Acute Disease ; Adult ; Altitude Sickness ; blood ; enzymology ; Glutathione ; blood ; Glutathione Peroxidase ; blood ; Humans ; Lipid Peroxidation ; Male ; Military Personnel ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Oxidoreductases ; metabolism ; Superoxide Dismutase ; blood

Poxviruses, a type of ds-DNA viruses which mainly target at the epithelial cell, are the pathogens of human and animals. During the revolution of poxviruses, the viruses encode multiple proteins that regulate the immune system to monitor the viral reproductive cycle in host cells. The nuclear kappa B (NF-kappaB) pathway is essential to signal transcription in the innate immune system. Therefore, poxviruses have adopted different strategies to elude immune detection and destruction regulated by NF-kappaB. Further research in this field would help us develop preventive and therapeutic preparation for pox. Given the renewed interest in poxvirus, we review the current understanding of how the various classes of poxviralimmunomodulatory proteins target and manipulate the NF-kappaB pathway.
Animals ; Host Specificity ; Humans ; NF-kappa B ; metabolism ; Poxviridae ; physiology ; Signal Transduction

OBJECTIVETo explore the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, T1 and susceptibility to mountain sickness.

METHODSForty-three soldiers with acute mountain sickness and 80 healthy soldiers matching with sex/age and training under the same condition were divided into case group and control group. A multiple polymerase chain reaction method was used to detect GSTM1 and GSTT1 genes in genomic DNA isolated from peripheral blood cells from both cases and controls.

RESULTSThe frequency of the GSTT1 positive genotype was significantly higher in cases (69.8%) than in controls (42.5%) (P = 0.004, OR = 3.12, 95% CI 1.42 approximately 6.86). The frequency of GSTM1 negative genotype was also higher in cases (72.1%) than in controls (52.5%) (P = 0.03, OR = 2.34, 95% CI 1.05 approximately 5.02). Persons with both GSTM1 and GSTT1 negative genotypes had 5-fold more risk than those with GSTT1 negative and GSTM1 positive genotypes in developing mountain sickness (OR = 5.04, 95% CI: 1.00 approximately 25.3).

CONCLUSIONGenetic polymorphisms of glutathione S-transferase M1, T1 may be the risk factors in the development of mountain sickness.

Acute Disease ; Adult ; Altitude Sickness ; genetics ; Case-Control Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors

The effects of resveratrol on the discharges of neurons in CA1 area of rat hippocampal slices were examined by using extracellular recording technique. The results are as follows: (1) In response to the application of resveratrol (0.05, 0.5, 5.0 micromol/L, n=52) into the superfusate for 2 min, the spontaneous discharge rate of 46/52 (88.5%) neurons was significantly decreased in a dose-dependent manner; (2) Application of L-glutamate (0.2 mmol/L) into the superfusate led to a marked increase in discharge rate of all 8 (100%) slices in an epileptiform pattern. The increased discharges were suppressed by application of resveratrol (5.0 micromol/L); (3) In 7 slices, perfusion of the selective L-type calcium channel agonist, Bay K8644 (0.1 micromol/L), induced a significant increase in the discharge rate of 6/7 (85.7%) slices. The increased discharges were suppressed by application of resveratrol (5.0 micromol/L); (4) In 9 slices, perfusion of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 50 micromol/L) into the superfusate significantly augmented the discharge rate of 7/9 (77.8%) slices. Resveratrol (5.0 micromol/L) applied into the superfusate reduced the increased discharges of all 7/7 (100%) neurons; (5) In 10 units, the large-conductance Ca(2+)-activated K(+) channel blocker (tetraethylammonium chloride, TEA, 1 mmol/L) significantly increased the discharge rate of 9/10 (90%) slices. Resveratrol (5.0 micromol/L) applied into the superfusate inhibited the discharges of 8/9 (88.9%) slices. These results suggest that resveratrol inhibits the electrical activity of CA1 neurons. This effect may be related to the blockade of L-type calcium channel and a subsequent reduction of calcium influx, and probably has no association with large-conductance Ca(2+)-activated K(+) channel.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Animals ; Calcium Channel Agonists ; pharmacology ; Calcium Channel Blockers ; pharmacology ; Calcium Channels, L-Type ; Electrophysiology ; Glutamic Acid ; pharmacology ; Hippocampus ; cytology ; physiology ; Male ; Neurons ; physiology ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology

BACKGROUNDDevelopment of vulnerable lesions is not limited to the target lesions, but a pan-coronary process. Such lesions are identified by positive remodeling (intravascular ultrasound (IVUS) and complex lesions (angiography)). The prevalence of lesions with vulnerable characteristics in patients with stable angina was not well known. The purpose of the present study was to evaluate the relationship between coronary artery remodeling and incidence of angiographic complex lesions and its calcification in stable angina patients.

