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Background: Pretransplant functional, motor, cognitive, and academic deficits are common in pediatric patients requiring heart transplantation (HT); some persist post-HT. We assessed the association between these quality of life (QoL) deficits and post-HT outcomes., Methods: Using SRTR data 2008-2023, we evaluated the functional, motor, cognitive, and academic status of pediatric HT recipients from listing to 15 years post-HT. We compared all-cause graft survival among patients with vs. without pre-HT deficits using Cox regressions. Among patients with a functioning graft at 1 year, we assessed the association between deficits at that time and subsequent graft failure., Results: In 6153 HT recipients, 85.3% had pre-HT functional status ≤ 80%, 53.1% of patients could not tolerate a full academic load; this decreased to 15.2% and 15.0% postoperatively, and was sustained. Definite or probable cognitive deficits were seen in 17.4% of patients and motor delays in 18.6%; both remained stable post-HT at 18.0% and 16.4%, respectively. Graft survival was worse in those with either pre- or post-HT deficits in functional status. Worse pre-HT functional status was associated with risk of graft failure (adjusted hazard ratio [aHR] per 10% decrease =  1.03 1.06 1.08 , p < 0.001); worse 1-year post-HT functional status was much more strongly associated with risk of graft failure (aHR =  1.13 1.18 1.23 , p < 0.001)., Conclusion: Pediatric HT recipients with decreased functional status are at higher risk for graft failure and mortality. These patients may benefit from early intervention aimed at improving functional status., (© 2024 Wiley Periodicals LLC.)

Wearable sensors for sweat glucose monitoring are gaining massive interest as a patient-friendly and non-invasive way to manage diabetes. The present work offers an alternative on-body method employing an all-printed flexible electrochemical sensor to quantify the amount of glucose in human sweat. The working electrode of the glucose sensor was printed using a custom-formulated ink containing multi-walled carbon nanotube (MWCNT), poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOPT: PSS), and iron (II, III) oxide (Fe 3 O 4 ) nanoparticles. This novel ink composition has good conductivity, enhanced catalytic activity, and excellent selectivity. The working electrode was modified using Prussian blue (PB) nanoparticles and glucose oxidase enzyme (GOx). The sensor displayed a linear chronoamperometric response to glucose from 1 μM to 400 μM, with a precise detection limit of ∼0.38 μM and an impressive sensitivity of ∼4.495 μAμM -1 cm -2 . The sensor stored at 4 °C exhibited excellent stability over 60 days, high selectivity, and greater reproducibility. The glucose detection via the standard addition method in human sweat samples acquired a high recovery rate of 96.0-98.6%. Examining human sweat during physical activity also attested to the biosensor's real-time viability. The results also show an impressive correlation between glucose levels obtained from a commercial blood glucose meter and sweat glucose concentrations. Remarkably, the present results outperform previously published printed glucose sensors in terms of detection range, low cost, ease of manufacturing, stability, selectivity, and wearability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent times, considerable attention has been given to examining the impact of micro/nanostructure on the thermoelectric characteristics of nonstoichiometric AgSbTe 2 . The present investigation employed direct melting of elements that produced p-type AgSbTe 2 with spontaneous nanostructuring due to cation ordering. The product predominantly features an Ag-deficient Ag 0.927 Sb 1.07 Te 2.005 phase with monoclinic Ag 2 Te nanoprecipitates and exhibits a degenerate semiconductor-like behavior with an energy band gap of 0.15 eV. A Seebeck coefficient of 251 μV K -1 and a power factor of 741 μW m -1 K -2 at near ambient temperature are attained with this composition. The variable range hopping (VRH) and linear magnetoresistance (LMR) confirmed that the low-temperature transport followed a VRH between the localized states. The composition also exhibited glass like thermal conductivity of 0.2 W m -1 K -1 arising from phonon scattering at all-scale hierarchical structures that led to a high ZT of 1.1 at room temperature. The direct melted ingots show a high relative density of ∼97%, Vickers hardness H v of ∼108.5 kgf mm -2 , and excellent thermal stability, making them an attractive choice for TEGs.

