BACKGROUND/AIMS: The prevalence and clinical characteristics of entecavir (ETV) resistance is not well known. The aim of this study was to determine the frequency of genotypic resistance in nonresponders and virologic breakthrough (VBT) patients. METHODS: The medical records of 76 chronic hepatitis B patients treated for a least 6 months from October 2006 to October 2008 were reviewed retrospectively. We divided patients into two groups: nucleoside analogue (NA)-naive patients (n=38) and LAM experienced patients (n=38). NA-naive and LAM experienced patients received ETV at 0.5 and 1.0 mg/day, respectively. The virologic response and VBT were investigated in both groups. We used the multiplex restriction fragment mass polymorphism (RFMP) method to test genotypic resistance at the rtI169, rtT184, rtS202, rtM204, and rtM250 sites. RESULTS: Age, gender, serum ALT, and HBV DNA level before treatment did not differ between the groups. Neither VBT nor nonresponse was observed in the NA-naive group, whereas VBT and nonresponse were observed in three patients each in the lamivudine (LAM)-experienced group; all six patients had YMDD mutation at study enrollment, all three patients with VBT had genotypic resistance to ETV, but the three nonresponse patients did not have genotypic resistance to ETV. CONCLUSIONS: We suspect that VBT is mostly associated with genotypic resistance to ETV. However, nonresponse might be associated with the continuance or reselection of the YMDD mutant in LAM-experienced patients.
Adult ; Antiviral Agents/*therapeutic use ; Drug Resistance, Viral/genetics ; Female ; Genotype ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B/genetics ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Lamivudine/therapeutic use ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length ; RNA-Directed DNA Polymerase/genetics ; Retrospective Studies

PURPOSE: To evaluate the usefulness of cerebral blood flow measurement applied to perfusion weighted image with short-scan time single shot gradient echo-planar technique in measuring cerebral blood volume(rCBV) of normal rabbits. MATERIALS AND METHODS: With 2.1-3.6 kg weighted rabbits, image is acquired when they are in supine position in children positioner. Perfusion weighted image is acquired to 44 seconds per 1 second successively. After 4 seconds later, Gd-DTPA 2ml are injected into int. jugular vein with 2 ml per second and normal saline is also injected after that. Same technique is applied 2 times per 30 minites in same rabbit. After Image is obtained in two part of cerebral cortex at vertex, convexity, in one of basal ganglia with choosing about 3-5mm2 areas. Curve of signal intensity changes in time sequence is drawn. After this images are transmitted by PC and software IDL, regional cerebral blood volume is measured with imaging processing program made by us. RESULTS: With 22 of 24 rabbits, satisfactory 1-2 signal intensity versus time curve is made. Cerebral blood capacity and contrast media stay time (ST) is measured in two cerebral cortex and basal ganglia refering in parietal cerebral cortex. Mean focal cerebral blood flow capacity ratio in cortex was 0.97+/-0.35 and in basal ganglia, 0.99+/-0.37, mean contrast media stay time in cortex was 9.83+/-1.63 sec and in basal ganglia, 9.42+/-1.14 sec, but there was no statistically significant difference between two areas (p=0.05). CONCLUSION: In cerebral cortex and basal ganglia, there is no difference in mean focal blood volume and mean contrast stay time. Therefore, PWI is useful in cerebral blood flow and early diagnosis, prognosis of cerebral ischemic disease. Hereafter, it is helpful in analysing cerebral blood flow changes with comparison difference in rCBV between normal tissue and ischemic tissue, and that with DWI finding in infarcted patient.
Basal Ganglia ; Blood Volume* ; Cerebral Cortex ; Child ; Contrast Media ; Early Diagnosis ; Gadolinium DTPA ; Humans ; Jugular Veins ; Perfusion ; Prognosis ; Rabbits* ; Rabeprazole ; Supine Position

