A Preventative Foot Care Programme for People with Diabetes with Different Stages of Neuropathy

Diabetes Research and Clinical Practice. Aug, 2002  |  Pubmed ID: 12062856

The aim of this study was to assess the efficacy of a preventative foot care programme, applied in a normal outpatient setting to decrease the incidence of foot ulcers in people with diabetes diagnosed as having neuropathy by neuropathy disability score (NDS), in relation to the severity of neuropathy based on the vibration perception threshold (VPT). A structured continuous preventative foot care programme was designed to ensure proper footwear, walking foot hygiene, callus care, nailcutting, water temperature checks, use of warming devices, bathroom surgery, foot care products and self-inspection. Continual foot-care education and treatment, including podiatry, were available. Evaluation was at least every 6 months. Diabetic patients (n=308) with neuropathy (NDS > or =6), 72.3+/-10.7 years old, 45% men, 10.9+/-8.8 years duration of diabetes, and HbA(1c) 6.5+/-1.3%, without a history of foot lesions were recruited over 3 years and followed-up for 4.6 (3-6) years. A low risk group (n=124) had a VPT<25 V while 184 had a VPT > or =25 V (high risk). In all 220 patients (71%) complied with the programme, compliance being 76 and 68% in low and high risk groups. The low risk group developed nine ulcers in nine patients, and the high risk group 24 ulcers in 19 patients. Of these eight and 19 ulcers, respectively, were in the non-compliant patient group, giving relative risk of 22 and eight compared with people attending the programme. Thus compliance with a preventative foot programme reduces the incidence of foot ulceration in people with diabetes with neuropathy. This decrease is relatively greater in patients with less severity of neuropathy. The simple design should be widely generalisable.

Acoustical Comparison Between Samples of Good and Poor Vibrato in Singers

Journal of Voice : Official Journal of the Voice Foundation. Jun, 2003  |  Pubmed ID: 12825650

The purpose of this research was to analyze samples of frequency vibrato taken from recordings of eight different singers, which were classified as examples of good or poor singing. The samples were analyzed by a software package, which makes use of the linear prediction coding (LPC) method to determine the time varying rate and extent of the frequency vibrato wave. Four parameters, which relate to the periodicity of the samples, were extracted from the time varying rate and extent and investigated in order to verify or reject the hypothesis that the best vibrato samples were the most symmetric ones. Ten samples per singer were analyzed, 5 good and 5 poor, for a total of 80 samples. The results show that the samples judged as good were the most periodic ones.

Flexions of the Popliteal Artery: Dynamic Angiography

The Journal of Invasive Cardiology. Dec, 2004  |  Pubmed ID: 15596876

Stenting of popliteal artery (PA) with self-expandable stents is a therapeutic option in selected patients with arterial disease. Fractures of these stents may occur, and they are thought to be related to development of hinge points (HPs) secondary to knee flexion. However, it remains obscure how movements of the knee affect the morphology of the PA and where HPs occur.

Endovascular Treatment of a Stenosed Anomalous Left Gastric Artery: Unique Open Artery of the Gastrointestinal Tract

The Journal of Invasive Cardiology. Mar, 2005  |  Pubmed ID: 15867460

Dynamic Anatomy of the Popliteal Artery: Might Culture Affect the Outcome of Endovascular Therapy?

Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists. Oct, 2005  |  Pubmed ID: 16212467

Regarding: "Endovascular Treatment of Popliteal Artery Aneurysms: Results of a Prospective Cohort Study"

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2005  |  Pubmed ID: 16275472

Postreceptoral Chromatic-adaptation Mechanisms in the Red-green and Blue-yellow Systems Using Simple Reaction Times

Journal of the Optical Society of America. A, Optics, Image Science, and Vision. May, 2006  |  Pubmed ID: 16642176

Simple visual-reaction times (VRT) were measured for a variety of stimuli selected along red-green (L-M axis) and blue-yellow [S-(L + M) axis] directions in the isoluminant plane under different adaptation stimuli. Data were plotted in terms of the RMS cone contrast in contrast-threshold units. For each opponent system, a modified Piéron function was fitted in each experimental configuration and on all adaptation stimuli. A single function did not account for all the data, confirming the existence of separate postreceptoral adaptation mechanisms in each opponent system under suprathreshold conditions. The analysis of the VRT-hazard functions suggested that both color-opponent mechanisms present a well-defined, transient-sustained structure at marked suprathreshold conditions. The influence of signal polarity and chromatic adaptation on each color axis proves the existence of asymmetries in the integrated hazard functions, suggesting separate detection mechanisms for each pole (red, green, blue, and yellow detectors).

