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Background and purpose: Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats. Experimental approach: Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively. Key results: In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L-NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats. Conclusions and implications: Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS. British Journal of Pharmacology (2008) 153, 468–479; doi:10.1038/sj.bjp.0707589; published online 26 November 2007

Cytokines mediate the balance between protective and destructive immunity in periodontitis. We sought to investigate the role of IL-33 in periodontitis. The expression of IL-33 in gingival tissue from healthy controls ( n = 10) and patients with chronic periodontitis ( n = 17) was investigated. Based on a murine model of periodontal disease, the function of IL-33 was determined first by administration of exogenous IL-33 and second by inhibition of IL-33 signaling using mice deficient in the IL-33 receptor ST2. Alveolar bone level, serum antibody, and lymphocyte responses were assessed in the murine model. Expression of IL-33 and ST2 was elevated in gingival tissues from patients with chronic periodontitis as compared with healthy tissues ( P < 0.05). Similarly, Il33 expression was higher in periodontal tissues of Porphyromonas gingivalis–infected mice as compared with sham-infected controls ( P < 0.05). IL-33 treatment of P. gingivalis–infected mice significantly exacerbated alveolar bone loss when compared with infection or IL-33 treatment alone ( P < 0.001). Conversely, P. gingivalis infection–induced alveolar bone loss was attenuated in mice lacking ST2. The percentages of T and B lymphocytes expressing nuclear factor κB ligand (RANKL) in the gingival tissues and T lymphocytes expressing RANKL in the cervical draining lymph nodes were higher in IL-33-treated P. gingivalis–infected mice versus phosphate buffered saline–treated P. gingivalis–infected controls (all P < 0.001). Targeting the RANKL pathway by osteoprotegerin administration abrogated periodontal bone destruction in P. gingivalis–infected, IL-33-treated mice. These data demonstrate a previously unrecognized role for IL-33 in exacerbating bone loss in a RANKL-dependent manner in the context of bacterial infection and suggest that this pathway may be amenable to manipulation as a novel therapeutic target in periodontitis.

The relevance of IL-33 and its receptor ST2 for bone remodeling is not well-defined. Our aim was to assess the role and underlying mechanisms of IL-33/ST2 in mechanically induced bone remodeling. BALB/c (wild type) and ST2 deficient (St2(-/-)) mice were subjected to mechanical loading in alveolar bone. Microtomography, histology, and real-time quantitative PCR were performed to analyze bone parameters, apoptosis and bone cell counts, and expression of bone remodeling markers, respectively. MC3T3-E1 osteoblastic cells and bone marrow cells were used to verify if mechanical force triggered IL-33 and ST2 expression as well as the effects of IL-33 on osteoclast differentiation and activity. Mechanical loading increased the expression of IL-33 and ST2 in alveolar bone in vivo and in osteoblastic cells in vitro. St2(-/-) mice had increased mechanical loading-induced bone resorption, number of osteoclasts, and expression of proresorptive markers. In contrast, St2(-/-) mice exhibited reduced numbers of osteoblasts and apoptotic cells in periodontium and diminished expression of osteoblast signaling molecules. In vitro, IL-33 treatment inhibited osteoclast differentiation and activity even in the presence of receptor activator of NF-κB ligand. IL-33 also increased the expression of pro-apoptotic molecules, including Bcl-2-associated X protein (BAX), cell-surface Fas receptor (FAS), FASL, FAS-associated death domain, tumor necrosis factor-related apoptosis-inducing ligand, and BH3 interacting-domain death (BID). Overall, these findings suggest that IL-33/ST2 have anti-osteoclastogenic effects and reduce osteoclast formation and activity by inducing their apoptosis.

Background and Objective The angiotensin type 1 (AT1) receptor has been implicated in the pathogenesis of inflammatory bone disorders. This study aimed to investigate the effect of an AT1 receptor antagonist in infection-induced and arthritis-associated alveolar bone loss in mice. Material and Methods Mice were subjected to Aggregatibacter actinomycetemcomitans oral infection or antigen-induced arthritis and treated daily with 10 mg/kg of the prototype AT1 antagonist, losartan. Treatment was conducted for 30 d in the infectious condition and for 17 d and 11 d in the preventive or therapeutic regimens in the arthritic model, respectively. The mice were then killed, and the maxillae, serum and knee joints were collected for histomorphometric and immunoenzymatic assays. In vitro osteoclast assays were performed using RAW 264.7 cells stimulated with A. actinomycetemcomitans lipopolysacharide (LPS). Results Arthritis and A. actinomycetemcomitans infection triggered significant alveolar bone loss in mice and increased the levels of myeloperoxidase and of TRAP+ osteoclasts in periodontal tissues. Losartan abolished such a phenotype, as well as the arthritis joint inflammation. Both arthritis and A. actinomycetemcomitans conditions were associated with the release of tumor necrosis factor alpha (TNF-α), interferon-gamma, interleukin-17 and chemokine (C-X-C motif) ligand 1 and an increased RANKL/osteoprotegerin ratio in periodontal tissues, but such expression decreased after losartan treatment, except for TNF-α. The therapeutic approach was as beneficial as the preventive one. In vitro, losartan prevented LPS-induced osteoclast differentiation and activity. Conclusion The blockade of AT1 receptor exerts anti-inflammatory and anti-osteoclastic effects, thus protecting periodontal tissues in distinct pathophysiological conditions of alveolar bone loss.

It has been suggested that low concentrations of angiotensin II cause vasoconstriction, whereas high concentrations evoke vasodilation. Thus, this work aimed to characterize functionally the mechanisms underlying angiotensin II-induced relaxation, at high concentration, in isolated rat aortic rings. Vascular reactivity experiments, using standard muscle bath procedures, showed that angiotensin II (1-30 microM) concentration-dependently induces relaxation of phenylephrine-precontracted rings with intact or denuded endothelium. The relaxation was not altered in the presence of ethylenediamine tetraacetic acid (EDTA), a nonselective inhibitor of metalloprotease. The selective antagonist of AT2 receptors, PD123319, inhibited angiotensin II-induced relaxation. Conversely, losartan or A-779, selective AT1 and Ang1-7 receptor antagonists, respectively, did not alter the relaxation induced by angiotensin II. HOE-140, a selective antagonist of the bradykinin B2 receptor, and amiloride, a Na+/H+ exchanger inhibitor, abolished angiotensin II-induced relaxation. Administration of exogenous bradykinin on precontracted tissues produced concentration-dependent relaxation, which was also inhibited by HOE-140. Preincubation of denuded-rings with NG-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), indomethacin, or tetraethylammonium (TEA) reduced angiotensin II-induced relaxation. The combination of L-NAME, indomethacin, and TEA completely abolished the relaxation induced by angiotensin II. 4-Aminopyridine (4-AP) as well as charybdotoxin reduced angiotensin II-induced relaxation. On the other hand, neither apamin nor glibenclamide altered the relaxation induced by angiotensin II. The major new finding of this work is that it demonstrated functionally the existence of AT2 receptors located on smooth muscle of rat aortic rings that mediated vasorelaxation via stimulation of B2 receptors by bradykinin, which in turns results in the activation of the NO-cGMP pathway, vasodilator cyclooxygenase product(s), and voltage-dependent and Ca+-activated large-conductance K+ channels.

