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Endothelial Damage (endothelial + damage)
Selected AbstractsCytokine profile of sickle cell disease in OmanAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2004Anil Pathare Abstract The aim of our study was to assess the cytokine profile of sickle cell disease (SCD) patients in steady state and in vaso-occlusive crisis (VOC). VOC has a complex nature, involving interactions between sickle red blood cells (RBC), the endothelium, and leucocytes. Endothelial damage due to recurrent adhesion of sickle RBCs may disrupt endothelial function, leading to altered cytokine release. It is therefore pertinent to study the cytokine profile of SCD patients in steady state and in crisis prior to exploring its contribution to vaso-occlusive manifestations, since it is believed that an altered balance of proinflammatory and anti-inflammatory cytokines plays an important role in painful crisis. Cytokines including IL-1,, IL-2, IL-4, IL-6, IL-8, TNF-,, and IFN-, were measured by commercially available ELISA kits in SCD patients (n = 60); in steady state (n = 26) and in painful crisis (n = 34) and compared with nonanemic age- and sex-matched normal Omani controls (n = 20). SCD patients in crisis showed elevated levels of TNF-, (P < 0.092) and IL-6 (P < 0.024) when compared with steady state. It was also observed that SCD patients in steady state showed a significant elevation in IL-1, (P < 0.04), IL-6 (P < 0.0001), and IFN-, (P < 0.02) as compared to normal subjects. It is thus evident that both type I and type II cytokines are significantly altered in SCD patients. In steady state, type II proinflammatory cytokines are elevated, whereas in crisis, an additional augmentation of type I cytokines occurs, with persistent elevation of type II cytokines, emphasizing the role of perturbed endothelium and activated monocytes in the pathophysiology of vaso-occlusion in sickle cell crisis. Am. J. Hematol. 77:323,328, 2004 © 2004 Wiley-Liss, Inc. [source] Endothelial dysfunction in Buerger's disease and its relation to markers of inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2006M. Joras Abstract Background, Buerger's disease (BD) is a segmental occlusive vascular disease. The aim of this study was to detect functional changes in brachial artery and asymptomatic morphological changes in extra-cranial carotid arteries not affected by the disease process and to assess markers of inflammation and endothelial damage. Materials and methods, Fourteen patients in the remission phase of BD and the same number of age- and sex-matched healthy controls were included in the study. The capability of endothelium-dependent (flow-mediated) and endothelium-independent dilation of the brachial artery and intima-media thickness of the carotid arteries were measured using high-resolution ultrasound. Laboratory parameters of endogenous fibrinolytic activity, inflammation and endothelial dysfunction were also measured. Results, Patients with BD had a diminished capability of endothelium-dependent vasodilation and higher levels of some circulating markers of inflammation, such as leukocytes, C-reactive protein, intercellular adhesion molecule-1 and E-selectin. Intercellular adhesion molecule-1 levels were related to some of the inflammatory markers (sedimentation rate, C-reactive protein, ,2-globulins and fibrinogen), while E-selectin was correlated with decreased endogenous blood fibrinolytic activity. Endothelium-dependent vasodilation was in negative correlation with the relative share of neutrophil granulocytes. There were no significant differences in intima-media thickness between patients with BD and controls. Conclusions, Our study has expressed generalized functional arterial disorder in patients with BD not accompanied by any measurable morphological changes of the carotid arterial wall. Functional deterioration of brachial artery could be related to increased levels of various inflammatory markers , the process which is most probably the basic pathogenetic mechanism of the disease. [source] Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failureEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003B. S. P. Chin Abstract Background, Congestive heart failure (CHF) carries a poor prognosis with a high mortality rate, frequent hospitalizations and increased risk of thrombotic complications such as stroke. Cytokines may contribute to the progression and prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6) and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which are raised in CHF. The procoagulant properties of both cytokines may be mediated via tissue factor (TF), a potent clotting activator. We hypothesized that plasma levels of these markers, as well as levels of plasma viscosity, fibrinogen, soluble