Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Objective: To investigate the effect of an aqueous extract of Protaetia brevitarsis (AEPB) on osteogenesis using preosteoblast MC3T3-E1 cells and zebrafish larvae. Methods: Flow cytometric analysis was used to measure the cytotoxicy. Alkaline phosphatase activity was detetmined using p-nitrophenyl phosphate as a substrate. Calcium deposition was detected using alizarin red staining along with osteogenic marker expression in preosteoblast MC3T3E1 cells. In addition, vertebral formation in zebrafish larvae was detected using calcein staining and osteogenic gene expression. Results: AEPB highly promoted the expression of osteogenic markers including runt-related transcription factor 2, osterix, and alkaline phosphatase, along with elevated levels of mineralization in MC3T3-E1 cells. Moreover, AEPB accelerated vertebral formation in zebrafish larvae accompanied by upregulated expression of osteogenic genes. FH535, an inhibitor of Wnt/β-catenin, suppressed AEPB-induced osteogenic gene expression and vertebral formation, indicating that AEPB stimulates osteogenesis by activating the Wnt/β-catenin signaling pathway. Conclusions: AEPB stimulates osteoblast differentiation and bone formation by activating β-catenin. Therefore, AEPB is a promising material that induces osteogenesis, and is useful for the treatment of bone resorption diseases.

Background/Aims: The safety of direct oral anticoagulants (DOACs) compared with warfarin in patients with both nonvalvular atrial fibrillation (AF) and clinically confirmed liver cirrhosis (LC) has not been well studied. We compared the risk of a major bleeding event between DOAC and warfarin treatments in this patient population. Methods: A total of 238 cirrhotic patients with AF were retrospectively analyzed. The major bleeding event risk was compared between DOAC- and warfarin-treated groups. The median follow-up duration was 5.6 years. Results: Among the 238 study patients with LC and AF, 128 (53.8%) received DOACs and 110 (46.2%) received warfarin. The mean patient age was 68.8 years, and 78.2% were men. A major bleeding event occurred in 10 and 20 patients in the DOAC and warfarin groups, respectively, most commonly caused by gastrointestinal bleeding (70.0%). The cumulative risk of major bleeding did not differ between the groups by log-rank test (p = 0.12). This finding did not change when using 60 propensity score-matched pairs. A multivariable Cox regression model indicated that the concomitant use of antiplatelet agents (adjusted hazard ratio [aHR], 2.06; 95% confidence interval [CI], 1.00 to 4.30; p = 0.048) and presence of esophageal or gastric varices confirmed by endoscopic examination (aHR, 2.31; 95% CI, 1.03 to 5.17; p = 0.04) were associated with major bleeding in the entire cohort. Conclusions A major bleeding event risk is not increased by DOAC compared with warfarin treatment. Antiplatelet agent use and varices are independently associated with a higher risk of major bleeding during anticoagulation.

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Acyl-CoA Dehydrogenase ; Biomarkers ; Blotting, Western ; Carcinoma, Hepatocellular ; Humans ; Immunoblotting ; Liver ; Liver Cirrhosis ; Mass Spectrometry ; Methionine Adenosyltransferase ; Methionine ; Proteomics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Two-Dimensional Difference Gel Electrophoresis

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K+ channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K+ conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.
4-Aminopyridine ; Acidosis ; Animals ; Contracts ; Female ; Hydrogen-Ion Concentration ; Lidocaine ; Membranes ; Methionine ; Mice ; Muscle, Smooth ; Muscles ; Myometrium ; Plasma ; Pregnancy ; Quinidine ; Relaxation ; Uterine Contraction ; Uterus

BACKGROUND/AIMS: Fabry disease is an X-linked recessive and progressive disease caused by alpha-galactosidase A (alpha-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. METHODS: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. RESULTS: Twenty-nine patients had elevated serum GL3 levels. The alpha-GaL A activity was determined for the 26 patients with high GL3 levels. The mean alpha-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased alpha-GaL A activity. Among the group with high GL3 levels, 15 women had a alpha-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and alpha-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. CONCLUSIONS: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3 levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease.
Adult ; Aged ; Fabry Disease/blood/*diagnosis ; Female ; Humans ; Kidney Failure, Chronic/blood/*therapy ; Male ; Middle Aged ; *Renal Dialysis ; Trihexosylceramides/*blood ; alpha-Galactosidase/genetics/metabolism

OBJECTIVE: To evaluate characteristic gait patterns of transfemoral amputees who have been using polycentric knee for a long time. METHOD: Subjects were 22 transfemoral amputees using prosthesis for 29.0 years and 23 age-matched healthy adults. The three-dimensional gait analysis was performed. Temporospatial, kinematic and kinetic parameters were measured. RESULTS: Cadence and walking velocity of amputees decreased (p<0.05). Single support period decreased in amputee limb. There were no significant differences in hip flexion moment and power. In amputated limb, knee flexion in loading response was not observed and ankle plantar flexion was less than sound limb and control group. Excessive compensations of amputee side hip joint were not significant. CONCLUSION: Long term polycentric knee unit transfemoral prosthesis users show asymmetry of gait pattern which can increase the risk of musculoskeletal problems. Epidemiologic investigation would be necessary for prevention and proper management.
Adult ; Amputees ; Animals ; Ankle ; Extremities ; Gait ; Hip ; Hip Joint ; Humans ; Knee ; Prostheses and Implants ; Walking