The rabbit carotid artery, injured by silicone collar, presents a perivascular inflammatory response and alterations in vascular responsiveness. Considering that angiotensin II (Ang II) plays an important role in cardiovascular physiology and pathology and that cardiovascular disease increases in postmenopausal women, the aim of this study was to investigate whether the Ang II contractile response in ovariectomized rat carotid artery is modified after a vascular injury by silicone collar. The positioning of the silicone collar around the common carotid artery for 14 days leads to an increased cross-sectional area of adventitial layer with inflammatory cells and an extensive angiogenesis. The Ang II-induced contraction was significantly decreased in collared arteries when compared with contralateral arteries. The reduction in the constrictor effect of Ang II in collared arteries was not modified by the presence of indomethacin (a non-selective inhibitor of cyclooxygenase) or PD 123,319 (a selective antagonist of the Ang II AT 2 receptor). Moreover, while endothelium removal induced an increase in the Ang II responsiveness of both arteries (collared and contralateral), the Emax induced by Ang II was still lower in collared arteries. However, the "in vitro" pretreatment of the arteries with an inhibitor of nitric oxide synthase enzyme (L-NAME) significantly enhanced the maximal contractions response to Ang II only in injured arteries. Furthermore, the expression of iNOS (inducible nitric oxide synthase) was observed in the adventitial layer of collared arteries, indicating that the NO formed in the adventitial layer has an important role in injured arteries. Moreover, our data show impairment of extracellular calcium mobilization, mediated by Ang II, in the collared artery, although the intracellular calcium mobilization was not modified by the injury. In conclusion, the increased production of NO and a decrease in the calcium influx displayed by Ang II in the collared artery appears to counteract and reduce the biologic effect of Ang II.

Background The first response to perivascular injury is observed in the adventitial layer. The purpose of this study was to determine the time course of vascular reactivity alterations after collar injury in rats. We also analyzed the relation between adventitial layer injury and vascular responsiveness to vasoconstrictor agents. Methods Wistar rats had a silicone collar positioned around the carotid artery. The ipsilateral and contralateral arteries were morphologically analyzed 4, 7, 14 and 28 days after injury, and cumulative concentration–response curves to phenylephrine (Phe), angiotensin II (Ang II) and KCl were obtained for arteries isolated from collared and sham-operated groups. Results Inflammatory cells and fibroblasts were observed in the adventitial layer of collared arteries 4, 7, 14 and 28 days after injury. Intimal thickening was observed in collared arteries only 14 and 28 days after perivascular injury. A decrease in maximum effect values (Emax) for Phe, Ang II and KCl was observed in the collared artery when compared with the contralateral artery at all times after injury, whereas an increase in vascular responsiveness was observed in the contralateral artery 4 days after injury. Conclusions The impairment of the contractile response preceded the intimal thickening. The compromise of vascular reactivity coincided with the presence of inflammatory cells and angiogenesis in the adventitial layer. The enhancement of the efficacy and potency of Ang II and Phe in collared-contralateral arteries 4 days after collar placement may be related to a receptor-mediated compensatory mechanism stimulated by the collar injury.

Explanations of the deposition process during electrophoretic deposition (EPD) are presented and their boundary conditions discussed. It is suggested increasing resistance during EPD is due to the deposit and not dilution of current carrying species in the suspension. Dialysis membrane experiments demonstrate ions carry significant current. Side-effects of two suspension-conditioning agents are described, i.e., TMAH and PEI. The former can induce “aging” in suspension as its surface adsorption varies with time and reduces suspension pH. PEI appears to adsorb on all ceramic and metal powders, so may be a universal EPD agent for stoichiometric deposition of ceramic/ceramic and ceramic/metal powder-mixtures. Novel structures produced by EPD are presented.

A wealth of evidence indicates that angiotensin II (Ang II) is involved in learning and memory. However, the precise role of this peptide in these cognitive processes is still controversial, with data indicating either an inhibitory or an enhancing action. The present study was designed to further investigate the effects of intracerebroventricular injections of Ang II (0.5, 1 or 3nmol/5microl) on a step-through passive avoidance task in male adult Wistar rats. When administered pretraining, Ang II did not affect the acquisition of passive avoidance, but markedly improved avoidance performance when given before the retrieval test. The latter effect was observed in retest sessions performed up to 72h after training. Administration of the peptide five minutes after training impaired retention of inhibitory avoidance. Therefore, Ang II may exert opposite effects on passive avoidance memory according to its interference with brain mechanisms leading to the storage or retrieval of this aversively motivated task.

This paper presents a probability density function formula for predicting the polarization dependent loss (PDL) in an optical transmission system composed of passive devices and connecting fibers. A new calculation technique, which enables the probability density function formula to be obtained theoretically, is used instead of the most complicated part of the Muller-matrix or Jones-matrix calculations, which has been thought to be necessary for analyzing PDL. This technique involves calculation of the transmission coefficients of the transmission system and its devices from their PDLs. In the theoretical development, the central limit theorem is used as the sole approximation. A Monte Carlo numerical simulation was done to verify the validity of the analytical theory. Very good agreement between simulation and analytical theory is obtained when the number of devices having PDL is four or more. An experiment also demonstrated the validity of the analytical theory. The theory can also explain some phenomena that occur in systems composed of optical amplifiers, even though it had originally been developed to explain PDL-related phenomena in systems composed of passive devices only.

International audience; Th9 cells protect hosts against helminthic infection but also mediate allergic disease. Here we show that nitric oxide (NO) promotes Th9 cell polarization of murine and human CD4(+) T cells. NO de-represses the tumour suppressor gene p53 via nitrosylation of Mdm2. NO also increases p53-mediated IL-2 production, STAT5 phosphorylation and IRF4 expression, all essential for Th9 polarization. NO also increases the expression of TGFβR and IL-4R, pivotal to Th9 polarization. OVA-sensitized mice treated with an NO donor developed more severe airway inflammation. Transferred Th9 cells induced airway inflammation, which was exacerbated by NO and blocked by anti-IL-9 antibody. Nos2(-/-) mice had less Th9 cells and developed attenuated eosinophilia during OVA-induced airway inflammation compared with wild-type mice. Our data demonstrate that NO is an important endogenous inducer of Th9 cells and provide a hitherto unrecognized mechanism for NO-mediated airway inflammation via the expansion of Th9 cells.

Interleukin-33 (IL-33) is associated with several important immune-mediated disorders. However, its role in uveitis, an important eye inflammatory disease, is unknown. Here, we investigated the function of IL-33 in the development of experimental autoimmune uveitis (EAU). IL-33 and IL-33 receptor (ST2) were expressed in murine retinal pigment epithelial (RPE) cells in culture, and IL-33 increased the expression of Il33 and Mcp1 mRNA in RPE cells. In situ, IL-33 was highly expressed in the inner nuclear cells of the retina of naïve mice, and its expression was elevated in EAU mice. ST2-deficient mice developed exacerbated EAU compared with WT mice, and administration of IL-33 to WT mice significantly reduced EAU severity. The attenuated EAU in IL-33-treated mice was accompanied by decreased frequency of IFN-γ+ and IL-17(+) CD4+ T cells and reduced IFN-γ and IL-17 production but with increased frequency of IL-5(+) and IL-4(+) CD4 T cells and IL-5 production in the draining lymph node and spleen. Macrophages from the IL-33-treated mice show a significantly higher polarization toward an alternatively activated macrophage phenotype. Our results therefore demonstrate that the endogenous IL-33/ST2 pathway plays an important role in EAU, and suggest that IL-33 represents a potential option for treatment of uveitis.

