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Edema Formation (edema + formation)
Selected AbstractsEffects of a new 1,3,4-thiadiazolium mesoionic compound, MI-D, on the acute inflammatory responseDRUG DEVELOPMENT RESEARCH, Issue 4 2004Júlio C. Cardoso Abstract A new mesoionic compound, 4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine (MI-D), is described along with some of its biological properties. Its effects on hepatic metabolism, on O and nitric oxide (NO) production, and in in vivo models for potential antinociceptive, antipyretic, and antiinflammatory activities were determined. In perfused rat liver, MI-D (25 µM) stimulated glycogenolysis (95%), and inhibited oxygen uptake (37%) with affecting glycolysis. In phorbol 12-myristate 13-acetate-stimulated macrophages, O generation was reduced (95%) by MI-D (15 µM), whereas the production of NO was unaffected. MI-D (2 mg/kg) inhibited (55%) the number of abdominal writhings induced by acetic acid. At 1 mg/kg, MI-D inhibited the febrile response (5 h) induced by lipopolysaccharide (LPS) and was also effective against a preexisting febrile response. Treatment with MI-D (1 mg/kg) reduced by 67% prostaglandin (PGE2) levels in the cerebrospinal fluid of LPS-exposed mice, and at a higher dose (8 mg/kg) MI-D inhibited paw edema formation (2 h) induced by carrageenan. MI-D has a spectrum of activities similar to other nonsteroidal antiinflammatory drugs, qualifying it as a potential anti-inflammatory drug. Drug Dev. Res. 61:207,217, 2004. © 2004 Wiley-Liss, Inc. [source] Anti-vascular endothelial growth factor receptor-2 (Flk-1/KDR) antibody suppresses contact hypersensitivityEXPERIMENTAL DERMATOLOGY, Issue 11 2004Hideaki Watanabe Abstract:, The angiogenic mediator vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have been studied extensively in neoplastic disease and some inflammatory conditions. Contact hypersensitivity (CHS) is a prototypic Langerhans' cell-dependent, T-helper (Th) 1 cell-mediated inflammatory skin disease that is now also thought to involve angiogenic mediators. The purpose of our study was to examine the role of angiogenesis and VEGF in CHS. We demonstrated that VEGF production is up-regulated in murine skin after challenge with dinitrofluorobenzene. Administration of a monoclonal antibody directed against the VEGFR-2 (DC101) resulted in a 28.8% decrease in CHS response (P < 0.001). Examination of the DC101-treated mouse skin 24 h after challenge revealed decreases in dermal inflammatory cellular infiltrates and total vessel area. Furthermore, mRNA and protein of the Th1-type cytokine interferon (IFN)-, was significantly down-regulated in skin of DC101-treated animals 24 h after challenge. The results of the study demonstrate that VEGFR-2 blockade significantly reduces vascular enlargement and edema formation and effects IFN-, expression in the skin during challenge in CHS. Our findings suggest that DC101 could function by reducing inflammatory cell migration and hence IFN-, expression during the CHS response. [source] Hereditary angioedema: an update on available therapeutic optionsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 9 2010Marcus Maurer Summary There is no cure for hereditary angioedema (HAE). Therapeutic approaches consist of symptomatic therapy for acute attacks, short-term prophylaxis before surgery, and long-term prophylaxis for those with frequent and severe attacks. In Germany, C1-INH concentrate and icatibant are licensed for acute therapy. C1-INH concentrate, which is obtained from human plasma, is administered intravenously to restore the deficient C1-INH activity. This therapy, which has been available for decades, is effective and well-tolerated. Batch documentation is required by German law. The synthetic decapeptide icatibant is administered subcutaneously. It competes with bradykinin, the responsible inducer of edema formation, for binding to the bradykinin B2 receptor. Icatibant is also effective and well-tolerated, even on repeated administration. An additional human C1-inhibitor, a recombinant human C1-inhibitor and the recombinant inhibitor of kallikrein ecallantide are currently under development. There are no licensed treatment options available in Germany for long- and short-term prophylaxis. Androgen derivatives are established in long-term prophylaxis. However, they are associated with many adverse effects, some of