After renal injury, selective damage occurs in the proximal tubules as a result of inhibition of glycolysis. The molecular mechanism of damage is not known. Poly(ADP-ribose) polymerase (PARP) activation plays a critical role of proximal tubular cell death in several renal disorders. Here, we studied the role of PARP on glycolytic flux in pig kidney proximal tubule epithelial LLC-PK1 cells using XFp extracellular flux analysis. Poly(ADP-ribosyl)ation by PARP activation was increased approximately 2-fold by incubation of the cells in 10 mM glucose for 30 minutes, but treatment with the PARP inhibitor 3-aminobenzamide (3-AB) does-dependently prevented the glucose-induced PARP activation (approximately 14.4% decrease in 0.1 mM 3-AB-treated group and 36.7% decrease in 1 mM 3-AB-treated group). Treatment with 1 mM 3-AB significantly enhanced the glucose-mediated increase in the extracellular acidification rate (61.1±4.3 mpH/min vs. 126.8±6.2 mpH/min or approximately 2-fold) compared with treatment with vehicle, indicating that PARP inhibition increases only glycolytic activity during glycolytic flux including basal glycolysis, glycolytic activity, and glycolytic capacity in kidney proximal tubule epithelial cells. Glucose increased the activities of glycolytic enzymes including hexokinase, phosphoglucose isomerase, phosphofructokinase-1, glyceraldehyde-3-phosphate dehydrogenase, enolase, and pyruvate kinase in LLC-PK1 cells. Furthermore, PARP inhibition selectively augmented the activities of hexokinase (approximately 1.4-fold over vehicle group), phosphofructokinase-1 (approximately 1.6-fold over vehicle group), and glyceraldehyde-3-phosphate dehydrogenase (approximately 2.2-fold over vehicle group). In conclusion, these data suggest that PARP activation may regulate glycolytic activity via poly(ADP-ribosyl)ation of hexokinase, phosphofructokinase-1, and glyceraldehyde-3-phosphate dehydrogenase in kidney proximal tubule epithelial cells.
Animals ; Cell Death ; Epithelial Cells* ; Glucose ; Glucose-6-Phosphate Isomerase ; Glycolysis ; Hexokinase ; Kidney* ; LLC-PK1 Cells ; Oxidoreductases ; Phosphofructokinase-1 ; Phosphopyruvate Hydratase ; Poly Adenosine Diphosphate Ribose* ; Poly(ADP-ribose) Polymerases* ; Pyruvate Kinase ; Swine

OBJECTIVE: To investigate the stem cell-like characteristics of human periodontal ligament (PDL) stromal cells outgrown from orthodontically extracted premolars and to evaluate the potential for myogenic differentiation. METHODS: PDL stromal cells were obtained from extracted premolars by using the outgrowth method. Cell morphological features, self-replication capability, and the presence of cell-surface markers, along with osteogenic, adipogenic, and chondrogenic differentiation, were confirmed. In addition, myogenic differentiation was induced by the use of 5-aza-2'-deoxycytidine (5-Aza) for DNA demethylation. RESULTS: PDL stromal cells showed growth patterns and morphological features similar to those of fibroblasts. In contrast, the proliferation rates of premolar PDL stromal cells were similar to those of bone marrow and adipogenic stem cells. PDL stromal cells expressed surface markers of human mesenchymal stem cells (i.e., CD90 and CD105), but not those of hematopoietic stem cells (i.e., CD31 and CD34). PDL stromal cells were differentiated into osteogenic, adipogenic, and chondrogenic lineages. Myotube structures were induced in PDL stromal cells after 5-Aza pretreatment, but not in the absence of 5-Aza pretreatment. CONCLUSIONS: PDL stromal cells isolated from extracted premolars can potentially be a good source of postnatal stem cells for oromaxillofacial regeneration in bone and muscle.
Azacitidine ; Bicuspid ; Bone Marrow ; DNA ; Durapatite ; Fibroblasts ; Hematopoietic Stem Cells ; Humans ; Mesenchymal Stromal Cells ; Molecular Biology ; Muscle Fibers, Skeletal ; Muscles ; Periodontal Ligament ; Regeneration ; Stem Cells ; Stromal Cells