Retrograde Rotablator in Limb Salvage: a New Technique Using an Open Approach

Cardiovascular and Interventional Radiology. Sep-Oct, 2006  |  Pubmed ID: 16802076

Conventional vascular surgery and balloon angioplasty have poor results in severe and diffuse atherosclerotic disease of the infrapopliteal arteries. High-speed rotational atherectomy (Auth Rotablator) has not succeeded either, because of poor long-term patency and the non-reflow phenomenon. We report a case of limb salvage with long occlusion of the three infrapopliteal vessels. The anterior tibial artery was treated with retrograde Auth Rotablator atherectomy by an open approach through the pedal artery, resulting in full patency of the anterior tibial artery and healing of the skin lesions. The microparticulate debris from the ablation was drained out through the pedal arteriotomy, avoiding the complications associated with conventional antegrade high-speed rotational atherectomy.

Delayed Manifestation of Abdominal Aortic Stenosis in a Child Presenting 10 Years After Blunt Abdominal Trauma

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2006  |  Pubmed ID: 17098550

We report the case of a 13-year-old boy who, at 3 years of age, was a rear seat-restrained passenger in a high-speed motor vehicle crash necessitating segmental small-bowel resection. The patient remained well for 10 years; then he began to have exercise-induced fatigue in his lower extremities. Routine physical examination revealed a bruit and thrill in the mid abdomen and diminished femoral pulses. Aortic stenosis was diagnosed and treated surgically. We discuss the pathophysiology of the lesion and review the literature. This is the first report of abdominal aortic stenosis 10 years after blunt abdominal trauma in a child.

Pulmonary Artery Access Embolization in Patients with Massive Hemoptysis in Whom Bronchial And/or Nonbronchial Systemic Artery Embolization is Contraindicated

Cardiovascular and Interventional Radiology. May-Jun, 2008  |  Pubmed ID: 18175175

The objective of this paper is to present an alternative therapeutic approach for the treatment of patients with massive hemoptysis in whom bronchial and/or nonbronchial systemic arterial embolization is not possible. We describe a percutaneous procedure for pulmonary segmental artery embolization. Between May 2000 and July 2006, 27 adult patients with hemoptysis underwent percutaneous treatment at our department; 20 of 27 patients were embolized via bronchial and or nonbronchial systemic arteries and 7 patients were embolized via pulmonary artery. Femoral arterial access for systemic artery catheterization and femoral vein access for pulmonary arterial catheterization were used. Gelfoam particles and coils were used for embolization. In this study, we report on three cases of massive hemoptysis from a systemic arterial source in whom bronchial and/or nonbronchial arteries embolization was not possible. Percutaneous embolization via the pulmonary artery access was successful in all three patients. In conclusion, embolization via pulmonary artery is presented as an alternative approach for the management of hemoptysis in patients in whom bronchial arterial embolization is not possible.

Probiotic Acidified Formula in an Animal Model Reduces Pulmonary and Gastric Bacterial Load

Journal of Pediatric Surgery. Mar, 2009  |  Pubmed ID: 19302853

We previously reported that a diet acidified with citric acid effectively reinforces gastric acid protection against bacterial colonization and translocation. In this study, our objective was to examine a biologically acidified formula hypothesized to be more physiologic than formula acidified with free acid. This study was Institutional Animal Care and Use Committee (IACUC) approved and designed to determine whether this diet is better tolerated and equally effective to acidification with citric acid against gut colonization and subsequent bacterial translocation in a premature infant rabbit model.

Do Galectins Play a Role in Venous Thrombosis? a Review

Thrombosis Research. May, 2010  |  Pubmed ID: 19959209

Galectins are a family of carbohydrate-binding proteins that have a high affinity to galactosides on cell surfaces and extra cellular glycoproteins. They are involved in a variety of biological functions, including modulation of cell apoptosis, cell activation and inflammation. Our laboratory has recently identified galectin-3 binding protein (Gal-3BP) as being up-regulated in a microparticle proteomics analysis for deep venous thrombosis (DVT) patients compared to negative controls. P-selectin, another glycoprotein involved in thrombus propagation, has proven a promising target for DVT management and has been widely studied by our group. Galectins are involved in P-selectin expression and can potentially be implicated in the venous thrombogenesis process. The function of galectins, their role in inflammation and thrombosis as well as their potential implications as a new pharmacological target for DVT management are reviewed in this manuscript.