which are severe. Many drug interactions also limit their use. They are contraindicated in pregnancy, lactation, for children and in cases of prostate cancer. Antifibrinolytics have fewer adverse effects but are also less effective than androgens. They are contraindicated in thromboembolic disease and impaired vision. If androgen therapy has too negative an effect on quality of life, it may be worth reducing the dose or discontinuing therapy entirely and treating attacks with acute therapy. [source] Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in ratsJOURNAL OF NEUROCHEMISTRY, Issue 6 2009Dai-Shi Tian Abstract Tamoxifen has been found to be neuroprotective in both transient and permanent experimental ischemic stroke. However, it remains unknown whether this agent shows a similar beneficial effect after spinal cord injury (SCI), and what are its underlying mechanisms. In this study, we investigated the efficacy of tamoxifen treatment in attenuating SCI-induced pathology. Blood,spinal cord barrier (BSCB) permeability, tissue edema formation, microglial activation, neuronal cell death and myelin loss were determined in rats subjected to spinal cord contusion. The results showed that tamoxifen, administered at 30 min post-injury, significantly decreased interleukin-1, (IL-1,) production induced by microglial activation, alleviated the amount of Evans blue leakage and edema formation. In addition, tamoxifen treatment clearly reduced the number of apoptotic neurons post-SCI. The myelin loss and the increase in production of myelin-associated axonal growth inhibitors were also found to be significantly attenuated at day 3 post-injury. Furthermore, rats treated with tamoxifen scored much higher on the locomotor rating scale after SCI than did vehicle-treated rats, suggesting improved functional outcome after SCI. Together, these results demonstrate that tamoxifen provides neuroprotective effects for treatment of SCI-related pathology and disability, and is therefore a potential neuroprotectant for human spinal cord injury therapy. [source] Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced cerebral edemaJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010Diana Carolina Ferrari Abstract Neonatal hypoxia/ischemia (HI) is a common cause of cognitive and behavioral deficits in children with hyperoxia treatment (HHI) being the current therapy for newborn resuscitation. HI induces cerebral edema that is associated with poor neurological outcomes. Our objective was to characterize cerebral edema after HI and determine the consequences of HHI (40% or 100% O2). Dry weight analyses showed cerebral edema 1 to 21 days after HI in the ipsilateral cortex; and 3 to 21 days after HI in the contralateral cortex. Furthermore, HI increased blood-brain barrier (BBB) permeability 1 to 7 days after HI, leading to bilateral cortical vasogenic edema. HHI failed to prevent HI-induced increase in BBB permeability and edema development. At the molecular level, HI increased ipsilateral, but not contralateral, AQP4 cortical levels at 3 and up to 21 days after HI. HHI treatment did not further affect HI-induced changes in AQP4. In addition, we observed developmental increases of AQP4 accompanied by significant reduction in water content and increase permeability of the BBB. Our results suggest that the ipsilateral HI-induced increase in AQP4 may be beneficial and that its absence in the contralateral cortex may account for edema formation after HI. Finally, we showed that HI induced impaired motor coordination 21 days after the insult and HHI did not ameliorate this behavioral outcome. We conclude that HHI treatment is effective as a resuscitating therapy, but does not ameliorate HI-induced cerebral edema and impaired motor coordination. © 2010 Wiley-Liss, Inc. [source] Melatonin limits lung injury in bleomycin treated miceJOURNAL OF PINEAL RESEARCH, Issue 2 2005Tiziana Genovese Abstract:, Melatonin is the principal secretory product of the pineal gland and its role as an immuno-modulator is well established. Recent evidence shows that melatonin is a scavenger of oxyradicals and peroxynitrite and exerts protective effects in septic shock, hemorrhagic shock and inflammation. The aim of this study was to investigate the effect of melatonin on the lung injury caused by bleomycin (BLM) administration. Mice subjected to intratracheal administration of BLM developed