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Acute respiratory distress syndrome (ARDS) is a contemporary term incorporating the historic 'acute lung injury' and the colloquial term 'shock lung'. ARDS remains a serious and enigmatic human disease, causing significant mortality. The mechanisms involved at the alveolar cell/capillary endothelial interface have been explored but to date we lack clarity on the role of intracellular calcium ([Ca]i) fluxes across this interface. To explore the mechanisms of Ca induced inflammatory reaction in epithelial cells and pulmonary microvascular endothelial cells (HMVEC) located at the two sides of blood-air barrier, lung epithelial A549 and HMVEC cells were treated with LPS. Our results demonstrated that LPS evoked the increase of [Ca]i, TNF-α and IL-8 in both cells types. The [Ca]i increases involved intracellular but not extracellular Ca sources in A549, but both intracellular and extracellular Ca sources in HMVEC cells. The effects of LPS on both cells types were completely inhibited by the combination of LPS and CaSR-targeted siRNA. Furthermore, LPS-inhibited cell proliferations were significantly reversed by the combined treatment. Therefore, LPS induced different mechanisms of [Ca]i increase during the activation of CaSR in A549 and HMVEC cells, which translates into functional outputs related to ARDS. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-a levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to 17a -ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-a along with hippocampal kynurenine/tryptophan ratio were determined in mature ovariectomized rats treated orally either by HP at three different doses 125, 250, and 500 mg/kg/day or by 17a-ethinylestradiol 30 ìg/kg/day for 30 days. Ovariectomized rats showed significant increase in immobility time in the forced swimming test. Along with elevation in serum and hippocampal TNF-a and corticosterone levels associated with significant increase in hippocampal kynurenine/tryptophan ratio. Immobility time in the forced swimming test was decreased in rats treated by different doses of HP in a dose dependent manner and 17a-ethinylestradiol with no concomitant changes in the open field test. Only Rats treated with HP exhibited significant decrease in the elevated serum and hippocampal TNF-á and corticosterone, which couldn't explain the associated insignificant effect on hippocampaus kynurenine/ tryptophan ratio in comparison to ovariectomized untreated rats. It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-a might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-a and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophankynurenine metabolism pathway. [ABSTRACT FROM AUTHOR]

Recent studies have shown that dexmedetomidine exerts an anti-inflammatory effect by reducing serum levels of inflammatory factors, however, the up-stream mechanism is still unknown. The transcription factor NF-κB enters the nucleus and promotes the transcription of its target genes, including those encoding the pro-inflammatory cytokines IL-6 and TNF-a. In this study, we established a rat model that simulates a clinical surgical procedure to investigate the anti-inflammatory effect of perineural administration of dexmedetomidine and the underlying mechanism. Dexmedetomidine reduced the sciatic nerve levels of IL-6 and TNF-a at both the mRNA and protein level. Dexmedetomidine also inhibited the translocation of activated NF-κB to the nucleus and the binding activity of NF-κB. The anti-inflammatory effect is confirmed to be dose-dependent. Finally, pyrrolidine dithiocarbamate also reduced the levels of IL-6 and TNF-a and the activation of NF-κB. In conclusion, dexmedetomidine inhibited the nuclear translocation and binding activity of activated NF-κB, thus reducing inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Introduction: Nowadays, finding new therapeutic compounds from natural products for treatment and prevention of a variety of diseases including cardiovascular disorders is getting a great deal of attention. This approach would result in finding new drugs which are more effective and have fewer side effects than the conventional medicines. The present study was designed to investigate the anti-inflammatory effect of the methanolic extract of Marrubiumvulgare, a popular traditional medicinal herb, on isoproterenol-induced myocardial infarction (MI) in rat model. Methods: Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg/12h of the extract given orally concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for two consecutive days was used to induce MI. Then, histopathological changes and inflammatory markers were evaluated. Results: Isoproterenol injection increased inflammatory response, as shown by a significant increase in peripheral neutrophil count, myocardial myeloperoxidase (MPO) activity and serum levels of creatinine kinase-MB (CK-MB) and TNF-a (p<0.001). In the groups treated with 10, 20 and 40 mg/kg of M.vulgare extract serum CK-MB was subsided by 55.4%, 52.2% and 69%, respectively. Also treatment with the extract (40 mg/kg) significantly reduced (p<0.001) MPO activity in MI group. The levels of TNF-a was also considerably declined in the serums of MI group (p<0.001). In addition, peripheral neutrophil count, was significantly lowered by all doses of the extract (p<0.001). Interstitial fibrosis significantly was attenuated in treated groups compared with control MI group. Conclusion: The results of study demonstrate that the M. vulgare extract has strong protective effects against isoproterenol-induced myocardial infarction and it seems possible that this protection is due to its anti-inflammatory effects. [ABSTRACT FROM AUTHOR]

Two or more isoforms of several cytokines including tumor necrosis factors (tnfs) have been reported from teleost fish. Although zebrafish (Danio rerio) and medaka (Oryzias latipes) possess two tnf-α genes, their genomic location and existence are yet to be described and confirmed. Therefore, we conducted in silico identification, synteny analysis of tnf-α and tnf-n from both the fish with that of human TNF/lymphotoxin loci and their expression analysis in zebrafish. We identified two homologs of tnf-α (named as tnf-a1 and tnf-α2) and a tnf-n gene from zebrafish and medaka. Genomic location of these genes was found to be as: tnf-α1, and tnf-n and tnf-α2 genes on zebrafish chromosome 19 and 15 and medaka chromosome 11 and 16, respectively. Several features such as existence of TNF family signature, conservation of genes in TNF loci with human chromosome, phylogenetic clustering and amino acid similarity with other teleost TNFs confirmed their identity as tnf-α and tnf-n. There were a constitutive expression of all three genes in different tissues, and an increased expression of tnf- α1 and -α2 and a varied expression of tnf-n ligand in zebrafish head kidney cells induced with 20 µg mL-1 LPS in vitro. Our results suggest the presence of two tnf-α homologs on different chromosomes of zebrafish and medaka and correlate this incidence arising from the fish whole genome duplication event. [ABSTRACT FROM AUTHOR]