Recently, the world's first transgenic dogs were produced by somatic cell nuclear transfer. However, cellular senescence is a major limiting factor for producing more advanced transgenic dogs. To overcome this obstacle, we rejuvenated transgenic cells using a re-cloning technique. Fibroblasts from post-mortem red fluorescent protein (RFP) dog were reconstructed with in vivo matured oocytes and transferred into 10 surrogate dogs. One puppy was produced and confirmed as a re-cloned dog. Although the puppy was lost during birth, we successfully established a rejuvenated fibroblast cell line from this animal. The cell line was found to stably express RFP and is ready for additional genetic modification.
Animals ; Animals, Genetically Modified ; Cloning, Organism/methods/*veterinary ; Dogs/*genetics ; Female ; Gastrointestinal Tract/metabolism ; Gene Expression Regulation ; Kidney/metabolism ; Liver/metabolism ; Luminescent Proteins/*genetics/metabolism ; Lung/metabolism ; Male ; Myocardium/metabolism ; Nuclear Transfer Techniques/veterinary ; Spleen/metabolism ; Trachea/metabolism

Asphyxia due to plastic bag is not common. The manner of death may be accidental, suicidal or homicidal. We report an asphyxial death using plastic bag, giving us difficulty in determining the manner of death, suicidal or homicidal. A 32-year-old female was found dead in bathroom and her head was wrapped in a supermarket shopping bag sealed with adhesive tape around the neck. Strangely she was handcuffed behind the back of the victim. Because of no evidence of violence on the body and the presence of a suicide note at the scene, the manner of death was concluded as suicide. This case emphasizes that the interpretation of postmortem examination should be incorporated with the proper investigation of circumstances at the scene of death to determine the manner of death.
Adhesives ; Adult ; Asphyxia ; Autopsy ; Female ; Head ; Humans ; Neck ; Plastics ; Suicide ; Violence

This work describes the pharmacological inhibition by KR 31378 and its acetyl metabolite, KR 31612, of the apoptotic cell death induced by H2O2 in the A7r5 cells. Exposure of A7r5 cells to H2O2 (0.5 mM) induced a concentration-dependent cytotoxicity in association with oligonucleosomal DNA fragmentation. H2O2-induced cell death was potently suppressed by KR 31378, KR 31612, alpha-tocopherol or trolox. Additionally, the apoptotic death of A7r5 cells (DNA ladders on electrophoresis) was also strongly suppressed by KR 31378 and KR 31612, but to a less degree by alpha-tocopherol and trolox. As a mechanistic study, incubation with H2O2 markedly showed a decreased Bcl-2 level and, in contrast, increased Bax protein and cytochrome C release, which were significantly and concentration-dependently reversed by KR 31378 and KR 31612 as well as by alpha-tocopherol and trolox. KR 31378 and alpha-tocopherol significantly reduced lipid peroxidation in accordance with reduced intracellular ROS and peroxyl radical. These results suggest that KR 31378 has a therapeutic potential against the apoptotic injury via mediation of antioxidative stress.
alpha-Tocopherol ; bcl-2-Associated X Protein ; Cell Death ; Cytochromes c ; DNA Fragmentation ; Lipid Peroxidation ; Negotiating

BACKGROUND AND OBJECTIVES: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model. METHODS: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment. RESULTS: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4uclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment. CONCLUSIONS These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.