The NOD-like receptors are cytoplasmic proteins that sense microbial by-products released by invasive bacteria. Although NOD1 and NOD2 are functionally expressed in cells from oral tissues and play a role triggering immune responses, the role of NOD2 receptor in the bone resorption and in the modulation of osteoclastogenesis is still unclear. We show that in an experimental model of periodontitis with Porphyromonas gingivalis W83, NOD2-/- mice showed lower bone resorption when compared to wild type. Quantitative polymerase chain reaction analysis revealed that wild-type infected mice showed an elevated RANKL/OPG ratio when compared to NOD2-/- infected mice. Moreover, the expression of 2 osteoclast activity markers—cathepsin K and matrix metalloproteinase 9—was significantly lower in gingival tissue from NOD2-/- infected mice compared to WT infected ones. The in vitro study reported an increase in the expression of the NOD2 receptor 24 hr after stimulation of hematopoietic bone marrow cells with M-CSF and RANKL. We also evaluated the effect of direct activation of NOD2 receptor on osteoclastogenesis, by the activation of this receptor in preosteoclasts culture, with different concentrations of muramyl dipeptide. The results show no difference in the number of TRAP-positive cells. Although it did not alter the osteoclasts differentiation, the activation of NOD2 receptor led to a significant increase of cathepsin K expression. We confirm that this enzyme was active, since the osteoclasts resorption capacity was enhanced by muramyl dipeptide stimulation, evaluated in osteoassay plate. These results show that the lack of NOD2 receptor impairs the bone resorption, suggesting that NOD2 receptor could contribute to the progression of bone resorption in experimental model of periodontitis. The stimulation of NOD2 by its agonist, muramyl dipeptide, did not affect osteoclastogenesis, but it does favor the bone resorption capacity identified by increased osteoclast activity.

This paper proposes a new optical access network system; the multi-bit rate passive double star (multi-bit rate-PDS) system. The multi-bit rate-PDS system passes multi-bit rate data streams between the optical service unit (OSU) and the optical network unit (ONU) using the time-unit packet (TP). This simplifies the provision of user flexibility and provides very economical network services to users. We describe the architecture and frame structure of the multi-bit rate-PDS system, and elaborate the advantage of its user accommodation. Furthermore, we show how to decide the multiplexed bit rates in the multi-bit rate-PDS system and how to realize the receiver circuit for multi-bit rate data packet streams.

Objective: To report the results of prenatal triple marker screening on a population of Japanese pregnant women. Methods: From April 1994 through March 1999, a total of 32,925 native Japanese women with singleton pregnancies requested a triple marker-screening test. Multiples of the median values for 3 markers and individual risks for each patient were calculated following adjustment for the Japanese weight correction factor. The risk cut-off values used for Down syndrome (T21), open spina bifida (OSB) and trisomy 18 (T18) were 1:295, 1:290, and 1:100, respectively. Follow-up information was collected postpartum and statistically analyzed. Results: Detection rates (DR) of T21 for women less than 35 years, over 35 years and overall were 58, 94, and 83%, respectively. DR of T18 for women less than 35 years, over 35 years and overall were 75, 79, and 79%, respectively. DR of open neural tube defects (ONTD) was 100%. Conclusions: The first cumulative data of an intervention program and prospective follow-up studies in Japan have proven to be similar to other published reports. Individual risk values were calculated for each pregnancy for T21, T18 and ONTD. This screening program is more effective than age-dependent screening for detecting T21, T18 and ONTD pregnancies.

To establish an available, economical technique for the large-scale purification of CD34(+) cells we used a nylon-fiber syringe (NF-S) for depletion of adherent cells and then selected CD 34(+) cells from peripheral blood mobilized by G-CSF, using MAb and magnetic heads.PBSC were mobilized and collected from adult, healthy volunteers. With the effect of concentration of anti-CD34 MAb (9C5) on the purification of CD34(+) cells from 1 2 10(8) NF-S treated cells (NF cells), the recovery and the purity of CD34(+) cells was identical for 5, 10, 20, 40 microg of 9C5. In this study, therefore, the concentration of 9C5 was maintained at5 microg/10(8) NF cells, with a cellhead ratio of 1:10.When half to one-third of leukapheresis product containing 121.5 + or - 26.0 2 10(8) mononuclear cells (mean + or - SD; n = 6) was processed for CD34(+) cell purification, 5.26 + or - 3.01 2 10(7) total purified cells were obtained with a purity of CD34(+) cells at 94.9 - 8.5%. The numbers of CD34(+) cells and total progenitor cells recovered in this process were 4.71 + or - 2.33 2 10(7) cells and 145.9 + or - 121.8 2 10(5) cells, respectively. The total recovery of CD34(+) cells was 37.0 + or - 21.0%. The depletion of monocyte by NF-S reduced the 9C5 anti-human CD34 MAb needed for purification of CD34(+) cells to one-third. Two patients were grafted with peripheral blood CD34(+) cells selected by this procedure and achieved a rapid and consistent hematopoiesis.Our clinical data show that these cells are capable of rapid reconstitution of hematopoiesis after high-dose chemotherapy. The procedure contains an additional step; however, consistent high purity of CD34(+) cells in the purified population and cost reduction were achieved, both critical issues in the better purging of malignant cells and for a wide clinical application.

We monitored 30 laboratory hemostatic parameters in an attempt to better comprehend alterations in coagulation and fibrinolysis in 10 patients with hematological malignancies subjected to autologous peripheral blood stem cell transplantation (APBSCT). These parameters were assessed before and just after high-dose conditioning chemotherapy, on days 1, 7, 14 and 28. Although, clinical manifestations associated with fibrino-coagulation disorders never occurred, including veno-occlusive disease, a statistically significant increase was seen in 7 of 30 parameters, compared to values seen before conditioning chemotherapy. These were subdivided into early and late phase parameters. The early phase parameters, which increased during the first day after the conditioning chemotherapy was given, then returned to baseline values, included protein C, plasma tissue factor and tissue-plasminogen activator. The late phase parameters, which increased over baseline values during days 7 to 28, included free-protein S, fibrinogen, plasmin-alpha2-plasmin inhibitor complex and soluble-thrombomodulin. The increase of early phase parameters, as produced by the liver and by endothelial cells, may reflect tissue damage by conditioning chemotherapy. Late phase parameters increased in parallel with C-reactive protein, which suggests a correlation with the degree of inflammation, such as the presence of infective disease during neutropenia. These subclinical alterations in coagulation and fibrinolysis which take on a biphasic pattern during the course of APBSCT should be kept in mind by the attending physicians during therapy.

