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At least 361 records · Page 20Linked to original sources
PubMed2004

Effect of retinoic acid in experimental diabetic nephropathy.

Although the pathogenetic mechanism of diabetic nephropathy has not been elucidated, an inflammatory mechanism has been suggested to contribute to its progression. Monocyte chemoattractant peptide (MCP)-1 attracts macrophages and T cells, and ultimately injures renal tissue. In early diabetic nephropathy, urinary excretion of MCP-1 was elevated, and increased as renal damage became more severe. Podocytes are expected to have an inflammatory role in diabetic nephropathy, as the surface expression of chemokine receptors such as CCR and CXCR on these cells has been recently reported. Although retinoid (retinal), a known anti-inflammatory agent, has been reported to be beneficial in some experimental models of renal disease, it has not been determined to prevent disease progression in diabetic nephropathy. We investigated the effects of all-trans retinoic acid on the production of MCP-1 under high glucose conditions in cultured mouse podocytes. We also evaluated whether all-trans retinoic acid inhibits inflammatory changes and improves renal function during the early stages of diabetic nephropathy in streptozotocin-induced diabetic rats. In cultured podocytes, high glucose stimuli rapidly upregulated the MCP-1 mRNA transcript and protein release. Treatment with retinoic acid tended to suppress the MCP-1 gene transcript, and significantly inhibited MCP-1 protein synthesis induced by high glucose stimulation. Urinary protein excretion and the urinary albumin : creatinine ratio (ACR) were significantly higher in diabetic rats 4 weeks after the induction of diabetes mellitus compared with control rats, and retinoic acid treatment markedly decreased both proteinuria and urinary ACR (proteinuria: 1.25+/-0.69 vs 0.78+/-0.72 mg/mgCr, P=0.056; urinary ACR: 0.47+/-0.25 vs 0.21+/-0.06 mg/mgCr, P=0.088). Urinary excretion of MCP-1 was rapidly increased 2 days after induction of diabetes mellitus in diabetic rats, and further increased until rats were 4 weeks of age, compared with control rats. Retinoic acid treatment resulted in 30% reduction of the urinary level of MCP-1 compared with vehicle-treated diabetic rats (119.3+/-74.2 vs 78.1+/-62.7 pg/mgCr, P=0.078). Immunohistochemistry revealed a significant increase in staining for MCP-1 and anti-monocyte/macrophage (ED-1) protein in the diabetic kidney, and retinoic acid treatment significantly suppressed intrarenal MCP-1 and ED-1 protein synthesis. In conclusion, podocytes are involved in the inflammatory reaction under diabetic circumstances, and these reactions were suppressed by retinoic acid. Retinoic acid also suppressed inflammatory changes in the diabetic rat kidney, and decreased proteinuria in diabetic rats. These results suggest that retinoic acid may have renoprotective effects in the early stages of diabetic nephropathy through an anti-inflammatory activity.

Animals↗
PubMed1997

Pharmacology of apolipoprotein A-I.

The role of HDL and its main protein component the apolipoprotein A-I as being antiatherogenic is well established. Experimental data give support for the involvement of at least three different types of mechanism: (1) the reverse cholesterol transport, (2) anti-inflammatory mechanisms and (3) antithrombotic mechanisms. Depending upon the stage and type of atherosclerosis, different mechanisms may be more or less important. Knowledge of pharmacology of apolipoprotein A-I has strongly increased during past years and clinical studies have started with infusions of apolipoprotein A-I phospholipid complexes.

Animals↗
PubMed2004

Leukocyte filtration and aprotinin: synergistic anti-inflammatory protection.

Cardiopulmonary bypass activates an array of cellular and humoral inflammatory mechanisms that culminate in diverse or organ-specific injury. A manifestation of inflammatory injury to the heart, atrial fibrillation ranks among the most frequent and potentially life-threatening postsurgical complications. Pulmonary manifestations of the inflammatory response are also of major concern. Neutrophils activated by passage through the extracorporeal circuit inflict local injury and provoke the inflammatory cascade by producing oxyradicals and proinflammatory factors. This study tested if a combination of leukocyte depletion and aprotinin suppression of neutrophils could minimize postbypass atrial fibrillation and pulmonary dysfunction. In part one, two randomized groups of 90 patients undergoing primary coronary artery bypass grafting received full Hammersmith aprotinin alone (control group) or combined with leukofiltration (study group) and were prospectively examined. The dual treatment decreased the incidence of postoperative atrial fibrillation (7 of 90, 7.8%) by 67% versus aprotinin alone (21 of 90, 23.3%). Respiratory gas exchange in these patients was assessed from pulmonary shunt fraction. In the first two hours postbypass, pulmonary shunt fraction in the dual treatment group increased 40% less than in the group receiving aprotinin alone (p = 0.002), and subsided more quickly and completely over the next six hours. In part two, the cardiopulmonary bypass group receiving aprotinin + leukofiltration was retrospectively compared with 45 patients undergoing off-pump coronary revascularization. A strong, albeit not statistically significant trend (p = 0.08) toward a lower incidence of atrial fibrillation was found in the dual treatment group versus the off-pump group (8 of 45, 17.8%). These findings suggest that combining mechanical and pharmacologic suppression of the systemic inflammatory response could mitigate its deleterious arrhythmic and pulmonary complications.

