Reduction In Lumen Size Research Articles

A systematic review of cardiovascular risk factors in patients with traumatic spinal cord injury.

Objective: The main risk factors for cardiac events, and particularly for the development of atherosclerosis, are diabetes mellitus, arterial hypertension, dyslipidemia and smoking. Patients with a traumatic spinal cord injury (SCI) may present with autonomic nervous system dysfunction depending on their level of spinal cord injury. Studies have found a rise in cardiovascular mortality. A systematic review was conducted that focused on this patient group's predisposition to vascular risk. Methods: We performed a PubMed and Cochrane database search. After applying specific search criteria, 42 articles were included in our analysis out of a total of 10,784 matches. The articles were selected with the aim of establishing cardiovascular risk factors in patients with traumatic spinal cord injury. Results: Patients with SCI are at an increased risk for peripheral artery disease even in the absence of cardiovascular risk factors. Major vascular changes to the arteries of patients with SCI include: a reduction in lumen size, increased vessel wall tension, higher vascular stiffness, an impaired reactive hyperemic response, and a lack of reduced vascular resistance. The findings for carotid atherosclerosis were inconclusive. This group of patients also has a higher disposition for diabetes mellitus, lipid metabolism disorders and coronary artery disease. Paraplegics are more likely to suffer from dyslipidemia, obesity and PAD, while tetraplegics are more likely to have diabetes mellitus. Conclusions: Patients with SCI are more likely to have cardiovascular risk factors and have cardiovascular disease compared to the normal population. Peripheral circulatory disorders are particularly common. Patients with SCI are now considered to be a new risk group for cardiovascular disease; however, large epidemiological studies are needed to verify in more detail the cardiovascular risk profile of this patient group.

Impact of aeration rate and dielectrophoretic force on fouling suppression in submerged membrane bioreactors

Membrane bioreactors (MBRs) present a unique opportunity in waste water treatment by combining the activated sludge process with membrane filtration. Although MBRs require less area, produce less volume of sludge and have high purification efficiency, they suffer from high membrane fouling. Membrane fouling can be reduced by applying aeration and Dep voltage. However, application of these two anti-fouling mechanisms would make the process expensive. Thus, a new aeration and DEP scheme of 5 min on – 5 min off is being suggested in this study. With this scheme, it was found that through application of DEP at 100 V and 0.3 L/min.m2 aeration flowrate and reduced lumen size of 6 mm, the membrane permeate flux can be increased by 58% compared to MBR without DEP and aeration. However, through energy analysis the optimum operating parameters were found to be at 0.3 L/min.m2 aeration flowrate and 50 V DEP using the suggested 5 min on-5 min off scheme. At the optimum operating condition, the permeability flux is 54% higher than MBR without DEP and aeration.

Microcystin-LR induces angiodysplasia and vascular dysfunction through promoting cell apoptosis by the mitochondrial signaling pathway

The harmful algal blooms are becoming increasingly problematic in the regions that drinking water production depends on surface waters. With a global occurrence, microcystins are toxic peptides produced by multiple cyanobacterial genera in the harmful algal blooms. In this study, we examined the effects of microcystin-LR (MC-LR), a representative toxin of the microcystin family, on vascular development in zebrafish and the apoptosis of human umbilical vein endothelial cells (HUVECs). In zebrafish larvae, MC-LR induced angiodysplasia, damaged vascular structures and reduced lumen size at 0.1 μM and 1 μM, leading to the decrease of the blood flow area in the blood vessels and brain hemorrhage, which showed that MC-LR could dose-dependently inhibit vascular development and cause vascular dysfunction. In MC-LR treated HUVECs, the proportion of early apoptosis and late apoptosis cells increased in a concentration-dependent manner. Different concentrations of MC-LR could also activate caspase 3/9 in HUVECs, increase the level of mitochondrial ROS and reduce mitochondrial membrane potential. Additionally, MC-LR could promote the expression of p53 and inhibit the expression of PCNA. The findings showed that MC-LR could promote apoptosis of HUVECs through the mitochondrial signaling pathway. Combined with these results, MC-LR may promote vascular endothelial cell apoptosis through mitochondrial signaling pathway, leading to angiodysplasia and vascular dysfunction.