The clonal growth of progenitor cells from myelodysplastic syndromes (MDS) can be subdivided into four growth patterns: (1) normal, (2) no growth or low plating efficiency, (3) low colony and high cluster number, and (4) normal or high colony number with a large number of clusters. The former two (1 and 2) can be referred to as nonleukemic patterns and latter two (3 and 4) as leukemic. In a search for a role for cytokines in leukemic-type growth of MDS progenitor cells, marrow CD34+ cells were purified up to 94% for 8 normal individuals and 88% for 12 MDS patients, using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells). The purified CD34+ cells were cultured for 14 days with various combinations of cytokines, including recombinant human macrophage colony-stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF), granulocyte-macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3), and stem cell factor (SCF; a ligand for c-kit) in serum-free medium. The clonal growth of MDS CD34+ cells supported by a combination of all of the above cytokines was subdivided into the two patterns of leukemic or nonleukemic, and then the role of individual or combined cytokines in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. Evidence we obtained showed that SCF plays a central role in the leukemic-type growth of MDS CD34+ cells and that G-CSF, GM-CSF; and/or IL-3 synergize with SCF to increase undifferentiated blast cell colonies and clusters over that seen in normal CD34+ cells. SCF is present in either normal or MDS plasma at a level of nanograms per milliliter, and this physiologic concentration of SCF can stimulate progenitor cells. This means that progenitor cells are continuously exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blast cells. This depends, at least in part, on cytokines such as G-CSF, GM-CSF, IL-3, and SCF.

The oral cavity is a complex environment that may harbor more than 750 bacterial species. Proper oral hygiene is essential to maintain the equilibrium of microbial community and oral health. The ecological balance can be compromised in inadequate microbial control situations and an oral infection can be evoked. The bacteria can aid in the formation of dental plaque and caries, leading to periodontal disease (PD) and periapical lesion (PL). PD is the most common chronic inflammatory disorder of microbial origin that affects toothsupporting tissues including the periodontal ligament and the alveolar bone. Dental caries is characterized by demineralization of enamel and dentine produced by microorganisms’ acids. This process can cause pulp necrosis and root canal infection and the progression through the root apex can induce PL. PD and PLs constitute inflammatory and immune response against oral pathogens. Both processes encompass pathogenic mechanisms of inflammation-mediated soft tissue destruction and bone resorption. The etiopathogenesis of these diseases have been extensively investigated over the last decades and the role of several cell types, cytokines and pathways has been described (Graves, 2008, Graves et al., 2011a, Nair, 1997). Last decades research have documented the importance and commitment of immune system to protect the host from pathogen and also the paradoxical effect accounting for the bone resorption observed in these diseases. More recently, the pattern of immune cell response involved in the lesions progression (i.e. Th1, Th2, Th17, Th9 or T regulatory) has received particular attention (Cardoso et al., 2009, Colic et al., 2009a, Gaffen & Hajishengallis, 2008, Ohlrich et al., 2009, Queiroz-Junior et al, 2011). Although chemokines and cytokines are pivotal to determine these Th patterns, not much is known regarding the expression of these markers in the regulation of bone resorption in sites of PD and PL. This

Interleukin (IL)-33, a member of the IL-1 cytokine family, is an important modulator of the immune system associated with several immune-mediated disorders. High levels of IL-33 are expressed by the central nervous system (CNS) suggesting a potential role of IL-33 in autoimmune CNS diseases. We have investigated the expression and function of IL-33 in the development of experimental autoimmune encephalomyelitis (EAE) in mice. We report here that IL-33 and its receptor ST2 (IL-33Rα) are highly expressed in spinal cord tissue, and ST2 expression is markedly increased in the spinal cords of mice with EAE. Furthermore, ST2-deficient (ST2(-/-) ) mice developed exacerbated EAE compared with wild-type (WT) mice while WT, but not ST2(-/-) EAE mice treated with IL-33 developed significantly attenuated disease. IL-33-treated mice had reduced levels of IL-17 and IFN-γ but produced increased amounts of IL-5 and IL-13. Lymph node and splenic macrophages of IL-33-treated mice showed polarization toward an alternatively activated macrophage (M2) phenotype with significantly increased frequency of MR(+) PD-L2(+) cells. Importantly, adoptive transfer of these IL-33-treated macrophages attenuated EAE development. Our data therefore demonstrate that IL-33 plays a therapeutic role in autoimmune CNS disease by switching a predominantly pathogenic Th17/Th1 response to Th2 activity, and by polarization of anti-inflammatory M2 macrophages.

Type 17 helper T (Th17) cells are implicated in the pathogenesis many of human autoimmune diseases. Development of Th17 can be enhanced by the activation of aryl hydrocarbon receptor (AHR) whose ligands include the environmental pollutant dioxin, potentially linking environmental factors to the increased prevalence of autoimmune disease. We report here that nitric oxide (NO) can suppress the proliferation and function of polarized murine and human Th17 cells. NO also inhibits AHR expression in Th17 cells and the downstream events of AHR activation, including IL-22, IL-23 receptor, and Cyp1a1. Conversely, NO did not affect the polarization of Th17 cells from mice deficient in AHR. Furthermore, mice lacking inducible nitric oxide synthase ( Nos2 −/− ) developed more severe experimental autoimmune encephalomyelitis than WT mice, with elevated AHR expression, increased IL-17A, and IL-22 synthesis. NO may therefore represent an important endogenous regulator to prevent overexpansion of Th17 cells and control of autoimmune diseases caused by environmental pollutants.

To investigate the roles of G-protein receptor kinases (GRKs) in the light responses of vertebrate photoreceptors, we generated transgenic zebrafish lines, the rods of which express either cone GRK (GRK7) or rod GRK (GRK1) in addition to the endogenous GRK1, and we then measured the electrophysiological characteristics of single-cell responses and the behavioural responses of intact animals. Our study establishes the zebrafish expression system as a convenient platform for the investigation of specific components of the phototransduction cascade. The addition of GRK1 led to minor changes in rod responses. However, exogenous GRK7 in GRK7-tg animals led to lowered rod sensitivity, as occurs in cones, but surprisingly to slower response kinetics. Examination of responses to long series of very dim flashes suggested the possibility that the GRK7-tg rods generated two classes of single-photon response, perhaps corresponding to the interaction of activated rhodopsin with GRK1 (giving a standard response) or with GRK7(giving a very small response). Behavioural measurement of optokinetic responses (OKR) in intact GRK7-tg zebrafish larvae showed that the overall rod visual pathway was less sensitive, in accord with the lowered sensitivity of the rods. These results help provide an understanding for the molecular basis of the electrophysiological differences between cones and rods.

A 31-year-old male presented with increase of aortic valve regurgitation 5 years after implantation of Prima Plus Stentless bioprosthesis in a bicuspid aortic valve. He underwent redo aortic valve replacement with a mechanical valve concomitant with replacement of the ascending aorta. Pathological examination of the explanted stentless valve presented no inflammatory cell infiltration. The prosthetic valve regurgitation was considered to be due to small injury at the 1st operation.

Introduction Periapical lesions are chronic inflammatory disorders of periradicular tissues caused by etiologic agents of endodontic origin. The inflammatory chemokines are thought to be involved in the latter observed osteolysis. With a murine model of experimental periapical lesion, the objective of this study was to evaluate the role of the chemokine receptor CCR2 in the lesion progression, osteoclast differentiation and activation, and expression of inflammatory osteolysis-related mediators. Methods For lesion induction, right mandibular first molars were opened surgically with a ¼ carbine bur, and 4 bacterial strains were inoculated in the exposed dental pulp; left mandibular first molars were used as controls. Animals were killed at 3, 7, 14, and 21 days after surgeries to evaluate the kinetics of lesion development. Results CCR2 KO mice showed wider lesions than WT mice. CCR2 KO mice also expressed higher levels of the osteoclastogenic and osteolytic factors, receptor activator of nuclear factor kappa B ligand (RANKL) and cathepsin K, of the proinflammatory cytokine tumor necrosis factor–alpha, and of the neutrophil migration related chemokine, KC. Conclusions These results suggest that CCR2 is important in host protection to periapical osteolysis.

