Acute Inflammatory Markers Research Articles

Polyamine and histopathological changes after unilateral endotoxin-induced uveitis and its contralateral effects.

The polyamines putrescine, spermidine and spermine are essential for normal cell function and proposed to be involved in inflammatory reactions. The polyamines were measured bilaterally in rabbit aqueous humor after unilateral endotoxin-induced uveitis. The contralateral eyes were injected with saline or not touched. Aqueous protein levels and leukocytes were determined and a histological evaluation was performed. Protein, leukocytes, putrescine and spermine increased in the treated eyes, but not in the untouched eyes. When saline was injected in the contralateral eye, a small increase in spermine was seen. Spermidine decreased first, but increased later, in both the endotoxin-injected and the other eye. Histopathologically, the treated eyes showed an infiltration of leukocytes, vasodilatation and in some cases optic nerve involvements. A mild reaction was also seen in the unchallenged contralateral eyes. The results show that polyamines might serve as a marker for acute inflammation in the eye and that the mechanism of putrescine and spermine induction is different from the one of spermidine. Polyamines are suggested to play a role in the cellular immune response.

Anti‐inflammatory effects of pyruvate‐enriched cardioplegia in pigs undergoing cardiopulmonary bypass

BackgroundReactive oxygen species produced during cardiopulmonary bypass (CPB) can elicit inflammation. Cardioplegia enriched with the intermediary metabolite pyruvate exerts antioxidant protection in myocardium of pigs subjected to CPB.HypothesisPyruvate‐fortified cardioplegia mitigates myocardial inflammation by increasing anti‐inflammatory cytokines, enhancing myocardial antioxidant defenses, and suppressing matrix metalloproteinase activity and neutrophil infiltration.MethodsIn situ swine hearts were arrested for 1 h with 4:1 blood:crystalloid cardioplegia, where the crystalloid component contained 188 mM glucose ± 24 mM pyruvate, then the hearts were reperfused and the pigs weaned from CPB. At 4 h post‐CPB, left ventricular myocardium was sampled for immunoblot analyses of the acute inflammation marker C‐reactive peptide (CRP), matrix metalloproteinase‐3 (MMP3) and tissue inhibitor of metalloproteinase‐2 (TIMP2), and to assess neutrophil infiltration by histology and myeloperoxidase activity.ResultsMyocardial CRP content increased over fivefold following CPB with control cardioplegia, but pyruvate cardioplegia prevented this increase. Circulating IL‐10 temporarily increased during and immediately after CPB; pyruvate cardioplegia provoked more sustained and robust enhancement of this anti‐inflammatory cytokine. CPB increased myocardial neutrophil infiltration and myeloperoxidase activity, but pyruvate‐fortified cardioplegia prevented these effects.ConclusionPyruvate‐enriched cardioplegia suppresses CPB‐induced inflammation, an effect potentially mediated by anti‐inflammatory cytokines and TIMP‐2. Support: OHF 02‐18‐522

An Evaluation of the Model for End‐Stage Liver Disease and Serum C‐Reactive Protein as Prognostic Markers in Intestinal Failure Patients on Parenteral Nutrition

Intestinal failure (IF) patients require parenteral nutrition (PN) to avoid malnutrition and death. However, they face complications of recurrent sepsis and liver failure. By the time liver failure is discovered, it is often too late for intervention and prognosis on the waiting list is grim. The Model for End-Stage Liver Disease (MELD) has traditionally been used to predict mortality in patients with liver failure but has never been analyzed in IF patients who are at risk for liver complications. C-reactive protein (CRP) is an acute inflammatory marker that has been shown to reflect disease progression in nonalcoholic steatohepatitis, a disease that in many ways resembles PN-associated liver disease. MELD and CRP are promising clinical markers of disease progression in IF patients on PN. The authors performed a retrospective, case-control study to compare levels of MELD and CRP within the entire population of 133 adult patients referred to Northwestern Memorial Hospital for IF from 1999 to 2006. Elevated MELD score is strongly predictive of increased mortality over the subsequent 6 months. Elevated CRP is strongly predictive over a smaller 3-month window. One-year mortality was significantly greater in patients who have either elevated MELD scores or serum CRP levels. In this study, the authors evaluated for the first time use of MELD and serum CRP as predictive markers of mortality in IF patients. Both seem to be promising clinical tools to identify which patients are at highest risk for complication.

