Postpartum post-dural puncture headache.
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Adult↗
Biomedical subjects
B Chandrasekar
Publications and source records attributed to B Chandrasekar.
NF-kappa B inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen.
Studies show that high Akt activity in breast carcinoma is associated with endocrine therapy resistance. Breast cancer cell lines expressing a constitutively active Akt are able to proliferate under reduced estrogen conditions, and are resistant to the growth inhibitory effects of tamoxifen. Understanding the targets of Akt signaling mediating tamoxifen resistance is of clinical significance. One possible target is nuclear factor kappa B (NF-kappa B), a transcription factor that plays a critical role in resistance to apoptosis and the induction of angiogenesis and invasion. In the present study, we found that Akt activity correlated with phosphorylation of I kappa B (the negative regulator of NF-kappa B), NF-kappa B DNA binding and tamoxifen resistance in vivo. Importantly, we found that co-treatment with the NF-kappa B inhibitor, parthenolide, or overexpression of I kappa B superrepressor restored tamoxifen sensitivity to our refractory Akt MCF-7 cells. These data suggest that activation of NF-kappa B via the PI3K/Akt signaling pathway may be a significant mechanism for development of endocrine therapy resistance in breast cancer, and that inhibition of NF-kappa B may be an effective treatment strategy to limit the progression of this disease.
Antineoplastic Agents, Hormonal↗
In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.
Periodontitis is a chronic inflammatory disease initiated by a multitude of bacteria. Persistent infection leads to generation of various inflammatory mediators, resulting in tissue destruction and osteoclastic resorption of the alveolar bone. This study describes a novel in vivo murine calvarial model to assess the effects of oral pathogens on the expression of three proinflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha] which are involved in bone resorption. We chose Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans as prototype oral pathogens. We also tested the effects of Streptococcus gordonii, an oral commensal supragingival microorganism, considered a non-pathogen. Live bacteria were injected into subcutaneous tissue overlying the parietal bone of mice calvaria for 6 days. At the end of the experimental period, tissues overlying the calvaria were removed and analyzed for proinflammatory cytokine expression by Northern blotting. Cytokine mRNA was not detected in the tissue over the calvaria of control animals. In contrast, P. gingivalis and A. actinomycetemcomitans elicited mRNA expression of all three cytokines, TNFalpha being the highest (TNFalpha > > IL-1beta > IL-6). P. gingivalis was more potent than A. actinomycetemcomitans in inducing cytokine expression. In contrast, S. gordonii induced only low levels of mRNA for IL-1beta and TNFalpha but no IL-6 mRNA induction. These results suggest that oral microorganisms with access to host tissues elicit a battery of proinflammatory cytokines. There were clear differences in profiles and, interestingly, a commensal bacterium also stimulated bone resorptive cytokine expression in host tissues.
Actinobacillus Infections↗
Coronary artery endothelial protection after local delivery of 17beta-estradiol during balloon angioplasty in a porcine model: a potential new pharmacologic approach to improve endothelial function.
OBJECTIVES: The goal of this research was to study the effect of locally delivered 17beta-estradiol (17beta-E) during angioplasty on endothelial function after percutaneous transluminal coronary angioplasty (PTCA) at four weeks. BACKGROUND: The endothelium plays a major role in the structural and functional integrity of coronary arteries and is damaged by PTCA. METHODS: Juvenile swine were subjected to PTCA, after which each artery was randomly-assigned to 600-microg 17beta-E delivered locally, an equal volume of vehicle (V) or PTCA alone. After four weeks, the improvement in endothelial function was assessed by angiography using intracoronary acetylcholine (Ach) infusion and by immunohistochemistry. RESULTS: At 10(-5) mol/l and 10(-4) mol/l Ach, significant vasoconstriction was noted in arteries treated with PTCA alone (p < 0.01 and p < 0.0001, respectively) and with PTCA plus V (p < 0.02 and p < 0.001, respectively). No significant vasoconstrictive response to Ach was observed in arteries treated with PTCA plus 17beta-E. Immunohistochemistry of vessels four weeks after PTCA revealed enhanced re-endothelialization (p < 0.0005) and endothelial nitric-oxide synthase (eNOS) expression (p < 0.0005) in PTCA plus 17beta-E-treated arteries compared with the other two treatment groups. Arteries treated with 17beta-E showed significantly lower neointima formation, which correlated inversely with the extent of re-endothelialization and eNOS expression. CONCLUSIONS: Locally delivered 17beta-E significantly enhances re-endothelialization and endothelial function after PTCA, possibly by improving the expression of eNOS. Since endothelial dysfunction can promote both restenosis and coronary spasm, local 17beta-E administration is a promising new approach to improve long-term results after PTCA.