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Purpose: To investigate the protective effect of corynoline isolated from Corydalis bungeana Turcz on lipopolysaccharides (LPS)-induced sepsis, and determine the possible mechanism of anti-sepsis effect of the isolated corynoline. Methods: Corynoline was extracted by column chromatography. LPS (100 ng/mL) was used to induce the release of TNF-a and IL-6 in RAW 264.7 cells, and the isolated corynoline was added. ELISA method was used to determine the levels of TNF-a and IL- 6. Furthermore, sepsis in mice was established by injection of LPS (2 mg/kg, i.v.), and the levels of TNF-a and IL-6 in plasma were determined by ELISA method. For survival rate test, LPS (15 mg/kg, i.v.) and heat-killed E. coli (1.0 ×1011H CFU/kg, i.v.) were used to establish sepsis in mice model, and the mice were observed in 7 days. Results: The results indicate that corynoline significantly elevated the survival rate of septic mice induced by LPS and heat-killed E. coli, in a dose-dependent manner (p < 0.05). Corynoline decreased the release of TNF-a and IL-6 induced by LPS, in a dose-dependent manner (p < 0.05). Conclusion: Treatment with corynoline significantly inhibits the mortality of LPS-induced septic mice, and the mechanism of action is probably related to the decrease of TNF-a and IL-6 release. Thus corynoline has the potential to be developed as an effective and safe drug for treating sepsis. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age and is characterized by chronic anovulation. Insulin resistance may be a key component of the pathogenesis of this disorder. Pioglitazone is a thiazolidinedione derivative that acts by improving insulin resistance via the peroxisome proliferator-activated receptor-γ (PPAR-γ) pathway. Reportedly, pioglitazone improves the anovulation status in patients with PCOS. In the present study, we examined whether pioglitazone directly affects ovarian follicular development and steroidogenesis using in vitro mouse preantral follicle culture system. Methods: An isolated individual in vitro mouse preantral follicle culture was used to test the effects of pioglitazone on the follicle development and steroidogenesis. Tumor necrosis factor-a (TNF-a), which plays a role in insulin resistance, has been reported to inhibit the follicle stimulating hormone (FSH)-induced follicular development and steroidogenesis in an in vitro mouse preantral follicle culture system. Therefore, we examined whether pioglitazone counteracts these effects by TNF-a. We assessed the follicle diameter and follicle survival and antral-like cavity formation rates, the 17ß-estradiol (E2) levels in the culture medium, and the ovulation rate using the in vitro preantral follicle culture. Results: Pioglitazone treatment counteracted the inhibition of TNF-a in FSH-induced follicle development in a dose-dependent manner. Pioglitazone, at a concentration of 5 µM, which was the minimum effective concentration, significantly counteracted the inhibition of TNF-a in FSH-induced follicle survival (29 versus 56%, P < 0.05), antral-like cavity formation (29 versus 48%, P < 0.05), E2 concentration in the culture medium (mean ± SEM = 21 ± 1 versus mean ± SEM = 27 ± 1 pg/mL, P < 0.05), and human chorionic gonadotropin-induced ovulation rate (9 versus 28%, P < 0.05). Conclusions: Pioglitazone counteracted the inhibition by TNF-a on FSH-induced follicle development and steroidogenesis in the in vitro mouse preantral follicle culture. The results suggest that pioglitazone may directly affect the follicular development and steroidogenesis. [ABSTRACT FROM AUTHOR]

We investigated whether d-opioid receptor (DOR)-induced neuroprotection involves the brain-derived neurotrophic factor (BDNF) pathway. We studied the effect of DOR activation on the expression of BDNF and other proteins in the cortex of C57BL/6 mice exposed to hypoxia (10% of oxygen) for 1-10 days. The results showed that: (1) 1-day hypoxia had no appreciable effect on BDNF expression, while 3- and 10-day hypoxia progressively decreased BDNF expression, resulting in 37.3% reduction (p < 0.05) after 10-day exposure; (2) DOR activation with UFP-512 (1 mg/kg, i.p., daily) partially reversed the hypoxia-induced reduction of BDNF expression in the 3- or 10-day exposed cortex; (3) DOR activation partially reversed the hypoxia-induced reduction in functional TrkB (140-kDa) and attenuated hypoxia-induced increase in truncated TrkB (90-kDa) in the 3- or 10-day hypoxic cortex; and (4) prolonged hypoxia (10 days) significantly increased TNF-a level and decreased CD11b expression in the cortex, which was completely reversed following DOR activation; and (5) there was no significant change in pCREB and pATF-1 levels in the hypoxic cortex. We conclude that prolonged hypoxia down-regulates BDNF-TrkB signaling leading to an increase in TNF-a in the cortex, while DOR activation up-regulates BDNF-TrkB signaling thereby decreasing TNF-a levels in the hypoxic cortex. [ABSTRACT FROM AUTHOR]