Effects of Aerobic and Anaerobic Combined Exercise Training on Body Compositions, Cardiovascular Variables, Blood Lipids and Acute Inflammatory Markers in Male Smoker and Non-smokers during 8 Weeks

Effects of Aerobic and Anaerobic Combined Exercise Training on Body Compositions, Cardiovascular Variables, Blood Lipids and Acute Inflammatory Markers in Male Smoker and Non-smokers during 8 Weeks

162 Alkaline Phosphatase Activity is Related to Acute Inflammation and Collagen Turnover During Acute and Chronic Wound Healing

Alkaline phosphatase (ALP) is an ubiquitous enzyme produced by different cell types. Previous reports have demonstrated ALP induction by extracellular matrix, ascorbic acid or IL-6. Using histochemical techniques, we evaluated the ex vivo activity of ALP in incisional and excisional acute wounds, chronic wounds, and keloids in animal and human models. We also compared in situ ALP activity with type I/III collagen levels using histological methods (Herovici technique). Results demonstrated that 1) during the first stage of acute wound healing the increase in ALP activity precedes high levels of type III collagen, meanwhile type I collagen diminishes. When ALP activity disappears, the proportion of type I/III collagen returns to normal. 2) ALP activity is almost null in chronic wounds, which are characterized by thick type I collagen fibers and some type III collagen throughout the tissue. However, when the wound is treated, ALP activity rises to maximum levels together with type III collagen, but type I collagen is absent. 3) In keloids ALP activity is also absent; however when the scar is treated with a proinflammatory cytokine downmodulator (collagen-polyvinylpyrrolidone) endogenous type I collagen diminishes, while type III collagen and ALP activity are increased. Based on the above results we suggest that ALP activity is an acute inflammation marker since the enzyme levels are increased in acute wounds but not in chronic inflammation processes. Nevertheless, when chronic lesions or scars are in the process of healing, the increase in ALP activity is clear. And as a result, we believe that treatments for chronic wounds or scars induce acute inflammation and consequently stimulate wound repair or fibrolysis. In conclusion, ALP activity is an important factor to be considered in acute and chronic wound repair and their healing process. This work was partially supported by Sociedad Mexicana de Investigacion Biomedica A.C.

Ryanodine receptors decant internal Ca2+ store in human and bovine airway smooth muscle

Several putative roles for ryanodine receptors (RyR) were investigated in human and bovine airway smooth muscle. Changes in intracellular Ca2+ concentration ([Ca2+]i) and membrane current were investigated in single cells by confocal fluorimetry and patch-clamp electrophysiology, respectively, whereas mechanical activity was monitored in intact strips with force transducers. RyR released Ca2+ from the sarcoplasmic reticulum in a ryanodine- and chloroethyl phenol (CEP)-sensitive fashion. Neither ryanodine nor CEP inhibited responses to KCl, cholinergic agonists or serotonin, indicating no direct role for RyR in contraction; in fact, there was some augmentation of these responses. In tissues pre-contracted with carbachol, the concentration-response relationships for isoproterenol and salmeterol were unaffected by ryanodine; relaxations due to a nitric oxide donor were also largely unaffected. Finally, it was examined whether RyR were involved in regulating [Ca2+]i within the subplasmalemmal space using patch-clamp electrophysiology as well as Ca2+ fluorimetry: isoproterenol increased [Ca2+]i- and Ca2+-dependent K+ current activity in a ryanodine-sensitive fashion. In conclusion, ryanodine receptors in airway smooth muscle are not important in directly mediating contraction or relaxation. The current authors speculate instead that these allow the sarcoplasmic reticulum to release Ca2+ towards the plasmalemma (to unload an overly full Ca2+ store and/or increase the Ca2+-buffering capacity of the sarcoplasmic reticulum) without affecting bronchomotor tone.