This study aimed to examine influenza vaccination coverage of North Korean defectors (NKD) in the Republic of Korea (Korea) and explore the factors affected the vaccination coverage. Total 378 NKD were analyzed. Four Korean control subjects were randomly matched by age and gender from the Korea National Health and Nutrition Examination Survey V (n = 1,500). The adjusted vaccination coverage revealed no statistical difference between the defectors group and indigenous group (29.1% vs. 29.5%, P = 0.915). In the aged under 50 group, the vaccination coverage of NKD was higher than that of Korean natives (37.8% vs. 25.8%, P = 0.016). However in the aged 50 yr and over group, the vaccination coverage of North Korean defectors was lower than that of the natives (28.0% vs. 37.6%, P = 0.189). Even the gap was wider in the aged 65 yr and over group (36.4% vs. 77.8%, P = 0.007). Gender and medical check-up experience within 2 yr showed association with the vaccination coverage of NKD. Influenza vaccination coverage of aged defectors' group (aged 50 yr and over) was lower than indigenous people though overall vaccination coverage was similar. Further efforts to increase influenza vaccination coverage of this group are needed.
Adult ; Age Distribution ; Aged ; Aged, 80 and over ; Democratic People's Republic of Korea/epidemiology ; Female ; Humans ; Influenza Vaccines/*therapeutic use ; Influenza, Human/*epidemiology/*prevention & control ; Male ; Middle Aged ; Refugees/*statistics & numerical data ; Republic of Korea/epidemiology ; Sex Distribution ; Vaccination/*utilization ; Young Adult

Anti-programmed cell death-1 (PD-1) humanized monoclonal antibody inhibits PD-1 activity by binding to the PD-1 receptor on T-cells and blocking PD-1 ligands and induces immune tolerance of cancer cells. It has been widely used for various kinds of cancer treatment. However, many immune-related adverse events (irAEs) have been reported because it modulates our immune system. In this case study, we reported a case of 42-year-old woman with Hashimoto's thyroiditis who showed rapid aggravation of thyroid goiter and acute hyperventilation syndrome after treatment with PD-1 inhibitor as a neoadjuvant chemotherapy for breast cancer.
Adult ; Breast Neoplasms ; Breast ; Drug Therapy ; Female ; Goiter ; Humans ; Hyperventilation ; Immune System ; Immune Tolerance ; Ligands ; Programmed Cell Death 1 Receptor ; T-Lymphocytes ; Thyroid Gland ; Thyroiditis

Background: Osteoporosis is characterized by a decrease in bone mineral density (BMD) and increased risk of fragility fractures. Serum iron level may interact with bone health status. This study investigated the correlations of BMD with serum iron level, hemoglobin level, and total iron-binding capacity (TIBC). Methods: We performed a retrospective analysis of data from the medical records of premenopausal women in South Korea. The women’s BMDs and the Z scores of the BMDs were verified using dual-energy X-ray absorption. The participants were stratified into quartiles for analyses of the associations of BMD with serum iron level, TIBC, and hemoglobin level. Results: A simple linear regression analysis revealed associations of changes in BMD with iron level (β=-0.001, standard error [SE]=0.001, P<0.001), hemoglobin level (β=0.015, SE=0.003, P<0.001), and TIBC (β=0.001, SE=0.001, P<0.001). This pattern was also observed in a multiple linear regression analysis. A multivariate logistic regression analysis of iron level and TIBC for low BMD revealed odds ratios of 1.005 (P<0.001) and 0.995 (P<0.001), respectively. Conclusion This study demonstrated clear relationships of changes in BMD with serum iron level and TIBC, and thus confirms the usefulness of these markers in the clinical evaluation of iron storage and BMD in younger women.

Recently, the incidence of candida infection has increased. Candida species often show hematogenous spread to the kidney, brain, heart, and eyes. And delayed onset of hematogenous spread is relatively rare. A 53-year-old female patient was admitted with left anterior chest pain with swelling and mild fever. She had been treated successfully with fluconazole for candidemia caused by C. albicans eight month ago. On admission chest CT scan revealed multiple subcutaneous abscesses involving the anterior chest. Percutaneous drainage of the abscess was performed. C. albicans was isolated from drained pus. Treatment with fluconazole did not to improve the abscess; therefore, micafungin and voriconazole were administered as a replacement. The patient recovered after 10-week administration.
Abscess ; Brain ; Candida ; Candidemia ; Chest Pain ; Drainage ; Echinocandins ; Eye ; Female ; Fever ; Fluconazole ; Heart ; Humans ; Incidence ; Kidney ; Lipopeptides ; Middle Aged ; Pyrimidines ; Suppuration ; Thoracic Wall ; Thorax ; Triazoles