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor a (TNF-a)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 µM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 µM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 µM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 µM) and 6 (IC50 = 79.05 ± 2.05 µM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 µM) and 4 (IC50 = 16.73 ± 0.25 µM) moderately inhibited the production of TNF-a and IL-6, respectively. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the antioxidant and anti-neuroinflammatory potentials of Olea europaea Linn. fruit pulp (OFP-EA) extract in LPS-stimulated BV-2 microglial cells. Methods: Cell viabilities were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay. Antioxidant properties were evaluated using 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity. Lipopolysaccharide (LPS) was used to stimulate BV-2 microglia. Nitric oxide (NO) production was measured using Griess assay. Inducible NO synthase (iNOS) expression and tumor necrosis factor-alpha (TNF-a) production were measured using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results: OFP-EA extract significantly (p<0.001 at 20-200 µg/ml, respectively) scavenged the free radicals in a dose-dependent fashion. The increased levels of No stimulated by LPS (34±2.41) were also inhibited by OFP-EA extract significantly and concentration dependently (27±2.32, 21±2.54, 17±1.92 and 11±1.94 at 10, 20, 40 and 80 µg/ml, respectively). Further, OFP-EA suppressed the elevated levels iNOS expression and TNF-a production (p<0.001 at 20, 40 and 80 µg/ml) in LPSstimulated BV-2 cells. Conclusion: Results indicate that OFP-EA extract exhibited strong antioxidant properties and inhibited the excessive production of pro-inflammatory mediators such as NO, iNOS and TNF-a in LPSstimulated BV-2 cells. The antioxidant activity exhibited by OFP-EA extract might play a critical role in ameliorating the inflammatory processes in LPS-stimulated BV-2 microglial cells. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the role of tumor necrosis factor (TNF)-α and the neuronal nitric oxide synthase enzyme in dysregulation of indoleamine 2,3-dioxygenase (IDO) enzyme, and hence serotonin availability in chronic mild stress (CMS), an animal model of depression. Methods: Rats were divided into five groups: two control and CMS-exposed for 6 weeks, and another three groups exposed to CMS and administered pentoxifylline 50 mg/kg/day intraperitoneally, 7-nitroindazole 40 mg/kg/day subcutaneously, or imipramine 20 mg/kg/day intraperitoneally for the previous 3 CMS weeks. Rats were assessed for neurochemical and immunohistochemical abnormalities. Results: Pentoxifylline-, 7-nitroindazole-, and imipramine-treated rats showed amelioration of CMS-induced behavioral deficits that was accompanied by significant reduction in kynurenine/serotonin molar ratio and nitrates/nitrites in frontal cortex and hippocampus. In the pentoxifylline and 7-nitroindazole groups, serum TNF-α was reduced relative to the CMS group (18.54 ± 0.85 and 19.16 ± 1.54 vs 26.20 ± 1.83 pg/mL, respectively; P , 0.05). Exposure to CMS increased TNF-α and IDO immunohistochemical staining scores in both hippocampus and midbrain raphe nuclei. 7-Nitroindazole and pentoxifylline significantly (P < 0.05) reduced TNF-α immunostaining in hippocampus and raphe nuclei, with significant (P < 0.01) reduction of IDO immunostaining in raphe nuclei. Likewise, imipramine reduced TNF-α immunostaining (P < 0.05) in hippocampus. Conclusion: Neuronal nitric oxide synthase and TNF-α may play a concerted role in modulating IDO enzyme activity in CMS-exposed rats and provide additional evidence for possible alternative approaches to switch the neurobiological processes in depression. [ABSTRACT FROM AUTHOR]

Alcohol intoxication can exacerbate hemodynamic instability following hemorrhagic shock. Impairment of hormonal, neurohumoral, and immune responses can contribute to such instability; however, the relationship between blood alcohol levels and the progression of hemorrhagic shock accompanied with these responses has not been clearly demonstrated. Herein, we examined this relationship in rats treated with various dose of alcohol. After oral administration of alcohol and then hemorrhage, the recovery of mean blood pressure (MBP); increase in plasma level of norepinephrine, epinephrine, and vasopressin; and survival interval decreased in a dose-dependent manner as the blood alcohol level increased. There were no significant differences in the production of proinflammatory cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-1ß among the groups. The present results demonstrated alcohol aggravates hemorrhagic shock in a dose-dependent manner not by alerting the immune response, but by suppressing hormonal and neurohumoral responses, thereby inhibiting hemodynamic autoregulation and shortening the survival interval. [ABSTRACT FROM AUTHOR]

Sterile bone inflammation is the hallmark of autoinflammatory bone disorders, including chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO). Autoinflammatory osteopathies are the result of a dysregulated innate immune system, resulting in immune cell infiltration of the bone and subsequent osteoclast differentiation and activation. Interestingly, autoinflammatory bone disorders are associated with inflammation of the skin and/or the intestine. In several monogenic autoinflammatory bone disorders mutations in disease-causing genes have been reported. However, regardless of recent developments, the molecular pathogenesis of CNO/CRMO remains unclear. Here, we discuss the clinical presentation and molecular pathophysiology of human autoinflammatory osteopathies and animal models with special focus on CNO/CRMO. Treatment options in monogenic autoinflammatory bone disorders and CRMO will be illustrated. [ABSTRACT FROM AUTHOR]

Abstract: Recent findings suggest that disgust can activate particular aspects of the immune system. In this study we examine whether disgust can also elevate core body temperature (BT), a further feature of an immune response to disease. In addition, we also examined whether food based disgust – a core eliciting stimulus – may be a more potent immune stimulus than non-food based disgust. Healthy males were randomly assigned to view one of four sets of images – food disgust, non-food disgust, food control and negative emotion control. Measures of BT, salivary immune and related markers, and self-report data, were collected before, and at two time points after image viewing. Disgust elevated BT relative to the negative emotion control condition, as did food images. Different mechanisms appeared to account for these effects on BT, with higher initial levels of Tumor Necrosis Factor alpha (TNF-a) and disgust, predictive of BT increases in the disgust conditions. Disgust also increased TNF-a, and albumin levels, relative to the control conditions. Type of disgust exerted little effect. These findings further support the idea that disgust impacts upon immune function, and that disgust serves primarily a disease avoidance function. [Copyright &y& Elsevier]

Endothelial dysfunction has an important role in genesis of atherosclerosis and is depicted by a series of inflammatory and endothelial biomarkers. Shear stress arising from repeated episodes of increased blood flow with physical activity (PA) is a possible mechanism that improves vascular endothelial function. Our purpose was to examine whether inflammatory markers mediate the association between PA and endothelial function. Subjects were young, healthy men recruited according to recreational PA habits: high-active (n=21) vs. sedentary (n=17). Active subjects reported >45 min/day of moderate-vigorous physical activities, >4 days/week over 6 months, while sedentary subjects reported no recreational physical activity. Fasting serum samples were analyzed for C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Endothelial function was determined using flow-mediated dilation of the brachial artery induced by post ischemic reactive hyperemia. Hyperemia response was greater in the high-active than in sedentary men (30.2±8.2 vs. 24.3±5.2 mL/min/100mL; P<0.001). There were no differences between the groups with respect to CRP, TNF-α, or IL-6. Concentrations of these inflammatory biomarkers were unrelated to reactive hyperemia differences attributable to PA. Improved hyperemic response seen in young physically active subjects may be influenced by factors beyond the inflammatory factors, e.g., enhanced nitric oxide production. Physical activity was associated with an increased vascular function in young adults, although a diminished inflammatory state was no revealed. Additional research is needed to clarify the role of PA on cytokine indicators of inflammation and how this relates to endothelial function. [ABSTRACT FROM AUTHOR]