P-selectin and von Willebrand factor (markers of abnormal rheology, clotting, platelet activation, and endothelial damage, respectively) will be useful in predicting morbidity and mortality in chronic stable CHF. Methods and results, One hundred and twenty consecutive out-patients with chronic stable CHF (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection fraction of 29 [6]%) were recruited and followed for 2 years during which 42 patients reached a clinical end-point of all-cause mortality and cardiovascular hospitalizations, including stroke and myocardial infarction. Plasma IL-6 (P = 0·003) and TF (P = 0·013) levels, but not other research indices, were higher in those who suffered events compared with those without events. Predictors of end-points were high (, median) TF (P = 0·011), and IL-6 (P = 0·023) levels, as well as the lowest quartile of a left ventricular ejection fraction (P = 0·007). A strong correlation was present between TF and IL-6 levels (r = 0·59; P < 0·0001) and with VEGF levels (r = 0·43; P < 0·0001). Conclusion, IL-6 and TF are predictors of poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to the progression and thrombotic complications of CHF via its actions on TF expression. Although VEGF did not independently predict outcome in chronic CHF, the possibility arises that it may act with IL-6 to induce TF expression. [source] The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and l -selectin function in vivoEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2000Thorlacius Background Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. Materials and Methods For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. Results We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. Conclusions Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L -selectin function but may instead be related to the anticoagulative capacity of fucoidan. [source] Endothelial-Independent Prevention of High Blood Pressure in L-Name-Treated Rats by Angiotensin II type I Receptor Antisense Gene TherapyEXPERIMENTAL PHYSIOLOGY, Issue 4 2003Phyllis Y. Reaves It has previously been established that a single systemic administration of retroviral vector containing angiotensin II type I receptor antisense (AT1R-AS) in the neonatal spontaneously hypertensive rat (SHR) prevents development of hypertension, and in addition cardiac hypertrophy and endothelial dysfunction. However, these studies could not determine whether the effects of AT1R-AS on high blood pressure (BP) and endothelial function were independent. Angiotensin receptor blockers have been shown to reduce BP in the L-NAME (N , -nitro-L-arginine methyl ester hydrochloride)-induced rat model of hypertension. Our objective in the present study was to use the L-NAME model of hypertension to determine whether AT1R-AS treatment would lower high BP and attenuate cardiac hypertrophy under conditions of permanent endothelial damage. A single bolus of LNSV-AT1R-AS viral particles in neonatal Wistar-Kyoto (WKY) rats was without affect on basal BP. Efficacy of the transgene incorporation was assessed by observing a significant reduction in angiotensin-induced dipsogenic response in the AT1R-AS-treated animals. Introduction of L-NAME in the drinking water for 10 weeks resulted in the establishment of hypertension only in the WKY rats treated with vector alone. These hypertensive (BP, 179 ± 4 mmHg) animals showed a 17% increase in heart weight/body weight ratio and a 60% reduction in ACh-induced vasorelaxation in phenylephrine-preconstricted arteries. The L-NAME-induced high BP and cardiac hypertrophy were attenuated in rats expressing AT1R-AS. However, endothelial dysfunction could not be prevented with the antisense therapy. These observations demonstrate that attenuation of endothelial dysfunction is not a prerequisite for the antihypertensive effects of AT1R-AS treatment. [source] Ranking the contributing risk factors in venous thrombosis in terms of therapeutic potential: Virchow's triad revisitedJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2006Masaki Kiyomura Abstract Aim: Thromboemoblism is an attendant feature of a variety of pathological conditions. We reconsidered Virchow's pathogenetic triad of stasis, humoral factors and vascular wall pathologies in the light of platelet behavior in vivo. Methods: Rat mesenteric microcirculation was examined by intravital microscopy. After isolated rat platelets had been injected i.v. into rats, their behavior in venules was examined under the following conditions: stasis from pressure, hemoconcentration from erythropoietin injections, or endothelial damage from tumor necrosis factor-,. Results: In the endothelial damage group, platelets displayed transient adhesion and rolling, while some platelets