Chronic Administration of Quercetin Induces Biomechanical and Pharmacological Remodeling in the Rat Coronary Arteries

Acute dilation brought about by the dietary flavonoid quercetin in coronary arterioles has been described earlier, but no information is available on its chronic effects. Male Wistar rats (body weight about 190 g) were divided to two groups: the quercetin-treated group (n=22) had quercetin supplementation of approximately 30 mg/kg/day, whereas the control group (n=20) had none. After eight weeks of treatment, intramural coronary arterioles with identical passive diameters (178+/-14 microm and 171+/-9 microm) were prepared and their biomechanics and pharmacological reactivities were tested using pressure arteriography ex vivo. The spontaneous tone of quercetin-treated arteries was higher (16.5+/-1.9 % vs. 12.9+/-0.9 %), which resulted in a reduced lumen size (144+/-9 microm vs. 167+/-12 microm), thicker vascular wall (22.6+/-1.8 microm vs. 17.4+/-1.6 microm) and decreased tangential wall stress (16.8+/-1.1 kPa vs. 20.5+/-1.6 kPa) in supplemented animals (in spontaneous tone at 50 mm Hg, p<0.01 in all these comparisons). Elevated basal NO release resulted in increased endothelial dilation in quercetin-treated animals, especially at higher intraluminal pressures (10.8+/-2.5 % vs. 5.7+/-1.3 % at 70 mm Hg, p<0.01). We found remodeling of the geometry of coronary arterioles to ensure higher dilatory reserve and nitrogen monoxide production, as well as lowered elastic stress of the vessel wall.

Sertoli Cells Are Susceptible to ZIKV Infection in Mouse Testis.

Flaviviruses including Dengue virus (DENV), Yellow fever virus (YFV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) are global health problems that caused several serious diseases such as fever, hemorrhagic fever, and encephalitis in the past century. Recently, Zika virus (ZIKV) which spreads from Asia to American and causes millions of infections emerges as a new dangerous member of the genus of Flavivirus. Unlike other well-known flaviviruses, ZIKV can be transmitted sexually and infect testes in murine models. Its impacts on sperm functions, and the exact susceptible cells, however, are not entirely clear. To investigate these issues, we infected interferon α/β and γ receptors deficient AG6 mice with ZIKV and examined the outcomes of infection using an assortment of physiological, histopathological, immunological, and virological techniques. We found that infected mice displayed signs of reproductive system disorder, altered androgen levels in serum, and high viral load in semen and testes. Additionally, histopathological examinations revealed marked atrophy of seminiferous tubules and significant reduction in lumen size. Notably, these were accompanied by positive staining of ZIKV antigens on sertoli cells, detection of viral particles and vacuole changes within cytoplasm of sertoli cells. The susceptibility of sertoli cells to ZIKV was further validated in vitro study using cell lines. Importantly, the disruption of tight junctions within testis and altered sperm morphology were also observed in ZIKV infected mice. It is well-known that tight junctions formed by adjacent sertoli cells are major component of blood testis barrier, which plays important roles in maintenance of microenvironment for spermagenesis in testis. Taken together, these results demonstrate that sertoli cells are susceptible to ZIKV infection, which results in the disruption of tight junctions in testis and causes abnormal spermatogenesis in mice. These results also imply that long-term impact of ZIKV infection on human male reproductive system requires close monitoring.

Mesenchymal stem cells and endothelial progenitor cells accelerate intra-aneurysmal tissue organization after treatment with SDF-1α-coated coils