Periodontal disease (PD) is characterized as an inflammatory process that compromises the support and protection of the periodontium. Patients with Down's syndrome (DS) are prone to develop PD. Neutrophils (NE) are the first line of defense against infection and their absence sets the stage for disease. Aim: To compare the activity and function of NE in the peripheral blood from DS patients with and without PD, assisted at the Center for Dental Assistance to Patients with Special Needs affiliated with the School of Dentistry of Araçatuba, Brazil. Methods: Purified NE were collected from peripheral blood of 22 DS patients. NE were used to detect the 5-lypoxigenase (5-LO) expression by RT-PCR. Plasma from peripheral blood was collected to measure tumor necrosis factor-a (TNF-α) and interleukin-8 (IL-8) by ELISA and nitrite (NO3) using a Griess assay. Results: Data analysis demonstrated that DS patients with PD present high levels of TNF-a and IL-8 when compared with DS patients without PD. However, there was no statistically significant difference in the levels of NO3 production between the groups. The levels of the inflammatory mediator 5-LO expression increased in DS patients with PD. Conclusions: According with these results, it was concluded that TNF-α and IL-8 are produced by DS patients with PD. Furthermore, DS patients with PD presented high levels of 5-LO expression, suggesting the presence of leukotriene B4 (LTB4) in PD, thus demonstrating that the changes in NE function due to the elevation of inflammatory mediators contribute to PD. [ABSTRACT FROM AUTHOR]

Abstract: Sepsis is a major cause of death in veterinary medicine, although a better prognosis can result from an early diagnosis. To speed the diagnosis, the biomarkers TNF-α and IL-6 can provide valuable information regarding systemic inflammatory response. The purpose of this study was to investigate the changes in cytokine levels in an experimental model of sepsis using ELISA and real-time PCR. Ten adult Beagles were studied; seven received an IV bolus of high dose lipopolysaccharide solution (1mg/kg) to induce sepsis. The remaining three beagles were the control group. Blood samples were collected before and 1, 3, 6, 12, 24 and 48h after administering LPS. Serum IL-6 level peaked at 3h (1.89±0.10ng/ml) and serum TNF-α peaked at 1h (1.11±0.01ng/ml). The expression of IL-6 mRNA in peripheral blood mononuclear cells (PBMC) increased 62-fold compared to the control group at 1h; TNF-α mRNA increased by 4.5-fold at 1h. The expressions of IL-6 and TNF-α mRNA in PBMCs changed more rapidly than serum IL-6 and TNF-α concentrations. In addition, TNF-α mRNA levels in PBMCs remained elevated longer than serum TNF-α. Our study establishes the basis for future work aimed at a better understanding of the systemic inflammatory response to infection and sepsis in canine patients. [Copyright &y& Elsevier]

The immunological and clinical parameters that are associated with asthma remission are poorly understood. The cytokine and local mediator changes associated with the resolution of asthma symptoms were examined in three groups of subjects 12-18 years of age (n = 15 in each group): (a) continuing asthma group (CA) who had persistent symptoms since early childhood, (b) an age, sex and atopic status-matched group who had persistent symptoms in early childhood but in whom these had resolved (RA), and (c) a non-atopic, non-asthmatic control group. Clinical parameters, sputum cell counts, peripheral blood mononuclear cell (PBMC) cytokine production and activation marker expression were determined. All of the CA had methacholine airway hyperresponsiveness compared with only half of the RA subjects. The CA showed elevated numbers of eosinophils and increased ECP and IL-5 in sputum, which were not observed in the RA. PBMC cytokine studies revealed increased production of the type 1 cytokines IL-12, IFN-? and TNF-a in the CA group compared with the RA group, under a range of activation conditions, however, the production of IL-4 and IL-5 were unchanged. These findings suggest that decreased type 1 cytokine expression as well as decreased eosinophilic inflammation is associated with the resolution of asthma symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Progressive functional impairments develop with chronic repetitive tasks possibly involving inflammatory mediators. Aim of this study was to analyze systemic inflammatory changes in relation to the possible occurrence of pain and/or disability in video terminal operators (VTOs) undergoing upper-extremity repetitive stress due to chronic overuse. Methods: Pain assessments, classification, and grade of impairment relied on self-report questionnaires administered to 21 VTOs and to 21 matched controls. The inflammatory status of the enrolled subjects was analyzed by determination of serum high sensitive C-reactive protein (hs-CRP) as well as systemic levels or monocyte expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Results: Serum levels of both cytokines were increased in VTOs compared to controls ( P = 0.005 for TNF-α and P = 0.004 for IL-6). TNF-α levels correlated to IL-6 ( P = 0.019), which, in turn, was associated to increased hs-CRP ( P = 0.012). DASH score allowed to categorize VTOs according to disability. VTOs with mild (DASH = 22) or moderate (DASH = 46) disability ( n = 10) had higher serum hs-CRP ( P = 0.001) and IL-6 ( P = 0.035) levels than VTOs without disabilities (DASH < 17) ( n = 11). Monocyte stimulatory TNF-α expression was increased in individuals with mild/moderate disability. Monocyte expression of TNF-α was independently associated to that of IL-6, which, in turn, was associated to increased systemic hs-CRP levels together with mild/moderate functional impairment and weekly commitment to the display screen. Conclusions: The results here reported indicate the occurrence of a low-grade inflammatory condition in VTOs with mild/moderate disability, which might allow the early recognition of arising musculoskeletal disorders induced by repetitive stress. [ABSTRACT FROM AUTHOR]