Acetylcholine↗
Ischemia-reperfusion of rat myocardium activates nuclear factor-KappaB and induces neutrophil infiltration via lipopolysaccharide-induced CXC chemokine.
BACKGROUND: Mechanisms by which neutrophils are attracted to the myocardium in ischemia/reperfusion are not fully defined. Lipopolysaccharide-induced CXC chemokine (LIX), cytokine-induced neutrophil chemoattractant (KC), and macrophage inflammatory protein-2 (MIP-2) are rodent chemokines with potent neutrophil-chemotactic activity. The goals of the present study were to evaluate the roles of these chemokines in a rat model of ischemia/reperfusion and to examine the mechanisms of chemokine induction by oxidative stress and cytokines in cultured cardiomyocytes. METHODS AND RESULTS: Male Wistar-Kyoto rats underwent 45 minutes of ligation of the left anterior descending coronary artery, followed by reperfusion for various periods. Compared with sham-operated controls, myocardium from reperfused animals had higher levels of free radicals, increased neutrophil infiltration evidenced histologically and by elevated myeloperoxidase activity, and increased nuclear factor (NF)-kappaB DNA binding activity. Ischemia-reperfusion also induced the expression of interleukin-1beta, tumor necrosis factor (TNF)-alpha, LIX, KC, and MIP-2 mRNA and protein. LIX expression was localized to resident myocardial cells, whereas KC and MIP-2 were expressed only in infiltrating inflammatory cells. Neutralization of LIX inhibited 79% of neutrophil infiltration into previously ischemic myocardium. In contrast, neutralization of KC and MIP-2 reduced neutrophil infiltration by only 28% and 37%, respectively. In cultured cardiomyocytes, LIX expression was induced by oxidative stress or TNF-alpha and was blocked by the NF-kappaB inhibitor pyrrolidinedithiocarbamate. CONCLUSIONS: LIX is expressed by resident myocardial cells during ischemia-reperfusion and is induced in cultured cardiomyocytes by oxidative stress or TNF-alpha via NF-kappaB activation. Although KC and MIP-2 are expressed by inflammatory cells infiltrating the myocardium during reperfusion after ischemia, neutrophil recruitment to reperfused rat myocardium is mainly due to cardiomyocyte expression of LIX.
Animals↗
The hamster as a model of human visceral leishmaniasis: progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-like cytokine response.
Active human visceral leishmaniasis (VL) is characterized by a progressive increase in visceral parasite burden, cachexia, massive splenomegaly, and hypergammaglobulinemia. In contrast, mice infected with Leishmania donovani, the most commonly studied model of VL, do not develop overt, progressive disease. Furthermore, mice control Leishmania infection through the generation of NO, an effector mechanism that does not have a clear role in human macrophage antimicrobial function. Remarkably, infection of the Syrian hamster (Mesocricetus auratus) with L. donovani reproduced the clinicopathological features of human VL, and investigation into the mechanisms of disease in the hamster revealed striking differences from the murine model. Uncontrolled parasite replication in the hamster liver, spleen, and bone marrow occurred despite a strong Th1-like cytokine (IL-2, IFN-gamma, and TNF/lymphotoxin) response in these organs, suggesting impairment of macrophage effector function. Indeed, throughout the course of infection, inducible NO synthase (iNOS, NOS2) mRNA or enzyme activity in liver or spleen tissue was not detected. In contrast, NOS2 mRNA and enzyme activity was readily detected in the spleens of infected mice. The impaired hamster NOS2 expression could not be explained by an absence of the NOS2 gene, overproduction of IL-4, defective TNF/lymphotoxin production (a potent second signal for NOS2 induction), or early dominant production of the deactivating cytokines IL-10 and TGF-beta. Thus, although a Th1-like cytokine response was prominent, the major antileishmanial effector mechanism that is responsible for control of infection in mice was absent throughout the course of progressive VL in the hamster.