Protein tyrosine phosphatases (PTPs) are key regulatory factors in inflammatory signaling pathways. Although PTPs have been extensively studied, little is known about their role in neuroinflammation. In the present study, we examined the expression of 6 different PTPs (PTP1B, TC-PTP, SHP2, MEG2, LYP, and RPTPβ) and their role in glial activation and neuroinflammation. All PTPs were expressed in brain and glia. The expression of PTP1B, SHP2, and LYP was enhanced in the inflamed brain. The expression of PTP1B, TC-PTP, and LYP was increased after treating microglia cells with lipopolysaccharide (LPS). To examine the role of PTPs in microglial activation and neuroinflammation, we used specific pharmacological inhibitors of PTPs. Inhibition of PTP1B, TC-PTP, SHP2, LYP, and RPTPβ suppressed nitric oxide production in LPS-treated microglial cells in a dose-dependent manner. Furthermore, intracerebroventricular injection of PTP1B, TC-PTP, SHP2, and RPTPβ inhibitors downregulated microglial activation in an LPS-induced neuroinflammation model. Our results indicate that multiple PTPs are involved in regulating microglial activation and neuroinflammation, with different expression patterns and specific functions. Thus, PTP inhibitors can be exploited for therapeutic modulation of microglial activation in neuroinflammatory diseases.
Brain ; Microglia ; Neuroglia ; Nitric Oxide ; Protein Tyrosine Phosphatase, Non-Receptor Type 2 ; Protein Tyrosine Phosphatases*

PURPOSE: This study evaluated the usefulness of a new scoring system in diagnosing acute appendicitis which expresses the patient's symptoms, physical examination, and laboratory findings more clearly and objectively. METHODS: A prospective study was conducted with 314 patients who were hospitalized with suspicion of acute appendicitis. After analyzing the symptoms, physical examination, and laboratory findings, 10 meaningful variables were selected, each of which were scored separately. The diagnostic value of the new scoring system was evaluated, and analyzed in comparison to the preexisting Alvarado score. RESULTS: Ten variables including vomiting, migration pain, fever, Dunphy's sign, Rovsing's sign, tenderness, rebound tenderness, increased white blood cell counts, increased neutrophil proportion, and increased CRP levels were associated with acute appendicitis. The new scoring system is developed by applying 1 point for each variable, with a total score of 10 points. In the new scoring system, a score above 5 points had sensitivity of 0.75, specificity of 0.73, positive predictive value of 0.92, and diagnostic accuracy of 0.71. The area under the receiver operating characteristic curve was 0.80, which is larger than 0.72 of the preexisting Alvarado score, and thus has a higher diagnostic accuracy. As acute appendicitis progresses, the average score tends to become significantly higher (P=0.001). CONCLUSION: The new scoring system, which objectively reflects the clinical variables of the patient's symptoms, physical examination and laboratory findings, will be useful in accurately diagnosing acute appendicitis and in quickly deciding a therapeutic policy in patients with right lower abdominal pain.
Abdominal Pain ; Appendicitis ; Fever ; Humans ; Leukocyte Count ; Neutrophils ; Physical Examination ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Vomiting

Spontaneous spinal epidural hematomas (SSEH) are rare, accounting for less than 1% of all spinal epidural lesions. The potential causes include coagulopathies, antithrombotic drugs, hypertension, increased venous pressure, and vascular malformations. A SSEH causes severe neurological deficits unless treated in a timely manner. As the number of patients who are diagnosed with ischemic heart disease and treated using percutaneous coronary intervention (PCI) increases, the prescription of dual antiplatelet agents is also increasing. We report a case of SSEH caused by dual antiplatelet agent therapy in a patient who had undergone PCI.
Accounting ; Aspirin ; Hematoma, Epidural, Spinal ; Humans ; Hypertension ; Myocardial Ischemia ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; Prescriptions ; Ticlopidine ; Vascular Malformations ; Venous Pressure

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACE-I) have been widely used for cardiac patients. This study investigated the effect of omitting ACE-I medication on hemodynamics during induction of anaesthesia and operation in patients chronically treated with ACE-I undergoing off pump coronary artery bypass graft surgery (OPCAB). METHODS: Sixty patients scheduled for OPCAB were included in this study. Patients not treated with ACE-I were included in control group (Group 1, n = 20). And then, patients treated with ACE-I more than 4 weeks were randomly divided into two groups: continuing group including patients who continued ACE-I medication until the morning of surgery (Group 2, n = 20) and discontinuing group including patients who discontinued ACE-I one day before the surgery (Group 3, n = 20). Norepinephrine (8microgram/ml) was infused when systolic blood pressure decreased below 90 mmHg during induction and operation. Amount of norepinephrine infused and hemodynamic data were recorded. RESULTS: Significantly larger amount of norepinephrine was infused in Group 2 than in other two groups during obtuse marginal artery anastomosis. Total amount of norepinephrine infused during the all coronary anatsomosis was significantly larger in Group 2 than those values in other two groups. CONCLUSIONS: Continuing ACE-I treatment until the morning of surgery significantly increased the use of norepinephrine during the anastomosis. In contrast, there was no significant difference in the use of norepinephrine between Group 1 and Group 3. Discontinuing ACE-I before the surgery may helpful to maintain hemodynamics stable during coronary anastomosis in OPCAB.
Angiotensin-Converting Enzyme Inhibitors ; Arteries ; Blood Pressure ; Coronary Artery Bypass, Off-Pump* ; Hemodynamics* ; Humans ; Norepinephrine ; Transplants