Aim. To study the association of the polymorphic variants of ACE (I/D), AT2R1 (A1166C), TNF-á (G308A), MTHFR (C677T) genes and their combinations with the risk of perinatal pathology and gestation reduction. Methods. The polymorphic variants of genes were analyzed by PCR and RFLP in 235 newborns with severe perinatal pathology and 110 clinically healthy term newborns. Results. An increased risk of severe perinatal pathology was associated with such genotypes: DD and ID (ACE), 1166AC, 1166CC (AT2R1), 677CT (MTHFR), 308AA and 308AG (TNF-a), this risk for homozygotes is almost 2-fold higher than for heterozygotes. Reduction of terms of gestation is associated with the genotype 677TT (MTHFR), and resistance to diseases in the perinatal period – with the genotype II (ACE) and 1166AA (AT2R1), 677CC (MTHFR) and the 308GG (TNFa), particularly when com- bined. Conclusions. The identified associations evidence the role of polymorphic variants of ACE, AT2R1, TNF-a, MTHFR genes in the development of severe perinatal pathology and can be used for its early prediction with subsequent correction of treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The present study examined impacts of dyslipidemic high-fat diet on the bone antioxidant system and bone metabolism in growing mice. Furthermore, the relationship was studied between them. Methods: Male C57BL/6 mice (4 wk old) were fed with normal diet, high-fat diet (HFD), or HFD supplemented with 0.1% antioxidant lipoic acid (LA). After 13-wk feeding, the markers of plasma lipids status, bone metabolism in plasma and in urine, and femora oxidative stress were measured. To provide molecular evidence for abnormal bone metabolism affected by HFD, bone cell-specific mRNA levels were tested by real-time quantitative polymerase chain reaction. Moreover, insulin-like growth factor I and tumor necrosis factor-alpha in plasma and their mRNA levels in femur were measured. Results: The feeding dyslipidemic HFD induced both inhibitory bone formation reactions and enhancement of bone resorption reactions, accompanied by impaired bone antioxidant system, low levels of insulin-like growth factor I in plasma and in bone, and high levels of tumor necrosis factor-alpha in plasma but not in bone. In contrast, these alternatives were prevented completely or partially in mice fed LA supplement. Further, plasma propeptide of І collagen C-propeptide as a marker of bone formation was positively correlated with both total antioxidant capacity (r =0.683, P <0.001) and reduced glutathione/oxidized glutathione ratio (r =0.565, P <0.003) of bone. Cross-linked N-telopeptides of bone type І collagen as a marker of bone resorption was negatively correlated with both total antioxidant capacity (r =−0.753, P <0.001) and glutathione/oxidized glutathione ratio (r =−0.786, P <0.001). Conclusion: Dyslipidemia induces impaired bone antioxidant system. Oxidative stress could be an important mediator of hyperlipidemia-induced bone loss. [Copyright &y& Elsevier]

The study was designed to evaluate the effect of the severity of Theileria lestoquardi ( hirci) infection on tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and sialic acid concentration in blood sera in a naturally infected sheep. Infected animals (diseased group) comprised 50 Iranian fat-tailed sheep, about 1–2 years old, naturally infected with Theileria lestoquardi ( hirci), were divided into three subgroups according to parasitemia rates (<2%, 2–4%, and >4%). As a control group, ten noninfected sheep were also selected. Hematological parameters and levels of TNF-α, IFN-γ, and sialic acid (TSA, LBSA, and PBSA) concentrations were measured in both groups. The results showed significant increases in the level of TNF-α, IFN-γ, and sialic acid concentrations in infected sheep compared with noninfected ones ( P < 0.05). The increased level of TNF-α and IFN-γ in infected sheep may indicate the role of these cytokines to inhibit the growth and development of the parasite in infected host cells. Also, it is speculated that preventing the establishment of parasites by inhibiting the differentiation of trophozoites to schizonts is another aspect of the enhanced activity of these substances. In addition, increased levels of sialic acid concentration during parasitemia presumably stimulate the host immune response and influence the parasite–host cell adhesion. Clearly, further molecular and biochemical investigations are needed to elucidate the exact mechanisms involved in immunopathogenesis of malignant ovine theileriosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate genetic effects on the pathogenesis of chronic obstructive pulmonary disease (COPD). The study was conducted as a prospective case–control study in a medical center in southern Taiwan. The patient group consisted of 145 male patients with smoking-related COPD and a control group of 139 resistant smokers from July 2004 to September 2009. We compared allele and genotype frequencies of three tag single nucleotide polymorphisms (SNP) of the TNF-α gene promoter region at −308, −863, and −1031 in all subjects. We also analyzed the influence of each genetic variant on pulmonary function parameters, body mass index (BMI), serum TNF-α levels, and outcomes among heavy smokers with or without COPD. COPD patients had a significantly lower A allele frequency (9.7 vs. 15.1%, OR = 0.6, p = 0.048, false discovery rate q = 0.144) and a significantly lower A carrier genotype frequency (19.3 vs. 30.2%, OR = 0.52, p = 0.042, q = 0.135) than resistant smokers. The −863 CA genotype was associated with a better FEV1/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m2, p = 0.048). In addition, COPD patients with the −1031 C carrier genotype had higher serum TNF-α levels (20.9 vs. 16.2 pg/ml, p = 0.01). BMI (hazard ratio = 0.84, 95% CI = 0.74–0.96, p = 0.008) was the only independent predictor for mortality. The TNF-α −863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers. [ABSTRACT FROM AUTHOR]

Exercise has the potential to impact disease by altering circulating anabolic and catabolic factors. It was the goal of this study to determine how different regimens of low-intensity and moderate-intensity exercise affected circulating levels of these anabolic and catabolic factors in HIV-infected men. Exercise-naive, HIV-infected men, medically cleared for study participation, were randomized into one of the following groups: a moderate-intensity group (MOD, who completed 30 min of moderate-intensity aerobic training followed by 30 min of moderate-intensity resistance training; a low-intensity group (LOW), who completed 60 min of treadmill walking; or a control group (CON), who attended the clinic but participated in no activity. Blood and saliva samples were collected at selected time points before, during, and after each of the 3 required sessions. Compared with baseline, the MOD group (n = 14) had a 135% increase in growth hormone (GH) (p < 0.05) and a 34% decrease in cortisol (CORT) (p < 0.05) at the post time point, a 31% increase in interleukin-6 (IL-6) (p < 0.05) at 30-min post exercise, and a 23% increase in IL-6 (p < 0.05) and a 13% decrease in soluble tumor necrosis factor receptor 2 (sTNFrII) (p < 0.05) at 60-min post exercise. The LOW (n = 11) group had a 3.5% decrease in sTNFrII (<0.05) at 30-min post exercise compared with baseline and a 49% decrease (p < 0.05) in GH at 60-min post exercise. The CON group (n = 13) had a decrease in GH at 30-min (62%, p < 0.05) and 60-min (61%, p < 0.05) post exercise compared with baseline. The increase in GH from baseline to post was greater in the MOD group (p < 0.05) and the decrease in CORT from pre to post was greater in the MOD group (p < 0.05) than in the other groups. These data suggest that individual sessions of both low-intensity and moderate-intensity exercise can alter circulating anabolic and catabolic factors in HIV-infected men. The changes in the MOD group present potential mechanisms for the increases in lean tissue mass seen with resistance exercise training. [ABSTRACT FROM AUTHOR]