Thrombogenesis with Continuous Blood Flow in the Inferior Vena Cava. A Novel Mouse Model

Thrombosis and Haemostasis. Aug, 2010  |  Pubmed ID: 20589322

Several rodent models have been used to study deep venous thrombosis (DVT). However, a model that generates consistent venous thrombi in the presence of continuous blood flow, to evaluate therapeutic agents for DVT, is not available. Mice used in the present study were wild-type C57BL/6 (WT), plasminogen activator inhibitor-1 (PAI-1) knock out (KO) and Delta Cytoplasmic Tail (DCT). An electrolytic inferior vena cava (IVC) model (EIM) was used. A 25G stainless-steel needle, attached to a silver coated copper wire electrode (anode), was inserted into the exposed caudal IVC. Another electrode (cathode) was placed subcutaneously. A current of 250 muAmps over 15 minutes was applied. Ultrasound imaging was used to demonstrate the presence of IVC blood flow. Analyses included measurement of plasma soluble P-selectin (sP-Sel), thrombus weight (TW), vein wall morphometrics, P-selectin and Von Willebrand factor (vWF) staining, transmission electron microscopy (TEM), scanning electron microscopy (SEM); and the effect of enoxaparin on TW was evaluated. A current of 250 muAmps over 15 minutes consistently promoted thrombus formation in the IVC. Plasma sP-Sel was decreased in PAI-1 KO and increased in DCT vs. WT (WT/PAI-1: p=0.003, WT/DCT: p=0.0002). Endothelial activation was demonstrated by SEM, TEM, P-selectin and vWF immunohistochemistry and confirmed by inflammatory cell counts. Ultrasound imaging demonstrated thrombus formation in the presence of blood flow. Enoxaparin significantly reduced the thrombus size by 61% in this model. This EIM closely mimics clinical venous disease and can be used to study endothelial cell activation, leukocyte migration, thrombogenesis and therapeutic applications in the presence of blood flow.

S-cone Excitation Ratios for Reaction Times to Blue-yellow Suprathreshold Changes at Isoluminance

Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). Sep, 2010  |  Pubmed ID: 20883334

We examined different contrast metrics to scale visual latencies for suprathreshold stimuli modulated along tritan confusion lines. S-cone increments ('blue') and decrements ('yellow') were isolated along two different tritan confusion lines, each one having a different luminance value. Reaction times (RT) were evaluated as a function of the Weber contrast and the S-cone excitation ratio between the test stimulus and the background. RTs were described using a model that generalizes Piéron's law and incorporates the notion of threshold units and power law scaling. Our results show that RTs for S-cone increments and decrements equate better when using the S-cone excitation ratio. However, a single function did not describe all RT data. S-cone RTs are better described by separate functions. We conclude that S-cone increments and decrements do not scale in the same manner. Both Weber contrast and the S-cone excitation ratio are plausible metrics at isoluminance. The implications for the S-cone pathways are discussed.

Competition with Wall Lizards Does Not Explain the Alpine Confinement of Iberian Rock Lizards: an Experimental Approach

Zoology (Jena, Germany). Oct, 2010  |  Pubmed ID: 20934315

Interspecific competition can limit the distribution of species along altitudinal gradients. It has been suggested that Western European rock lizards (genus Iberolacerta) are restricted to mountains due to the expansion of wall lizards (Podarcis), but there is no experimental evidence to corroborate this hypothesis. This study examines if interference competition with Podarcis muralis is a plausible explanation for the alpine confinement of Iberian rock lizards Iberolacerta cyreni. In a first experiment, we used an enclosure with four types of microhabitats to investigate whether adult rock and/or wall lizards shifted microhabitat or refuge preferences in the presence of the other species, and to detect aggressive interactions between them. In a second experiment, we staged heterospecific encounters between naïve, laboratory-born juveniles to identify behavioural differences and agonistic interactions. In the enclosure, neither rock nor wall lizards changed their microhabitat preferences in the presence of the other species. Nevertheless, rock lizards increased the diversity of microhabitats and nocturnal refuges used in the single species trials, which had twice the number of conspecifics. Aggressive interactions involved mainly large rock lizard males. Juveniles did not show any interspecific agonistic behaviour, but rock lizards spent more time basking and less time moving. Thus, we found no evidence of competition between both species in terms of habitat shifts or agonistic interactions, although intraspecific interactions seemed to explain the behaviour of adult rock lizards. We conclude that other factors are currently determining the alpine confinement of rock lizards.