PURPOSE: Taurine is a simple sulfur-containing amino acid and enriched in brain, retina, heart and skeletal muscles. In the central nervous system, taurine has been implicated in major phenomena. Current studies have demonstrated the neuroprotective effect of taurine in adult rat model, but limited data are available for those during the neonatal periods. The aim of this study was to determine whether taurine could reduce hypoxic-ischemic (HI) brain injury in the developing brain via modulation of nitric oxide synthase. METHODS: In in vitro model, embryonic cortical neuronal cell culture procedure was done in Sprague-Dawley (SD) rats at 18 days of gestation. The cells were divided into the hypoxia group, taurine-treated group before and after a hypoxic insult. The each groups compared with normoxia group. In in vivo model, left carotid artery ligation was done in 7-day-old SD rat pups. the pups were exposed to hypoxia, received an injection of 30 mg/kg of taurine, and sacrificed at day 1, day 3, day 7, day 14 and day 28. We assayed the expression of iNOS, eNOS and nNOS mRNA using real-time PCR and western-blotting. RESULTS: In in vitro model, brain cell damage of hypoxia group was more than in the normoxia group. Cell damage's recovery was more in the taurine-treated group before a hypoxic insult than in the taurine-treated group after a hypoxic insult. The expression of iNOS mRNA was less in the hypoxia group than in the normoxia group both in vitro and in vivo models. The expression of eNOS and nNOS was more in the hypoxia group. CONCLUSION: Taurine has neuroprotective property over perinatal HI brain injury due to modulation of NOS, as evidenced by causing a decrease in eNOS and nNOS and increase in iNOS expression. The neuroprotective effect of taurine administration was maximal at day 7 and day 14 after a hypoxic injury.
Adult ; Animals ; Anoxia ; Brain ; Brain Injuries ; Carotid Arteries ; Cell Culture Techniques ; Central Nervous System ; Heart ; Humans ; Ligation ; Muscle, Skeletal ; Neurons ; Neuroprotective Agents ; Nitric Oxide ; Nitric Oxide Synthase ; Pregnancy ; Rats ; Real-Time Polymerase Chain Reaction ; Retina ; RNA, Messenger ; Taurine

OBJECTIVE: To evaluate the changes of gait patterns during crossing obstacles of different heights in hemiplegic stroke patients and to compare gait characteristics with those of healthy control subjects. METHOD: Subjects were 13 hemiplegic stroke patients and 9 age-matched healthy adults. Subjects stepped over obstacles with each height of 3, 8 and 13 cm. The three- dimensional gait analysis was performed. Temporospatial, kinematic and kinetic parameters were measured in both lead and trail limb. The pre- and post-obstacle distance, pre- and post-obstacle swing time and toe clearance were also measured. RESULTS: With increase in height of obstacles, ratio of single limb support time, angle of hip, knee flexion in swing phase and hip extensor moment increased in both lead and trail limbs. In the lead limb, post-obstacle distance and toe clearance also increased (p<0.05). Compared with control groups, the angle of knee flexion, hip extensor and hip flexor moment and pre- and post-obstacle distance decreased significantly in the lead limb of hemiplegic patients (p<0.05). In the trail limb of hemiplegic patients, the angle of hip flexion, hip flexor moment and post-obstacle distance decreased (p<0.05). CONCLUSION: Understanding strategies for adequate control and coordination of the swing limb during crossing obstacles may be the basis for the safe training of obstacle crossing in hemiplegic stroke patients.
Adult ; Extremities ; Gait ; Hip ; Humans ; Knee ; Stroke ; Toes

PURPOSE: We analyzed the treatment outcomes and prognostic factors of breast conserving surgery, followed by postoperative radiotherapy. MATERIALS AND METHODS: A total of 424 breast cancer patients treated with breast conserving surgery and postoperative radiotherapy between February 1992 and January 2001 were retrospectively analyzed. A quadrantectomy and axillary lymph node dissection was performed in 396 patients. A total of 302 patients had T1 disease, and 122 patients had T2 disease. Lymph node involvement was confirmed in 107 patients. Whole breast irradiation was administered at up to 50.4 Gy in 28 fractions, followed by a 10 Gy boost in 5 fractions to the tumor bed. In addition, 57 patients underwent regional lymph node irradiation. Moreover, chemotherapy was administered in 231 patients. A regimen consisting of cyclophosphamide, methotrexate, and 5-fluorouracil was most frequently used with 170 patients. The median follow-up time was 64 months. RESULTS: The 5-year local control rate was 95.6%. During the follow-up period, local tumor recurrence was observed in 15 patients. The 5-year overall and disease-free survival rates were 93.1% and 88.7%, respectively. The 5-year overall survival rates, by stage, were 94.8% for stage I, 95.0% for stage IIA, 91.1% for stage IIB, 75.9% for stage IIIA, and 57.1% for stage IIIC. As for disease-free survival, the corresponding figures, by stage (in the same order), were 93.1%, 89.4%, 82.8%, 62.0%, and 28.6%, respectively. The advanced N stage (p=0.0483) was found to be a significant prognostic factor in predicting poor overall survival, while the N stage (p=0.0284) and age at diagnosis (p=0.0001) were associated with disease-free survival. CONCLUSION: This study has shown that breast conserving surgery and postoperative radiotherapy for early breast cancer results was excellent for local control and survival.
Breast Neoplasms