Aged↗
PubMed1995

Release of anti-inflammatory mediators after mechanical trauma correlates with severity of injury and clinical outcome.

Excessive synthesis of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta] after trauma has been correlated with poor outcome. Recently, naturally occurring inhibitors of TNF-alpha and IL-1 beta have been characterized such as soluble TNF receptors (sTNFRs) and IL-1 receptor antagonist (IL-1ra). The present study was undertaken to determine whether injury results in a rise of circulating sTNFRs and IL-1ra. If so, whether plasma levels of these anti-inflammatory mediators correlate with severity of injury and clinical outcome of these patients. Injured patients (n = 213) showed significantly increased sTNFR and IL-1ra plasma levels throughout the observation period of 14 days, compared with healthy volunteers (n = 127). Patients with severe injury (Injury Severity Score > 16 points) revealed higher levels (p < 0.05) of sTNFRs and IL-1ra than patients with minor trauma (Injury Severity Score < or = 16 points). Patients who died from injury demonstrated increased (p < 0.05) sTNFR p55 and IL-1ra plasma levels, compared with survivors. Thus, anti-inflammatory mechanisms are activated after trauma dependent on severity of injury. Because increased plasma levels of anti-inflammatory reacting proteins portended poorly for patient survival, these mediators may contribute to prediction of outcome after severe injury.

Adult↗
PubMed1992

Expression of interleukin (IL)-1 beta, IL-6 and their respective receptors in the normal rat brain and after injury.

The expression of interleukin (IL)-1 beta, IL-6 and their respective receptors has been studied in the rat brain before and up to 24 h after injury. Messenger RNA transcripts of these four genes were detected by in situ hybridization (ISH) in different structures of the intact brain. The distribution was very similar for IL-1 beta, IL-6 and IL-6 receptor (IL-6R). The expression of IL-1R was more widespread. Within hours after injury, an increased expression of IL-1 beta, and thereafter of IL-6 was documented. The expression of IL-1R and IL-6R was also increased. This expression was bilateral and not restricted to the injured area. Within 24 h, all ISH patterns had returned to normal. The molecular data were confirmed by protein data. Indeed, the distribution of IL-6 (detected by immunocytochemistry) agreed with the ISH patterns for IL-6. Furthermore, extracellular fluid was collected by microdialysis at the site of the lesion during 12 h and successive fractions were assayed for the presence of bioactive IL-1 and IL-6. Increases in IL-1 and later in IL-6 levels were detected. The rapid and concomitant increased expression of IL-1 beta, IL-6 and their receptors after injury stresses their possible early role in inflammatory mechanisms also in the brain, before any recruitment of inflammatory cells from remote nervous and not nervous areas.

Animals↗
PubMed2006

Osteopontin expression in substantia nigra in MPTP-treated primates and in Parkinson's disease.

Parkinson's disease (PD) is characterised by the loss of dopaminergic neurones in the substantia nigra (SN) but the pathogenic mechanism remains unknown. Cell death involves oxidative stress and inflammatory mechanisms, and these may be altered by the actions of the glycosylated phosphoprotein osteopontin (OPN). OPN is present in the rat SN, but its presence in human and non-human primate brain has not been extensively studied. Both OPN mRNA and protein were present in the normal marmoset SN, and OPN protein was localised to nigral neurones although these were not dopaminergic cells and it was not present in glial cells. In contrast, OPN protein was found in dopaminergic neurones in the normal human SN but again not in glial cells with some accumulation in the extracellular matrix. Following MPTP treatment of common marmosets, OPN protein expression was decreased, although its mRNA levels were unchanged and it was not present in either activated microglia or astrocytes. In the SN in PD, OPN protein expression was decreased in the remaining dopaminergic neurones and it was present in activated microglia but not in astrocytes. This was not specific to PD as OPN protein expression was also decreased in the SN in multiple system atrophy and progressive supranuclear palsy with an identical localisation of the protein. The presence of OPN in the normal human and non-human primate SN coupled to its decreased expression following nigral cell degeneration suggests that it may play an important role in dopaminergic neurone survival.