Introduction: Alterations involving antioxidant respon e and immunological competence are consequences of malnutrition. The aim of this study is to assess the effect of nutritional recovery on serum concentrations of nitric oxide (NO). malonaldehyde (MDA) and TN Fa in the severely malnourished child. Methods: 47 children were prospectively studied (2 months to 8 years old): 27 children with mixed type severe malnutrition and 20 controls who attended the Department of Education and Nutritional Recovery at the Chiquinquin\ Hospital in Maracaibo-Venezuela. NO and the MDA were detennined by Diazotization trial and derivatives of the barbituric acid respectively; TN F-a was assessed by the ELISA technique. Results: 0 and MDA concentrations showed no significant difference with controls, although there was a significant decrease with respect to pre-treatment values (p :5 0,0001 for NO and p :5 0.00 1 for MDA Values for TNF-a were significantly different from controls and pre-treatment values (p< 0,000 I ). Conclusions: utritional recovery therapy affects the decrease in serum concentrations of 0, M DA and TNF-a, probably due to the supplementation of vitamins and tmcronutrients during this treatment [ABSTRACT FROM AUTHOR]

Endotoxemia caused by lipopolysaccharide (LPS) produced an inflammatory condition contributing to multiple organ failure. This study was carried out to investigate the effects of thymoquinone (TQ), the main constituent of Nigella sativa seeds, against LPS-induced hepatotoxicity. The obtained data revealed that LPS markedly depleted liver reduced glutathione (GSH) and significantly increased the level of malondialdehyde (MDA) and the activity of caspase-3 enzyme in the liver. Serum tumour necrosis factor-alpha (TNF-α) and bilirubin levels and the activities of alkaline phosphatase (ALP) and gamma-glutamyl transferase (γ-GT) enzymes were markedly increased in LPS-treated rats. TQ supplementation resulted in normalization of liver GSH and decreases in the levels of MDA and caspase-3 activity in the liver with reduction of serum TNF-α, serum total bilirubin and the actvities of ALP and γ-GTenzymes. Histopathological examination revealed that TQ administration improved LPS-induced pathological abnormalities in liver tissues. The present study conclude that TQ reduced acute endoxemia-induced liver dysfunction at least in part by its anti-inflammatory, antiapoptotic and antioxidant activities. [ABSTRACT FROM AUTHOR]

Little is known about the immunologic maturation in the early stages of life. The aim of this study was to investigate maturation of immune system from birth to 1 yr of age and to compare immune functions between mothers and their children. Also the effect of atopy to the immune responses of children was examined. Cord blood samples (n = 228) and peripheral blood samples of children (n = 200) and their mothers (n = 208) 1 yr after birth were collected. Whole blood samples were stimulated for 24 and 48 h with Staphylococcal enterotoxin B (SEB), lipopolysaccharide (LPS) and the combination of phorbol ester and ionomycin (P/I). Production of TNF-α, IFN-γ, IL-5, IL-8 and IL-10 was determined using ELISA. Significant mother-to-child correlation was detected in cytokine-producing capacity at the age of 1 yr. TNF-α (P/I, SEB and LPS stimulation), IFN-γ (P/I and SEB), IL-5 (P/I and SEB) and IL-10 (P/I, SEB and LPS) producing capacity increased from birth to 1 yr of age. In general, stimulated cytokine responses were higher in mothers’ than in children’s blood samples, except in the case of P/I and LPS-stimulated IL-8, which were highest at birth. Maternal inhalation atopy was associated with increased cord blood IL-5 (24 and 48 h) and IL-10 (48 h) production following P/I stimulation. Also children of food atopic mothers expressed elevated cord blood IL-10 (48 h, P/I) responses and decreased IFN-γ/IL-5 ratio (24 h, P/I). In addition, the production of IFN-γ (24 and 48 h, P/I) and the IFN-γ/IL-5 ratio (24 h and 48 h, P/I) at the age of 1 yr was lower among children with food atopic mothers. In conclusion, our results suggest that both adaptive and innate immune responses increase from birth to 1 yr of age, but are still weak in comparison to adult responses. Cytokine responses of children begin to correlate with those of their mothers during the first year of life. Although only few associations were observed between atopy and cytokine-producing capacity, our results suggest that children of atopic mothers express Th2-polarized cytokine pattern. [ABSTRACT FROM AUTHOR]

The activation of macrophages by microorganisms plays an important role in host defense and immunopathology. Loranthi ramulus (LR) is commonly used as a traditional drug and health food in Korea. Here, we investigated the regulatory effects of LR on macrophage-mediated immune responses. Treatment of macrophages with LR resulted in the enhanced cell-surface expression of CD80, CD86 and major histocompatibility complex (MHC) class II, as well as the enhanced production of nitric oxide (NO) and tumor necrosis factor (TNF)-α, and also iNOS and TNF-α mRNA expression. These alterations of LR-treated cells were associated with the activation of NF-κB and mitogen-activated protein kinases (MAPKs). LR increased the phosphorylation of MAPKs (JNK, ERK1/2, p38 MAPK) and the activation of NF-κB in Raw 264.7 cells. These results suggest that LR has increased NO and TNF-α production through phosphorylation of all three MAPKs following IκBα degradation and NF-κB activation. In conclusion, our results demonstrate that LR can effectively promote the activation of macrophages, suggesting that LR may possess the potential to regulate immune responses. [ABSTRACT FROM AUTHOR]