significant lung injury characterized by a marked neutrophil infiltration [assessed by myeloperoxidase (MPO) activity] and by tissue edema. In addition, an increase of immunoreactivity to nitrotyrosine, poly-ADP-ribose (PAR) was also observed in the lung of BLM-treated mice. Also, lung injury induced by BLM administration was correlated with a significant loss of body weight and with a significant mortality. Administration of melatonin (10 mg/kg i.p.) daily significantly reduced the (i) loss of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation and (v) histological evidence of lung injury. Administration of melatonin also markedly reduced the nitrotyrosine and PAR formation. Taken together, our results demonstrate that treatment with melatonin significantly reduces lung injury induced by BLM in the mice. [source] Interactions between surface proteins of Streptococcus pyogenes and coagulation factors modulate clotting of human plasmaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2003H. Herwald Summary., Invasive and toxic infections caused by Streptococcus pyogenes are connected with high morbidity and mortality. Typical symptoms of these infections are hypotension, edema formation, tissue necrosis, and bleeding disorders. Here we report that components of the coagulation system including fibrinogen, factors V, XI, and XII, and H-kininogen, are assembled at the surface of S. pyogenes through specific interactions with bacterial surface proteins. In plasma environment, absorption of fibrinogen by S. pyogenes causes a hypocoagulatory state resulting in prolonged clotting times and impaired fibrin network formation. Moreover, the binding of coagulation factors and the subsequent activation of the coagulation system at the bacterial surface lead to the formation of a fibrin network covering S. pyogenes bacteria adhering to epithelial cells. The results suggest that interactions between S. pyogenes and components of the coagulation system contribute to some of the symptoms seen in severe infections caused by this important human pathogen. [source] Critical role of the vascular endothelial cell in health and disease: a review articleJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2004Todd C. Duffy DVM Abstract Objective: To review the human and veterinary literature on the role of the vascular endothelial cell in health, as well as during hypoxic and inflammatory disease states. Data sources: Data from human and veterinary literature were reviewed through a Pubmed search and a manual search of the references listed in articles covering some aspect of vascular endothelial cell function. Human data synthesis: The development of techniques that allow the maintenance and growth of endothelial cells in culture has produced an explosion of new research in the area of endothelial cell physiology. This plethora of data has revealed the critical role that vascular endothelial cells play in both health and disease states. Interspecies variations can occur with respect to the vascular endothelial cell physiology and its response to pathologic conditions. Veterinary data synthesis: There is a paucity of information regarding the role of the vascular endothelial cell in health or disease of small animals. Many human studies use species cared for by veterinarians, providing information that may be applied to small animals and that may be used to construct future studies. Conclusion: An organ system itself, the vascular endothelium is an essential component of all organs in the body. The endothelial cell lining functions to maintain selective permeability between the blood and the tissue it supplies, regulate vascular tone, sustain blood fluidity through regulation of coagulation, and modulate interaction of leukocytes with the interstitium and inflammatory reactions. During disease states, the endothelial cell functions locally to limit the boundaries of the disease process. If these functions are not controlled, they can become a part of the pathogenic process, contributing to blood stasis and thrombosis, potentiation of local inflammation and interstitial edema formation, subsequent tissue hypoxia, and multiple organ dysfunction. Pharmacological investigations targeting the modulation of endothelial function during disease states have not yet advanced treatment protocols. Since all critically ill animals are at risk for some degree of endothelial cell