In the present investigation, we present the comparison of the structural, magnetic, magnetocaloric and magnetoresistance behavior of solid state and sol-gel derived La 0.7 Sr 0.3 MnO 3 . X-ray diffraction together with Rietveld refinement confirms the rhombohedral structure of the synthesised samples with the R 3̄ c space group. The ferromagnetic-to-paramagnetic transition temperature decreases from 360 K to 346 K for the nanocrystalline sample. The XPS measurements confirm the presence of Mn 3+ in the synthesised samples. Furthermore, the polycrystalline sample exhibits a considerable -Δ S M of 4.68 J kg -1 K -1 at 360 K for a field change of 50 kOe and a relative cooling power (RCP) of 205 J kg -1 . A -Δ S M of 1.14 J kg -1 . Critical exponent analysis has also been performed on both samples to establish the universality class. Both samples exhibit a distinct metal-to-insulator transition, which increases with grain size from 187 K to 334 K as a result of grain growth and decreased grain boundary. As the grain size increases, the resistivity decreases and shifts towards high temperatures with increasing magnetic fields. The itinerant electron model (IEO) which is based on the hopping of O 2p itinerant electrons has been used to explain the resistivity behaviour of the samples. It is found that the negative magnetoresistance also increases with a decrease in grain size where the highest %MR of 26% can be observed for the nanocrystalline sample. These results make La -1 was obtained for the nanocrystalline sample at 346 K with an RCP of 83 J kg -1 . Critical exponent analysis has also been performed on both samples to establish the universality class. Both samples exhibit a distinct metal-to-insulator transition, which increases with grain size from 187 K to 334 K as a result of grain growth and decreased grain boundary. As the grain size increases, the resistivity decreases and shifts towards high temperatures with increasing magnetic fields. The itinerant electron model (IEO) which is based on the hopping of O 2p itinerant electrons has been used to explain the resistivity behaviour of the samples. It is found that the negative magnetoresistance also increases with a decrease in grain size where the highest %MR of 26% can be observed for the nanocrystalline sample. These results make La 0.7 Sr 0.3 MnO 3 a suitable candidate for multifunctional applications.

Background: Interest in nephrology careers is declining, possibly due to perceptions of the field and/or training aspects. Understanding practices of medical schools successfully instilling nephrology interest could inform efforts to attract leading candidates to the specialty., Methods: The American Society of Nephrology Workforce Committee's Best Practices Project was one of several initiatives to increase nephrology career interest. Board-certified nephrologists graduating medical school between 2002 and 2009 were identified in the American Medical Association Masterfile and their medical schools ranked by production. Renal educators from the top 10 producing institutions participated in directed focus groups inquiring about key factors in creating nephrology career interest, including aspects of their renal courses, clinical rotations, research activities, and faculty interactions. Thematic content analysis of the transcripts (with inductive reasoning implementing grounded theory) was performed to identify factors contributing to their programs' success., Results: The 10 schools identified were geographically representative, with similar proportions of graduates choosing internal medicine (mean 26%) as the national graduating class (26% in the 2017 residency Match). Eighteen educators from 9 of these 10 institutions participated. Four major themes were identified contributing to these schools' success: (1) nephrology faculty interaction with medical students; (2) clinical exposure to nephrology and clinical relevance of renal pathophysiology materials; (3) use of novel educational modalities; and (4) exposure, in particular early exposure, to the breadth of nephrology practice., Conclusion: Early and consistent exposure to a range of clinical nephrology experiences and nephrology faculty contact with medical students are important to help generate interest in the specialty., (© 2019 S. Karger AG, Basel.)