Toll-like Receptor 9 Signaling is Critical for Early Experimental Deep Vein Thrombosis Resolution

Arteriosclerosis, Thrombosis, and Vascular Biology. Jan, 2011  |  Pubmed ID: 20966396

Toll-like receptors (TLR) bridge innate immunity and host responses, including inflammation. Sterile inflammation such as a venous thrombus (Vt) may involve TLR signaling, including TLR9.

Interleukin-6: a Potential Target for Post-thrombotic Syndrome

Annals of Vascular Surgery. Feb, 2011  |  Pubmed ID: 21131172

Deep vein thrombosis (DVT) and its associated sequelae, post-thrombotic syndrome (PTS), are significant health care problems in the United States. It is estimated that a maximum of 60% of patients diagnosed with DVT develop PTS, which is characterized by extensive perivenous and mural fibrosis. Interleukin-6 (IL-6) has been linked to fibrosis, and high circulating plasma levels have been found to increase the risk of developing DVT. The aim of this study was to elucidate the role of IL-6 in the progression of vein wall fibrosis by using a mouse model of DVT.

Emerging Opportunistic Yeast Infections

The Lancet Infectious Diseases. Feb, 2011  |  Pubmed ID: 21272794

A growing population of immunosuppressed patients has resulted in increasingly frequent diagnoses of invasive fungal infections, including those caused by unusual yeasts. The incidence of non-albicans species of Candida is increasing compared with that of Candida albicans, and several species, such as Candida glabrata and Candida krusei, may be resistant to azole antifungal therapy. Trichosporon species are the second most common cause of fungaemia in patients with haematological malignant disease and are characterised by resistance to amphotericin and echinocandins and poor prognosis. Rhodotorula species belong to the family Cryptococcaceae, and are a cause of catheter-related fungaemia, sepsis, and invasive disease in severely immunosuppressed patients. An increasing number of sporadic cases of invasive fungal infections by non-neoformans cryptococci have been reported in immunocompromised hosts, especially for patients with advanced HIV infection or cancer who are undergoing transplant. Other uncommon yeasts that can cause invasive disease in severely immunosuppressed patients include Geotrichum, Hansenula, Malassezia, and Saccharomyces. Host immune status is a crucial determinant of the type of invasive fungal infection a patient is at risk for. Diagnosis can be challenging and relies heavily on traditional cultures of blood and other sterile sites, although serum (1,3)-β-D-glucan testing might have an adjunctive role. Although rare yeasts are emerging as opportunistic human pathogens, diagnosis remains challenging and treatment suboptimal.

Male Mice Have Increased Thrombotic Potential: Sex Differences in a Mouse Model of Venous Thrombosis

Thrombosis Research. May, 2011  |  Pubmed ID: 21296387

Our objectives were to characterize sex differences during venous thrombosis, using the electrolytic inferior vena cava model of the disease.

Temporal Changes in Deep Venous Thrombosis Risk After Electrical Injury

Journal of Burn Care & Research : Official Publication of the American Burn Association. May-Jun, 2011  |  Pubmed ID: 21436716

Previous work has used the National Burn Repository to examine deep venous thrombosis (DVT) after electrical injury. However, these studies were limited and could not examine when DVT occurs after electrical injury. In addition, the utility of risk assessment models for DVT risk stratification has not been examined in this patient population. The authors performed a retrospective chart review of electrically injured patients at a single, American Burn Association- and American College of Surgeons-verified burn center over a 9-year period. Risk factors were identified and used to calculate Caprini scores at baseline and time of discharge. Outcomes of interest included symptomatic DVT or pulmonary embolism and time to DVT or pulmonary embolism. A total of 77 electrically injured patients were identified. DVT incidence was 6.5%. Patients with DVT had significantly higher TBSA (27.8% vs 3.8%), mean number of operations (4.8 vs 0.3), central venous catheter insertion (100% vs 5.3%), ventilator days (16.2 vs 0.3), intensive care unit days (24.4 vs 0.9), and mean change in Caprini score (18.6 vs 1.3) during hospitalization. Baseline Caprini scores were low, and DVT events occurred only after multiple risk factors were present; the average time-to-event was hospital day 17. Among patients with Caprini score >8, DVT incidence increased to 62%. In our single-center experience, the Caprini score was able to quantify DVT risk after electrical injury. In our series of 77 patients, the overall incidence of DVT was 6.5%. However, among patients whose Caprini score reached >8 during hospitalization, DVT incidence increased to 62%.