exhibited stationary adhesion to venular endothelium. The stasis and hemoconcentration groups exhibited only a slight change in adhesive response. Conclusion: Endothelial dysfunction appears to be the most important contributing factor in the development of venous thrombosis. As such, targeting this dysfunction is suggested for therapeutic intervention. [source] Progenitor cell trafficking in the vascular wallJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009M. HRISTOV Summary., Adult endothelial as well as smooth muscle progenitor cells are engaged in the complex pathophysiology of atherosclerosis including primary remodeling with development and progression of atherosclerotic plaques as well as secondary complications associated with ischemia, endothelial damage, neointimal growth and transplant arteriosclerosis. These adult vascular precursor cells correspond to similar embryonic stem cell-derived progeny and are primarily located in bone marrow and peripheral blood. Recently, specific investigation on their recruitment emerged as a novel fundamental in the pathogenesis of arterial remodeling, plaque stability and angiogenesis. This multifaceted process of mobilization and homing is regulated by numerous chemokines, adhesion molecules and growth factors that guide and control the trafficking of vascular progenitor cells to the arterial wall after injury or during ischemia. [source] Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital modelJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2009M. J. E. KUIJPERS Summary.,Background:,Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. Objectives:,We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. Methods:,Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe,/, mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. Results:,Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. Conclusions:,Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo. [source] Increased soluble CD40 ligand levels in cystic fibrosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2004A. Falco Summary., Chronic inflammation represents a key pathogeneric event in the progression of lung disease in cystic fibrosis (CF). To identify novel mechanisms of the inflammatory reaction in CF and analyze its relation with coagulative activation, we carried-out a cross-sectional study to evaluate circulating levels of the inflammatory mediators soluble (s) CD40L, C-reactive protein (CRP), interleukin (IL)-1,, the coagulation markers activated factor VII (FVIIa) and prothrombin fragment (F) 1+2, as well as urinary 11-dehydro-thromboxane (TX)B2, an index of in vivo platelet activation, in 34 CF patients and 34 matched healthy subjects. We observed that CF patients displayed significantly increased circulating levels of sCD40L compared to controls [2.8 (0.4,15.6) vs 1.1 (0.2,2.7) ng mL,1 ,P = 0.0003]. sCD40L levels inversely correlated with forced expiratory volume at 1 second (FEV1) (, = ,0.788, P = 0.0001), whereas it directly correlated with CRP and IL-1, levels (, = 0.621, P = 0.0004; and , = 0.745, P = 0.0001, respectively), which were also elevated in CF patients. CF patients had also enhanced levels of FVIIa and F1+2 compared to controls [39.2 (22.6,69.8) vs 22.3 (16.2,32.4) mU mL,1, P = 0.0001; 0.60 (0.30,1.80) vs 0.17 (0.10,0.40) nmol L,1, P = 0.0001, respectively]. A direct correlation was observed between sCD40L and both plasma FVIIa (, = 0.691, P = 0.0001) and F1+2 (, = 0.545, P = 0.0017) as well as between sCD40L and urinary 11-dehydro-TXB2 (, = 0.433, P = 0.0129). Our findings suggest that in CF patients, sCD40L could represent a biochemical link between the inflammatory state, and endothelial damage and coagulative activation, leading to progressive impairment of pulmonary function. [source] Decreased portal flow volume increases the area of necrosis caused by radio frequency ablation in pigsLIVER INTERNATIONAL, Issue 3 2007Tsuyoshi Yoshimoto Abstract Background/aims: Although radio frequency ablation (RFA) has been widely accepted as an effective treatment for hepatocellular carcinoma (HCC), severe complications are not uncommon. Major complications seem to occur as a result of over-ablation beyond the intended area. As most patients with HCC have underlying cirrhosis, we speculated that decreased portal flow might cause the necrosis associated with RFA. To confirm this hypothesis, we examined the area of necrosis resulting from RFA under varying conditions of portal flow in a porcine model. Methods: RFA was performed using ultrasonographic guidance in anesthetized pigs. During the RFA procedure, portal flow was regulated by a balloon catheter, which was set in a portal trunk. The necrosis area was measured after sacrifice and was compared with the hyperechoic area that