A few thallium based layered chalcogenides of α-NaFeO 2 structure-type are known for their excellent thermoelectric properties and interesting topological insulator nature. TlScQ 2 belongs to this structural category. In the present work, we have studied the electronic structure, electrical and thermal transport properties and thermal stability of the title compounds within the temperature range 2-600 K. Density functional theory (DFT) predicts a metallic nature for TlScTe 2 and a semiconducting nature for TlScSe 2 . DFT calculations also show significant lowering of energies of frontier bands upon inclusion of spin-orbit coupling contribution in the calculation. The electronic structure also shows the simultaneous occurrence of holes and electron pockets for the telluride. Experiments reveal that the telluride shows a semi-metallic behaviour whereas the selenide is a semiconductor. The thermoelectric properties for both the materials were also investigated. Both these materials possess very low thermal conductivity which is an attractive feature for thermoelectrics. However, they lack thermal stability and decompose upon warming above room temperature, as evidenced from high temperature powder X-ray diffraction and thermal analysis.

We report on the observation of double transition - a first order and a second order transition in Gd 5 Si 2-x Co x Ge 2 with x = 0, 0.1, 0.2 and 0.4 with the appearance of short-range ferromagnetic correlations. The first order phase transition is due to a combined magnetostructural transition from monoclinic paramagnetic phase to orthorhombic ferromagnetic phase on cooling while the second order transition arises from an orthorhombic paramagnetic to ferromagnetic phase on cooling. Structural studies show that the substituted compounds crystallize in a combination of Gd 5 Si 2 Ge 2 and Gd 5 Si 4 phases. Low-temperature X-ray diffraction measurements confirm the complete transformation from monoclinic to orthorhombic phase. DC magnetization measurements reveal an anomalous low field magnetic behaviour indicating a Griffiths-like phase. This unusual behaviour is attributed to the local disorder within the crystallographic structure indicating the presence of short-range magnetic correlations and ferromagnetic clustering, which is stabilized and enhanced by competing intra-layer and inter-layer magnetic interactions. The magnetostructural transition results in entropy changes (-ΔS M ) of 9 J kg -1 K -1 at 260 K for x = 0.1, 8.5 J kg -1 K -1 at 245 K for x = 0.2 and 4.2 J kg -1 K -1 at 210 K for x = 0.4 for a field change of 50 kOe. Co substitution induces compelling crystallographic and magnetoresponsive effects in the Gd-Si-Ge system, which could be useful for potential and smart applications such as solid-state magnetic refrigeration and sensitive magnetic switching from paramagnetic to ferromagnetic state. Universal curve analysis has been carried out on the substituted samples to study the order of the magnetic transition.

Background: Early therapy improves the outcome in patients with chronic hepatitis B with acute flare (CHB-AF). However in mesoendemic countries, it is difficult to differentiate CHBAF from acute hepatitis B (AHB). The aim of this study was to formulate a clinical score to differentiate CHB-AF from AHB in patients presenting with an acute hepatitis-like picture., Methods: Patients with a protracted clinical course of >2 months with elevated liver enzymes and positive hepatitis B virus DNA, who had undergone liver biopsy were included in this study. The clinical and laboratory profiles were compared between patients with biopsy suggestive of CHB-AF and AHB., Results: Of the 75 patients included, 32 patients had a liver biopsy suggestive of CHB-AF. At 6 months, HBsAg clearance was lower in the CHB-AF group (9.4 vs. 76.7%). Presence of prodrome, platelet count, aspartate aminotransferase (AST), alanine aminotransferase and bilirubin levels and presence of anti-core antibody (IgM anti HBc) were lower in CHB-AF group (P<0.01). Using the receiver operating characteristic curve, peak bilirubin level, peak AST levels and least platelet count within the first 8 weeks had the highest predictive power. Optimal values of platelet <2.4×10 5 /µL, peak bilirubin <4.5 mg/dL and AST <550 IU/L were given a point each. On internal validation a score of 2 had 86% specificity, 70.1% sensitivity and 82.7% diagnostic accuracy in predicting CHB-AF., Conclusion: Bilirubin, AST and platelet count (BAP) score may be helpful in differentiating CHB-AF from AHB. A score of >2 could strongly suggest CHB-AF. However the score requires further validation.