Exome Sequencing Identifies MAX Mutations As a Cause of Hereditary Pheochromocytoma

Nature Genetics. Jul, 2011  |  Pubmed ID: 21685915

Hereditary pheochromocytoma (PCC) is often caused by germline mutations in one of nine susceptibility genes described to date, but there are familial cases without mutations in these known genes. We sequenced the exomes of three unrelated individuals with hereditary PCC (cases) and identified mutations in MAX, the MYC associated factor X gene. Absence of MAX protein in the tumors and loss of heterozygosity caused by uniparental disomy supported the involvement of MAX alterations in the disease. A follow-up study of a selected series of 59 cases with PCC identified five additional MAX mutations and suggested an association with malignant outcome and preferential paternal transmission of MAX mutations. The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is further supported by the lack of functional MAX in rat PCC (PC12) cells and by the amplification of MYCN in neuroblastoma and suggests that loss of MAX function is correlated with metastatic potential.

Flexions of the Popliteal Artery: Technical Considerations of Femoropopliteal Stenting

The Journal of Invasive Cardiology. Oct, 2011  |  Pubmed ID: 21972163

Popliteal artery morphology changes while undergoing knee motion. A main flexion (i.e., the 'hinge point') and other flexions (termed 'accessory flexions') were described as a result of popliteal artery adaptation to knee flexion. Knee dynamics challenge the outcome of popliteal artery endovascular procedures. Complications such us stent fractures were reported despite rapidly improving technology. Understanding popliteal artery dynamics allows us to develop an endovascular technique that facilitates the avoidance of the difficulties of one of the most mobile arteries in the body. Here we report two cases with a novel stent implantation technique in the popliteal artery. The method includes diagnostic angiography, lesion angioplasty, and stenting using both extended and flexed knee in lateral view. The pressure gradients were measured with knee in extension and flexion before and after each step. A successful outcome was achieved in both cases. This method allows us: 1) to identify the flexions of the popliteal artery and its relationship with the lesions; 2) to detect those obstructions not visible with an extended knee; 3) to understand that the hinge point and accessory flexions can develop undesired and unexpected artery obstruction after a stent implantation only observed in knee flexion; and 4) to identify the morphological changes caused in the popliteal artery and its subsequent solution.

Scattering Characterization of Nanopigments in Metallic Coatings Using Hyperspectral Optical Imaging

Applied Optics. Nov, 2011  |  Pubmed ID: 22086047

We have determined the reflectance spectra of colored metallic coatings with high spatial resolution by using a hyperspectral imaging system. Reflectance spectra were converted to color coordinates revealing characteristic color maps in the color space. Principal-component analysis was applied to decorrelate the spatial variability of the reflectance spectra. We found that the eigenvalue spectra follow different power laws. The scaling exponent was analyzed by considering random-walk-type processes. An estimation of the Hurst exponent was done, suggesting anomalous diffusion from multiple light scattering. The results show that hyperspectral imaging combined with principal-component analysis provides a valuable method for nondestructive testing of complex turbid media.

Impaired Fibrinolytic System in ApoE Gene-deleted Mice with Hyperlipidemia Augments Deep Vein Thrombosis

Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. Nov, 2011  |  Pubmed ID: 22119245