METHODSOne hundred and sixty-one stable angina patients (95 males, aged (68 +/- 11) years) with 161 de novo target lesions were studied using pre-interventional IVUS. Remodeling index was defined as the lesion divided by reference vessel area; positive remodeling was defined as remodeling index > 1.05. Besides the 161 target lesions, there were 613 angiographic lesions with > 30% diameter stenoses, classified as complex or smooth. Multiple complexes were defined as more than one complex lesion in one patient. Stenoses of at least 70% were described as tight. Calcium arc area was used as a new method to quantify coronary calcification.

RESULTSFifty-six patients had positive remodeling target lesion, while 105 did not. The overall number of lesions with a diameter stenoses > 30% was similar in patients with or without positive remodeling, and the frequency of angiographically complex lesions was higher in positive remodeling patients, especially at non-target site. Calcium arc area was smaller in patients with positive remodeling.

CONCLUSIONSPositive remodeling on intravascular ultrasound was associated with more complex lesions angiographic findings, especially at non target site. Positive remodeling was found less calcified in patients with stable angina.

Aged ; Aged, 80 and over ; Angina Pectoris ; diagnostic imaging ; pathology ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Male ; Middle Aged ; Ventricular Remodeling ; physiology

BACKGROUNDCathepsin S and its endogenous inhibitor cystatin C are implicated in the pathogenesis of atherosclerosis, especially in the plaque destabilization and rupture leading to acute coronary syndrome. However, whether circulating cathepsin S and cystatin C also change in association with coronary plaque morphology is unknown yet.

METHODSWe recruited 98 patients with unstable angina (UA, n = 6) or stable angina (SA, n = 2) who had a segmental stenosis resulting in > 20% and < 70% diameter reduction in one major coronary artery on coronary angiography. Thirty-one healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate plaque morphology. Plasma cathepsin S and cystatin C were measured as well.

RESULTSAt the culprit lesion site, plaque area ((7.85 +/- 2.83) mm(2) vs (6.53 +/- 2.92) mm(2), P = 0.027), plaque burden ((60.92 +/- 11.04)% vs (53.87 +/- 17.52)%, P = 0.025), remodeling index (0.93 +/- 0.16 vs 0.86 +/- 0.10, P = 0.004) and eccentricity index (0.74 +/- 0.17 vs 0.66 +/- 0.21, P = 0.038) were bigger in UA group than in SA group. Plasma cathepsin S and cystatin C were significantly higher in patients than in controls (P < 0.01). Plasma cathepsin S was higher in UA group ((0.411 +/- 0.121) nmol/L) than in SA group ((0.355 +/- 0.099) nmol/L, P = 0.007), so did the plasma cystatin C ((0.95 +/- 0.23) mg/L in UA group, (0.84 +/- 0.22) mg/L in SA group; P = 0.009). Plasma cathepsin S positively correlated with remodeling index (r = 0.402, P = 0.002) and eccentricity index (r = 0.441, P = 0.001), and plasma cystatin C positively correlated with plaque area (r = 0.467, P < 0.001) and plaque burden (r = 0.395, P = 0.003) in UA group but not in SA group.

CONCLUSIONSPlasma cathepsin S and cystatin C increased significantly in UA patients. In angina patients, higher plasma cathepsin S may suggest the presence of vulnerable plaque, and higher plasma cystatin C may be a clue for larger atherosclerotic coronary plaque.

Adult ; Aged ; Aged, 80 and over ; Cathepsins ; blood ; Coronary Artery Disease ; blood ; diagnostic imaging ; pathology ; Cystatin C ; blood ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Ultrasonography, Interventional ; methods

OBJECTIVETo analyze the risk factors related to in-hospital bleeding for patients with acute coronary syndrome (ACS).