The poor solubility, poor biocompatibility and disposal issues make fluorescent quantum dots such as CdSe, CdS, ZnS, InP, InAs, etc. impractical for imaging tissues or intercellular structures. As calcium phosphate is the main inorganic component of human bone and teeth, hydroxyapatite (Ca10(PO4)6(OH)2, HAp) is highly biocompatible and bioactive. Since HAp nanoparticles are not luminescent, a novel inorganic biocompatible fluorescent probe was suggested by doping HAp with lanthanides. Here we report the growth of chemically pure fluorescent HAp nanoparticles synthesized by a new methodology, liquid phase pulsed laser ablation using third harmonics (355 nm) of Nd-YAG laser. Europium doped HAp nanoparticles show emission with prominent peaks at 531 nm, 572 nm, 601 nm and 627 nm upon excitation at a wavelength of 325 nm. The red luminescence could also be observed under visible excitation at 459 nm and is suitable for living cell applications.

Background: Patients with chronic kidney disease have been under-represented in randomized trials of drug-eluting stents relative to bare-metal stents and are at high risk of mortality., Study Design: Cohort study with propensity score matching., Settings & Participants: All adults with chronic kidney disease and severely decreased glomerular filtration rate (GFR; serum creatinine >2.0 mg/dL or dialysis dependence) undergoing percutaneous coronary intervention with stent placement between April 1, 2003, and September 30, 2005, at all acute-care nonfederal hospitals in Massachusetts., Predictor: Patients were classified as drug-eluting stent-treated if all stents were drug eluting and bare-metal stent-treated if all stents were bare metal. Patients treated with both types of stents were excluded from the primary analysis., Outcomes & Measurements: 2-year crude mortality risk differences (drug-eluting - bare-metal stents) were determined from vital statistics records, and risk-adjusted mortality, myocardial infraction (MI), and revascularization differences were estimated using propensity score matching of patients with severely reduced GFR based on clinical and procedural information collected at the index admission., Results: 1,749 patients with severely reduced GFR (24% dialysis dependent) were treated with drug-eluting (n = 1,256) or bare-metal stents (n = 493) during the study. Overall 2-year mortality was 32.8% (unadjusted drug-eluting stent vs bare-metal stent; 30.1% vs 39.8%; P < 0.001). After propensity score matching 431 patients with a drug-eluting stent to 431 patients with a bare-metal stent, 2-year risk-adjusted mortality, MI, and target-vessel revascularization rates were 39.4% versus 37.4% (risk difference, 2.1%; 95% CI, -4.3 to 8.5; P = 0.5), 16.0% versus 19.0% (risk difference, -3.0%; 95% CI, -8.2 to 2.1; P = 0.3), and 13.0% versus 17.6% (risk difference, -4.6%; 95% CI, -9.5 to 0.3; P = 0.06)., Limitations: Observational design, ascertainment of serum creatinine level >2.0 mg/dL and dialysis dependence from case report forms., Conclusions: In patients with severely decreased GFR, treatment with drug-eluting stents was associated with a modest decrease in target-vessel revascularization not reaching statistical significance and was not associated with a difference in risk-adjusted rates of mortality or MI at 2 years compared with bare-metal stents., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Drug-induced pancreatitis is a rare but serious complication of many drugs, some of which have been well documented. Here we present a case of a middle-aged man with chronic myeloid leukemia who developed acute pancreatitis after being initiated on imatinib mesylate. The case history, the pharmacodynamics, uses, and adverse effects of imatinib mesylate are discussed in detail.