Aged↗
PubMed2003

Tissue chamber model of acute inflammation in farm animal species.

A tissue chamber model of acute inflammation for use in comparative studies in calves, sheep, goats and pigs has been established and validated. Tissue chambers were prepared from silicon rubber tubing, of inner diameter 12.7 mm, length 115 mm and volume 15 ml, with 10 holes, each of 6mm diameter, at each end. In each animal two or four chambers were inserted at subcutaneous sites. Six weeks after implantation an acute inflammatory reaction in a single cage was generated by the intracaveal injection of 0.5 ml of 1% carrageenan solution. Serial samples of exudate (injected chamber), transudate (non-injected chamber) and blood were collected for measurement of exudate and transudate leucocyte count, prostaglandin (PG)E(2) concentration in exudate and serum thromboxane (Tx)B(2) concentration. In addition, skin temperature changes over exudate and transudate chambers were recorded. In all four species, carrageenan induced an acute inflammatory response, indicated by increases to peak values followed by return towards baseline in skin temperature, leucocyte count and PGE(2) concentration. For each of these variables in calves, sheep and goats the increases were significantly greater for exudate than for transudate. The degree of intra-species variation in each variable was acceptable. Marked inter-species differences were recorded: skin temperature rise was greatest in calves and least in sheep and goats; exudate PGE(2) concentration was increased in the order sheep>goat>pig>calf; serum TxB(2) concentration was increased in the order calf>goat>sheep>pig and exudate leucocyte count was increased to a greater extent in the pig than in the three ruminant species. The model has advantages over some previously described tissue chamber models of inflammation and will be suitable for use in comparative studies of inflammatory mechanisms and the pharmacokinetics and pharmacodynamics of anti-inflammatory drugs.

Acute Disease↗
PubMed2004

Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.

Physiological anti-inflammatory mechanisms can potentially be exploited for the treatment of inflammatory disorders. Here we report that the neurotransmitter acetylcholine inhibits HMGB1 release from human macrophages by signaling through a nicotinic acetylcholine receptor. Nicotine, a selective cholinergic agonist, is more efficient than acetylcholine and inhibits HMGB1 release induced by either endotoxin or tumor necrosis factor-alpha (TNF-alpha). Nicotinic stimulation prevents activation of the NF-kappaB pathway and inhibits HMGB1 secretion through a specific 'nicotinic anti-inflammatory pathway' that requires the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). In vivo, treatment with nicotine attenuates serum HMGB1 levels and improves survival in experimental models of sepsis, even when treatment is started after the onset of the disease. These results reveal acetylcholine as the first known physiological inhibitor of HMGB1 release from human macrophages and suggest that selective nicotinic agonists for the alpha7nAChR might have therapeutic potential for the treatment of sepsis.

Acetylcholine↗
PubMed1990

Cyclosporin A modulation of the acute inflammatory response: an explanation for the effect of CsA on host defences in infection.

Previous studies have shown that the administration of cyclosporin A (CsA) to animals with experimentally induced pyelonephritis resulted in considerable exacerbation of infection. T-lymphocytes are not involved in the host response to pyelonephritis but neutrophils are known to be a key component in the pathogenesis of this infection, so the effect of CsA on this inflammatory component was investigated. CsA administration did not affect the metabolic activity of neutrophils in vitro nor their ability to phagocytose and kill microorganisms. However, the ability of neutrophils to mobilize to a sterile inflammatory focus in vivo was significantly impaired. Further experiments, using models of pyelonephritis and subcutaneous infection, demonstrated that the CsA-induced suppression of neutrophil mobilization was directly related to the observed increase in bacterial numbers and exacerbation of tissue damage. Additionally, the actual effect of CsA on host defences and the outcome of infection was found to be dependent on the level of the initial infectious challenge. The results of this study provide an explanation for the current pattern of infectious disease in patients treated with CsA, in whom infection with extracellular pathogens is still common. It is also clear that the effect of CsA on inflammatory mechanisms may explain the efficacy of the agent in inflammatory diseases such as rheumatoid arthritis. This suggests a wider therapeutic role for CsA than is currently recognized.