BACKGROUND AND OBJECTIVES: We sought to investigate an anti-atherosclerotic and anti-inflammatory effect of sodium-glucose cotransporter-2 (SGLT-2) inhibitors in normoglycemic atherosclerotic rabbit model.METHODS: Male New Zealand white rabbits (n=26) were fed with a 1% high-cholesterol diet for 7 weeks followed by normal diet for 2 weeks. After balloon catheter injury, the rabbits were administered with the Dapagliflozin (1mg/kg/day) or control-medium for 8 weeks (n=13 for each group). All lesions were assessed with angiography, optical coherence tomography (OCT), and histological assessment.RESULTS: Atheroma burden (38.51±3.16% vs. 21.91±1.22%, p<0.01) and lipid accumulation (18.90±3.63% vs. 10.20±2.03%, p=0.047) was significantly decreased by SGLT-2 inhibitor treatment. The SGLT-2 inhibitor group showed lower macrophage infiltration (20.23±1.89% vs. 12.72±1.95%, p=0.01) as well as tumor necrosis factor (TNF)-α expression (31.17±4.40% vs. 19.47±2.10%, p=0.025). Relative area of inducible nitric oxide synthase+ macrophages was tended to be lower in the SGLT-2 inhibitor-treated group (1.00±0.16% vs. 0.71±0.10%, p=0.13), while relative proportion of Arg1⁺ macrophage was markedly increased (1.00±0.27% vs. 2.43±0.64%, p=0.04). As a result, progression of atherosclerosis was markedly attenuated in SGLT-2 inhibitor treated group (OCT area stenosis, 32.13±1.20% vs. 22.77±0.88%, p<0.01). Mechanistically, SGLT-2 treatment mitigated the inflammatory responses in macrophage. Especially, Toll-like receptor 4/nuclear factor-kappa B signaling pathway, and their downstream effectors such as interleukin-6 and TNF-α were markedly suppressed by SGLT-2 inhibitor treatment.CONCLUSIONS: These results together suggest that SGLT-2 inhibitor exerts an anti-atherosclerotic effect through favorable modulation of inflammatory response as well as macrophage characteristics in non-diabetic situation.
Angiography ; Atherosclerosis ; Catheters ; Constriction, Pathologic ; Diet ; Humans ; Interleukin-6 ; Macrophages ; Male ; Nitric Oxide ; Plaque, Atherosclerotic ; Rabbits ; Toll-Like Receptors ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha

Active serologic surveillance is necessary to control the spread of the avian influenza virus (AIV). In this study, we evaluated a commercially-available cELISA in terms of its ability to detect AIV antibodies in the sera of 3,358 animals from twelve species. cELISA detected antibodies against reference H1- through H15-subtype AIV strains without cross reactivity. Furthermore, the cELISA was able to detect antibodies produced following a challenge of the AIV H9N2 subtype in chickens, or following vaccination of the AIV H9 or H5 subtypes in chickens, ducks and geese. Next, we tested the sensitivity and specificity of the cELISA with sera from twelve different animal species, and compared these results with those obtained by the hemagglutination-inhibition (HI) test, the "gold standard" in AIV sera surveillance, a second commercially-available cELISA (IZS ELISA), or the agar gel precipitation (AGP) test. Compared with the HI test, the sensitivities and specificities of cELISA were 95% and 96% in chicken, 86% and 88% in duck, 97% and 100% in turkey, 100% and 87% in goose, and 91% and 97% in swine, respectively. The sensitivities and specificities of the cELISA in this study were higher than those of IZS ELISA for the duck, turkey, goose, and grey partridge sera samples. The results of AGP test against duck and turkey sera also showed significant correlation with the results of cELISA (R-value >0.9). In terms of flock sensitivity, the cELISA correlated better with the HI test than with commercially-available indirect ELISAs, with 100% flock sensitivity.
Animals ; Antibodies, Viral/*blood ; Birds ; Enzyme-Linked Immunosorbent Assay/methods/*veterinary ; Horses ; Influenza A virus/*immunology ; Influenza Vaccines/immunology ; Influenza in Birds/blood/*immunology/prevention & control ; Sensitivity and Specificity ; Serologic Tests ; Species Specificity ; Swine

Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) is a peripheral neuropathy characterized by multifocal weakness and associated sensory impairment. MADSAM is associated with multifocal persistent conduction block and other signs of demyelination. The incidence of cranial nerve involvement in MADSAM was recently reported to be approximately 15%. However, reports of hypoglossal neuropathy occurring in MADSAM are rare. Unilateral hypoglossal neuropathy in MADSAM is usually misdiagnosed as motor neuron disease. We report a patient with MADSAM presenting with tongue hemiatrophy.
Cranial Nerves ; Demyelinating Diseases ; Diagnosis, Differential ; Humans ; Hypoglossal Nerve Diseases ; Incidence ; Motor Neuron Disease ; Motor Neurons ; Peripheral Nervous System Diseases ; Tongue