Aims: Determine A1C, blood pressure (BP), and total cholesterol (TC) (Diabetes ABCs) control in a community-based endocrinology practice (CBEP) and compare levels to national averages. Additionally, determine patient factors associated with ABC control., Methods: A retrospective chart audit of 395 consecutive patients seen for diabetes management was conducted for years 2000-2004 to examine levels of control of the ABCs. Multivariate models were used to determine patient factors associated with control., Results: Significantly more patients met the goal of A1C <7% in the CBEP compared to national estimates (CBEP: 47.1% vs. NHANES 1999-2000: 37%, p=0.003). Similar patterns were observed for BP (CBEP: 53.2% vs. NHANES 1999-2000: 35.8%, p<0.0001), TC (CBEP: 82% vs. NHANES 1999-2000: 48.2%, p<0.0001), and all three ABCs (CBEP: 22%, vs. NHANES 1999-2000: 7.3%, p<0.0001). The proportion of patients meeting all three ABC goals in the CBEP increased significantly over time (p<0.0001). Multivariate models demonstrated that patients not needing insulin (p<0.0001), and taking fewer BP (p<0.0001), and cholesterol-lowering medications (p<0.02) were significantly more likely to have ABCs in control., Conclusions: Attainment of ABC goals is feasible in a CBEP and can be achieved at rates higher than national averages. Attention to factors that affect these goals is warranted.

Silver silica nanocomposites were obtained by the sol-gel technique using tetraethyl orthosilicate (TEOS) and silver nitrate (AgNO(3)) as precursors. The silver nitrate concentration was varied for obtaining composites with different nanoparticle sizes. The structural and microstructural properties were determined by x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM). X-ray photoelectron spectroscopic (XPS) studies were done for determining the chemical states of silver in the silica matrix. For the lowest AgNO(3) concentration, monodispersed and spherical Ag crystallites, with an average diameter of 5 nm, were obtained. Grain growth and an increase in size distribution was observed for higher concentrations. The occurrence of surface plasmon resonance (SPR) bands and their evolution in the size range 5-10 nm is studied. For decreasing nanoparticle size, a redshift and broadening of the plasmon-related absorption peak was observed. The observed redshift and broadening of the SPR band was explained using modified Mie scattering theory.

Vessel wall matrix changes occur after injury, although this has not been well studied in the venous system. This study tested the hypothesis that the thrombus dictates the vein wall response and vein wall damage is directly related to the duration of thrombus contact. To determine the injury response over time, rats underwent inferior vena cava (IVC) ligation to produce a stasis thrombus, with harvest at various time points to 28 days (d). Significant vein wall matrix changes occurred with biomechanical injury (stiffness) peaking at 7-14 d, with concurrent early reduction in total collagen, an increase in early matrix metalloproteinase (MMP)-9 and late MMP-2, and concomitant increase in tumor necrosis factor (TNF)alpha, monocyte chemoattractant(MCP)-1 and tumor growth factor (TGF)beta (all P<0.05). To isolate the effect of the thrombus and its mechanism of genesis, rats underwent 7 d or limited stasis (24 hours), non-stasis thrombosis, or non-thrombotic IVC occlusion (Silicone plug). Vein wall stiffness was increased seven-fold, with a five-fold reduction in collagen, and 5.5- to seven-fold increase in TNFalpha, MCP-1, and TGFbeta with 7 d stasis as compared with controls (all P<0.05). By Picosirus red staining analysis, collagenolysis was significantly greater with 7 d stasis injury (P=0.01) but neither MMP-9 nor MMP-2 activity correlated with injury mechanism. In addition, vein wall cellular proliferation and uPA gene expression paralled the stasis thrombotic injury. Limited stasis, non-stasis thrombosis and non-thrombotic IVC occlusion showed a lesser inflammatory response. These data suggest both a static component and the thrombus directs vein wall injury via multiple mechanisms.