An inline amplifier system was constructed with erbium-doped fiber amplifiers spaced at 100 km and 80 km intervals. The system transmits 2.5 Gb/s signals over 2500 km with continuous-phase frequency-shift-keying heterodyne detection and over 4500 km with intensity-modulation direct detection. With respect to amplifier output signal power levels, it is experimentally shown that there exists a dynamic range within which long-distance signal transmission can be achieved with only small receiver sensitivity degradation. The range's upper and lower limits are determined by fiber nonlinearities and amplifier noise characteristics, respectively. >

We investigated the effect of nitric oxide synthase (NOS) inhibition on polymorphonuclear cell (PMN) influx in zymosan or lipopolysaccharide (LPS)-induced arthritis and peritonitis.Wistar rats received intra-articular (i.art.) zymosan (30-1000 microg) or LPS (1-10 microg). Swiss C57/Bl6 mice genetically deficient in intercellular adhesion molecule-1 (ICAM-1(-/-)) or in beta(2)-integrin (beta(2)-integrin(-/-)) received zymosan either i.art. or i.p. PMN counts, leukotriene B(4) (LTB(4)), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) levels were measured in joint and peritoneal exudates. Groups received the NOS inhibitors N(G)-nitro-L-arginine methyl ester (LN), nitro-L-arginine, N-[3-(aminomemethyl)benzyl] acetamide or aminoguanidine, prior to zymosan or LPS, given i.p. or s.c. in the arthritis and peritonitis experiments respectively. A group of rats received LN locally (i.art. or i.p.), 30 min prior to 1 mg zymosan i.art.Systemic or local NOS inhibition significantly prevented PMN migration in arthritis while increasing it in peritonitis, regardless of stimuli, concentration of NOS inhibitors and species. NOS inhibition did not alter TNF-alpha and IL-10 but decreased LTB(4) in zymosan-induced arthritis. LN administration significantly inhibited PMN influx into the joints of ICAM-1(-/-) and beta(2)-integrin(-/-) mice with zymosan-arthritis, while not altering PMN influx into the peritoneum of mice with zymosan-peritonitis.Nitric oxide has a dual modulatory role on PMN influx into joint and peritoneal cavities that is stimulus- and species-independent. Differences in local release of LTB(4) and in expression of ICAM-1 and beta(2)-integrin account for this dual role of NO on PMN migration.

Surgical treatment for ischemic heart disease (IHD) has changed after the administration of off-pump coronary artery bypass grafting (CABG) [OPCAB] and left ventricular restoration (LVR). We studied the development of the treatment and the surgical results.Since May 2000 when the indication for OPCAB and LVR was defined, surgical treatment for IHD has been performed in 1,251 patients. The age ranged from 32 to 91 (mean 66 +/- 10) years and there were 977 men and 274 women. The elective operation was 1,130 and emergency 121. Definite indication for OPCAB was calcified ascending aorta, significant cerebrovascular disease, hemorrhagic tendency, and single vessel lesion. Conventional CABG (C-CAB) was the first choice and morbidity and surgical results were examined.OPCAB was performed in 297 (29.9%) and combined operation with CABG was required in 258 patients (20.6%). In elective operation, hospital mortality was one in OPCAB and one in C-CAB. In OPCAB and C-CAB, stroke was none and one, and mediastinitis was 0 and 0, respectively.The technique for OPCAB is necessary for CABG; however, it is not appropriate to persist with only OPCAB for CABG. Combined operation is often required with CABG and it is essential to perform precise C-CAB.

p27(Kip1) is a cyclin kinase inhibitor that induces cell cycle arrest. In this study, the efficacy of fusion protein TAT- p27(Kip1) to inhibit cell proliferation in rat perivascular injured carotid arteries was tested.The cDNA of p27(Kip1) and GFP (green fluorescein protein) fused to the TAT epitope, which allows cell penetration, yielded TAT-p27 (Kip1) and TAT-GFP fusion proteins. In vitro biological activity on cell proliferation was evaluated by [(3)H] thymidine DNA incorporation in rabbit aortic endothelial cells (REC). An in vivo model used a silicone collar filled with saline positioned around the carotid vessel for 14 days to produce an increased adventitia cross-sectional area.TAT-p27(Kip1) inhibited REC proliferation in vitro using either 100, 200, and 500 nM compared to control (88.2 +/- 4.4, 81.3 +/- 7, 71.9 +/- 4.2 vs. 100 +/- 6.7%, N = 3, respectively, p0.05). This response was stable for purified proteins stored at -20*C for at least 23 days. In vivo , TAT-p27(Kip1) solution reduced adventitia cross-sectional area in a dose-dependent manner compared to TAT-GFP (area in mm(2) - TAT-p27(Kip1): 200 nM, 0.160 +/- 0.018; 500 nM, 0.050 +/- 0.005 vs. TAT-GFP: 500 nM, 0.595 +/- 0.066 vs. the contralateral: 0.047 +/- 0.005, N = 7, p0.01).Taken together, these results provide evidence that TAT-p27(Kip1) can inhibit vascular cells proliferation. It is the first successful demonstration that the cell permeable TAT-p27(Kip1) has potential as a vascular anti-proliferative agent.

Measurements are reported of the Raman scattering of phonons in many crystals of K2CuxZn1-xF4 with different Cu concentrations x. With decreasing x, a structural change is confirmed at x approximately 0.8 besides the one at x approximately 0.4. Comparing the observed polarized spectra for 1>or=x>0.8 with those for 0.8>x>0.4, the authors find a transition at x approximately 0.8 from the D2h to an apparent D4h symmetry, which corresponds to a change of the long-range order of the cooperative Jahn-Teller distortion of CuF6 octahedra from three-dimensional to two-dimensional. Below x approximately 0.4, the long-range antiferrodistortive order in each c plane is destroyed as reported by Natsume and Yamada (NY) in 1985. The observed Stokes line including several lines which were missed in the report by NY for x>0.8, 0.8>x>0.4 and 0.4>x are well explained on the assumption of the space groups of D2h18, D4h5 and D4h17, respectively.

In this study, we have addressed the role of H2S in modulating neutrophil migration in either innate (LPS-challenged naive mice) or adaptive (methylated BSA (mBSA)-challenged immunized mice) immune responses. Treatment of mice with H2S synthesis inhibitors, dl-propargylglycine (PAG) or β-cyanoalanine, reduced neutrophil migration induced by LPS or methylated BSA (mBSA) into the peritoneal cavity and by mBSA into the femur/tibial joint of immunized mice. This effect was associated with decreased leukocyte rolling, adhesion, and P-selectin and ICAM-1 expression on endothelium. Predictably, treatment of animals with the H2S donors, NaHS or Lawesson’s reagent, enhanced these parameters. Moreover, the NaHS enhancement of neutrophil migration was not observed in ICAM-1-deficient mice. Neither PAG nor NaHS treatment changed LPS-induced CD18 expression on neutrophils, nor did the LPS- and mBSA-induced release of neutrophil chemoattractant mediators TNF-α, keratinocyte-derived chemokine, and LTB4. Furthermore, in vitro MIP-2-induced neutrophil chemotaxis was inhibited by PAG and enhanced by NaHS treatments. Accordingly, MIP-2-induced CXCR2 internalization was enhanced by PAG and inhibited by NaHS treatments. Moreover, NaHS prevented MIP-2-induced CXCR2 desensitization. The PAG and NaHS effects correlated, respectively, with the enhancement and inhibition of MIP-2-induced G protein-coupled receptor kinase 2 expression. The effects of NaHS on neutrophil migration both in vivo and in vitro, together with CXCR2 internalization and G protein-coupled receptor kinase 2 expression were prevented by the ATP-sensitive potassium (KATP+) channel blocker, glybenclamide. Conversely, diazoxide, a KATP+ channel opener, increased neutrophil migration in vivo. Together, our data suggest that during the inflammatory response, H2S augments neutrophil adhesion and locomotion, by a mechanism dependent on KATP+ channels.