According to current scientific knowledge, excess tumour necrosis factor-α (TNF-α) and low insulin-like growth factor-I (IGF-I) are pathogenic-risk factors that constitute therapeutic targets for Alzheimer's disease (AD). Changes in serum TNF-α, total and dissociable IGF-I levels were determined by ELISA in 207 AD patients completing a 24-wk, double-blind, placebo-controlled trial to evaluate the effects of the neurotrophic compound Cerebrolysin (Cere: 10, 30 or 60 ml for 12 wk). At week 24, Cere reduced TNF-α and enhanced dissociable IGF-I with respect to placebo in a dose-related manner. TNF-α decreased in parallel with behavioural disturbances. Increases in total IGF-I were induced by 60 ml Cere and correlated significantly with improvements in global function, disabilities and behaviour in late-onset AD patients. These results showing for the first time the opposite influence of one anti-dementia treatment on serum TNF-α and IGF-I suggest the contribution of both factors to the clinical effects of Cere, and probably other drugs. [ABSTRACT FROM AUTHOR]

Abstract: Background: Immune activation has been shown to be involved in the pathophysiology of anxiety states and major depression and pregnancy is associated with a characteristic immune activation to sustain the fetus. Despite the possibility of a relation between immune parameters and postpartum mood disturbance, few studies have explored this association. Further, no study to-date has examined CSF. Methods: Fifty-six Greek parturients were recruited and a detailed medical and obstetric history was recorded. All of them completed the Postpartum Blues Questionnaire (on admission and on days 1–4 postpartum) and the Edinburgh Postnatal Depression Scale (at first and sixth week postpartum). At delivery, a blood sample and a CSF sample while puncturing for epidural analgesia were taken from 33 participants; blood samples only were obtained from the rest of the 23 parturients. TNF-a and IL-6 were quantified with an ELISA assay. Results: A multiple regression analysis of psychometric scores depending on cytokine levels revealed that cytokine levels were positively associated with depressive mood during the first four days postpartum (p =0.035 for CSF IL-6, p =0.025 for CSF TnF-a, p =0.023 for serum TnF-a) and also at sixth week postpartum (p =0.012 for CSF IL-6, p =0.072 for CSF TnF-a). Pregnancy duration had an adverse association to psychometric scores. Conclusions: It is suggested that immune mechanisms may play a role in the etiopathology of postpartum depressive mood shifts. The role of a “rebound” reaction of the maternal immune system postnatal should be further investigated. [Copyright &y& Elsevier]

Résumé: Objectifs: Déterminer les variations d’expression des ARNm de la leptine dans les cellules mononuclées du sang (PBMC) de patients atteints de spondylarthrite ankylosante (SA) ainsi que la production de cytokines pro-inflammatoires. Méthodes: Vingt patients présentant une SA active ont été inclus, et l’index d’activité BASDAI et les taux de protéines de la phase aiguë ont été mesurés. L’expression des ARNm et de protéine de la leptine, de l’interleukine (IL)-6, du facteur nécrosant des tumeurs (TNF)-α étaient déterminée dans les PBMC de patients atteints de SA par RT-PCR semi-quantitative et par Elisa. Les résultats de dosage ainsi que les paramètres biologiques d’activité de la maladie ont été comparés à ceux de 20 sujets sains. Les modifications d’expression des cytokines pro-inflammatoires des PBMC en réponse à la leptine ont aussi été déterminées. Résultats: L’expression des ARNm de la leptine, de l’IL-6 et du TNF-α des patients atteints de SA était significativement plus élevée que chez les témoins. Il existait aussi des différences significatives dans les taux de cytokines et de leptine des surnageants de culture. De plus, les taux de leptine étaient corrélés à ceux de l’IL-6 (r =0,871, p <0,001) et des scores BASDAI (r =0,691, p <0,001) chez les patients atteints de SA. La stimulation des PBMC par de la leptine exogène induisait une augmentation significative et dose-dépendante de la production d’IL-6 et de TNF-α par les PBMC de patients atteints de SA. Ces augmentations étaient plus prononcées que chez les témoins. Conclusion: Nos résultats montrent que, chez les patients atteints de SA, la production de leptine augmente et que cette molécule induit une production significativement accrue de cytokines pro-inflammatoires par les PBMC. L’ensemble de ces données suggère un rôle pro-inflammatoire de la leptine dans la SA. [Copyright &y& Elsevier]

Background:Cell death-inducing DFFA (DNA fragmentation factor-α)-like effector A (CIDEA) is a protein that regulates lipolysis in human adipocytes through cross-talk involving tumor necrosis factor-α (TNF-α). TNF-α downregulates CIDEA mRNA although it is unclear whether this is mediated through transcriptional or post-transcriptional mechanisms. CIDEA has important metabolic effects in human fat cells and genetic variations in the human CIDEA gene have been correlated to the development of obesity. However, little is known about the factors regulating CIDEA expression in human adipocytes. We set out to describe the transcriptional control of human CIDEA.Methods:A 1.1-kb genomic fragment upstream of the transcriptional start site (TSS) of human CIDEA was cloned and deletion fragments were generated. Transcriptional activity of the promoter was analyzed by luciferase reporter assays in in vitro-differentiated human adipocytes. The effect of TNF-α was assessed in human adipocytes and murine 3T3-L1 cells transfected with deletion fragments of the CIDEA promoter. Protein–DNA interactions were analyzed by electrophoretic mobility shift assays (EMSA).Results:Basal transcriptional activity was found in a 97-bp region upstream of the TSS. We studied the effect of three common haplotypes in the promoter region but found no significant difference in transcriptional activity among them. Incubation of in vitro-differentiated human adipocytes as well as 3T3-L1 cells with TNF-α reduced the transcriptional activity of the human CIDEA promoter, demonstrating a direct effect on CIDEA transcription. EMSAs and mutational analysis indicated that this was mediated by a nuclear factor-κB (NF-κB) site at position −163/−151.Conclusion:We demonstrate that basal transcription of the human CIDEA gene is confined to the 97 first bases upstream of TSS and that TNF-α negatively regulates transcription of this gene, which at least in part involves NF-κB activation.International Journal of Obesity (2008) 32, 1380–1387; doi:10.1038/ijo.2008.101; published online 8 July 2008 [ABSTRACT FROM AUTHOR]