METHODSClinical and therapeutic data of 3807 patients who were registered with acute coronary syndrome in SINO-GRACE in China from March 2001 to December 2007 were reviewed. A total of 57 patients were grouped to bleeding group and 234 out of the remaining 3750 patients without bleeding were randomly chosen and served as non-bleeding group. Hemorrhage-related factors were screened and compared between the two groups. Unitary logistic regression analysis was performed to detect the possible factors related to hemorrhage. Factors with P < 0.1 were further analyzed by stepwise regression method and multivariate conditional logistic regression analyses.

RESULTS(1) Age, history of coronary artery bypass graft (CABG), previous hemorrhage, renal failure and heart failure as well incidence of acute coronary syndrome were significantly higher in bleeding group than in non-bleeding group (all P ≤ 0.05). Patients were more often treated with clopidogrel and glycoprotein (GP) IIb/IIIa receptor antagonist in bleeding group than in non-bleeding group. (2) Single factor logistic regression analysis showed that age > 70 years, history of previous bleeding, renal failure, heart failure, clopidogrel and GP IIb/IIIa receptor antagonists use, non-ST-segment elevation myocardial infarction, inferior wall, lateral myocardial infarction, CABG were risk factors for bleeding (all P < 0.05). (3) Multivariate logistic regression analysis showed that history of renal failure (OR = 19.77, 95%CI 4.38 - 89.18, P < 0.01) and clopidogrel (OR = 19.77, 95%CI 4.38 - 89.18, P < 0.01) and GPIIb/IIIa receptor antagonist (OR = 343.57, 95%CI 40.39 - 999.99, P < 0.01) use were the independent risk factors for bleeding.

CONCLUSIONOur results show that renal failure history and clopidogrel and GPIIb/IIIa receptor antagonist use are independent risk factors for in-hospital bleeding in patients with acute coronary syndrome.

Acute Coronary Syndrome ; complications ; pathology ; Age of Onset ; Aged ; Female ; Hemorrhage ; etiology ; Hospitalization ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Platelet Glycoprotein GPIIb-IIIa Complex ; antagonists & inhibitors ; Renal Insufficiency ; Risk Factors ; Ticlopidine ; analogs & derivatives ; therapeutic use

OBJECTIVESTo evaluate the inhibitory effect mediated by combination of small interfering RNAs (siRNAs) targeting different sites of hepatitis B virus (HBV) transcripts on the viral replication and antigen expression in vitro.

METHODS(1) Seven siRNAs targeting surface (S), polymerase (P) or precore (PreC) region of HBV genome were designed and chemically synthesized. (2) HBV-producing HepG2.2.15 cells were treated with or without siRNAs for 72 h. (3) HBsAg and HBeAg in the cell culture medium were detected by enzyme-linked immunoadsorbent assay. (4) Intracellular viral DNA was quantified by real-time PCR (Polymerase Chain Reaction). (5) HBV viral mRNA was reverse transcribed and quantified by real-time PCR. (6) The change of cell cycle and apoptosis was determined by flow cytometry.

RESULTSOur data demonstrated that synthetic small interfering RNAs (siRNAs) targeting S and PreC gene could efficiently and specifically inhibit HBV replication and antigen expression. The expression of HBsAg and HBeAg and the replication of HBV could be specifically inhibited in a dose-dependent manner by siRNAs. Furthermore, our results showed that the combination of siRNAs targeting various regions could inhibit HBV replication and antigen expression in a more efficient way than the use of single siRNA at the same final concentration. No apoptotic change was observed in the cell after siRNA treatment.

CONCLUSIONOur results demonstrated that siRNAs exerted robust and specific inhibition on HBV replication and antigen expression in a cell culture system and combination of siRNAs targeting different regions exhibited more potency.

Apoptosis ; Cell Cycle ; Cell Line, Tumor ; DNA, Viral ; biosynthesis ; Flow Cytometry ; Gene Expression Regulation, Viral ; genetics ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B e Antigens ; metabolism ; Hepatitis B virus ; genetics ; physiology ; Humans ; RNA, Small Interfering ; genetics ; metabolism ; Virus Replication ; genetics