Recurrences of aneurysms remain the major drawback of detachable coils for the endovascular treatment of intracranial aneurysms. The aim of the present study is to develop new modified coils, coating the surface of platinum coils with silk fibroin (SF) consisting of stromal cell-derived factor-1α (SDF-1α), and evaluate its acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model. The morphological characteristics of SDF-1α-coated coils were examined using scanning electron microscopy (SEM). Fifty experimental aneurysms were created and randomly divided into five groups: three groups were embolized with SDF-1α-coated coils (8 mm) and two of these groups need transplantation of mesenchymal stem cells (MSCs) or endothelial progenitor cells (EPCs); one group was embolized with bare coils (8 mm) and another group severed as control. After coil implantation for 14 or 28 days, the coils were harvested and histological analysis was performed. SEM photographs showed that SF/SDF-1α-coated coils have uniform size and a thin film compared with bare coils. In the group treated with SDF-1α-coated coils, tissue organization was accelerated and the proliferation of α-smooth muscle actin positive cells was promoted in the aneurysmal sac. Compared with unmodified coils, on day 28, tissue organization was significantly greater in the group treated with SDF-1α-coated coils and MSC or EPC transplantation. These results suggest that SDF-1α-coated coils with MSC or EPC transplantation may be beneficial in the aneurysm healing and endothelialization at the orifice of embolized aneurysm.

Multimodality Intra-Arterial Imaging Assessment of the Vascular Trauma Induced by Balloon-Based and Nonballoon-Based Renal Denervation Systems.

Renal denervation is a new treatment considered for several possible indications. As new systems are introduced, the incidence of acute renal artery wall injury with relation to the denervation method is unknown. We investigated the acute repercussion of renal denervation on the renal arteries of patients treated with balloon-based and nonballoon-based denervation systems by quantitative angiography, intravascular ultrasound, and optical coherence tomography (OCT). Twenty-five patients (50 renal arteries) underwent bilateral renal denervation with 5 different systems, 3 of which balloon-based (Paradise [n=5], Oneshot [n=6], and Vessix V2 [n=5)]) and 2 nonballoon-based (Symplicity [n=6] and EnligHTN [n=3]). Analysis included quantitative angiography and morphometric intravascular ultrasound measurements pre and post procedure and assessment of vascular trauma (dissection, edema, or thrombus) by OCT after denervation. A significant reduction in lumen size by quantitative angiography and intravascular ultrasound was observed in nonballoon denervation but not in balloon denervation. By postdenervation OCT, dissection was seen in 14 arteries (32.6%). The percentage of frames with dissection was higher in balloon-based denervation catheters. Thrombus and edema were detected in 35 (81.4%) and 32 (74.4%) arteries, respectively. In arteries treated with balloon-based denervation that had dissection by OCT, the balloon/artery ratio was higher (1.24 [1.17-1.32] versus 1.10 [1.04-1.18]; P<0.01). A varying extent of vascular injury was observed after renal denervation in all systems; however, different patterns were identified in balloon-based and in nonballoon-based denervation systems. In balloon denervation, the presence of dissections by OCT was associated with a higher balloon/artery ratio.

Abstract 353: Triciribine, a Selective Akt Inhibitor, Inhibits Myofibroblast Differentiation and Ameliorates Pulmonary Vascular Remodeling in Pulmonary Hypertension

Objectives: Idiopathic pulmonary fibrosis (IPF) is an incurable, chronic and progressive disease with severely poor prognosis and often leads to pulmonary hypertension (PH). Persistent myofibroblast (MF) differentiation in response to TGFβ, marked by de novo expression of αSMA stress fibers, is the central orchestrator of tissue fibrosis and vasculopathy. Our previous studies indicated the integral role of Akt in myofibroblast differentiation and fibrosis. Here, we investigated the efficacy of Triciribine (TCBN), a selective Akt inhibitor, currently in clinical trials for cancer therapy, as a potential therapeutic option for IPF and PH. Methods: WT and Akt1 null mice, as well as those treated with TCBN were subjected to 3 week hypoxia along with normoxia control, and the lungs were used for imaging and western analysis to study the biochemical, structural and vascular changes in the lungs. Cutting edge techniques such as microfil-cast based vascular imaging, confocal imaging and analysis of extracellular matrix protein turnover was performed for the data collection and analysis. Results: Under hypoxia, WT mice exhibited robust vascular remodeling leading to thickening of the artery wall, reduction in lumen size and loss of capillaries in the lungs. This effect was significantly less in Akt1 null mice. Treatment with TCBN significantly ameliorated vascular remodeling in mice due to hypoxia, and resulted in normalization of the vasculature with increased lumen size, reduced wall thickness and increased number of capillary branches as compared to untreated controls. TCBN also affected expression of a number of different extracellular matrix proteins and matrix metalloproteases in addition to changes in the expression of contractile proteins alpha-actin, myocardin and serum response factor in the adventitial fibroblasts. Conclusions: Our results demonstrate the crucial role of Akt as an integral mediator of MF differentiation in IPF and PH. Further, TCBN could potentially be a therapeutic option for IPF and PH.