Objective. To investigate the mechanism underlying neutrophil migration into the articular cavity in experimental arthritis and, by extension, human inflammatory synovitis. Methods. Antigen-induced arthritis (AIA) was generated in mice with methylated bovine serum albumin (mBSA). Migration assays and histologic analysis were used to evaluate neutrophil recruitment to knee joints. Levels of inflammatory mediators were measured by enzyme-linked immunosorbent assay. Antibodies and pharmacologic inhibitors were used in vivo to determine the role of specific disease mediators. Samples of synovial tissue and synovial fluid from rheumatoid arthritis (RA) or osteoarthritis patients were evaluated for CXCL1 and CXCL5 expression. Results. High levels of CXCL1, CXCL5, and leukotriene B4 (LTB4) were expressed in the joints of arthritic mice. Confirming their respective functional roles, repertaxin (a CXCR1/CXCR2 receptor antagonist), anti-CXCL1 antibody, anti-CXCL5 antibody, and MK886 (a leukotriene synthesis inhibitor) reduced mBSA-induced neutrophil migration to knee joints. Repertaxin reduced LTB4 production in joint tissue, and neutrophil recruitment induced by CXCL1 or CXCL5 was inhibited by MK886, suggesting a sequential mechanism. Levels of both CXCL1 and CXCL5 were elevated in synovial fluid and were released in vitro by RA synovial tissues. Moreover, RA synovial fluid neutrophils stimulated with CXCL1 or CXCL5 released significant amounts of LTB4. Conclusion. Our data implicate CXCL1, CXCL5, and LTB4, acting sequentially, in neutrophil migration in AIA. Elevated levels of CXCL1 and CXCL5 in the synovial compartment of RA patients provide robust comparative data indicating that this mechanism plays a role in inflammatory joint disease. Together, these results suggest that inhibition of CXCL1, CXCL5, or LTB4 may represent a potential therapeutic strategy in RA.

IL-33, a new member of the IL-1 family, signals through its receptor ST2 and induces T helper 2 (Th2) cytokine synthesis and mediates inflammatory response. We have investigated the role of IL-33 in antigen-induced hypernociception. Recombinant IL-33 induced cutaneous and articular mechanical hypernociception in a time- and dose-dependent manner. The hypernociception was inhibited by soluble (s) ST2 (a decoy receptor of IL-33), IL-1 receptor antagonist (IL-1ra), bosentan [a dual endothelin (ET)A/ETBreceptor antagonist], clazosentan (an ETAreceptor antagonist), or indomethacin (a cyclooxygenase inhibitor). IL-33 induced hypernociception in IL-18−/−mice but not in TNFR1−/−or IFNγ−/−mice. The IL-33-induced hypernociception was not affected by blocking IL-15 or sympathetic amines (guanethidine). Furthermore, methylated BSA (mBSA)-induced cutaneous and articular mechanical hypernociception depended on TNFR1 and IFNγ and was blocked by sST2, IL-1ra, bosentan, clazosentan, and indomethacin. mBSA also induced significant IL-33 and ST2 mRNA expression. Importantly, we showed that mBSA induced hypernociception via the IL-33 → TNFα → IL-1β → IFNγ → ET-1 → PGE2signaling cascade. These results therefore demonstrate that IL-33 is a key mediator of immune inflammatory hypernociception normally associated with a Th1 type of response, revealing a hitherto unrecognized function of IL-33 in a key immune pharmacological pathway that may be amenable to therapeutic intervention.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:22:42Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:33:52Z : No. of bitstreams: 1 2-s2.0-42449127014.pdf: 609396 bytes, checksum: 1d7f5f941cb20a900121085eb2c496f7 (MD5) Made available in DSpace on 2014-05-27T11:22:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-12-01 The aim of this article is to show the clinical and histochemical alterations of the first periodontal ligament, on the right side, after upper molars teeth extraction on the left side in gerbils. After two months, the periodontal ligaments were removed and processed for histochemical analysis. The data showed that TRAP reaction was able to evidence the osteoclastic activity in the hyperfunction hemimandible, right side, explaining the functional changes in the periodontal ligament after teeth extraction, and a little gingival recession and radicular exposure of teeth without function was observed at inferior molars of the left side. Faculty of Dentistry of Ribeirão Preto University of São Paulo, São Paulo Biosciences Institute- Molecular and Cellular Biology (UNESP), Rio Claro, São Paulo Faculty of Medicine of Ribeirão Preto University of São Paulo, São Paulo Faculdade de Odontologia de Ribeirão Preto USP Departamento de Morfologia, Estomatologia e Fisiologia, Av. Café S/N, CEP: 14040-904, Ribeirão Preto SP Biosciences Institute- Molecular and Cellular Biology (UNESP), Rio Claro, São Paulo

Epidemiological data suggest that the risk of ethanol-associated cardiovascular disease is greater in men than in women. This study investigates the mechanisms underlying gender-specific vascular effects elicited by chronic ethanol consumption in rats.Vascular reactivity experiments using standard muscle bath procedures were performed on isolated thoracic aortae from rats. mRNA and protein for inducible NO synthase (iNOS) and for endothelial NOS (eNOS) was assessed by RT-PCR or western blotting, respectively.In male rats, chronic ethanol consumption enhanced phenylephrine-induced contraction in both endothelium-intact and denuded aortic rings. However, in female rats, chronic ethanol consumption enhanced phenylephrine-induced contraction only in endothelium denuded aortic rings. After pre-incubation of endothelium-intact rings with L-NAME, both male and female ethanol-treated rats showed larger phenylephrine-induced contractions in aortic rings, compared to the control group. Acetylcholine-induced relaxation was not affected by ethanol consumption. The effects of ethanol on responses to phenylephrine were similar in ovariectomized (OVX) and intact (non-OVX) female rats. In the presence of aminoguanidine, but not 7-nitroindazole, the contractions to phenylephrine in rings from ethanol-treated female rats were greater than that found in control tissues in the presence of the inhibitors. mRNA levels for eNOS and iNOS were not altered by ethanol consumption. Ethanol intake reduced eNOS protein levels and increased iNOS protein levels in aorta from female rats.Gender differences in the vascular effects elicited by chronic ethanol consumption were not related to ovarian hormones but seemed to involve the upregulation of iNOS.