Use of warm priming solution in open heart surgery: its effects on hemodynamics and acute inflammation

Cardiac surgery causes an acute inflammatory response and organ damage. In this study, for the first time in the literature, we compared the effects of priming solutions at 20 degrees C and 36 degrees C on acute inflammatory markers and hemodynamic parameters. Forty patients were recruited and randomized into two groups, each consisting of 20 participants who underwent elective coronary artery bypass grafting operation. Groups were primed with the same solution at different temperatures. Hemodynamic parameters were recorded. Blood samples were drawn pre-operatively and at the 15(th) and 60(th) minutes of aortic cross-clamping and the 24(th) hour following surgery. Serum pre-albumin, alpha-1 antitrypsin, and tumor necrosis factor-alpha levels were determined. The groups were compared statistically. Both of the groups were comparable for mean aortic cross-clamping time and mean time for cardiopulmonary bypass. Mean blood pressure value was significantly lower and the mean amount of ephedrine hydrochloride used was significantly higher in the cold priming group. Spontaneous beating of the heart after removal of aortic cross-clamp significantly was more frequent in the warm priming group. A significant rise was observed in systemic inflammatory markers in the cold priming group. In our study, the lesser amount of ephedrine hydrochloride used and the higher frequency of spontaneous beating of the heart in the warm priming group may be considered as improvements in hemodynamic status. Use of warm priming solution also induced a significant improvement in the acute inflammatory markers. We recommend the use of warm priming solution in open heart surgery.

Role of Nicotinic and Estrogen Signaling during Experimental Acute and Chronic Bladder Inflammation

Inflammation is a physiological process that characterizes many bladder diseases. We hypothesized that nicotinic and estrogen signaling could down-regulate bladder inflammation. Cyclophosphamide was used to induce acute and chronic bladder inflammation. Changes in bladder inflammation were measured histologically and by inflammatory gene expression. Antagonizing nicotinic signaling with mecamylamine further aggravated acute and chronic inflammatory changes resulting from cyclophosphamide treatment. Estrogen and nicotinic signaling independently attenuated acute bladder inflammation by decreasing neutrophil recruitment and down-regulating elevated lipocalin-2 and cathepsin D expression. However, the combined signaling by the estrogen and nicotinic pathways, as measured by macrophage infiltration and up-regulation of interleukin-6 expression in the bladder, synergistically reduced chronic bladder inflammation. The elevated expression of p65 nuclear localization in bladders treated with cyclophosphamide or cyclophosphamide with mecamylamine suggested nuclear factor-kappa B activation in the chronic inflammatory process. The complementary treatment of 17 beta-estradiol and the nicotinic agonist anabasine resulted in the translocation of p65 to the cytoplasm, again greater than either alone. Activation of nuclear factor-kappaB can result in macrophage activation and/or elevation in epithelial proliferation. These data suggest that 17 beta-estradiol and anabasine reduce chronic bladder inflammation through reduction of nuclear translocation of p65 to suppress cytokine expression.

Effects of Different Epidural Analgesic Compositions on Postoperative Pain Relief and Systemic Response to Surgery

Effects of Different Epidural Analgesic Compositions on Postoperative Pain Relief and Systemic Response to SurgeryDespite many achievements during the last decade, postoperative pain remains the dominant complaint after major surgery and has great potential to be influenced by the anaesthesiologist. Reports suggest that short-term effective anaesthesia and analgesia can have long-lasting beneficial effects on recovery from surgery. The aim of our study is to compare the effect of epidural analgesia, using different compositions, including glucocorticoids (methylprednisolone), and habitual composition of bupivacaine-morphine, in regard to analgesic and anti-inflammatory properties. A total of 129 patients participated in the study in four different treatment groups: patients from Group I received glucocorticoid methylprednisolone succinate and long-acting opioid morphine hydrochloride, Group II received local anaesthetic bupivacaine hydrochloride and morphine hydrochloride, Group III received methylprednisolone succinate and short-acting opioid fentanyl, and Group IV received glucocorticoid methylprednisolone succinate. We obtained good analgesic profiles in all groups. However, significantly better results were achieved using the combination of methylprednisolone and morphine. Epidural methylprednisolone in dose 80 mg/24 h is more effective, compared to the conventional local anaesthetics-opioid composition, when administered as a part of multimodal preventive postoperative analgesia after major joint replacement surgery. Epidural methylprednisolone has a reliable anti-inflammatory and immunomodulatory potential. It attenuates profiles of acute inflammatory response markers as Interleukin-6 and C-reactive protein and stress hormone cortisol. The novelty of this study was application of epidural glucocorticoids for acute postoperative pain relief as part of daily perioperative care. By developing studies on anti-inflammatory and immunomodulatory properties of glucocorticoids, we expect to improve patient rehabilitation in the postoperative period.