Tracheal reconstruction for comlex acute tracheal stenosis.

Tracheal stenosis refers to a reduction in the size of the tracheal lumen and can be due to a myriad of reasons, but the most common remains trauma. In iatrogenic situations, internal trauma is the most likely culprit, resulting from prolonged intubation. Our case reviews a patient who developed severe tracheal stenosis (90% reduction in lumen size) within a month of a threeday- long intubation, and presented to the emergency room with dyspnea, orthopnea, and stridor. Tracheal reconstruction with resection of the stenosed segment and end-to-end anastomosis was done. The patient returned a month later with re-stenosis, and underwent tracheal dilatation. Subsequently, he was discharged with a tracheostomy with no problems thereafter.

A Comparative Study of Orthodontic Coil Springs

Several types of force delivering system are used to carry out tooth movement in orthodontics. Coil springs being one of them are used for the same thus requiring minimal operator manipulation. Aims and objectives: The purpose of this study was to determine the effect of wire diameter, lumen size and length of coil spring on the load produced as a function of displacement of SS and NiTi coil spring. Materials and methods: The study consisted of 60 samples of open and closed coil springs (30 each). Open coil springs were tested in compression and closed coil spring in tension using a Lloyd universal testing machine. The data obtained was subjected to statistical analysis using student’s t-test. Results: Mean values, standard deviation and t-value were calculated. Statistically significant difference were obtained in between the groups (p < 0.05), (p < 0.001). Discussion: The heaviest load value at 60% compression was recorded in 0.010 × 0.030 spring with 20 cm initial length due to its large wire diameter and reduced lumen size among the coil springs tested. Straight line of load deflection curve bears clinical significance due to unpredictable behavior of spring beyond a certain limit. Permanent deformation exhibited by SS coil spring is due to high stiffness is low spring fact. Conclusion: Coil linear load delivered by SS open coil springs on compression changes the original length from 33 to 50% which depends on wire diameter and lumen size of coil spring.

Gax gene transfer inhibits vascular remodeling induced by adventitial inflammation in rabbits

Aims Adventitial fibroblasts (AFs) and inflammation play an important role in neointimal formation and vascular remodeling. The present study was aimed to investigate the therapeutic effects and underlying mechanisms of transcriptional regulator Gax gene transfection in aortic remodeling induced by adventitial inflammation. Methods and results Fifty rabbits fed a chow diet were randomly divided into a normal control group ( n = 10) and experimental group ( n = 40). All rabbits in the experimental group underwent collar placement around the abdominal aorta and intra-collar injection of lipopolysaccharide (LPS) to induce adventitial inflammation and they were further divided into model control group, saline-treated group, green fluorescence protein (Ad-GFP)-treated group and Gax gene (Ad-Gax)-treated group, respectively. Four weeks after treatment, the model control group, saline-treated group and Ad-GFP-treated group showed thickened neointima and adventitia, reduced lumen size and increased eccentricity and remodeling index of the abdominal aorta in comparison with the normal control group, whereas Ad-Gax-treated group exhibited attenuated neointimal formation and vascular remodeling ( P < 0.01–0.05) .The vascular expression levels of interleukin (IL)-1β, IL-6, IL-8, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1, Smads, mitogen-activated protein kinases (MAPKs), integrins and nuclear factor kappa B (NF-kB) were significantly higher in the model control group, saline-treated group and Ad-GFP-treated group than those in the normal control group ( P < 0.01–0.05). In contrast, the local expression levels of these cytokines were substantially reduced by Ad-Gax gene transfer ( P < 0.01–0.05). Similarly, the serum levels of inflammatory cytokines including C-reactive protein (CRP), transforming growth factor (TGF)-β1, IL-1, IL-6, IL-8, tumor necrosis factor (TNF)-α, MCP-1, VCAM-1 and ICAM-1 were significantly higher in the model control group, saline-treated group and Ad-GFP-treated group than those of the Ad-Gax-treated group ( P < 0.01–0.05). In vitro studies showed that Gax overexpression diminished inflammatory cytokine expression in LPS-stimulated arterial fibroblasts. Conclusions Adventitial inflammation induces vascular remodeling via the interactions of multiple inflammatory cytokines and local Gax gene transfer in vivo can significantly inhibit these interactions and thereby attenuate local inflammation and vascular remodeling.

