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

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

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

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

OBJECTIVETo investigate the relationship between heat stress proteins 70 (HSPs70) gene polymorphism and the risk of acute mountain sickness.

METHODSFifty-six soldiers with acute mountain sickness and 173 soldiers without that were chosen as cases and controls. HSP70-1, HSP70-2 genotypes were analyzed by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.

RESULTSThe HSP70-1 polymorphism was similar in two groups. The genotype frequency of HSP70-2 B/B in acute mountain sickness group (23.2%) was significantly higher than that in the control (6.9%, P < 0.05, OR = 4.02).

CONCLUSIONThere is a significantly increased association of HSP70-2 B/B genotype with the risk of acute mountain sickness. Individuals with HSP70-2 B/B genotype may have weaker adaptive ability than those without this genotype under altitude stress. The results contribute to provide scientific bases for finding these individuals in specified occupational people, ensuring their health and enhancing work efficiency.

Acute Disease ; Adolescent ; Adult ; Altitude ; Altitude Sickness ; epidemiology ; genetics ; Genotype ; HSP70 Heat-Shock Proteins ; genetics ; Humans ; Male ; Polymorphism, Genetic ; Young Adult

BACKGROUNDCilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary bare metal stent implantation for thrombosis and restenosis prevention. This prospective randomized and double blind trial was designed to investigate the safety and efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis.

METHODSOne hundred and twenty patients who underwent elective stent were randomly assigned to treatment group with cilostazol 200 mg/d (n = 60), clopidogrel 75 mg/d and aspirin 100 mg/d or to control group with clopidogrel treatment 75 mg/d (n = 60) and aspirin 100 mg/d. Follow-up coronary angiography was performed 6 - 9 months later.

RESULTSNine months major adverse cardio-cerebral event (MACCE) were lower in treatment groups (P < 0.05). The quantitative coronary angiography (QCA) at 6 months follow-up showed that minimum lumen diameter (MLD) was higher in treatment group than that of control group [(2.14 +/- 0.52) mm vs (1.82 +/- 0.36) mm, P < 0.05]. Late lumen loss (LL) [(0.82 +/- 0.42) mm vs (1.31 +/- 0.58) mm; P < 0.01], restenosis rate (RR) (14% vs 32%; P < 0.05) and target lesion revascularizaion (TLR) rate (5% vs 17%; P < 0.05) were lower in treatment group than in control group.

CONCLUSIONCilostazol therapy is an effective regimen for prevention not only stent thrombosis but also RR and TLR through reducing MLD without the risk of increasing bleeding.

Adult ; Aged ; Coronary Angiography ; Coronary Disease ; blood ; therapy ; Double-Blind Method ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Prospective Studies ; Stents ; Tetrazoles ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

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.