The Alabama Preterm Birth Study: Umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants

This study was undertaken to evaluate the frequency of umbilical cord blood infections with Ureaplasma urealyticum and Mycoplasma hominis in preterm 23- to 32-week births and to determine their association with various obstetric conditions, markers of placental inflammation, and newborn outcomes. 351 mother/infant dyads with deliveries between 23 and 32 weeks' gestational age who had cord blood cultures for U. urealyticum and M. hominis had their medical records abstracted, other placental cultures performed, cord interleukin-6 levels determined, placentas evaluated histologically, and infant outcomes determined. U. urealyticum and/or M. hominis were present in 23% of cord blood cultures. Positive cultures were more common in infants of nonwhite women (27.9% vs 16.8%; P = .016), in women less than 20 years of age, in those undergoing a spontaneous compared to an indicated preterm delivery (34.7% vs 3.2%; P = .0001), and in those delivering at earlier gestational ages. Intrauterine infection and inflammation were more common among infants with a positive U. urealyticum and M. hominis culture as evidenced by placental cultures for these and other bacteria, elevated cord blood interleukin-6 levels, and placental histology. Infants with positive cord blood U. urealyticum and M. hominis cultures were more likely to have neonatal systemic inflammatory response syndrome (41.3% vs 25.7%; P = .007; adjusted odds ratio, 1.86; 1.08-3.21) and probably bronchopulmonary dysplasia (26.8% vs 10.1%; P = .0001; adjusted odds ratio 1.99; 0.91-4.37), but were not significantly different for other neonatal outcomes, including respiratory distress syndrome, intraventricular hemorrhage, or death. U. urealyticum and M. hominis cord blood infections are far more common in spontaneous vs indicated preterm deliveries and are strongly associated with markers of acute placental inflammation. Positive cultures are associated with neonatal systemic inflammatory response syndrome and probably bronchopulmonary dysplasia.

A case with transient increases in serum S100A8/A9 levels implying acute inflammatory responses after pancreatic islet transplantation

We investigated a patient with type 1 diabetes mellitus undergoing pancreatic islets transplantation. In this patient, we evaluated the clinical usefulness of serial measurement of serum S100A8/A9 complex levels for detecting acute inflammatory responses associated with rejection of transplanted pancreatic islets. The serum S100A8/A9 complex was a more sensitive marker for acute inflammation associated with islet transplant rejection than the serum C-reactive protein. Thus, the serial measurement of the serum S100A8/A9 complex concentration is useful for monitoring the patients with pancreatic islet transplantation.

Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders*

Patients with trauma-associated acute lung injury have better outcomes than patients with other clinical risks for lung injury, but the mechanisms behind these improved outcomes are unclear. We sought to compare the clinical and biological features of patients with trauma-associated lung injury with those of patients with other risks for lung injury and to determine whether the improved outcomes of trauma patients reflect their baseline health status or less severe lung injury, or both. Analysis of clinical and biological data from 1,451 patients enrolled in two large randomized, controlled trials of ventilator management in acute lung injury. Compared with patients with other clinical risks for lung injury, trauma patients were younger and generally less acutely and chronically ill. Even after adjusting for these baseline differences, trauma patients had significantly lower plasma levels of intercellular adhesion molecule-1, von Willebrand factor antigen, surfactant protein-D, and soluble tumor necrosis factor receptor-1, which are biomarkers of lung epithelial and endothelial injury previously found to be prognostic in acute lung injury. In contrast, markers of acute inflammation, except for interleukin-6, and disordered coagulation were similar in trauma and nontrauma patients. Trauma-associated lung injury patients had a significantly lower odds of death at 90 days, even after adjusting for baseline clinical factors including age, gender, ethnicity, comorbidities, and severity of illness (odds ratio, 0.44; 95% confidence interval, 0.24-0.82; p = .01). Patients with trauma-associated lung injury are less acutely and chronically ill than other lung injury patients; however, these baseline clinical differences do not adequately explain their improved outcomes. Instead, the better outcomes of the trauma population may be explained, in part, by less severe lung epithelial and endothelial injury.

Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model

Adipose-derived stem cells (ASCs) are readily accessible multipotent mesenchymal stem cells and are known to secrete multiple growth factors, and thereby to have cytoprotective effects in various injury models. In the present study, the authors investigated the neuroprotective effect of ASCs in an intracerebral hemorrhage (ICH) model. ICH was induced via the stereotaxic infusion of collagenase, and human ASCs (three million cells per animal) isolated from human fresh fat tissue, were intravenously administered at 24 h post-ICH induction. Acute brain inflammation markers, namely, cell numbers positively stained for terminal transferase dUTP nick end labeling (TUNEL), myeloperoxidase (MPO), or OX-42, and brain water content were checked at 3 days post-ICH. In addition, the authors quantified brain degeneration by measuring hemispheric atrophy and perihematomal glial thickness at 6 weeks post-ICH, and determined modified limb placing behavioral scores weekly over 5 weeks post-ICH. The results showed that brain water content, TUNEL+, and MPO+ cell numbers were significantly reduced in the ASC-transplanted rats. ASC transplantation attenuated neurological deficits from 4 to 5 weeks post-ICH, and reduced both the brain atrophy and the glial proliferation at 6 weeks. Transplanted ASCs were found to densely populate perihematomal areas at 6 weeks, and to express endothelial markers (von Willebrand factor and endothelial barrier antigen), but not neuronal or glial markers. In summary, ASCs transplantation in the ICH model reduced both acute cerebral inflammation and chronic brain degeneration, and promoted long-term functional recovery.

Biomarkers of Lung Injury in Primary Graft Dysfunction following Lung Transplantation

Primary graft dysfunction, a form of reperfusion pulmonary edema that occurs early after lung transplantation, shares key clinical and pathological features with acute lung injury and its more severe form, the acute respiratory distress syndrome. However, in contrast to acute lung injury/acute respiratory distress syndrome, in which biomarkers in plasma, urine and lung edema fluid have prognostic and pathogenetic value, the role of biomarkers in primary graft dysfunction has been less thoroughly explored. This review summarizes human and animal studies on biomarkers in primary graft dysfunction, including cytokines and markers of acute inflammation, VEGF, endothelial markers and adhesion molecules, markers of coagulation and fibrinolysis and markers of lung epithelial injury. Similarities to the literature in acute lung injury/acute respiratory distress syndrome are highlighted where appropriate, and future directions for research on the role of biomarkers in primary graft dysfunction are suggested.

C-Reactive Protein: Interaction with the Vascular Endothelium and Possible Role in Human Atherosclerosis

C-reactive protein (CRP) is the first acute phase protein that has been described in the literature. It is phylogenetically ancient and - with serum amyloid P - belongs to proteins named as "pentraxin". After being considered a marker of acute inflammation for several decades and fruitfully used in clinical practice, CRP has been recently considered as a potential contributor to inflammatory diseases including atherosclerosis as well as a marker of cardiovascular risk. With regard to the first topic, inflammation is now believed to represent the underlying mechanism leading to the formation of human atheroma and favouring both the destabilization of vulnerable plaques and the formation of occlusive thrombi. In this regard, numerous studies indicated that modest changes in circulating CRP levels, as detected by highly sensitive methods, can be extremely useful in predicting cardiovascular and perhaps cerebrovascular diseases in apparently healthy individuals as well as in patients affected by atherosclerosis. Subjects manifesting with identical low density cholesterol and/or blood pressure levels have different rates of cardiovascular accidents on the basis of different circulating CRP concentrations. In addition, women with identical cardiovascular risk profiles developed more type 2 diabetes in the presence of higher circulating CRP levels and thereby are expected to display divergent cardiovascular prognosis. Therefore, even slight changes in circulating CRP concentrations - assuming that blood is collected appropriately and CRP is measured with correct methods - could help clinicians in defining individual cardiovascular risk. In this review, we have firstly described the current understanding of the structure of CRP, its function, and interaction with the vascular endothelial cell. Then, we have discussed how to measure circulating CRP and the more recent findings on the suggested role of circulating CRP as a novel cardiovascular risk factor.

Amiodarone has anti-inflammatory and anti-oxidative properties: An experimental study in rats with carrageenan-induced paw edema

Amiodarone is a widely used anti-arrhythmic agent. We have investigated alterations in the glutathione (GSH) level and the activities of anti-oxidative enzymes (superoxide dismutase, catalase, glutathione s-transferase and glutathione reductase) and myeloperoxidase, as marker of acute inflammation, following oral administration of amiodarone and diclofenac in rats with carrageenan-induced paw edema. In the present study, we found that 1) Amiodarone reduced the development of carrageenan-induced paw edema, to a greater degree than diclofenac; 2) Amiodarone and diclofenac alleviated increases in the activities of catalase and glutathione s-transferase enzymes resulting from edema; 3) Amiodarone and diclofenac ameliorated depressions in the GSH level and the activities of superoxide dismutase and glutathione reductase enzymes caused by carrageenan injection; and 4) All doses of amiodarone and diclofenac caused an amplification in myeloperoxidase activity resulting from induced paw edema. These results suggest that the anti-inflammatory effect of amiodarone on carrageenan-induced acute inflammation can be attributed to its ameliorating effect on the oxidative damage.