Investigation into the mechanism of anti-asthmatic action of Lepidium sativum

We have studied the possible mechanism of anti-asthmatic action of ethanolic extracts of dried seeds of Lepidium sativum (EXLS, 400 mg/kg) using various experimental models. EXLS produced an increase in the Pre-Convulsion Dyspnoea time induced by histamine and acetylcholine aerosol, a significant reduction in the elevated leucocyte counts in the Broncho-Alveolar Lavage fluid of sensitized guinea-pigs and reduction in the paw edema volume as compared to the control rats. Treatment with EXLS also produced decrease in the elevated histamine release from the sensitized guinea-pig lungs. The anti-asthmatic anti-inflammatory responses of EXLS was supported by improvement in microscopic changes like infiltration of inflammatory cells, submucosal edema, epithelial desquamation and reduced lumen size of the bronchi. The <TEX>$pD_2$</TEX> values of histamine in tracheal chain and taenia-coli were significantly greater and that in lung strip was lower in the sensitized animals as compared to control. Treatment of sensitized guinea pigs with EXLS significantly decreased <TEX>$pD_2$</TEX> values of histamine in all three preparations. Our data suggest the prevention of hyper-responsiveness in bronchial smooth muscles and inhibition of the immediate hypersensitive reaction, histamine release in the lungs and the infiltration of various inflammatory cells as the possible mechanisms of anti-asthmatic activity of EXLS.

Oligonucleotide Microarrays Reveal Regulated Genes Related to Inward Arterial Remodeling Induced by Urokinase Plasminogen Activator

Accumulating evidence suggests that urokinase plasminogen activator (uPA) is involved in vascular remodeling and lumen stenosis after angioplasty and stenting. We have shown previously that increased uPA expression greatly promotes neointima formation and inward arterial remodeling after balloon injury. To evaluate the role of inflammation in early mechanisms responsible for inward arterial remodeling induced by uPA and elucidate the mechanisms of remodeling, we characterized changes in the expression profiles of 8,799 genes in injured rat carotid arteries 1 and 4 days after recombinant uPA treatment compared to vehicle. We used a standard model of the balloon catheter injury of the rat carotid followed by periadventitial application to the injured vessel of either uPA dissolved in Pluronic gel, or plain gel. Vessels were harvested and analyzed by immunohistochemistry, morphometry, microarray gene expression profiling and quantitative RT-PCR. Periadventitial application of uPA significantly reduced lumen size and vessel area encompassed by the external elastic lamina at both 1 and 4 days after treatment. Inflammatory cells accumulated in the arterial adventitia at both 1 and 4 days after uPA treatment. On the 4th day, increases in the areas and arterial cell numbers of all arterial layers were found. Among 79 differentially expressed known genes 1 day after uPA application, 12 proinflammatory genes, including TNF-α and TACE, and 15 genes related to mitochondrial metabolism and oxidative stress regulation were identified. Four days after injury in uPA-treated arteries, 3 proinflammatory and 2 oxidation-related genes were differentially expressed. We conclude that uPA likely promotes inward arterial remodeling by regulating oxidative stress and inflammation after arterial injury.