Acute-Phase Reaction↗
PubMed2006

Clinical review: molecular mechanisms underlying the role of antithrombin in sepsis.

In disseminated intravascular coagulation (DIC) there is extensive crosstalk between activation of inflammation and coagulation. Endogenous anticoagulatory pathways are downregulated by inflammation, thus decreasing the natural anti-inflammatory mechanisms that these pathways possess. Supportive strategies aimed at inhibiting activation of coagulation and inflammation may theoretically be justified and have been found to be beneficial in experimental and initial clinical studies. This review assembles the available experimental and clinical data on biological mechanisms of antithrombin in inflammatory coagulation activation. Preclinical research has demonstrated partial interference of heparin--administered even at low doses--with the therapeutic effects of antithrombin, and has confirmed--at the level of cellular mechanisms--a regulatory role for antithrombin in DIC. Against this biological background, re-analyses of data from randomized controlled trials of antithrombin in sepsis suggest that antithrombin has the potential to be developed further as a therapeutic agent in the treatment of DIC. Even though there is a lack of studies employing satisfactory methodology, the results of investigations conducted thus far into the mechanisms of action of antithrombin allow one to infer that there is biological plausibility in the value of this agent. Final assessment of the drug's effectiveness, however, must await the availability of positive, prospective, randomized and placebo-controlled studies.

Animals↗
PubMed2002

Acute mast cell-dependent neutrophil recruitment in the skin is mediated by KC and LFA-1: inhibitory mechanisms of dexamethasone.

This study examined adhesive and signaling pathways and anti-inflammatory mechanisms of dexamethasone in acute mast cell-dependent neutrophil recruitment in the skin in mice. Mast cell activation dose- and time-dependently triggered influx of predominately neutrophils and secretion of cytokine-induced neutrophil chemoattractant (KC). Neutralization of KC attenuated neutrophil recruitment upon mast cell activation. Mast cell activation- and KC-induced neutrophil responses were significantly decreased in lymphocyte function-associated antigen-1 (LFA-1)-deficient mice. Dexamethasone inhibited neutrophil accumulation elicited by mast cell activation. It is interesting that dexamethasone significantly reduced the mast cell-dependent secretion of KC, whereas neutrophil recruitment induced by exogenous KC was insensitive to dexamethasone treatment. Thus, KC is a fundamental mediator of neutrophil recruitment in acute mast cell-dependent skin inflammation, and mast cell activation- and KC-induced neutrophil responses are LFA-1-dependent. Moreover, dexamethasone inhibits mast cell-regulated skin infiltration of neutrophils mainly by attenuating KC secretion. Thus, this study elucidates important interactions between chemokines and adhesion molecules in mast cell-dependent neutrophil recruitment and provides new insight into mechanisms of dexamethasone in skin inflammation.

Animals↗
PubMed2001

Uncoupling of inflammatory and destructive mechanisms in arthritis.

OBJECTIVE: To update clinicians on recent advances in the differentiation of the mechanisms of inflammation and cartilage destruction in the pathogenesis of rheumatoid arthritis (RA). METHODS: We present analysis of recent published literature and abstracts that elucidates the independent actions of pivotal proinflammatory cytokines. These experimental data provide the framework for understanding the uncoupling of destructive and inflammatory mechanisms in arthritis. RESULTS: Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in the inflammation that occurs in RA. Interleukin-1 (IL-1) has a dominant effect on cartilage destruction that occurs later in the disease process. TNF-independent IL-1 production occurs in many RA model situations. Cytokine balance determines the erosive nature of the disease. CONCLUSION: IL-1 is at least as important as TNF-alpha in promoting the disease process. The pathways by which the inflammatory and destructive changes occur suggest that targeted anticytokine intervention will arrest the cartilage damage that occurs in patients with RA.

Animals↗
PubMed2001

Periodontal manifestations of systemic disease.