Early deep venous thrombosis (DVT) resolution is associated with neutrophil (PMN) influx. This study examined the role of PMNs in thrombus neovascularization and vein wall injury after DVT. A rat model of DVT by inferior vena cava (IVC) ligation was performed with control serum or rabbit anti-rat PMN serum administered perioperatively with sacrifice at 2 and 7 days. At 2 days, neutropenic rats had 1.6-fold larger thrombi (P = .04) and 1.4-fold higher femoral venous pressures by water manometry (P = .008) but no difference in thrombus neovascularization was observed. By 7 days, DVT sizes were similar, but vein wall injury persisted in the neutropenic rats with a 2.0-fold increase in vein wall stiffness by microtensiometry (P < .05), as well as a 1.2-fold increased thickness (P = .04). Collagen and profibrotic growth factors were significantly increased in neutropenic IVC at 7 days (all P < .05). Vein wall and intrathrombus uPA byWestern immunoblotting, and intrathrombus MMP-9 gelatinase activity were significantly less in neutropenic rats than controls (P < .001). Conversely, MMP-2 was significantly elevated in neutropenic IVC at 2 days after DVT. However, neutropenia induced 24 hours after DVT formation resulted in no significant increase in vein wall stiffness or collagen levels at 7 days, despite 1.4-fold larger thrombi (P < .05). These data suggest a critical early role for PMN in post DVT vein wall remodeling.

Hypothesis: Deep venous thrombosis (DVT) confers vein wall injury associated with fibrosis and extracellular matrix (ECM) turnover, likely mediated by matrix proteases. This study investigated the expression of proteases and collagen involved in early vein wall remodeling., Methods: In the mouse, DVT was produced by ligation of the infrarenal inferior vena cava (IVC) or sham operation, and tissue was harvested at 4, 8, and 12 days. The vein wall tissue was processed for real-time reverse transcriptase-polymerase chain reaction (6 to 8 per time point), Western immunoblotting (5 per time point), and gelatin zymography (5 per time point). Analysis of variance was used for multiple comparisons, and a P < .05 was significant., Results: Thrombus resolution was documented by a 38% decrease in the thrombosed IVC weight from day 4 to day 12 (P = .007). Total vein wall collagen increased over time, with a corresponding increase in procollagen I and III, and expression peaked at 12 days (24-fold and 6.1-fold, respectively, P < .02). Matrix metalloproteinase-2 (MMP-2) gene expression was 23-fold greater at 12 days after thrombus formation compared with sham or 4 days after thrombosis (P < .05). Total MMP-2 activity was also significantly elevated at 12 days compared with sham (P < .05). MMP-9 expression was 19-fold and 27-fold higher at days 4 and 8, respectively, relative to sham (P < .05), with no difference in activity. MMP-14 expression was twofold to 3.6-fold greater at day 12 compared with earlier time points and shams (P < .001), but no differences in protein levels were found. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) protein levels were not significantly different from sham over time; however, the ratio of uPA to PAI-1 was decreased through 8 days., Conclusions: Vein wall remodeling after DVT is similar to wound healing and is associated with increased procollagen gene expression and total collagen. It is also associated with increased early MMP-9 expression, followed by MMP-2 expression and activity after DVT resolution., Clinical Relevance: Deep vein thrombosis is an often neglected problem that long term is associated with the postphlebitic syndrome of limb swelling, pain, and often ulceration. The basic mechanisms of the vein wall damage that results have not been delineated. The following study describes the vein wall matrix metalloproteinase gene and activity response induced over time in the vein wall after DVT. Additionally, the corresponding collagen upregulation and proximate plasmin system mediators are determined. With this knowledge, potential therapies to reduce vein wall injury directly might be possible.