dysfunction, treatment regimens should focus on promoting capillary blood flow and tissue oxygen delivery. [source] Flow in Lymphatic Networks: Interaction between Hepatic and Intestinal Lymph VesselsMICROCIRCULATION, Issue 4 2001RANDOLPH H. STEWART ABSTRACT Objective: Lymph from both the liver and intestine flows into the cisterna chyli. We hypothesized that increasing liver lymph flow would increase cisterna chyli pressure and, thereby, decrease intestinal lymph flow, potentiating intestinal edema formation. Methods: Anesthetized dogs were instrumented to measure and manipulate portal vein pressure and cisterna chyli pressure. The effects of directly increasing portal pressure with and without directly increasing cisterna chyli pressure on intestinal wet-to-dry ratio and intestinal ascites formation rate were determined. Target values for portal and cisterna chyli pressures were determined following elevation of inferior vena caval pressure to levels seen in patients with obstructive caval disease. Results: Direct elevation of portal pressure (Pport) alone to 17.5 mm Hg caused a significant increase in intestinal wet-to-dry ratio (3.98 ± 0.24 vs. 3.40 ± 0.43) and the rate of ascites formation (0.36 ± 0.12 vs. 0.05 ± 0.03 mL/g dry wt/h). Simultaneous direct elevation of cisterna chyli pressure to 6.0 mm Hg and Pport to 17.5 mm Hg caused further increases in intestinal wet-to-dry ratio (5.52 ± 1.20) and ascites formation (0.57 ± 0.11 mL/g dry wt./h). Conclusions: Inferior vena caval hypertension increases liver lymph flow that elevates cisterna chyli pressure, which inhibits intestinal lymph flow and augments intestinal edema formation. [source] Fluid challenge in patients at risk for fluid loading-induced pulmonary edemaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2004M. Matejovic Background:, This study evaluated the effects of protocol-guided fluid loading on extravascular lung water (EVLW) and hemodynamics in a group of patients at high risk for volume expansion-induced pulmonary and systemic edema. Methods:, Nine acutely admitted septic patients with acute lung injury (ALI) were prospectively studied. In addition to sepsis and ALI, the following criteria indicating increased risk for edema formation had to be fulfilled: increased vascular permeability defined as microalbuminuria greater than fivefold normal and hypoalbuminemia <30 g l,1. Two hundred-ml boluses of a 10% hydroxyethyl starch (HES) was titrated to obtain best filling pressure/stroke volume relation. Extravascular lung water and intrathoracic blood volume (ITBV) were measured using a transpulmonary double-indicator dilution technique. Baseline data were compared with data at the end of fluid loading and 3 h postchallenge. Results:, At study entry the mean EVLW was 13 ml kg,1, and the mean EVLW/ITBV ratio (indicator of pulmonary permeability) was 0.72 (normal range 0.20,0.30). To attain optimal preload/stroke volume relation 633 ± 240 ml of HES was needed. Fluid loading significantly increased preload (CVP, PAOP and ITBV), and stroke volume. Effective pulmonary capillary pressure (Pcap) rose only slightly. As a result, the Pcap,PAOP gradient decreased. Despite increased cardiac output, EVLW did not change by plasma expansion. Conclusion:, In this selected group of at-risk patients, the optimization of cardiac output guided by the concept of best individual filling pressure/stroke volume relationship did not worsen permeability pulmonary edema. [source] Assessment of spinal cord pathology following trauma using early changes in the spinal cord evoked potentials: A pharmacological and morphological study in the ratMUSCLE AND NERVE, Issue S11 2002Hari Shanker Sharma PhD Abstract The possibility that spinal cord pathology following trauma can be assessed with early changes in the spinal cord evoked potentials (SCEPs) was examined in a rat model. Spinal cord injury (SCI) was produced in Equithesin-anesthetized (3 ml/kg, i.p.) rats through a longitudinal incision into the right dorsal horn at the T10,11 segments. The SCEPs were recorded with epidural electrodes placed over the T9 (rostral) segment of the cord. The SCEPs consisted of a small positive amplitude and a broad and high negative amplitude (NA). SCI resulted in an instant depression of the rostral NA that lasted for 1 h. However, the latency of NA continued to increase over time. At 5 h, spinal cord blood flow declined