Chemokines are small chemotactic cytokines that can induce the migration of leukocytes, activate inflammatory/immune responses and have recently been implicated in the regulation of tumor growth and organ-specific spread. In this setting, the macrophage inflammatory protein-la (CCL3) chemokine displays a diversity of roles that may contribute to the directional migration of squamous cells into cervical lymph nodes or to the defense against tumor initiation and progression. Thus, the aim of this study was to determine, for the first time, the expression of CCL3 and their receptors, CCR1 and CCR5, by real-time polymerase chain reaction in samples obtained from oral squamous cell carcinoma (OSCC) and healthy gingival tissue (control). In addition, we investigated the immunoexpression of these molecules in neoplastic cells (parenchyma), inflammatory/immune cells (stroma) in primary OSCC and in metastatic and non-metastatic lymph node tissues. The relationship of CCL3/CCR1 with survival data was also evaluated. The analysis of mRNA expression revealed a significantly higher expression of CCL3 and CCR1 in OSCC compared with the controls (P 0.05). However, we observed the density of CCL3 + nodal cells to be significantly higher in metastatic lymph nodes when compared with non-metastatic lymph nodes in the same patients (P

AC ionizer with high frequency became more common in semiconductor industries. Neutralization mechanism of such equipment is, however, not well understood because the measurement of extremely small ion current is interfered by AC induction. Our attempt is to use the Faraday cage that is directly connected to an AC ionizer. At frequencies of 1 Hz and 10 Hz, clear pulse shape ion currents were measured. The amounts of transported charges increase with both applied voltage and pressure. The effect of pressure is more significant than voltage. At higher frequency, the measured current changes from pulse to sinusoidal shape. From the delay time of 1 kHz, the average air velocity between the needle and Faraday cage was calculated. From DC corona measurement inside the nozzle, it became clear that the portion of transported charge to the Faraday cage is quite small.

Made available in DSpace on 2022-04-29T08:43:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-04-05 A change in the microcirculatory hemodynamic is one of the most important events in inflammation. In the dental pulp, which is a connective tissue surrounded by a mineralized dentine substrate, disturbance in the blood flow as well as plasma extravasation may increase the pulp pressure and cause local ischemia. The octapeptide angiotensin II (AngII) regulates vascular tone and stimulates the release of pro-inflammatory cytokines by acting through the AT1 and AT2 receptors. The AT1 receptor is responsible for the classical effects of AngII. The AT2 receptor is involved in other effects, such as vasodilation. Therefore, we aimed to evaluate the role of AT1 and AT2 receptors on the pulpal inflammation. The pulp tissue was mechanically exposed and after different periods the teeth were extracted and submitted to histopathological and RT-PCR analyses. The histological sections showed a number of congested and dilated blood vessels associated with a notable presence of inflammatory cells. RT-PCR data revealed that the AT1 receptor was down-regulated at 24 h after the pulp exposure. The AT2 receptor expression was up-regulated by a 9-hour period, and then decreased between 12- and 24-hour periods. It was demonstrated that the renin-angiotensin system plays an important role in the pulpal inflammation, with regulation of AngII receptor levels. © 2006 Elsevier B.V. All rights reserved. Department of Biochemistry and Immunology Faculty of Medicine of Ribeirão Preto University of São Paulo, 14049-900 Ribeirão Preto Department of Pharmacology Faculty of Medicine of Ribeirão Preto University of São Paulo, 14049-900 Ribeirão Preto Departament of Physiology and Pathology Araraquara School of Dentistry State University of Sao Paulo, 14801-903 Araraquara

Kinin receptors are involved in the genesis of inflammatory pain. However, there is controversy concerning the mechanism by which B(1) and B(2) kinin receptors mediate inflammatory hypernociception. In the present study, the role of these receptors on inflammatory hypernociception in mice was addressed. Mechanical hypernociception was detected with an electronic pressure meter paw test in mice and cytokines were measured by ELISA. It was observed that in naive mice a B(2) (d-Arg-Hyp(3), d-Phe(7)-bradykinin) but not a B(1) kinin receptor antagonist (des-Arg(9)-[Leu(8)]-bradykinin, DALBK) inhibited bradykinin- and carrageenin-induced hypernociception. Bradykinin-induced hypernociception was inhibited by indomethacin (5 mg/kg) and guanethidine (30 mg/kg), while not affected by IL-1ra (10 mg/kg) or antibody against keratinocyte-derived chemokine (KC/CXCL-1, 500 ng/paw) or in TNFR1 knockout mice. By contrast, in previously lipopolysaccharide (LPS)-primed mouse paw, B(1) but not B(2) kinin receptor antagonist inhibited bradykinin hypernociception. Furthermore, B(1) kinin receptor agonist induced mechanical hypernociception in LPS-primed mice, which was inhibited by indomethacin, guanethidine, antiserum against TNF-alpha or IL-1ra. This was corroborated by the induction of TNF-alpha and IL-1beta release by B(1) kinin receptor agonist in LPS-primed mouse paws. Moreover, B(1) but not B(2) kinin receptor antagonist inhibited carrageenin-induced hypernociception, and TNF-alpha and IL-1beta release as well, in LPS-primed mice. These results suggest that in naive mice the B(2) kinin receptor mediates inflammatory hypernociception dependent on prostanoids and sympathetic amines, through a cytokine-independent mechanism. On the other hand, in LPS-primed mice, the B(1) kinin receptor mediates hypernociception by a mechanism dependent on TNF-alpha and IL-1beta, which could stimulate prostanoid and sympathetic amine production.

Objective The aim of this study was to compare the expression of nuclear factor κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in odontogenic epithelial tumors and dentigerous cysts. Study design The expression of these molecules was evaluated in solid/multicystic ameloblastomas (n = 12) and unicystic ameloblastomas (n = 8), keratocystic odontogenic tumors (n = 19), dentigerous cysts (n = 9), and dental follicles (n = 9) by immunohistochemistry. Results In odontogenic epithelium, a similar expression of RANK, RANKL, and OPG was observed in all samples. With regard to stroma, the number of RANK-positive and RANKL-positive cells was higher in solid/multicystic ameloblastomas compared with dentigerous cysts. Dental follicles had lower numbers of RANK-positive, RANKL-positive, and OPG-positive cells than solid/multicystic ameloblastomas and keratocystic odontogenic tumors. The majority of solid/multicystic ameloblastomas (75%) and unicystic ameloblastomas (62.5%) had higher numbers of RANKL-positive than OPG-positive cells. In contrast, 62.4% of keratocystic odontogenic tumors and 100% of dentigerous cysts exhibited a higher content of OPG-positive than RANKL-positive cells. Conclusion Our results indicate differences in the RANK, RANKL, and OPG expression in odontogenic epithelial tumors. The imbalance of these factors could contribute to the differential bone/tooth resorption activity in these lesions.

In this paper, we illustrate a decision support system of modeling the room designs suited for personal preference. The preference to colors is differed to individual personality. Nevertheless, modeling the room design is depended on the designer's sensitivity until now. Therefore, the technique of modeling the various room designs people satisfy is needed. In this paper, we propose automatic modeling system of the room design using interactive genetic algorithm (IGA). IGA has the advantage of learning the user's interactive evaluation, which is applied to the production of new room designs suited for the personal preference. The proposed system can help a decision support of modeling the various room designs, and reduce the burdens of designers significantly. In proposed system, the design evolution of IGA can reflect the user preference, and we present the effectiveness of the system by simulations.