appeared during ablation. In another session, RFA was performed close to the hepatic vein and endothelial damage was examined. Results: The necrosis area caused by RFA was significantly larger when the portal flow volume was decreased by 50% or more. The hyperechoic lesion was always larger than the area of pathological necrosis regardless of portal flow volume. Under conditions of decreased portal flow, the vessel endothelium near the ablated area was more readily damaged. Conclusion: Decreased portal flow volume resulted in enlargement of the area of necrosis caused by RFA. Our results indicate that over-ablation could easily occur in patients with advanced cirrhosis, and that this could lead to major complications. Ultrasonographic guidance may be helpful for avoiding over-ablation. [source] Role of Policosanols in the Prevention and Treatment of Cardiovascular DiseaseNUTRITION REVIEWS, Issue 11 2003Krista A. Varady BASc Policosanols are a mixture of aliphatic alcohols derived from purified sugar cane. When administered at 5 to 20 mg/day, policosanols have been shown to decrease the risk of atheroma formation by reducing platelet aggregation, endothelial damage, and foam cell formation in animals. Additionally, policosanols have been shown to lower total and low-density lipoprotein (LDL) cholesterol levels by 13 to 23% and 19 to 31%, respectively, while increasing high-density lipoprotein (HDL) cholesterol from 8 to 29%. Policosanols are thought to improve lipid profiles by reducing hepatic cholesterol biosynthesis while enhancing LDL clearance. When compared with statins, policosanols exhibit comparable cholesterol-lowering effects at much smaller doses. The mixture is well tolerated when administered to animals; however, a more precise safety profile is needed for humans. In summary, policosanols are a promising resource in the prevention and therapy of cardiovascular disease (CVD), but these results need to be confirmed in independent laboratories. [source] Familial amyloidotic polyneuropathy (ATTR Val30Met) with widespread cerebral amyloid angiopathy and lethal cerebral hemorrhagePATHOLOGY INTERNATIONAL, Issue 6 2001Naomi Sakashita We report an autopsy case of familial amyloidotic polyneuropathy (FAP) with cerebral hemorrhage. A 38-year-old woman with a typical FAP pedigree started developing severe diarrhea and sensori-motor polyneuropathy at the age of 28 years; autonomic nervous system, heart and renal dysfunction manifested themselves in the following years. Genetic analysis revealed a single amino acid substitution at codon 30 of transthyretin (ATTR Val30Met). Ten years after her initial symptoms, the patient died of a sudden convulsive attack and respiratory failure. Autopsy revealed lethal cerebral hemorrhages and uremic lungs. Histochemical and immunohistochemical analyses revealed TTR-derived amyloid protein in every tissue examined, particularly in glomeruli and peripheral vessels. Severe meningo-cerebrovascular amyloidosis was also detected. Because uremia causes oxidative damage to the vascular system and amyloid formation is closely associated with oxidative stress, it is possible that uremic endothelial damage facilitated an unusual cerebral amyloid deposition. In typical FAP (ATTR Val30Met), cerebral amyloid angiopathy does not usually have clinical manifestations. However, cerebral amyloid angiopathy should be considered to explain FAP symptoms when some risk factors such as uremic vascular damage are accompanying features. [source] ORIGINAL RESEARCH,BASIC SCIENCE: Cavernous Neurotomy in the Rat is Associated with the Onset of an Overt Condition of HypogonadismTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2009Linda Vignozzi MD ABSTRACT Background., Most men following radical retropubic prostatectomy (RRP) are afflicted by erectile dysfunction (ED). RRP-related ED occurs as a result of surgically elicited neuropraxia, leading to histological changes in the penis, including collagenization of smooth muscle and endothelial damage. Aim., To verify whether hypogonadism could contribute to the pathogenesis of RRP-ED. Methods., Effects of testosterone (T), alone or in association with long-term tadalafil (Tad) treatment in a rat model of bilateral cavernous neurotomy (BCN). Main Outcome Measures., Penile tissues from rats were harvested for vasoreactivity studies 3 months post-BCN. Penile oxygenation was evaluated by hypoxyprobe immunostaining. Phosphodiesterase type 5 (PDE5), endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) mRNA expression were quantified by Real Time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results., In BCN rats, we observed the onset of an overt condition of hypogonadism, characterized by reduced T plasma level, reduced ventral prostate weight, reduced testis function (including testis weight and number of Leydig cells), with an inadequate compensatory increase of luteinizing hormone. BCN induced massive penile hypoxia, decreased muscle/fiber ratio, nNOS, eNOS, PDE5 expression, increased sensitivity to the nitric oxide donor, sodium nitroprusside (SNP), and reduced the relaxant response to acetylcholine (Ach), as well as unresponsiveness to acute Tad dosing. In BCN rats, chronic Tad-administration normalizes penile oxygenation, smooth muscle loss, PDE5 expression, SNP sensitivity, and the responsiveness to the acute Tad administration. Chronic Tad treatment was ineffective in counteracting the reduction of nNOS and eNOS expression, along with Ach responsiveness. T supplementation, in combination with Tad, reverted some of the aforementioned alterations, restoring smooth muscle content, eNOS expression, as well as the relaxant response of penile strips to Ach, but not nNOS expression. Conclusion., BCN was associated with hypogonadism, probably of central origin. T supplementation in hypogonadal BCN rats ameliorates some aspects of BCN-induced ED, including collagenization of penile smooth muscle and endothelial dysfunction, except surgically induced altered nNOS expression.Vignozzi L, Filippi S, Morelli A, Marini M, Chavalmane A, Fibbi B, Silvestrini E, Mancina R, Carini M, Vannelli GB, Forti G, and Maggi M. Cavernous neurotomy in the rat is associated with the onset of an overt condition of hypogonadism. J Sex Med 2009;6:1270,1283. [source] Neutrophils and B lymphocytes in ANCA-associated vasculitisAPMIS, Issue 2009VÉRONIQUE WITKO-SARSAT The pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is unknown but is most consistent with a primary role for neutrophils in the acute injury. Thus, neutrophils are cardinal cells in the pathophysiological process in AAV because they are both effector cells responsible for endothelial damage and targets of autoimmunity. In addition, because of their capacity to synthesize a wide variety of cytokines and chemokines, neutrophils can be considered as important modulators of the inflammatory and potentially of the autoimmune process. ANCA directed against two main autoantigens, namely proteinase 3 and myeloperoxidase, are likely to play a modulatory role in the inflammatory process. Interestingly, neutrophils are an important source of lymphocyte stimulator (BLy), a cytokine that plays a fundamental role in B-cell physiology, including differentiation, proliferation and immunoglobulin production. The issue of B-cell activation and/or dysregulation in vasculitis will be discussed. [source] Screening for atherosclerosis in patients with rheumatoid arthritis: Comparison of two in vivo tests of vascular functionARTHRITIS & RHEUMATISM, Issue 1 2003S. Van Doornum Objective Inflammation appears to play a central role in atherosclerosis, and endothelial damage mediated by systemic inflammation may contribute to the increased cardiovascular mortality in rheumatoid arthritis (RA). Brachial artery flow-mediated dilatation (FMD) and pulse wave analysis (PWA) are measures of vascular function. The aim of this study was to determine if FMD and PWA are abnormal in patients with RA. Methods Twenty-five RA patients and 25 matched healthy controls were studied. All were free of traditional cardiovascular risk factors. FMD was measured in all subjects. PWA was performed in 18 RA patients and 18 controls, with results expressed as large and small artery compliance (C1 and C2). Modified Sharp scores were calculated in 13 RA patients. Results Results (mean ± SD) in RA patients and controls, respectively, were as follows: FMD 107.6 ± 4.6% versus 108.5 ± 4.1% (P = 0.49), C1 14.8 ± 2.8 ml/mm Hg × 10 versus 17.9 ± 3.1 ml/mm Hg × 10 (P = 0.0033), C2 4.5 ± 2.3 ml/mm Hg × 100 versus 7.7 ± 3.7 ml/mm Hg × 100 (P = 0.0039). There was an inverse correlation between C2 and modified Sharp scores in the RA patients (Spearman's rho ,0.69, P = 0.0085). Conclusion FMD was normal in these RA patients, whereas arterial compliance was markedly reduced. PWA appears to be a more sensitive measure of vascular dysfunction than FMD in RA and may be the preferred surrogate marker of vascular dysfunction in longitudinal studies of RA patients. The inverse correlation between C2 and the modified Sharp score, a measure that reflects disease activity over time, supports the notion that chronic inflammation plays a role in RA-associated atherosclerosis. [source] Absence of corneal endothelium injury in non-human primates treated with and without ophthalmologic drugs and exposed to 2.8,GHz pulsed microwaves,,BIOELECTROMAGNETICS, Issue 4 2010Shin-Tsu Lu Abstract Microwave-induced corneal endothelial damage was reported to have a low threshold (2.6,W/kg), and vasoactive ophthalmologic medications lowered the