BACKGROUND: Hyperlipidemia increases the level of blood plasminogen activator inhibitor-1 (PAI-1) that is responsible for regulating fibrinolysis by inhibiting both urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA). While this fibrinolytic pathway is well known, the role of PAI-1 in venous thrombosis (VT) under hyperlipidemic conditions has not been fully established. We sought to determine the effects of PAI-1 in an in vivo hyperlipidemic model of VT. METHODS: C57BL/6 wild-type (WT) mice, apolipoprotein E gene-deleted mice (ApoE-/-) having hyperlipidemia, and PAI-1 gene-deleted (PAI-1-/-) mice were used in this study. Inferior vena cava (IVC) ligation below the level of the renal veins was performed to create a stasis VT. Endpoints included measuring acute thrombosis (day 2) and chronic thrombosis (days 6 and 14). At euthanasia, blood samples were collected for plasmin and PAI-1 activity. In addition, the IVC and its thrombus were evaluated for thrombus weight (TW), u-PA activity, and differential leukocyte count while the vein wall only was analyzed for monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase (MMP) 2, and MMP-9. RESULTS: Compared to WT at day 2, ApoE-/-mice demonstrated a statistically significant 14% increase in TW (P < .05) and a significant 41% increase in circulating PAI-1 activity (P < .05), while showing a trend of decreased plasmin activity. In addition, TW in ApoE-/-mice was 45% higher than PAI-1-/-mice at day 2 (P < .05), 33% at day 6 (P < .01), and 41% at day 14 (P < .01). ApoE-/-mice exhibited undetectable levels of u-PA in both vein wall and thrombus, compared to WT, at all time points. Also, vein wall MMP-2 was significantly decreased by 64% at day 6 (P < .01) and 58% at day 14 (P < .05). MMP-9 was significantly decreased by 71% at day 2 (P < .01) and 48% at day 6 (P < .01), in ApoE-/-mice compared to WT mice. In addition, in ApoE-/-mice, MCP-1 was significantly decreased by 38% at day 2 (P < .01) and 67% at day 6 (P < .01) vs WT mice. As expected in ApoE mice, following a decrease in MCP-1, monocyte recruitment was significantly decreased at days 6 (P < .01) and 14 (P < .05). CONCLUSIONS: A significant increase of circulating PAI-1 levels in hyperlipidemic mice correlated with an early increase in TW due to impaired fibrinolysis. The undetectable levels of u-PA in ApoE-/-mice correlated to a decrease in vein wall MMP-2, MMP-9, MCP-1, and a decrease in monocyte recruitment diminishing thrombus resolution.

Myeloid Cell Tissue Factor Does Not Contribute to Venous Thrombogenesis in an Electrolytic Injury Model

Thrombosis Research. Dec, 2011  |  Pubmed ID: 22192154

INTRODUCTION: Tissue factor (TF) is a potent initiator of the extrinsic coagulation cascade. The role and source of TF in venous thrombotic disease is not clearly defined. Our study objective was to identify the contribution of myeloid cell TF to venous thrombogenesis in mice. MATERIALS AND METHODS: The mouse electrolytic inferior vena cava model was used to induce thrombosis. The following groups of mice were used (1) TF(flox/flox)LysMCre(+) mice that have reduced TF expression in myeloid cells, (2) TF(flox/flox)LysMCre(-) littermate controls, (3) Wild type mice given a monoclonal anti-mouse TF antibody (1H1) to inhibit TF activity, and (4) Wild type mice given rat IgG. Evaluations at baseline, day 2, and day 6 post thrombosis included thrombus weight, vein wall inflammatory cell migration, vein wall TF mRNA, and plasma D-dimer levels. RESULTS: Inhibition of TF significantly decreased thrombus weight 2days post venous thrombosis. In contrast, TF(flox/flox)LysMCre(+) had no change in thrombus weight when compared to littermate controls. The absence of myeloid cell TF did not affect infiltration of neutrophils or monocytes into the vein wall. TF mRNA expression in the vein wall decreased at 2days but then returned to baseline levels by 6days post thrombosis. D-dimer levels peaked at 2days post thrombosis in mice with or without myeloid cell TF. CONCLUSIONS: TF is important in the formation of venous thrombi in the macrovasculature. However, TF expression by myeloid cells does not significantly contribute to venous thrombogenesis in this model.

Inflammation and Thrombosis: New Insights

Frontiers in Bioscience (Scholar Edition). 2012  |  Pubmed ID: 22202081

Vessel wall endothelial damage initiates a local inflammatory response, which promotes a prothrombotic state driven by tissue factor, adhesion molecules, and pro-inflammatory cytokines. Understanding how natural inflammatory mechanisms promote a procoagulant state, may lead to the development of new pharmacological interventions targeted at thrombosis.