Hyperhomocysteinemia is a known risk factor for cardiovascular diseases, but the underlying mechanisms of this pathology are complex. We aimed to evaluate the effect of hyperhomocysteinemia in vasorelaxations induced by alpha(1D)-adrenoceptor agonists. Vascular reactivity of rat carotid artery to the alpha-adrenoceptor agonist, phenylephrine, was enhanced in hyperhomocysteinemia. Mechanical removal of endothelium did not modify the carotid responsiveness to phenylephrine, compared to control. Phenylephrine induces endothelium-dependent relaxation, in the presence of 5-methyl urapidil (alpha(1A)-adrenoceptor antagonist). We hypothesised that endothelial-relaxant alpha(1)-adrenoceptors are impaired by hyperhomocysteinemia. Incubation with prazosin (selective alpha(1)-adrenoceptor antagonist) or BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7, 9-dione dihydrochloride) (selective alpha(1D)-adrenoceptor antagonist), similarly inhibited phenylephrine-induced relaxations in both control and hyperhomocysteinemic carotids. Immunohistochemistry showed enhanced immunoreactivity for eNOS and iNOS in hyperhomocysteinemic rats. In carotid arteries from hyperhomocysteinemic rats there was a decrease in superoxide dismutase activity and enhanced superoxide anion production. We conclude that alpha(1D)-adrenoceptors mediate endothelium-dependent relaxation triggered by phenylephrine in rat carotid artery and affect the final tone. Furthermore, the enhanced phenylephrine-induced contraction in carotid artery due to hyperhomocysteinemia is endothelium-dependent and involves a loss of the inhibitory effect of relaxant alpha(1D)-adrenoceptors by reducing NO biodisponibility.

Summary form only given. This paper reports the results of WDM transmission experiments done using the FSA commercial submarine amplifier system: which manages the fiber cable dispersion to transmit a single-NRZ l0-Gbit/s signal.

It has been suggested that low concentrations of angiotensin II cause vasoconstriction whereas high concentrations evoke vasodilation. Thus, this work aimed to functionally characterize the mechanisms underlying the relaxation induced by angiotensin II at high concentrations in isolated rat carotid rings. Experiments using standard muscle bath procedures showed that angiotensin II (0.01–3 μM) concentration dependently induces relaxation of phenylephrine-pre-contracted rings. No differences between intact or denuded endothelium were found. The angiotensin II-induced relaxation was strongly inhibited by saralasin, the non-selective antagonist of angiotensin II receptors but not by the selective antagonists of AT 1 and AT 2 receptors, losartan and PD123319, respectively. However, A-779, a selective angiotensin-(1–7) receptor antagonist, reduced the relaxation induced by angiotensin II. Administration of exogenous angiotensin-(1–7) on pre-contracted tissues produced concentration-dependent relaxation, which was also inhibited by A-779. HOE-140, the selective antagonist of the bradykinin in B 2 receptor did not produce any significant effect on angiotensin II-induced relaxation. Pre-incubation of denuded-rings with N G-nitro- l -arginine methyl ester ( l -NAME) or 1H-[1,2,4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced angiotensin II-induced relaxation. On the other hand, neither indomethacin nor tetraethylammonium (TEA) produced any significant effect. The major new finding of this work is that high concentrations of angiotensin II induce relaxation of the rat carotid via activation of the NO-cGMP pathway through a mechanism that seems to be partially dependent on activation of angiotensin-(1–7) receptors.

The authors report 2.5 and 10 Gbit/s transoceanic distance transmission in a commercial FSA optical amplifier system which has 90 km repeater spacing. The unique fibre dispersion management technique and amplifier passband management scheme used in the system are successfully demonstrated. The SNR improvement achieved with polarisation scrambling is also reported.

The patient was 75-year-old woman. The patient was referred to our hospital for operation due to a developing right coronary artery aneurysm. The coronary artery angiography showed that the aneurysm was 3 cm in diameter which had not existed two years previously, and with a 75% distal stenosis. The operation was made during cardiac arrest. A sapheous vein graft was used to bypass to the distal artery first. Then the aneurysm was resected, and both proximal and distal arteries were ligated. The pacemaker was implanted on the third postoperative day for sick sinus syndrome, the patient got a better recovery. Surgical treatment should be recommended to coronary artery aneurysm, and sapheous vein was a good selection for bypass graft when the diameter of native artery was relatively large.

For multi-media communications, high capacity and flexible data transmission systems, such as the Passive Optical Network (PON), are in strong demand. In such point-multipoint communication systems, however, it is necessary to handle data packets at the same bit-rate. This precondition makes the PON system inflexible. If the PON system could handle multi-bit-rate packets, the user could choose the type of Optical Network Unit (ONU) needed making it easy to accommodate multiple users. Accordingly, we developed a 3R regeneration circuit for multi-bit-rate packets for use at the Optical Line Termination (OLT) point. It will greatly improve the flexibility of the PON system. We intend to extend the circuit to handle wider ranges of bit rates.

To report clinical experiences with disseminated intravascular coagulation (DIC) associated with aortic aneurysms (AA) and discuss therapeutic strategy.uncontrolled, observational study in a university hospital.among 547 patients with AA treated between 1991 and 1999, 10 patients (7 males, 3 females, mean age 68.5+/-2.5) presenting a preoperative DIC score (defined by the Ministry of Health and Welfare in Japan) of 6 or higher were analyzed. The etiology was dissection for 5 and non-dissection for 5 patients. Six of 10 patients had a bleeding tendency. Eight patients received preoperative anticoagulant therapy. Prosthetic replacement was undertaken for 8 patients except for 2 patients in poor condition.There were no operative deaths in 8 surgical cases. One non-surgical case died of deteriorated bleeding tendency. The mean DIC score was 8.0+/-0.6 at admission, which was reduced to 4.4+/-0.5 at discharge (p0.05). Prothrombin time, platelet counts, and fibrinogen levels tended to be normalized by the 7th postoperative day. Serum FDP levels decreased with surgery, but tended to increase at the time of discharge and the later follow-up period. Hematologic disturbances and bleeding tendency recurred in 2 patients in the follow-up period.In the majority of patients presenting DIC with aortic aneurysm, surgical treatment can be performed safely if adequately managed by anticoagulant therapy. Consumptive coagulopathy usually resolved after surgical intervention, but some patients developed DIC in the later period. If DIC recurs, it is essential to search for contributory causes.

In a transcription/translation-based autoregulatory feedback loop of vertebrate circadian clock systems, a BMAL1-CLOCK heterodimer is a positive regulator for the transcription of the negative element gene Per. The chicken pineal gland represents a photosensitive clock tissue, but the pineal clock genes constituting the oscillator loop have been less well characterized.We identified expression of the Per2, Bmal1, Bmal2 and Clock genes in the chicken pineal gland. Messenger RNA levels of these genes exhibited overt circadian rhythms in the pineal cells, both in vivo and in culture. In vitro functional analyses revealed the formation of cBMAL1-cCLOCK and cBMAL2-cCLOCK heteromers. Both of the cBMAL-cCLOCK heteromers activated E-box element-dependent transcription, which was negatively regulated by cPER2 in luciferase assays. Co-expression of cCLOCK, cBMAL1 and cBMAL2 co-operatively activated E-box element-dependent transcription, and a greater level of expression of cBMAL2 inhibited the activation. In the cultured pineal cells, an over-expression of either cBMAL1 or cBMAL2 disrupted the circadian rhythm of melatonin production.The functional characterization of the chicken pineal clock molecules supports the key roles of BMAL1, BMAL2 and CLOCK which contribute to the E-box-dependent transcriptional regulation in the circadian clock system.