Animals↗
Complications of cardiac catheterization in the current era: a single-center experience.
Consecutive cardiac catheterization procedures done over a 2-yr period (April 1996 to March 1998) were prospectively analyzed to determine and characterize procedure-related complications (in-hospital and 1-mo follow-up), as they occur at present. During the study period, 11,821 procedures (7,953 diagnostic and 3,868 therapeutic) were performed. The majority of procedures (> 60%) were done in high-risk patients. Stents were implanted in 33% of patients, and adjunctive abciximab was used in 6.6% of therapeutic procedures. The overall complication rate was 8% (3.6% of diagnostic procedures and 15.1% of therapeutic procedures). The procedure-related mortality rates were 0.2%, 0.1%, and 0.5% for total, diagnostic, and therapeutic procedures, respectively. Cardiac complications were seen in 3.9% (1.5% of diagnostic and 9% of therapeutic procedures). Emergency cardiac surgery was required in 0.05% of the diagnostic procedure group and 0.3% of the therapeutic procedure group (total, 0.1%). Despite marked changes in patient population and practice, the complication rates of cardiac catheterization remain very low.
Abciximab↗
Malnutrition alters the innate immune response and increases early visceralization following Leishmania donovani infection.
Malnutrition is a risk factor for the development of visceral leishmaniasis. However, the immunological basis for this susceptibility is unknown. We have developed a mouse model to study the effect of malnutrition on innate immunity and early visceralization following Leishmania donovani infection. Three deficient diets were studied, including 6, 3, or 1% protein; these diets were also deficient in iron, zinc, and calories. The control diet contained 17% protein, was zinc and iron sufficient, and was provided ab libitum. Three days after infection with L. donovani promastigotes, the total extradermal (lymph nodes, liver, and spleen) and skin parasite burdens were equivalent in the malnourished (3% protein) and control mice, but in the malnourished group, a greater percentage (39.8 and 4.0%, respectively; P = 0.009) of the extradermal parasite burden was contained in the spleen and liver. The comparable levels of parasites in the footpads in the two diet groups and the higher lymph node parasite burdens in the well-nourished mice indicated that the higher visceral parasite burdens in the malnourished mice were not due to a deficit in local parasite killing but to a failure of lymph node barrier function. Lymph node cells from the malnourished, infected mice produced increased levels of prostaglandin E(2) (PGE(2)) and decreased levels of interleukin-10. Inducible nitric oxide synthase activity was significantly lower in the spleen and liver of the malnourished mice. Thus, malnutrition causes a failure of lymph node barrier function after L. donovani infection, which may be related to excessive production of PGE(2) and decreased levels of IL-10 and nitric oxide.
Animals↗
Calorie restriction attenuates inflammatory responses to myocardial ischemia-reperfusion injury.
The life-prolonging effects of calorie restriction (CR) may be due to reduced damage from cumulative oxidative stress. Our goal was to determine the long-term effects of moderate dietary CR on the myocardial response to reperfusion after a single episode of sublethal ischemia. Male Fisher 344 rats were fed either an ad libitum (AL) or CR (40% less calories) diet. At age 12 mo the animals were anaesthetized and subjected to thoracotomy and a 15-min left-anterior descending coronary artery occlusion. The hearts were reperfused for various periods. GSH and GSSG levels, nuclear factor-kappaB (NF-kappaB) DNA binding activity, cytokine, and antioxidant enzyme expression were assessed in the ischemic zones. Sham-operated animals served as controls. Compared with the AL diet, chronic CR limited oxidative stress as seen by rapid recovery in GSH levels in previously ischemic myocardium. CR reduced DNA binding activity of NF-kappaB. The kappaB-responsive cytokines interleukin-1beta and tumor necrosis factor-alpha were transiently expressed in the CR group but persisted longer in the AL group. Furthermore, expression of manganese superoxide dismutase, a key antioxidant enzyme, was significantly delayed in the AL group. Collectively these data indicate that CR significantly attenuates myocardial oxidative stress and the postischemic inflammatory response.
Animals↗
Local delivery of 17-beta-estradiol decreases neointimal hyperplasia after coronary angioplasty in a porcine model.