The effects of resveratrol on the discharges of neurons in rat subfornical organ (SFO) slices were examined by using extracellular recording technique. The results are as follows: (1) In response to the application of resveratrol (1, 5, 10 mumol/L, n=65) into the superfusate for 2 min, the spontaneous discharge rate of 60/65 (92.3%) neurons was significantly decreased in a dose-dependent manner;(2) Application of L-glutamate (0.3 mmol/L) into the superfusate led to a marked increase in discharge rate of all 12 (100%) neurons in an epileptiform pattern. The increased discharges of 10/12 (83.3%) neurons were suppressed by application of resveratrol (5 mumol/L);(3) In 8 neurons, the selective L-type calcium channel agonist, Bay K8644 (0.1 mumol/L), induced a significant increase in discharge rate of all 8 (100%) neurons. The increased discharges of all 8 (100%) neurons were suppressed by resveratrol (5 mumol/L);(4) In 14 neurons, nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) 50 mumol/L significantly increased the discharge rate of 11/14 (78.6%) neurons. Resveratrol (5 ?mol/L) applied into the superfusate reduced the increased discharges of 9/11 (81.8%) neurons;(5) In 12 neurons, the large-conductance Ca(2+)-activated K(+) channel blocker tetraethylammonium chloride (TEA) 1 mmol/L significantly increased the discharge rate of 10/12 (83.3%) neurons. Resveratrol (5 mumol/L) inhibited the increased discharges of 9/10 (90%) neurons. These results suggest that resveratrol inhibits the electrical activity of SFO neurons. This effect may be related to its properties of blockade of L-type voltage-gated calcium channel and nitric oxide (NO) promoting, and probably has no association with large-conductance Ca(2+)-activated K(+) channel.

BACKGROUNDMany patients with acute coronary syndrome (ACS) develop recurrent angina (RA) during hospitalization. The aim of this non-randomized, prospective study was to investigate the predictive factors of RA in unselected patients with ACS enrolled in the global registry acute coronary events (GRACE) during hospitalization in China.

METHODSBetween March 2001 and October 2004, enrolled were 1433 patients with ACS, including ST segment elevation myocardial infarction (662, 46.2%), non-ST segment elevation myocardial infarction (239, 16.7%) and unstable angina (532, 37.1%). The demographic distribution, medical history and clinical data were collected to investigate the predictive factors of RA by Logistic regression.

RESULTSDuring hospitalization 275 (19.2%) patients were documented with RA including unstable angina (53.2%), non-ST segment elevation myocardial infarction (27.5%), ST segment elevation myocardial infarction (19.3%). A comorbidity of dyslipidemia, prior angina, percutaneous coronary intervention (PCI) within 6 months was more common in patients with RA, P < 0.05. In the patients with RA, a significantly higher proportion of patients with acute pulmonary edema was observed, 23 (8.4%) versus 43 (3.7%), P = 0.001. Acute renal failure was present in 8 (2.9%) of patients with RA versus 19 (1.6%) of patients without RA, P = 0.165. Hemorrhagic events were present in 6 (2.2%) of patients with RA versus 8 (0.7%) of patients without RA, ventricular tachycardia/ventricular fibrillation events in 12 patients (4.3%) versus 22 patients (1.9%), congestive heart failure in 69 patients (25.0%) versus 94 patients (8.1%), myocardial re-infarction in 28 patients (10.1%) versus 15 patients (1.3%), P < 0.05, respectively. A lower proportion of patients with RA underwent in-hospital PCI, 687 (59.3%) versus 114 (41.5%), P = 0.000. A higher proportion of patients with RA received heparin, 260 (94.5%) versus 1035 (89.4%), P = 0.006; and beta-blockers 176 (64.0%) versus 864 (74.5%), P = 0.000. Multivarible regression analysis showed that RA was associated with prior angina (OR 2.086, 95% CI 1.466 - 2.967), in-hospital PCI (OR 0.579, 95% CI 0.431 - 0.778), in-hospital congestive heart failure (OR 2.410, 95% CI 1.634 - 3.555), myocardial re-infarction (OR 7.695, 95% CI 3.701 - 15.999), beta-blocker (OR 0.626, 95% CI 0.458 - 0.855), and heparin (OR 3.411, 95% CI 1.604 - 7.382).

CONCLUSIONSIn-hospital congestive heart failure, myocardial re-infarction, prior angina history and use of heparin are stronger independent predictors of RA; beta-blockers and PCI are also important predictive factors for RA.

Acute Coronary Syndrome ; epidemiology ; Adult ; Aged ; Angina Pectoris ; etiology ; therapy ; China ; epidemiology ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Registries