Introduction: Deep venous thrombosis (DVT) resolution involves fibrinolysis, neovascularization, and fibrosis. We hypothesized that promoting neovascularization would accelerate DVT resolution., Methods: A rat model of stasis DVT was produced with proximal ligation of the inferior vena cava (IVC) and all visible tributaries. One microg of interferon inducible protein (IP-10; angiostatic chemokine), basic fibroblast growth factor (bFGF; pro-angiogenic cytokine), epithelial neutrophil activating protein (ENA-78; pro-angiogenic chemokine), or saline solution control was injected into the IVC after ligation, and then via tail vein injection daily until sacrifice at either 4 or 8 days. Peripheral blood counts were measured, and thrombus weight was recorded at sacrifice. Laser Doppler in vivo imaging was used to estimate post-thrombotic IVC blood flow. Immunohistologic assessment of the thrombosed IVC for polymorphonuclear neutrophils (PMNs), monocytes (ED-1), and laminin (neovascular channels) was performed or the thrombus was separated from the IVC and assayed for keratinocyte cytokine (KC), monocyte chemotactic protein-1 (MCP-1), bFGF with enzyme-linked immunosorbent assay (ELISA), and total collagen with a direct colorimetric assay., Results: Peripheral blood and intrathrombus PMNs and monocytes were not significantly different in the treated or control rats. There were no differences in any measure at 4 days. At 8 days, thrombus neovascularity, but not weight or collagen content, was increased in rats treated with bFGF or ENA-78 compared with control rats (17.6 +/- 0.93, 16.2 +/- 0.97 vs 13.2 +/- 0.79; channels/5 high-power fields (hpf; n = 6-10; P <.05). Post DVT IVC blood flow was significantly increased in bFGF-treated rats but not in rats treated with IP-10 or ENA-78, as compared with control rats. Rats treated with ENA-78 had increased intrathrombus bFGF compared with control rats (85 +/- 27 pg/mg protein vs 20 +/- 6 pg/mg protein; n = 6; P <.05), but other mediators were not significantly different in treated rats compared with control rats., Conclusion: Pro-angiogenic compounds increase thrombus neovascularization, but this does not correlate with smaller or less fibrotic DVT. Mechanisms other than neovascularization may be more important to hasten DVT dissolution. Clinical relevance Improved therapy for deep venous thrombosis (DVT) will ideally increase the rate of thrombus dissolution and eliminate the bleeding risks of anticoagulation. This study evaluated promoting DVT neovascularization with angiogenic chemokines, and, while successful by experimental measures, this did not translate into smaller DVT. Solely promoting thrombus neovascularization will not likely speed resolution.

Objectives: Neutrophil influx is one of the first events in a formed deep venous thrombosis (DVT), but whether these cells are active participants in the resolution process is not clear. This study tests the hypothesis that neutrophils (PMN) are active participants in DVT resolution., Methods: Thrombosis was induced by inferior vena caval (IVC) ligation in male Sprague-Dawley rats, and rats were sacrificed at 2, 4, or 7 days for evaluation of the thrombus. Neutropenia was induced by rabbit anti-rat PMN serum, and controls received rabbit serum. Venography was performed at the 7-day time point. Immunohistochemical staining was performed to quantify intrathrombus PMNs and monocytes, and the myeloperoxidase (MPO) assay was performed to assess intrathrombus neutrophil activity. Intrathrombus concentrations of kerotinocyte cytokine (KC), macrophage inflammatory protein-2 (MIP-2), gamma interferon inducible protein-10 (IP-10), macrophage inflammatory protein-1 alpha (MIP-1 alpha), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha were quantified by enzyme immunoassay at each time point and normalized to total protein. Total collagen was determined at day 7., Results: Peripheral blood smears showed a 94% PMN reduction at 2 days (P <.05), recovering to 44% of control at 7 days. Intrathrombus PMNs were significantly lower in neutropenic rats at 2 and 4 days, but there were no differences in intrathrombus monocytes. The MPO assay confirmed reduced neutrophil activity at 4 days. Thrombi from neutropenic rats were larger at 2 and 7 days compared with controls. In vivo thrombus area at 7 days as assessed by venography was also greater in neutropenic rats as compared with controls. The intrathrombus KC concentration was increased more than 20-fold in the neutropenic rats at 2 days, but there were no significant differences in other intrathrombus chemokines. Finally, intrathrombus collagen was increased over threefold in neutropenic rats as compared with controls., Conclusion: Neutropenia impairs DVT resolution by several measures, most likely by altering normal fibrinolytic activity and thrombus collagen turnover.

