There are growing evidences suggesting a pivotal role of oxidative stress in the pathophysiology of preeclampsia. We investigated oxidative stress in the rat model of preeclampsia, and in clinical cases. Pregnant female rats were injected intraperitoneally with deoxycorticosterone acetate (DOCA) and given 0.9% saline as drinking water during their pregnancy. We assessed plasma F2-isoprostane (8-iso-PGF2alpha) and malondialdehyde (MDA) in a rat model, and the same markers in the plasma of maternal blood and fetal cord blood in pregnant women with preclampsia. Blood samples from the umbilical arteries and veins were collected separately. The concentrations of MDA were increased in the preeclampsia groups of animal and humans, compared with the control group; it was significantly increased in the umbilical artery and vein of the preeclampsia group. The concentrations of F2-isoprostane were elevated in the preeclampsia groups of animal and humans, compared with the control group, and the increase in F2-isoprostane concentration was prominent in the umbilical vein than umbilical artery of the preeclampsia group. Therefore, it appears that the placenta has an important role in the pathophysiology of preeclampsia, and the F2-isoprostanes of the umbilical vein may serve as a relatively reliable marker for ischemic/hypoxic injury to the fetus during the perinatal period.
Animals ; Desoxycorticosterone ; Drinking Water ; F2-Isoprostanes ; Female ; Fetal Blood ; Fetus ; Humans ; Malondialdehyde ; Models, Animal* ; Oxidative Stress ; Placenta ; Plasma ; Pre-Eclampsia* ; Pregnancy ; Pregnant Women ; Rats* ; Umbilical Arteries ; Umbilical Veins ; Veins

BACKGROUND AND OBJECTIVES: This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I PIP, a marker of myocardial fibrosis, was related to the change of the ventricular filling dynamics in patients with early type 2 diabetes mellitus (DM). SUBJECTS AND METHODS: Echocardiography was performed in 28 patients with type 2 DM and 32 age-matched healthy controls, ranging from 31-69 years of age, with normal left ventricular (LV) systolic function and ECG at rest. Subjects with diabetic complications, including microalbuminuria, nephropathy (Cr>1.3 mg/dL), severe obesity (BMI> or =30 kg/m2), LV hypertrophy (LV septal thickness and/or posterior wall thickness 12 mm on M-mode) and hypertension, were excluded. The serum concentrations of PIP and Transforming growth factor TGF-beta1 were measured by enzyme immunoassay methods. RESULTS: The type 2 DM group had lower mitral (Type 2 DM vs. Control: 0.88+/-0.28 vs. 1.17+/-0.34, p<0.01) and tricuspid E/A ratios (1.15+/-0.25 vs. 1.30+/-0.25, p=0.01) than the control group. The level of serum PIP was higher (p<0.05) in patients with type 2 DM than in the control group (131.1+/-45.6 vs. 109.3+/-32.5). The difference in the duration between transmitral forward (A) and pulmonary venous retrograde (Ar) waves (A-Ar) was considered an estimate of a passive diastolic function. A-Ar was inversely related with the serum PIP level in type 2 diabetes (r=-0.43, p=0.03). CONCLUSION: These results show a relationship between the LV diastolic function and the serum concentration of PIP in early type 2 DM. These findings suggest that the determination of the serum level of PIP is a useful method for the screening and early diagnosis of myocardial fibrosis associated with DM.
Collagen Type I ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Diastole ; Early Diagnosis ; Echocardiography ; Electrocardiography ; Fibrosis* ; Humans ; Hypertension ; Hypertrophy ; Immunoenzyme Techniques ; Mass Screening ; Obesity, Morbid ; Procollagen ; Transforming Growth Factor beta1 ; Transforming Growth Factors