Statins, Inflammation and Deep Vein Thrombosis: a Systematic Review

Journal of Thrombosis and Thrombolysis. Jan, 2012  |  Pubmed ID: 22278047

Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin. The effects of statins on thrombosis are unclear, prompting this literature review. A literature search was performed (1950 to February 2011) with MEDLINE, EMBASE, and PUBMED databases including the following keywords: "statins", "hydroxymethylglutaryl-CoA reductase inhibitors", "VTE", "PE", "DVT", and either "anti-coagulation" or "inflammation". Editorials, reviews, case reports, meta-analysis and duplicates were excluded. Inflammatory biomarkers of DVT, include interleukin (IL)-6, CRP, IL-8, and monocyte chemotactic protein 1 (MCP-1). Statin therapy reduces IL-6 expression of CRP and MCP-1, usually elevated in VTE. Reduction of IL-6 induced MCP-1 has been linked to vein wall fibrosis, promoting post thrombotic syndrome (PTS) and recurrent DVT in patients. Also, our review suggests that the anti-thrombotic effects are likely exhibited through the anti-inflammatory properties of statins. This work supports that statin therapy has the ability to decrease the incidence and recurrence of VTE and the potential to decrease PTS. This is mainly due to the anti-inflammatory effects of statins and may explain why normolipidemic patients, with elevated CRP, appear to have the greatest reduction in VTE. Given their low risk of bleeding, statins have the potential to serve as a safe adjunctive pharmacological therapy to current treatments in select patients with VTE, however further investigations into this concept are needed and essential.

Increased PAI-1 in Females Compared to Males is Protective for Abdominal Aortic Aneurysm Formation in a Rodent Model

American Journal of Physiology. Heart and Circulatory Physiology. Feb, 2012  |  Pubmed ID: 22307671

The serine proteases, along with their inhibitor plasmin activator inhibitor-1 (PAI-1), have been shown to play a role in abdominal aortic aneurysm (AAA) formation. The aim of this study is to determine if PAI-1 may be a protective factor for AAA formation and partially responsible for the gender difference observed in AAAs. Male and female wild type (WT) C57BL/6 and PAI-1 -/- mice, 8-12 weeks of age underwent aortic perfusion with porcine pancreatic elastase. Animals were harvested 14 days following perfusion and analyzed for phenotype, Western blot, and matrix metalloproteinase (MMP) 9 and 2 activity. WT males had an average increase in aortic diameter of 80%, while females only increased 32% (p<0.001). PAI-1 -/- males increased 204% and females 161%, significantly more than their WT counterparts (p<0.001). Western blot revealed 61% higher PAI-1 protein levels in the WT females compared to the WT males (p=0.01). Zymography revealed higher levels of pro MMP2 and active MMP2 in the PAI-1 -/- males and females compared to their WT counterparts. PAI-1 -/- females had significantly higher serum plasmin levels compared to WT females (p=0.003). In conclusion, WT female mice are protected from aneurysm formation and have higher levels of PAI-1 compared to males during experimental aneurysm formation. Additionally both male and female PAI-1 -/- animals develop significantly larger aneurysms than WT animals, correlating with higher pro and active MMP 2 levels. These findings suggest that PAI-1 is protective for aneurysm formation in the elastase model of AAA and plays a role in the gender differences seen in AAA formation.

1/f Noise in Human Color Vision: the Role of S-cone Signals

Journal of the Optical Society of America. A, Optics, Image Science, and Vision. Feb, 2012  |  Pubmed ID: 22330409

We examine the functional role of S-cone signals on reaction time (RT) variability in human color vision. Stimuli were selected along red-green and blue-yellow cardinal directions and at random directions in the isoluminant plane of the color space. Trial-to-trial RT variability was not statistically independent but correlated across experimental conditions and exhibited 1/f noise spectra with an exponent close to unity in most of the cases. Regarding contrast coding, 1/f noise for random chromatic stimuli at isoluminance was similar to that for achromatic stimuli, thus suggesting that S-cone signals reduce variability of higher order color mechanisms. If we regard spatial coding, the effect of S-cone density in the retina on RT variability was investigated. The magnitude of 1/f noise at 16 min of arc (S-cone free zone) was higher than at 90 min of arc in the blue-yellow channel, and it was similar for the red-green channel. The results suggest that S-cone signals are beneficial and they modulate 1/f noise spectra at postreceptoral stages. The implications related to random multiplicative processes as a possible source of 1/f noise and the optimal information processing in color vision are discussed.