threshold by a factor of 10,0.26,W/kg. In an attempt to confirm these observations, four adult male Rhesus monkeys (Macaca mulatta) under propofol anesthesia were exposed to pulsed microwaves in the far field of a 2.8,GHz signal (1.43,±,0.06,µs pulse width, 34,Hz pulse repetition frequency, 13.0,mW/cm2 spatial and temporal average, and 464,W/cm2 spatial and temporal peak (291,W/cm2 square wave equivalent) power densities). Corneal-specific absorption rate was 5.07,W/kg (0.39,W/kg/mW/cm2). The exposure resulted in a 1.0,1.2,°C increase in eyelid temperature. In Experiment I, exposures were 4,h/day, 3 days/week for 3 weeks (nine exposures and 36,h total). In Experiment II, these subjects were pretreated with 0.5% Timolol maleate and 0.005% Xalatan® followed by 3 or 7 4-h pulsed microwave exposures. Under ketamine,xylazine anesthesia, a non-contact specular microscope was used to obtain corneal endothelium images, corneal endothelial cell density, and pachymetry at the center and four peripheral areas of the cornea. Ophthalmologic measurements were done before and 7, 30, 90, and 180 days after exposures. Pulsed microwave exposure did not cause alterations in corneal endothelial cell density and corneal thickness with or without ophthalmologic drugs. Therefore, previously reported changes in the cornea exposed to pulsed microwaves were not confirmed at exposure levels that are more than an order of magnitude higher. Bioelectromagnetics 31:324,333, 2010. Published 2010 Wiley-Liss, Inc. [source] Circulating biomarkers for vascular endothelial growth factor inhibitors in renal cell carcinoma,CANCER, Issue S10 2009Amado J. Zurita MD Abstract In recent years, there has been significant progress in the clinical development and application of antiangiogenic therapies in renal cell carcinomas, particularly inhibitors of the vascular endothelial growth factor (VEGF) pathway. Despite this progress, no validated methods are currently available for identifying which patients are most likely to respond to treatment or experience toxic effects, selecting the optimal dose, or determining whether the intended molecular target has been effectively inhibited. However, recent studies have suggested that some of the biomarkers currently under investigation in clear cell renal cell carcinoma for VEGF pathway inhibitors are promising. These biomarkers include circulating proangiogenic factors and receptors; markers of hypoxia and endothelial damage; and cellular populations in peripheral blood, such as circulating endothelial cells. Further preclinical and translational validation studies are still needed to determine their practical utility in the clinical setting. Cancer 2009;115(10 suppl):2346-54. © 2009 American Cancer Society. [source] Stroke in children: inherited and acquired factors and age-related variations in the presentation of 48 paediatric patientsACTA PAEDIATRICA, Issue 7 2009Francesca Del Balzo Abstract Aim:, Stroke is relatively rare in children and the clinical presentation of paediatric stroke is often subtle. Numerous predisposing risk factors are known, and these can be both inherited and acquired. They include cardiac disease, vascular abnormalities, endothelial damage, infectious diseases, collagen tissue diseases, certain inborn errors of metabolism and anticardiolipin antibody, lupus anticoagulant and deficiencies of protein C, protein S, antithrombin or plasminogen. In addition, abnormal activated protein C resistance (or Factor V Leiden), Factor II G20219A variant, and the thermolabile variant of methylenetetrahydrofolate reductase (MTHFR C677T) need to be considered. Methods:, To explore the prevalence of different predisposing conditions in paediatric stroke patients, we evaluated 48 patients, including subjects with ischaemic and haemorrhagic stroke subtypes. Results:, Only 7 out of 48 (14.5%) had no recognizable risk factors: the majority of paediatric stroke patients had pre-existing risk factors that predisposed to the condition. The major genetic risk factor in our series of patients was homozygosity for the MTHFR C677T mutation (7 out of 48 patients); three more patients were found to be heterozygous for the Factor V Leiden mutation. Acquired predisposing conditions were present in 23 out of 48 patients and included pulmunar stenosis, head trauma, hyperlipidaemia and varicella infection. A total of 17 patients had both genetic and acquired predisposing factors. Conclusion:, Our results emphasize that multiple predisposing risk factors commonly predispose to paediatric stroke. In addition, the primary clinical presentation appeared to differ between the older and younger children: hemiparesis was the typical presentation in children <1 year of age while seizure predominated in older children. [source] | |||||||||||||