BACKGROUND AND OBJECTIVES: Peripartum cardiomyopathy (PPCM) is a rare form of heart failure affecting women between the last month of pregnancy and the first five months after delivery. The etiology and prognostic factors of PPCM remains poorly understood, although some risk factors have been described. SUBJECTS AND METHODS: In order to characterize the features of PPCM, clinical and echocardiographic data, obtained from 19 patients who fulfilled diagnostic criteria of PPCM, from January 1996 to march 2001, were retrospectively analyzed. We divided the sample into 2 groups, which were classified according to clinical and echocardiographic improvements. (Group I; patients who improved, Group II; patients who did not improved, or deteriorated). RESULTS: Patients with PPCM (n=19, age: 32+/-5 yrs, NYHA Class: II-IV, LVEF: 34.1+/-8.8%, follow-up period: 14.2+/-16.3 months) had a high frequencies of the following clinical factors: Anaemia (16/19, 84.2%); Pre-eclampsia (11/19, 57.9%); Multiparity (11/19, 57.9%); aged over 30 yrs old at delivery (11/19, 57.9%). During follow up, 10 patients improved to NYHA Class I, 8 patients failed to improve, or deteriorated, and 1 patient died due to ventricular fibrillation. Group II (n=9, age: 31+/-3 yrs, follow up LVEF: 38.8+/-12.9%), as compared to Group I (n=10, age: 33+/-6 yrs, follow up LVEF: 56.4+/-6.4%), had greater left ventricular end-systolic dimension (LVESD, 53.0+/-7.7 mm vs 45.9+/-4.8 mm; p<0.05). CONCLUSION: PPCM has a high rate of progression to dilated cardiomyopathy. Therefore, in pregnant women with common clinical findings of PPCM, including anemia, pre-eclampsia, multiparity and old age at delivery, the initial echocardiographic assessment for cardiac function is essential, and serial follow-up is required.
Anemia ; Cardiomyopathies* ; Cardiomyopathy, Dilated ; Echocardiography ; Female ; Follow-Up Studies ; Heart Failure ; Humans ; Parity ; Peripartum Period* ; Pre-Eclampsia ; Pregnancy ; Pregnant Women ; Retrospective Studies ; Risk Factors ; Ventricular Fibrillation

BACKGROUND AND OBJECTIVES: Radiation therapy is one of the promising new treatment for restenosis, which is a major problem for the long-term success after angioplasty. We compared radiation therapy only and combined therapy of paclitaxel and radiation on neointimal hyperplasia after injury of rat carotid artery to see whether we can reduce the effective dosage of radiation and thus diminish untoward consequence of radiation if paclitaxel could function as a cell-cycle selective radiosensitizer. MATERIAL AND METHODS: A standardized carotid balloon catheter arterial injury was produced in 65 rats. First group was composed of a single dose of paclitaxel 1 mg/kg body weight, 2 mg/kg or 4 mg/kg, which was administrated intraperitoneally at 2 hours after injury. Second group received external radiation at doses of 2.5 or 5 Gy at 24 hours after injury. Third group was treated with combined paclitaxel-radiation: paclitaxel was injected at 2 hours after injury and then external radiation was delivered 24 hours later. At 21 days after injury, the cross-sectional area of neointima and the ratio of intima/medial area were determined from axial sections using image analysis. RESULTS: Single dose of paclitaxel had no effect in reducing smooth muscle cell proliferation. Minimum effective single dose to inhibit neointimal hyperplasia was 5 Gy. Combined paclitaxel-radiation group except subgroup with paclitaxel 1 mg/kg and 2.5 Gy radiation showed significant reduction of neointimal area compared to group with 2.5 Gy radiation. CONCLUSION: Low-dose external radiation combined with paclitaxel can more effectively inhibit smooth muscle cell pro-liferation and neointimal hyperplasia than radiation only in the rat carotid injury model.
Angioplasty ; Animals ; Body Weight ; Carotid Arteries ; Catheters ; Hyperplasia* ; Myocytes, Smooth Muscle ; Neointima ; Paclitaxel* ; Radiation Dosage ; Rats*

We recently experienced 2 cases of a novel cardiomyopathy following various stressful conditions. Here, we report on this novel cardiomyopathy showing transient left ventricular apical wall motion abnormalities following stress. Our cases exhibited an acute onset, transient left ventricular apical wall motion abnormalities with chest symptoms, electrocardiographic changes and minimal enzyme release, which mimicked acute myocardial infarction without stenosis on the coronary angiograms. The novel cardiomyopathy developed in our patients following aggravation of a systemic disorder (acute pyelonephritis with septicemia) and noncardiac surgery (total hysterectomy). Both our cases exhibited the typical echocardiographic findings of asynergy of the apical region with hypercontraction of the basal segment of the left ventricle, and wall motion abnormalities, which improved rapidly within a few weeks.
Cardiomyopathies* ; Constriction, Pathologic ; Echocardiography ; Electrocardiography ; Heart Ventricles ; Humans ; Myocardial Infarction* ; Pyelonephritis ; Thorax