Adenosine is an endogenous neuroprotectant via anti-excitotoxic effects at A(1) receptors, and blood flow promoting and anti-inflammatory effects at A(2a) receptors. Previous studies showed improved motor function after fluid percussion injury (FPI) in rats treated with the broad-spectrum adenosine receptor agonist 2-chloroadenosine (2-CA). We studied the effects of 2-CA, a specific A(1) agonist (2-chloro-N(6)-cyclopentyladenosine, CCPA), and a specific A(1) antagonist (8-cyclopentyl-1,3-dipropylxanthine, DPCPX) on motor task and Morris water maze (MWM) performance, and histopathology (contusion volume, hippocampal cell counts) after controlled cortical impact (CCI) in mice. Each agent (12 nmol), or respective vehicle (saline or DMSO) was injected into dorsal hippocampus beneath the contusion immediately after CCI or craniotomy (sham). 2-CA treatment attenuated wire grip deficits after CCI (P<0.05 versus other treatments). DPCPX treatment exacerbated deficits on beam balance (P<0.05 versus sham). No treatment effect was seen on MWM performance, although there was a deleterious effect of the DMSO vehicle used for DPCPX. Contusion volume tended to be attenuated by 2-CA (P=0.08 versus saline) and increased after either DMSO or DPCPX (P<0.05 versus all groups). CA1 and CA3 counts were decreased in all groups versus sham. However, treatment with the selective A(1) agonist CCPA attenuated the CA3 cell loss (P<0.05 versus other treatment). We suggest that the beneficial effect of the broad spectrum adenosine receptor agonist 2-CA on motor function after CCI is not mediated solely by effects at the A(1) receptor.

Background: Therapy for deep vein thrombosis (DVT) resolution in those patients in whom a complication or contraindication to anticoagulation occurs is limited. As prior work suggests that thrombus maturation involves early influx of neutrophils (PMN) and neovascularization, we hypothesized that administering the proinflammatory/proangiogenic chemokine interleukin (IL)-8 might accelerate thrombus resolution., Materials and Methods: An established rodent model of DVT (inferior vena cava [IVC] ligation) was used whereby daily intravenous recombinant human IL-8 (1 microg) or vehicle control was administered, with sacrifice at 4 and 8 days. Prior to sacrifice and at harvest, duplex ultrasound of the DVT and femoral venous pressure measurements were performed. Thrombi were analyzed by immunohistochemical techniques for PMN, monocytes, and neovascularization; for chemokines, by enzyme-linked immunoassay; and fibrosis, by hydroxyproline assay and trichrome staining., Results: IL-8 accelerated thrombus dissolution 4 days after IVC ligation, with 6-fold increased thrombus blood flow by duplex ultrasound and a 23% increased absolute femoral venous pressure compared with controls (both P < 0.05). These findings may be partially explained by the fact that animals receiving IL-8, as compared with controls, had 2.5-fold greater thrombus neovascularization (with a trend continuing to 8 days) and increased PMN at 4 days. Thrombus vascular endothelial growth factor was significantly reduced at 8 days postligation, while monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha were not altered by IL-8 administration. At 8 days post-IVC-ligation, fibrosis was 12-fold greater with IL-8 treatment compared with controls., Conclusions: A proinflammatory/proangiogenic thrombus milieu, as conferred by IL-8, enhances thrombus resolution and underscores the important relationship between neovascularity and inflammation., (Copyright 2001 Academic Press.)