BACKGROUND: Neointimal hyperplasia is an important mechanism of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Systemically administered estrogen is known to inhibit neointimal formation after arterial injury. OBJECTIVES: We sought to assess the efficacy of locally delivered 17-beta-estradiol (BE) in inhibiting neointimal hyperplasia after PTCA. METHODS: Eighteen juvenile farm pigs were studied. Coronary angioplasty was performed in all three coronary arteries of each animal. After PTCA, each coronary artery in each pig was randomized to receive either local delivery of 600 microg BE, vehicle alone or PTCA only. Twelve animals were euthanized at 28 days for morphometric analysis, and four animals were euthanized at seven days for immunohistochemical analysis of vascular smooth muscle cell (SMC) proliferative activity. Two animals died a few days after PTCA and were excluded. RESULTS: On morphometric study, the arterial segments treated with BE demonstrated significantly less neointimal proliferation. Arteries treated with BE had reductions in several indexes of restenosis compared with arteries treated with vehicle alone or PTCA only: neointimal area (0.4+/-0.09 mm2 for BE vs. 1.14+/-0.33 mm2 for vehicle alone vs. 0.88+/-0.2 mm2 for PTCA only, p<0.05), percent neointima (12.16+/-2.57% vs. 25.46+/-4.73% vs. 23.02+/-3.97%, p<0.025), neointima/media area (0.59+/-0.14 vs. 1.75+/-0.41 vs. 1.67+/-0.43, p<0.01) and restenotic index (1.3+/-0.14 vs. 2.42+/-0.22 vs. 2.4+/-0.23, p<0.005). Immunohistochemistry showed decreased SMC proliferative activity in BE-treated arteries compared with the other two treatment groups (p<0.05). CONCLUSIONS: Local delivery of BE significantly decreases neointimal hyperplasia after PTCA in pigs, probably by the inhibition of SMC proliferation.
Angioplasty, Balloon, Coronary↗
Induction of nuclear factor kappaB but not kappaB-responsive cytokine expression during myocardial reperfusion injury after neutropenia.
Neutrophils may contribute to myocardial ischemia/reperfusion (I/R) injury by generating reactive oxygen intermediates (ROIs). ROIs activate nuclear factor (NF)-kappaB, which regulates genes for cytokines with negative inotropic effects (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha). We investigated the impact of neutrophil depletion on NF-kappaB DNA binding activity, and expression of these cytokines during myocardial I/R injury. Male WKY rats (n = 28) received a single dose of antineutrophil antiserum (i/v). Twenty two hours later, when the peripheral blood neutrophil counts were profoundly decreased (94% reduction), the animals underwent 15 min of left anterior descending coronary artery ligation followed by reperfusion for 0.25, 0.5, 1, 2, 3, and 6 h (n = 4/group). Saline-treated animals underwent a similar protocol, and served as controls (n = 28, 4/group). Neutrophil accumulation, defined by myeloperoxidase activity, was present in controls, but not in anti-PMN antisera-treated animals (at least p <0.05 at 1, 2, 3, and 6 h R). Despite this difference, in both saline- and antiserum-treated animals, the GSH levels were very similar and fell significantly (p < 0.0001) at 15 min R; the levels increased gradually over time. In contrast, GSSG levels rose at 15 and 30 min R (p < 0.05), and declined thereafter. NF-kappaB DNA binding activity increased in both groups at 15 min and again at 3 h of R. Both NF-kappaBp50 and p65 subunits were detected by supershift assay. In saline-injected controls both mRNA and protein for IL-1beta, IL-6, and TNF-alpha were detected at 1 h R; levels remained high until 3 h, then fell (except IL-6, which was elevated at 6 h). In neutropenic animals, however, a significant decrease in mRNA (at least 1.7-fold, p < 0.05) as well as protein levels (at least 2. 3-fold, p < 0.01) for all three cytokines was observed. Thus, while neutrophils had minimal effects on oxidative stress (GSH/GSSG) and oxidative stress-responsive NF-kappaB activity, they contributed significantly to myocardial cytokine expression.
Animals↗
Chronic beta-adrenergic stimulation induces myocardial proinflammatory cytokine expression.