Lipocalin-2 Regulates the Inflammatory Response During Ischemia and Reperfusion of the Transplanted Heart

Ischemia and reperfusion (IR) are known to negatively affect early allograft function following solid organ transplantation. Lipocalin-2 (Lcn-2) has been described as a marker and potential positive modulator of acute inflammation during these processes. Using a heterotopic murine heart transplant model we previously found that IR resulted in a pronounced upregulation of Lcn-2 mRNA in the heart at 12 (22.7-fold increase) and 24 h (9.8-fold increase) of reperfusion. We now confirm this increase at the protein level and provide evidence for infiltrating polymorphonuclear cells as the primary source of Lcn-2 protein. Lcn-2 levels are increased 6.6-fold at 12 h, 11.4-fold at 24 h and 6.4 fold at 48 h after reperfusion. In Lcn-2(-/-) grafts the number of infiltrating granulocytes is reduced by 54% (p < 0.05) at 2 h, 79% (p < 0.01) at 12 h, 72% (p < 0.01) at 24 h and 52% (p < 0.01) at 48 h after reperfusion compared to Lcn-2(+/+) grafts, without any differences in cardiomyocyte apoptosis. These data suggest a function of Lcn-2 in the initiation of the inflammatory response. Moreover, an increase in Lcn-2 is not only restricted to the transplanted heart, but is also observed in the kidney, hinting at a possible involvement of Lcn-2 in the systemic response to IR.

Lifelong exposure to a phytoestrogen-enriched diet increases markers of acute inflammation in a model of TNBS-induced colitis in rats

Inflammatory disorders of the gastro-intestinal tract (IBD) such as Ulcerative Colitis and Crohn's Disease are very common in Europe and the US. However, their incidence in East Asia has been traditionally low. It is also known that the risk of IBD is increased in Asian immigrants that adopt the lifestyle of the US or western European countries, suggesting a strong role of environmental factors in IBD. For breast cancer it has been shown that a lifelong exposure to phytoestrogen-rich diets such as soy-containing foods consumed in East Asia decreases the risk to develop a tumor of this kind. Therefore, it might also be involved in the protection against IBD. We tested the influence of lifelong exposure to a phytoestrogen-rich diet on markers of acute inflammation in an animal model of TNBS-induced colitis. Wistar rats were already exposed in utero to diets containing high or low levels of phytoestrogens. After subsequent nursing, animals had free access to standard diets enriched or not enriched with phytoestrogens. At the age of 11 weeks, colitis was chemically induced with an enema of the hapten TNBS (20mg/kg b.wt.) following a 24h fast.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis - a two-year longitudinal MRI/MRSI study of corpus callosum

Backgrounds Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. Goal and methods To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. Results Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. Conclusion These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

Multiple risk markers for atherogenesis associated with chronic inflammation are detectable in patients with renal stones

Patients with renal stones are known to be at risk of clinical complications such as cardiovascular disease (CVD), nephropathy, and cancer. Recently, it has been realized that almost all risk markers for CVD, nephropathy, etc. are all markers associated with the sequence of reactions of chronic inflammation. It has been reported that chronic inflammation is involved not only in the pathogenesis of nephrolithiasis but also contributes to the development of clinical complications in this condition; therefore, we decided to find out whether these multiple markers are detectable in patients with renal stones so that they can be used to predict the risk of clinical complications in these patients. There were 33 patients with nephrolithiasis included in this study. We found that almost all major markers of chronic inflammation were elevated in patients with renal stones, including proinflammatory cytokine, acute inflammation markers, adhesion molecules, urinary microalbumin (uMA), myeloperoxidase (MPO), 8-hydroxydeoxyguanosine (8-OHdG), 3-nitrotyrosine (3NT), and monocyte chemoattractant protein. It appears that it is possible to assess the risk of clinical complications by monitoring these markers in patients with renal stones.