During the highly pathogenic avian influenza (HPAI) H5N8 virus outbreak in Korea, a dog in layer farm contaminated by H5N8 was reported seropositive for HPAI H5N8. To investigate the possibility of adaptation and transmission of HPAI H5N8 to dogs, we experimentally inoculated dogs with H5N8. Viral genes were weakly detected in nasal swabs and seroconversions in inoculated and contact dogs. Although the H5N8 virus did not induced severe clinical signs to dogs, the results suggest that surveillance of farm dogs should continue as a species in which the avian influenza virus may acquire infectivity to mammals through frequent contact with the virus.
Agriculture ; Animal Experimentation ; Animals ; Dogs* ; Genes, Viral ; Influenza in Birds* ; Korea ; Mammals ; Seroconversion ; Virulence

A/Puerto Rico/8/34 (PR8)-derived recombinant viruses have been used for seasonal flu vaccines; however, they are insufficient for vaccines against some human-fatal H5N1 highly pathogenic avian influenza (HPAI) viruses (HPAIV) due to low productivity. Additionally, the polymerase basic 2 (PB2) protein, an important mammalian-pathogenicity determinant, of PR8 possesses several mammalian-pathogenic mutations. We previously reported two avian PB2 genes (01310 and 0028) related to efficient replication in embryonated chicken eggs (ECEs) and nonpathogenicity in BALB/c mice. In this study, we generated PR8-derived H5N1 recombinant viruses harboring hemagglutinin (attenuated) and neuraminidase genes of a clade 2.3.2.1c H5N1 HPAIV (K10-483), as well as the 01310 or 0028 PB2 genes, and investigated their replication and immunogenicity. Compared with a control virus harboring six internal PR8 genes (rK10-483), the recombinant viruses possessing the 01310 and 0028 PB2 genes showed significantly higher replication efficiency in ECEs and higher antibody titers in chickens. In contrast to rK10-483, none of the viruses replicated in BALB/c mice, and all showed low titers in Madin-Darby canine kidney cells. Additionally, the recombinant viruses did not induce a neutralization antibody but elicited decreased protective immune responses against K10-483 in mice. Thus, the highly replicative and mammalian nonpathogenic recombinant H5N1 strains might be promising vaccine candidates against HPAI in poultry.
Animals ; Chickens ; Efficiency ; Eggs ; Hemagglutinins ; Influenza in Birds* ; Influenza Vaccines ; Kidney ; Mice ; Neuraminidase ; Ovum ; Poultry ; Reverse Genetics ; Seasons ; Vaccines ; Virulence

BACKGROUND AND OBJECTIVES: The coronary vasospasm has been shown to play an important role in the pathogenesis of not only variant angina but also ischemic heart disease in general, including other forms of angina pectoris, acute myocardial infarct, and sudden death. The angiographic features of coronary vasospasm are focal and diffuse patterns in clinical setting. We attempted to clarify the differences in vessel wall morphologic appearance between the sites of focal and diffuse vasospasm by intravascular ultrasound(IVUS). MATERIAL AND METHODS: We studied 23 patients(32 segments) with variant angina in whom coronary angiograms were normal and coronary spasm was documented by intracoronary injection of acetylcholine. Coronary spasm was defined as luminal diameter reduction > or = 90% compared with baseline coronary artery diameter. Focal spasm was defined if the length of spastic narrowing was less than 10mm. By IVUS, we observed atheromatous plaques in 32 spasm segments with either focal or diffuse vasospasm. We measured maximal intimal thickness, luminal cross-sectional area(CSA), and external elastic membrane-CSA in spasm sites. RESULT: When comparing maximal intimal thickness between focal (n=15) and diffuse vasospasm segments(n=17), there was significantly greater thickness at focal spasm segments(1.21+/-0.36mm vs. 0.70+/-0.23mm, P<0.001). The maximal plaque area was similar between two groups but tended to be greater in focal spasm segments(6.03+/-2.06mm2 vs. 4.92+/-2.59mm2, P=NS). When circular shaped factor(CSF : standardized index of eccentricity) was compared, focal spasm segments were greater than diffuse spasm segments(0.89+/-0.06 vs. 0.97+/-0.02, P<0.001). At the segments of focal spasm, remodeling index was greater compared to the segments of diffuse spasm(1.02+/-0.16 vs. 0.86+/-0.13, P<0.001). CONCLUSION: Focal spasm segments were more eccentric and had greater atheromatous plaque than diffuse spasm segments. Positive remodeling pattern was observed at the segments of focal spasm and negative remodeling pattern at the segments of diffuse spasm. There were morphologic differences of vessel wall appearance between focal and diffuse spasm sites.
Acetylcholine ; Angina Pectoris ; Coronary Vasospasm* ; Coronary Vessels ; Death, Sudden ; Muscle Spasticity ; Myocardial Infarction ; Myocardial Ischemia ; Phenobarbital ; Plaque, Atherosclerotic ; Spasm