Periodontitis is a chronic bacterial infection of the supporting structures of the teeth. The host response to infection is an important factor in determining the extent and severity of periodontal disease. Systemic factors modify periodontitis principally through their effects on the normal immune and inflammatory mechanisms. Several conditions may give rise to an increased prevalence, incidence or severity of gingivitis and periodontitis. The effects of a significant number of systemic diseases upon periodontitis are unclear and often it is difficult to causally link such diseases to periodontitis. In many cases the literature is insufficient to make definite statements on links between certain systemic factors and periodontitis and for several conditions only case reports exist whereas in other areas an extensive literature is present. A reduction in number or function of polymorphonuclear leukocytes (PMNs) can result in an increased rate and severity of periodontal destruction. Medications such as phenytoin, nifedipine, and cyclosporin predispose to gingival overgrowth in response to plaque and changes in hormone levels may increase severity of plaque-induced gingival inflammation. Immuno-suppressive drug therapy and any disease resulting in suppression of the normal inflammatory and immune mechanisms (such as HIV infection) may predispose the individual to periodontal destruction. There is convincing evidence that smoking has a detrimental effect on periodontal health. The histiocytoses diseases may present as necrotizing ulcerative periodontitis and numerous genetic polymorphisms relevant to inflammatory and immune processes are being evaluated as modifying factors in periodontal disease. Periodontitis severity and prevalence are increased in diabetics and worse in poorly controlled diabetics. Periodontitis may exacerbate diabetes by decreasing glycaemic control. This indicates a degree of synergism between the two diseases. The relative risk of cardiovascular disease is doubled in subjects with periodontal disease. Periodontal and cardiovascular disease share many common risk and socio-economic factors, particularly smoking, which is a powerful risk factor for both diseases. The actual underlying aetiology of both diseases is complex as are the potential mechanisms whereby the diseases may be causally linked. It is thought that the chronic inflammatory and microbial burden in periodontal disease may predispose to cardiovascular disease in ways proposed for other infections such as with Chlamydia pneumoniae. To move from the current association status of both diseases to causality requires much additional evidence. Determining the role a systemic disease plays in the pathogenesis of periodontal disease is very difficult as several obstacles affect the design of the necessary studies. Control groups need to be carefully matched in respect of age, gender, oral hygiene and socio-economic status. Many studies, particularly before the aetiological importance of dental plaque was recognised, failed to include such controls. Longitudinal studies spanning several years are preferable in individuals both with and without systemic disease, due to the time period in which periodontitis will develop.

Calcium Channel Blockers↗
PubMed2006

[Activation of TH1/TH2 pathways detected through the expression of CCR4 and CCR5 on the ocular surface of glaucomatous patients treated over the long term].

PURPOSE: The aim of this work was to study, using flow cytometry, the expression of two chemokine receptors, CCR4 and CCR5, known to be related to the TH2 and TH1 systems, respectively, and the expression of HLA-DR, a hallmark of inflammation, on conjunctival impression cytology specimens (ICS) of glaucomatous patients treated over the long term. PATIENTS AND METHODS: In this case-control study, ICS were taken in a series of 35 glaucomatous patients treated with topical antiglaucoma drugs for more than 1 year (seven with beta-blockers, ten with prostaglandins, and 18 receiving multiple treatments), and 20 normal subjects. Conjunctival cells were collected and incubated with specific monoclonal antibodies directed against CCR4, CCR5, and HLA-DR, in order to measure, in a masked manner using flow cytometry, the percentage of cells positive to each marker in the conjunctival epithelium. RESULTS: Compared to normal subjects, HLA DR expression was significantly elevated in glaucomatous patients, with a tendency toward higher levels in the multitreatment group and lower levels in patients treated with prostaglandins, which did not differ significantly from control values. Both CCR4 and CCR5 significantly increased in glaucoma patients on multitreatment or monotherapy compared with normal subjects. CONCLUSION: This study demonstrates the overexpression of these two chemokine receptors in the conjunctival epithelium of patients treated for more than 1 year. Our results showing the simultaneous overexpression of CCR4 and CCR5 thus suggest that the chronic use of topical treatments may concurrently stimulate the TH1 and TH2 systems. These results evoke inflammatory mechanisms, combining allergy and toxicity, and confirm the complexity of inflammatory reactions occurring in the ocular surface of glaucoma patients.

Case-Control Studies↗
PubMed2001

Anti-inflammatory cytokine IL-10 and T cell cytokine profile in periodontitis granulation tissue.