128: Quantitative Analysis of Coronary Plaques is Highly Accurate in Quantifying Positive Remodeling and Reduction of Lumen Size

128: Quantitative Analysis of Coronary Plaques is Highly Accurate in Quantifying Positive Remodeling and Reduction of Lumen Size

OLIGONUCLEOTIDE MICROARRAYS REVEAL REGULATED GENES RELATED TO INWARD ARTERIAL REMODELING INDUCED BY UROKINASE PLASMINOGEN ACTIVATOR

Accumulating evidence suggests that urokinase plasminogen activator (uPA) is involved in vascular remodeling and lumen stenosis after angioplasty and stenting. We have shown previously that increased uPA expression greatly promotes neointima formation and inward arterial remodeling after balloon injury. To evaluate the role of inflammation in early mechanisms responsible for inward arterial remodeling induced by uPA and elucidate the mechanisms of remodeling, we characterized changes in the expression profiles of 8,799 genes in injured rat carotid arteries 1 and 4 days after recombinant uPA treatment compared to vehicle. We used a standard model of the balloon catheter injury of the rat carotid followed by periadventitial application to the injured vessel of either uPA dissolved in Pluronic gel, or plain gel. Vessels were harvested and analyzed by immunohistochemistry, morphometry, microarray gene expression profiling and quantitative RT-PCR. Periadventitial application of uPA significantly reduced lumen size and vessel area encompassed by the external elastic lamina at both 1 and 4 days after treatment. Inflammatory cells accumulated in the arterial adventitia at both 1 and 4 days after uPA treatment. On

Coronary Endothelium: A Key to Life Expectancy

Endothelial dysfunction occurs early in the development of atherosclerosis. Normal endothelium maintains vascular stucture and tone by balancing vasoconstriction with vasodilatation. With endothelial dysfunction, production of nitric oxide (NO) is impaired, leaving unopposed vasoconstrictive substances such as angiotensin II. The endothelium releases factors that balance growth promotion and growth inhibition. Physiologically, growth-inhibiting activity predominates, maintaining the blood vessel wall homeostasis. With endothelial dysfunction, growth-promoting factors dominate, resulting in vascular overgrowth and deformation, which lead to thickening of the media and reduction in lumen size. These vascular changes are common in hypertension, renal failure, myocardial infarction, stroke, and diabetes. QUESTIONS 1. Which of the 3 layers of an artery initiate atherogenic lesions? a. the media b. the intima c. the adventitia

Mechanism of vibration‐induced vascular damage in rat‐tail artery

Years of powered tool use can lead to hand-arm vibration syndrome, a vasospastic and neurodegenerative disease of the fingers. In our rat-tail vibration model, vascular smooth muscle cells (VSMC) are injured in 4 hrs. They exhibit cell surface protrusions which appear as vacuoles at the light microscopic level. The mechanism of vibration-induced VSMC injury was examined in the current study. Tails of male Sprague-Dawley rats (292 ± 11 g) were vibrated for 4 hrs with or without general anesthesia. Vibration without anesthesia caused significant vasoconstriction (20% reduction in lumen size compared to sham vibrated without anaesthesia), and the contracting VSMC formed 44.8 ± 7.0 vacuoles. Anesthesia prevented vasoconstriction and vacuole formation during vibration. Additional rats had their tail arteries treated for 15 min with 1 mM norepinephrine in situ to induce vasoconstriction (44% reduction in lumen size compared to sham treated) and extensive vacuolation (112.4 ± 20.6). The anesthetized rats were then vibrated for 4 hrs to determine whether the vacuoles would be disrupted. In toluidine-blue stained semithin sections, the VSMC lacked vacuoles and exhibited light and dark intracellular banding patterns. The extracellular matrix was filled with particulate material, which was confirmed to be cellular debris by electron microscopy. The present findings suggest that vibration damages vasoconstricted arteries by dislodging and fragmenting the VSMC protrusions. Loss of cell membrane and cytoplasm in these vacuoles may compromise VSMC function. Supported by Medical College of Wisconsin and in part by NIOSH grant R01 OH003493.

