dependent manner. This observation sheds light on a potential explanation for the occurrence of hydrocephalus as a secondary complication in intracranial treatments utilizing DMSO as a solvent.
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•Dimethyl sulfoxide induces ventriculomegaly in a dose-dependent pattern in mice.•Dose-dependent DMSO may underlie ependymal apoptosis.•Increased concentrations of DMSO induce toxicity-dependent apoptosis in astrocytes.
Las enfermedades cardiovasculares (ECV) son la causa principal de morbimortalidad a nivel mundial, afectando especialmente a la población mayor de 60 años, pueden manifestarse según su origen en ...enfermedad coronaria (infarto agudo de miocardio, angina pectoris, insuficiencia cardiaca, y muerte súbita) y enfermedad cerebrovascular (accidentes cerebrovasculares y eventos isquémicos transitorios). Varios factores de riesgo asociados al desarrollo de las ECV han sido descritos; los factores clásicos (modificables y no modificables), y otros que se han añadido a la lista como producto de las nuevas evidencias como es el caso de la inflamación, trombosis, estrés, alteraciones en los niveles de péptidos natriuréticos, metales pesados/contaminantes ambientales, insuficiencia renal y algunos agentes infecciosos. El objetivo de este artículo es presentar el estado del arte asociado con los factores de riesgo cardiovasculares (FRC) clásicos y las evidencias que soportan los FRC emergentes.
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