Th2 cells are more abundant than Th1 cells in periodontitis lesions, but the relative importance of the Th1 and Th2 subsets in periodontal disease is not understood. In addition, the role of proinflammatory and anti-inflammatory cytokines in this disease process is unclear. Biopsies were obtained from 10 patients with early onset periodontitis (EOP) and 10 patients with adult periodontitis (AP). From all of the patients in the AP group we were able to obtain and section the gingival tissue to serve as controls. We used polyclonal monospecific antibodies to detect cells expressing IL-2, IL-4, IL-6, IL-10 and IL-15, tumour necrosis factor (TNF-alpha) and interferon-gamma (IFN-gamma) in formalin-fixed, paraffin-embedded sections of granulation tissue from periodontitis lesions. We also employed a series of oligonucleotide probes to detect cells expressing the cytokine transcripts in the same tissue biopsies. Cells that expressed IL-4 or IL-6 were more numerous than cells expressing either IL-2 or IFN-gamma. Th2 cells were more numerous in EOP and AP tissues. IL-15 substitutes for IL-2 in a number of biological activities related to the Th1 immune response, and interestingly, in periodontal lesions the IL-15-expressing cells outnumbered IL-2-expressing cells, suggesting that this is the pattern of immune regulation by T cells in the periodontium. The functional balance in the T cell subsets detected by their cytokine profiles underlies the importance of the anti-inflammatory mechanisms taking place in the diseased tissue. The numbers of inflammatory leucocytes that express the anti-inflammatory cytokine IL-10 are much more widely distributed than those that express the proinflammatory cytokines IL-6 and TNF-alpha. This study suggests that large numbers of infiltrating inflammatory cells as well as accessory cells are involved in the down-regulation of the inflammatory and immune response in periodontitis.

Adult↗
PubMed1979

Histamine, norepinephrine and serotonin content of nasal polyps.

Histamine, norepinephrine and serotonin were assayed and localized by fluorescence histochemistry in normal mucosa and nasal polyps because of their possible role in the development of inflammation and edema. Histamine was present in greater concentration in nasal polyps than in normal mucosa. Norepinephrine was present primarily in the base of nasal polyps and in greater concentration than in normal mucosa. Patients with aspirin sensitivity and asthma had much lower histamine concentrations in their nasal polyps than all other patients with nasal polyps. A proposal for a possible mechanism of formation of nasal polyps based on vascular and inflammatory mechanisms and incorporative roles for histamine and norepinephrine is presented.

Adolescent↗
PubMed2000

Methylphenylethynylpyridine (MPEP) Novartis.

SIBIA and Novartis are investigating the use of excitatory amino acid agonists and antagonists for the metabotropic receptor and the ionotropic receptors AMPA and NMDA. Preliminary experiments indicate they may have potential in the treatment of epilepsy, stroke, anxiety, pain and neurodegenerative disease. Methylphenylethynylpyridine (MPEP) is the lead compound in the series [347212]. Other compounds in the series that arose from the collaboration were SIB-1893, and its equipotent analog, SIB-1757, both of which are subtype-selective, potent antagonists of mGluR5. Chemical derivation of SIB-1893 resulted in the discovery of MPEP, a selective, systemically active noncompetitive mGluR5 antagonist. Studies using these agents have yielded data to support the involvement of mGluR5 in inflammatory mechanical hyperalgesia [311829], [311828], [311823], [311880], [319655]. MPEP is the most potent of these compounds with an IC50 value of 12 nM for inhibition of quisqualate-stimulated phosphoinositide hydrolysis in recombinant human mGluR5a-expressing cells. MPEP exhibited no cross reactivity with mGluR1 and other mGluRs, or against representative NMDA, AMPA and kainate receptors up to concentrations of 100 microM. The compound, administered orally (100 mg/kg) produced a 70% reversal of mechanical hyperalgesia in the Freund's complete adjuvant model of inflammatory pain [319261]. By October 1999, investigations with SIB-1757 and SIB-1893 had been discontinued in favor of MPEP [347212].

Analgesics, Non-Narcotic↗
PubMed2001

[Systemic markers of inflammation after coronary angioplasty].

UNLABELLED: THE RISK OF RESTENOSIS: Coronary angioplasty is an effective treatment of stable and instable coronary disease and its principle limitation, despite technical progress, remains restenosis. In instable angina, the physiopathologic and prognostic role of inflammation proteins is well documented. THE ROLE OF THE C-REACTIVE PROTEIN (CRP): Is a validated risk factor for patients presenting with heart failure, whether instable or stable angina and in the general population. This risk factor is distinct from tobacco abuse, hypercholesterolemia or diabetes. In all the series studied to date, the frequency of restenosis following coronary angioplasty increases when CRP values are high prior to surgery and continue to rise up to the 48th or 72nd hour. PERSPECTIVES: New therapeutic measures widen the possibilities of mechanical strategies (angioplasty with or without stent) and treatment of inflammatory mechanisms in the atheromatous plaques (statines, brachytherapy or "covered" stents).

Angioplasty, Balloon, Coronary↗