BACKGROUND AND OBJECTIVES: Receptor for advanced glycosylation end product (RAGE) plays an important role in the development of myocardial fibrosis in diabetics. Activation of peroxisome proliferator activated receptor (PPAR)-gamma agonist, rosiglitazone, reduces the RAGE expression. We investigated whether rosiglitazone could prevent left ventricle (LV) diastolic dysfunction and attenuate the myocardial fibrosis in a type 2 diabetic rat model. MATERIALS AND METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with rosiglitazone (20 mg/kg/d) for 20 weeks. At the age of 20 and 40 weeks, all rats underwent intraperitoneal glucose tolerance tests, hemodynamic studies and Doppler echocardiography. At the age of 40 weeks, the hearts were examined by performing histopathological and immunohistochemical analyses. RESULTS: At the age of 40 weeks, rosiglitazone significant improved the parameters of the LV diastolic function such as the E/A ratio (treated vs. untreated: 1.7+/-0.1 vs. 1.5+/-0.1, p<0.05), the deceleration time and the isovolumic relaxation time in the OLETF rats, and this was correlated histologically to the reduced LV collagen volume fraction in the rosiglitazonetreated OLETF rats (3.2+/-1.3% vs. 5.7+/-2.0%, respectively, p<0.001). Rosiglitazone also significantly reduced the percentage of staining of the LV CTGF (7.4+/-2.5% vs. 15.4+/-4.7%, respectively, p<0.001) and RAGE (1.1+/-0.4% vs. 2.0+/-0.8%, respectively, p<0.001), as compared with the untreated OLETF rats. CONCLUSION: These results suggest that rosiglitazone could prevent LV diastolic dysfunction and attenuate myocardial fibrosis in type 2 diabetic rats by its inhibition of the RAGE and CTGF expression. PPAR-gamma agonist may provide a potential therapeutic approach for diabetic heart disease.
Animals ; Collagen ; Deceleration ; Echocardiography, Doppler ; Fibrosis* ; Glucose Tolerance Test ; Glycosylation ; Heart ; Heart Diseases ; Heart Ventricles ; Hemodynamics ; Intercellular Signaling Peptides and Proteins ; Models, Animal* ; Peroxisomes ; Rage ; Rats* ; Rats, Inbred OLETF ; Relaxation

Antiviral activity against Influenza virus of 14 Lactobacillus species isolated from food was monitored. Lactobacillus species were isolated from traditional Korean fermented food. Each live Lactobacillus was administered into the nasal cavity of SPF 6-week-old BALB/c mice. After the Lactobacillus treatment, Influenza virus (A/NWS/33/H1N1) was inoculated to each mouse. Clinical signs and mortality was monitored for 21 days. Each Lactobacillus strain showed various level of antiviral activity against Influenza virus. As a result of this study, this mouse experiment model, including intranasal treatment of live Lactobacillus species, could be effective model in evaluating immunomodulatory response of probiotics against respiratory viruses.
Administration, Intranasal* ; Animals ; Influenza, Human ; Lactobacillus ; Mice* ; Models, Animal ; Mortality ; Nasal Cavity ; Orthomyxoviridae* ; Probiotics