BACKGROUND: The sympathetic nervous system and proinflammatory cytokines are believed to play key roles in the pathophysiology of congestive heart failure. To evaluate a possible relationship between these neurohormonal systems, we studied the effects of chronic beta-adrenergic stimulation on the myocardial and systemic elaboration of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. METHODS AND RESULTS: Male rats received either L-isoproterenol (2.4 mg. kg(-1). d(-1), n=8) or saline (n=7) via miniosmotic pumps for 7 days. Myocardial cytokine expression was analyzed by both Northern and Western blotting and localized in the tissue using immunohistochemistry. ELISA was performed to measure circulating levels of cytokines. In myocardium from control animals, neither TNF-alpha nor IL-1beta were detected, whereas IL-6 was present at very low levels. Isoproterenol led to a significant (P<0.01) increase in mRNA and protein expression of all 3 cytokines. Immunohistochemistry did not detect immunoreactivity for either cytokine in myocardium from controls; however, all 3 cytokines were readily detected (P<0.05) throughout the myocardium, localized to resident cells and vessels, in animals treated with isoproterenol. Neither treatment group had detectable levels of cytokines in the serum. CONCLUSIONS: Chronic beta-adrenergic stimulation induces myocardial, but not systemic, elaboration of TNF-alpha, IL-1beta, and IL-6.
Adrenergic beta-Agonists↗
beta-adrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling.
BACKGROUND: Whether beta-adrenergic blockade modulates myocardial expression of inflammatory cytokines and nitric oxide (NO) in heart failure is unclear. METHODS AND RESULTS: We administered oral metoprolol or no therapy to rats for 12 weeks after large myocardial infarction and subsequently examined left ventricular (LV) remodeling; myocardial tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 expression; and NO. In untreated rats, echocardiography revealed significant (P<0.001) LV dilatation and systolic dysfunction compared with sham. Papillary muscle studies revealed isoproterenol hyporesponsiveness to be unaltered by NO synthase (NOS) inhibition. Circulating NO metabolites were undetectable. In noninfarcted myocardium, although inducible NOS (iNOS) mRNA was absent, TNF-alpha, IL-1beta, and IL-6 mRNA and protein were markedly elevated compared with sham (P<0.001), with 2-fold higher expression (P<0.025) of IL-6 compared with TNF-alpha or IL-1beta. Metoprolol administration starting 48 hours after infarction (1) attenuated (P<0.02) LV dilatation and systolic dysfunction, (2) preserved isoproterenol responsiveness (P<0.025) via NO-independent mechanisms, and (3) reduced myocardial gene expression and protein production of TNF-alpha and IL-1beta (P<0. 025) but not IL-6, which remained high. CONCLUSIONS: During heart failure development, adrenergic activation contributes to increased myocardial expression of TNF-alpha and IL-1beta but not IL-6, and one mechanism underlying the beneficial effects of beta-adrenergic blockade may involve attenuation of TNF-alpha and IL-1beta expression independent of iNOS and NO.
Adrenergic beta-Antagonists↗
Platelets and restenosis.
Restenosis is currently the major limitation of percutaneous transluminal coronary angioplasty (PTCA). Factors such as elastic recoil, migration of vascular smooth muscle cells from media to intima, neointimal proliferation and vascular remodeling underly the restenotic process. Presently there is no effective therapy available for restenosis. The role of platelets in the development of thrombosis and abrupt closure after PTCA is well recognized. However, the effects of platelets in PTCA extend well beyond the early phase. Although antiplatelet agents such as glycoprotein IIb/IIIa antagonists have been reported to reduce target vessel revascularization, major unresolved controversies still exist. This report reviews the potential role of platelets in restenosis. Various drugs, successfully tested in experimental studies and in a small number of human studies, that inhibit the effect of platelets on the restenotic process are also reviewed.
Angioplasty, Balloon, Coronary↗
Differential regulation of nitric oxide synthase isoforms in experimental acute chagasic cardiomyopathy.
We have previously demonstrated induction and high level expression of IL-1beta, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1.5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1.5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites.
Acute Disease↗
Incidence and risk factors predictive of unstable angina resulting from restenosis after percutaneous angioplasty of saphenous vein grafts.