by 30% in the T9 segment, whereas the spinal cord water content and the permeability of the blood,spinal cord barrier (BSCB) were markedly increased. Damage to the nerve cells, glial cells, and myelin was quite common in the spinal cord, as seen by light and electron microscopy. Pretreatment with p -chlorophenylalanine, indomethacin, ibuprofen, and nimodipine attenuated the SCEP changes immediately after trauma and resulted in a marked reduction in edema formation, BSCB permeability, and blood flow changes at 5 h. However, pretreatment with cyproheptadine, dexamethasone, phentolamine, and propranolol failed to attenuate the SCEP changes after SCI and did not reduce the cord pathology. These observations suggest that early changes in SCEP reflect secondary injury-induced alterations in the cord microenvironment. Obviously, these changes are crucial in determining the ultimate magnitude and severity of cord pathology. © 2002 Wiley Periodicals, Inc. Muscle Nerve Supplement 11: S83,S91, 2002 [source] Preventative antiinflammatory effect of potamogetonan, a pectin from the common pondweed Potamogeton natans L.PHYTOTHERAPY RESEARCH, Issue 7 2007Sergey V. Popov Abstract The pectic polysaccharide named potamogetonan (PN) was obtained using extraction of the leaves and stems of the common pondweed Potamogeton natans L. by an aqueous ammonium oxalate. The purified potamogetonan PN-300 was obtained using membrane ultrafiltration of PN and proved to be pectin with a molecular weight of 300 kDa. The capacity of potamogetonan PN-300 to prevent inflammation was assessed using a carrageenan paw edema test in mice. Oral administration of PN-300 24 h prior to induction of inflammation was found to reduce edema formation in a dose-related manner. The maximal effect of PN-300 was observed at 1 h after carrageenan injection (60% reduction of footpad swelling) and was comparable to that of indomethacin. The delayed edema (5 h) was less affected by pre-administration of PN-300 (33% reduction). PN-300 was found to improve the survival of mice subjected to a lethal dose of LPS. The anti-endotoxemic effect of PN-300 was shown to be mediated by decreased TNF- , and IL-1, and increased IL-10 production. Thus, a pectin named potamogetonan PN-300 was isolated from P. natans and was shown to possess a preventive antiinflammatory effect following oral administration. Copyright © 2007 John Wiley & Sons, Ltd. [source] Concomitant Endothelin-1 Overexpression in Lung Transplant Donors and Recipients Predicts Primary Graft DysfunctionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010M. Salama Primary graft dysfunction (PGD) causes significant morbidity following lung transplantation (LTX). Mortality is high in PGD and therapeutic strategies are limited. To investigate whether endothelin-1 (ET-1) that mediates increased vascular permeability and edema formation in lung grafts can predict PGD, ET-1 mRNA expression was examined in lung tissue biopsies of 105 donors and recipients obtained shortly before LTX. Serum ET-1 concentration was assessed by ELISA. PGD grade was diagnosed and scored by oxygenation and radiological characteristics according to ISHLT guidelines. PGD grade 3 developed in 11% of patients. ET-1 mRNA expression was significantly increased in both donor (p < 0.0001) and recipient (p = 0.01) developing PGD as compared to no PGD group. Pretransplant ET-1 serum concentrations were elevated in recipients with PGD as compared to no PGD group (p < 0.0001), although serum ET-1 was not different between donors whose grafts developed PGD grades 0,3. In regression analysis, concomitant elevated donor tissue ET-1 and recipient serum ET-1 predicted PGD grade 3. This study indicates that pretransplant ET-1 mRNA overexpression in donors associated with elevated pretransplant serum ET-1 in recipients contribute to PGD development and that their assessment might be beneficial to predict PGD and to identify recipients who could benefit from a targeted ET-1 blockade. [source] Triggering of proteinase-activated receptor 4 leads to joint pain and inflammation in miceARTHRITIS & RHEUMATISM, Issue 3 2009Jason J. McDougall Objective To investigate the role of proteinase-activated receptor 4 (PAR-4) in mediating joint inflammation and pain in mice. Methods Knee joint blood flow, edema, and pain sensitivity (as induced by thermal and mechanical stimuli) were assessed in C57BL/6 mice