GABAA receptors play a role in fluid secretion in rat fetal lung

Fluid secretion in the fetal lung is driven by Cl−secretion and is essential for lung development. However, the mechanism of Cl− and fluid secretion in the fetal lung is not completely clear. GABAA receptors are ligand-gated Cl−channels. We show that native GABAA receptors in fetal distal lung epithelial cells are composed of α3-, α4-, β1-, β2-, and π-subunits by co-immunoprecipitation. GABA increased lumen size and Cl− concentration on fetal lung organ culture while GABA receptor antagonists, picrotoxin and biccuculine had an opposite effect. The knock-down of GABAA receptor π subunit by RNA interference also inhibited the fluid secretion. In vitro phosphorylation studies denoted that only β1-subunit of GABAA receptors was phosphorylated on serine residue and this phosphorylation was enhanced in the fetal distal lung epithelial cells stimulated with PMA. Inhibitors of protein kinase C, phospholipase C and P2Y receptor all reduced lumen size in the presence of GABA and inhibited the phosphorylation of the β1-subunit on fetal lung organ culture. Taken together, our results suggest that fetal distal lung epithelial cells contain functional ionotropic GABAA receptors. These receptors could participate in fluid secretion in the fetal lung and this process is regulated by protein phosphorylation (supported by NIH HL-052146, HL-071628 and March of Dimes to LL).

Nifedipine pretreatment reduces vibration‐induced vascular damage

A rat-tail vibration model of hand-arm vibration was employed to test whether preemptive administration of nifedipine (5 mg/kg) to block vasoconstriction prevents vibration-induced arterial damage. The tails of vibrated and nifedipine-pretreated vibrated Sprague-Dawley rats were exposed continuously to 4 h of 60-HZ vibration at 49 m/s(2) rms. In nonvibrated anesthetized rats, the ventral tail arteries were bathed for 15 min in situ in 1 mM epinephrine or 1 mM norepinephrine to induce structural changes indicative of intense vasoconstriction. Arteries were processed for light and electron microscopy 45 min after treatment. Compared to sham control, 4-h vibration significantly (P < 0.01) reduced lumen size, generated endothelial disruption (7.0 +/- 2.6%), elevated nuclear factor of activated T cells c3 (NFATc3) expression in endothelial and smooth muscle cells, and increased smooth muscle cell vacuolization. The findings demonstrate that blockage of vibration-induced vasoconstriction with nifedipine prevents acute vascular damage. Smooth muscle and endothelial cells structurally altered by vasoconstriction are rendered susceptible to damage by vibration.

Tenascin-C—coated platinum coils for acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model

Detachable platinum coils are widely used in the endovascular treatment of intracranial aneurysms. The use of coil placement produces a higher incidence of aneurysm recurrence compared with surgical clipping. To reduce the incidence of recurrence by promoting clot organization, the authors designed a platinum coil coated with tenascin-C (TNC), an extracellular matrix glycoprotein, and then histologically examined tissue responses. Platinum coils were prepared by successive coatings with cationic polyethyleneimine and anionic heparin and then TNC or basic fibroblast growth factor (bFGF) was immobilized by affinity binding to the heparin. Six unmodified, six heparin-coated, six bFGF-coated, or eight TNC-coated platinum coils were inserted into ligated common carotid arteries (CCAs) of adult male rats, and CCA segments were harvested after 14 or 28 days. The percentages of organized areas occupying the luminal cavity in unmodified, heparin-coated, bFGF-coated, and TNC-coated groups were 4.8 +/- 4.6, 1.6 +/- 1.1, 17.9 +/- 10.7, and 93.4 +/- 6.9%, respectively. In addition, the mean lumen size in the TNC-coated group (0.35 +/- 0.23 mm2) was reduced to less than half that of the unmodified group (0.72 +/- 0.21 mm2). Immunohistochemical analysis revealed that alpha-smooth muscle actin-positive cells were a major cellular component of the organized tissue within the TNC-coated coils but not in the bFGF group. Collagen fibrils in the organized areas were also much thicker and denser with TNC-coated coils than with bFGF-coated coils. Placement of TNC-coated coils can remarkably accelerate organization of luminal cavities and reduce their volume, providing improved efficacy of these coils for endovascular embolization.