Abstract: The present study was designed to investigate whether administration of CoPPIX, an HO-1 inducer, could significantly inhibit TNF-α and Hmgb1 expression and thus attenuate the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Acute lung injury was induced successfully by intratracheal administration of LPS (0.5 mg/kg) in male BALB/c mice. CoPPIX or ZnPPIX (an HO-1 inhibitor) was administered to mice 24 h prior to LPS exposure. It was found that CoPPIX (5, 10 mg/kg, i.p.) caused a significant reduction in the total cells and neutrophils in BALF, a significant reduction in the W/D ratio and EBA leakage at 24 h after LPS challenge. Furthermore, the histopathologic findings indicated that alveolitis with leukocyte infiltration in the alveolar space was less severe in the CoPPIX-treated mice than in the mice treated with LPS alone. In addition, CoPPIX was also believed to have down-regulated the expression of LPS-induced proinflammatory cytokines, including early proinflammatory cytokine TNF-a, and late proinflammatory cytokine Hmgb1. In contrast, no obvious difference was observed between the ZnPPIX group and the LPS group. These findings demonstrate the significant protection of CoPPIX against LPS-induced ALI, and the effect mechanism of CoPPIX was associated with decreasing the expression of TNF-a and Hmgb1. [Copyright &y& Elsevier]

To investigate the histological changes of synovium in cases of effect attenuation occurring after the use of infliximab in the treatment of rheumatoid arthritis (RA), we histologically assessed synovial tissue from ten methotrexate-treated RA patients and 12 infliximab-treated RA patients after arthroscopic synovectomy. The synovium was observed using hematoxylin and eosin (H&E) stain and analyzed immunohistochemically for expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell transmembrane protein, cluster of differentiation 20 (CD20), nuclear factor kappa B (NFkB), bromodeoxyuridine (BrdU), and vascular endothelial growth factor (VEGF). H&E staining showed significant vascular proliferation in the synovium of the RA patients in the infliximab group ( p < 0.05). Immunohistochemical examinations showed that TNF-α was completely blocked in patients with effect attenuation who received infliximab ( p < 0.05). IL-6 was more strongly expressed in the interstitial cells of synovium of patients who received infliximab than in the cells of patients in the control group ( p < 0.05). MMP-3 was expressed on the surface of synovium, and CD20 and BrdU were strongly expressed in the infliximab group compared with the control group ( p < 0.05). NFkB was expressed in both groups. VEGF was decreased in the infliximab group compared with control. These findings indicate that the expression pattern of immunohistochemical findings in synovium was changed in effect attenuation cases among RA patients treated with infliximab. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies suggest that intermittent and prolonged normobaric hyperoxia (HO) results in brain ischemic tolerance (BIT), reducing ischemic brain injury. We have attempted to determine the time course of HO-induced BIT, and to explore the putative roles of tumor necrosis factor-α (TNF-α) converting enzyme (TACE), TNF-α, and nuclear factor-κB (NF-κB) activation in mediating this effect. Two core experimental protocols were applied to rats (experiments 1 [E1] and 2 [E2] respectively). E1 rodents comprised six subgroups, breathing room air (RA; O2=21%), or 95% oxygen (HO) for 4, 8, 16 h (4RA, 8RA, 16RA and 4HO, 8HO, 16HO respectively). E2 rodents were divided into subgroups, exposed to 95% inspired HO for 4 h/day for six consecutive days (intermittent hyperoxia, InHO) or for 24 continuous hours (prolonged hyperoxia, PrHO). Each of these had a control group exposed to 21% oxygen in the same chamber. Twenty-four hours after pretreatment, each group was randomly divided to receive 60 min right middle cerebral artery occlusion (MCAO-operated), sham-operation (without MCAO), or no operation (intact). After 24 h reperfusion, neurologic deficit score (NDS), brain water content, Evans Blue extravasation (as a marker of blood–brain barrier permeability), TACE expression, serum TNF-α, and phosphor- κBα levels were assessed in all animals, and infarct volume in the MCAO-operated subgroups. E1: Compared with the control (RA) group, infarct volume was reduced by 58.6% and 64.4% in 16 h and 24 h respectively. NDS and Evans Blue extravasation was also reduced in 16 h and 24 h. There was no statistical difference among 4 h and 8 h. E2: Preconditioning with prolonged and intermittent HO decreased NDS, infarct volume and upregulated TACE and increased phosphor-κBα and serum TNF-α level significantly. Although further studies are needed to clarify the mechanisms of brain ischemic tolerance, InHO and PrHO may partly exert their effects via triggering TACE/TNF-α/NF-κB. [Copyright &y& Elsevier]

Abstract: Aim: This study was designed to assess cardiac adrenergic nerve activity, using iodine (I)-123-labeled metaiodobenzylguanidine (MIBG), in patients with impaired glucose tolerance (IGT) and to investigate its relation to circulating levels of proinflammatory cytokines. Methods: We studied 22 patients with IGT (aged 34–68 years) and 18 age-matched healthy controls, using I-123 MIBG cardiac imaging. The early (10 min) and late (4 h) heart to mediastinum MIBG uptake (H/M) ratio and washout were calculated. Levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), and its soluble receptor [soluble TNF receptor II (sTNFRII)] were measured by immunoassay of blood samples from patients and controls. Results: The early and late MIBG uptake was lower (both P<.001) and the WR was higher (P<.001) in patients than in controls. The analysis showed innervation defects in 20 of the 22 patients. Nearly half (45.4%) showed severe adrenergic innervation defects in both the inferior wall and the apex. Regarding cytokines, patients showed significantly elevated TNF-a (P=.005), sTNFRII (P<.001), and IL-6 (P<.001) levels compared to controls. IL-6 and sTNFRII were found to correlate with the WR (r=0.468, P=.028 and r=0.455, P=.034, respectively). Conclusion: Patients with IGT show reduced MIBG cardiac uptake with a segmental pattern. The reduced cardiac sympathetic innervation was related to the elevated proinflammatory cytokine levels and could be considered an index of early atherosclerotic process in these patients. [Copyright &y& Elsevier]