following intraarticular injection of either the selective PAR-4 agonist AYPGKF-NH2 or the inactive control peptide YAPGKF-NH2. The mechanism of action of AYPGKF-NH2 was examined by pretreatment of each mouse with either the PAR-4 antagonist pepducin P4pal-10 or the bradykinin antagonist HOE 140. Finally, the role of PAR-4 in mediating joint inflammation was tested by pretreating mice with acutely inflamed knees with pepducin P4pal-10. Results PAR-4 activation caused a long-lasting increase in joint blood flow and edema formation, which was not seen following injection of the control peptide. The PAR-4,activating peptide was also found to be pronociceptive in the joint, where it enhanced sensitivity to a noxious thermal stimulus and caused mechanical allodynia and hyperalgesia. The proinflammatory and pronociceptive effects of AYPGKF-NH2 could be inhibited by pepducin P4pal-10 and HOE 140. Finally, pepducin P4pal-10 ameliorated the clinical and physiologic signs of acute joint inflammation. Conclusion This study demonstrates that local activation of PAR-4 leads to proinflammatory changes in the knee joint that are dependent on the kallikrein,kinin system. We also show for the first time that PARs are involved in the modulation of joint pain, with PAR-4 being pronociceptive in this tissue. Thus, blockade of articular PAR-4 may be a useful means of controlling joint inflammation and pain. [source] Liposome-Encapsulated Hemoglobin Alleviates Brain Edema After Permanent Occlusion of the Middle Cerebral Artery in RatsARTIFICIAL ORGANS, Issue 2 2009Akira T. Kawaguchi Abstract Liposome-encapsulated hemoglobin (LEH) was proven to be protective in cerebral ischemia/reperfusion injury. The present study evaluated LEH in a rat model of permanent middle cerebral artery (MCA) occlusion to clarify its effect during ischemia and reperfusion. Five minutes after thread occlusion of the MCA, rats were infused with 10 mL/kg of LEH (LEH, n = 13), and compared with normal controls (n = 11). Additional animals received the same MCA occlusion with no treatment (CT, n = 11), saline (saline, n = 10), empty liposome solution (EL, n = 13), or washed red blood cells (RBC, n = 7). Severity of brain edema was determined 24 h later by signal strength in T2-weighted magnetic resonance imaging of the cortex, striatum, hippocampus, and pyriform lobe. The results showed that brain edema/infarction observed in any vehicle-infused control was significantly more severe than in LEH-treated rats. There was a tendency toward aggravated edema in rats receiving ELs. LEH infusion at a dose of 10 mL/kg significantly reduced edema formation as compared to other treatments in a wide area of the brain 24 h after permanent occlusion of the MCA. Low oncotic pressure of EL and LEH solution (vehicle solution) appeared to cause nonsignificant aggravation of edema and reduced protective effects of LEH. [source] The therapeutic effects of retinal laser treatment and vitrectomy.ACTA OPHTHALMOLOGICA, Issue 5 2001A theory based on oxygen, vascular physiology ABSTRACT. The physiologic mechanism of photocoagulation can been seen in the following steps. The physical light energy is absorbed in the melanin of the retinal pigment epithelium. The adjacent photoreceptors are destroyed and are replaced by a glial scar and the oxygen consumption of the outer retina is reduced. Oxygen that normally diffuses from the choriocapillaris into the retina can now diffuse through the laser scars in the photoreceptor layer without being consumed in the mitochondria of the photoreceptors. This oxygen flux reaches the inner retina to relieve inner retinal hypoxia and raise the oxygen tension. As a result, the retinal arteries constrict and the bloodflow decreases. Hypoxia relief reduces production of growth factors such as VEGF and neovascularization is reduced or stopped. Vasoconstriction increases arteriolar resistance, decreases hydrostatic pressure in capillaries and venules and reduces edema formation according to Starling's law. Vitrectomy also improves retinal oxygenation by allowing oxygen and other nutrients to be transported in water currents in the vitreous cavity from well oxygenated to ischemic areas of the retina. Vitrectomy and retinal photocoagulation both improve retinal oxygenation and both reduce diabetic macular edema and retinal neovascularization. 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