BACKGROUND: The current study was designed to determine the incidence and risk factors for unstable angina resulting from restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) of saphenous vein graft (SVG), about which little data are available. METHODS AND RESULTS: A retrospective analysis of a consecutive series of 212 patients undergoing PTCA of SVG was performed. Procedural success was achieved in 200 patients (94.3%) who formed the study group. During a follow-up of 16.8 +/- 10.2 months, 24.5% of patients presented with unstable angina resulting from restenosis. There was a higher prevalence of dyslipidemia (81. 6% vs 51.2%, P <.0002) and greater postprocedural residual stenosis (14.2% +/- 12.6% vs 7.1% +/- 11.0%, P =.007) in patients with unstable angina caused by restenosis compared with the remaining patient population. By multivariate analysis, dyslipidemia (odds ratio [OR] 3.55, 95% confidence interval [CI] 1.64-8.39, P <.002) and to a lesser extent postprocedural residual stenosis (OR 1.04, 95% CI 1.01-1.07, P <.05) were predictive of unstable angina resulting from restenosis. Among dyslipidemic patients, those not on lipid-lowering drugs during the index procedure had a significantly higher incidence of unstable angina caused by restenosis than did those on lipid-lowering drugs (P <.05). CONCLUSION: Unstable angina caused by restenosis presents in as many as one fourth of patients undergoing PTCA of SVG. Dyslipidemia strongly, and to a lesser extent postprocedural residual stenosis, predicts its occurrence. Scrupulous attention to these modifiable risk factors may help reduce the incidence of unstable angina after SVG angioplasty.
Adult↗
Aortic valve disease and left dominant coronary system a significant association.
OBJECTIVES: To study the dominance of coronary artery distribution in patients with aortic valve disease. MATERIAL AND METHODS: The prevalence of left dominant coronary artery system in patients with aortic valve disease was compared with patients without aortic valve disease undergoing coronary angiography. Group 1 consisted of 237 patients with symptomatic aortic valve disease and Group 2 consisted of 241 consecutive patients without aortic valve disease undergoing cardiac catheterisation. RESULTS: Forty two patients in Group 1 and 20 patients in Group 2 (p < 0.01) showed a left dominant pattern of supply. Fifteen patients in Group 1 and eight patients in Group 2 showed a co-dominant pattern of supply (p = NS). Among patients in Group 1, there was no significant difference in the increased prevalence of left dominant system between patients with congenital or acquired aortic valve disease or between the different categories of aortic valve lesions. CONCLUSION: Patients with aortic valve disease show a statistically significant higher prevalence of left dominant pattern of blood supply. This higher prevalence of left dominance is seen in all categories of aortic valve lesions, namely, predominant aortic stenosis, predominant aortic regurgitation and in combined aortic stenotic and regurgitant lesions.
Adolescent↗
Regulation of CCAAT/Enhancer binding protein, interleukin-6, interleukin-6 receptor, and gp130 expression during myocardial ischemia/reperfusion.
BACKGROUND: Interleukin (IL)-6 is elevated in myocardium after ischemia and reperfusion. The IL-6 promoter/enhancer region contains response elements for nuclear factor-kappaB, AP-1, and CCAAT/enhancer binding protein (C/EBP). Expression and regulation of C/EBP in rat myocardium after ischemia and reperfusion has not been defined, nor has the behavior of the specific IL-6 receptor (IL-6R) or the signal transducer gp130. METHODS AND RESULTS: C/EBP DNA binding activity was not detected in shams or in previously ischemic tissue at 15 minutes of reperfusion; it was detected at 30 minutes of reperfusion, increased at 1 hour of reperfusion, and declined by 6 hours of reperfusion. A supershift was observed with anti-C/EBP-beta but not with anti-alpha or anti-delta antibodies. mRNA and protein levels of IL-6 and gp130 were detected at low levels in controls, increased at 1 hour of reperfusion, and remained high until 6 hours of reperfusion. IL-6R mRNA and protein were not detected in controls, but its mRNA was induced at 1 hour of reperfusion and its protein at 2 hours of reperfusion. Although effects of reperfusion were rapid, in ischemic tissue not reperfused, low levels of C/EBP were detected at 4 hours, and at 24 hours the levels were slightly elevated. Significant upregulation in IL-6, IL-6R, and gp130 occurred only at 24 hours of sustained ischemia. CONCLUSIONS: Reperfusion after a brief period of ischemia caused induction of myocardial C/EBP (beta-subunit). The rapid and sustained production of IL-6 with concomitant expression of IL-6 receptor and gp130 suggest that these factors may participate in a local inflammatory cascade after myocardial ischemia and reperfusion.
Animals↗