The mammalian target of rapamycin (mTOR) plays a role in various cellular phenomena, including autophagy, cell proliferation, and differentiation. Although recent studies have reported its involvement in nociceptive responses in several pain models, whether mTOR is involved in orofacial pain processing is currently unexplored. This study determined whether rapamycin, an mTOR inhibitor, reduces nociceptive responses and the number of Fos-immunoreactive (Fos-ir) cells in the trigeminal nucleus caudalis (TNC) in a mouse orofacial formalin model. We also examined whether the glial cell expression and phosphorylated p38 (p-p38) mitogen-activated protein kinases (MAPKs) in the TNC are affected by rapamycin. Mice were intraperitoneally given rapamycin (0.1, 0.3, or 1.0 mg/kg); then, 30 min after, 5% formalin (10 l) was subcutaneously injected into the right upper lip. The rubbing responses with the ipsilateral forepaw or hindpaw were counted for 45 min. High-dose rapamycin (1.0 mg/kg) produced significant antinociceptive effects in both the first and second phases of formalin test. The number of Fos-ir cells in the ipsilateral TNC was also reduced by high-dose rapamycin compared with vehicle-treated animals. Furthermore, the number of p-p38-ir cells the in ipsilateral TNC was significantly decreased in animals treated with high-dose rapamycin; p-p38 expression was co-localized in microglia, but not neurons and astrocytes. Therefore, the mTOR inhibitor, rapamycin, reduces orofacial nociception and Fos expression in the TNC, and its antinociceptive action on orofacial pain may be associated with the inhibition of p-p38 MAPK in the microglia.

The mammalian target of rapamycin (mTOR) plays a role in various cellular phenomena, including autophagy, cell proliferation, and differentiation. Although recent studies have reported its involvement in nociceptive responses in several pain models, whether mTOR is involved in orofacial pain processing is currently unexplored. This study determined whether rapamycin, an mTOR inhibitor, reduces nociceptive responses and the number of Fos-immunoreactive (Fos-ir) cells in the trigeminal nucleus caudalis (TNC) in a mouse orofacial formalin model. We also examined whether the glial cell expression and phosphorylated p38 (p-p38) mitogen-activated protein kinases (MAPKs) in the TNC are affected by rapamycin. Mice were intraperitoneally given rapamycin (0.1, 0.3, or 1.0 mg/kg); then, 30 min after, 5% formalin (10 l) was subcutaneously injected into the right upper lip. The rubbing responses with the ipsilateral forepaw or hindpaw were counted for 45 min. High-dose rapamycin (1.0 mg/kg) produced significant antinociceptive effects in both the first and second phases of formalin test. The number of Fos-ir cells in the ipsilateral TNC was also reduced by high-dose rapamycin compared with vehicle-treated animals. Furthermore, the number of p-p38-ir cells the in ipsilateral TNC was significantly decreased in animals treated with high-dose rapamycin; p-p38 expression was co-localized in microglia, but not neurons and astrocytes. Therefore, the mTOR inhibitor, rapamycin, reduces orofacial nociception and Fos expression in the TNC, and its antinociceptive action on orofacial pain may be associated with the inhibition of p-p38 MAPK in the microglia.

Isoniazid is one of the most commonly used antituberculosis drug. Acute into xication is characterized by repetitious convulsions, high anion gap metabolic a cidosis and coma. The basis of theraphy consists of parental pyridoxine admi nistration in a dose equivalent to that of isoniazid ingested. Here we present a case of seizure and metabolic acidosis due to only renal adjustment dosage of Isoniazid in an elderly woman.
Acid-Base Equilibrium ; Acidosis* ; Aged* ; Coma ; Female ; Humans ; Isoniazid* ; Parents ; Pyridoxine ; Seizures*

BACKGROUND: Soluble ST2 (sST2) has emerged as a biomarker of heart failure. Previous studies indicated 35 ng/mL of sST2 as the clinically prognostic cut-off value. This study aims to establish reference intervals in a Korean population using an sST2 assay and to evaluate the applicability of the cut-off value. METHODS: From March to May 2014, sST2 levels were assayed in serum samples of 255 cardio-healthy Koreans (128 men and 127 women) using the Presage ST2 ELISA kit (Critical Diagnostics, USA). The reference interval for sST2 was defined using the nonparametric percentile method according to the CLSI EP28-A3c guideline. RESULTS: The median sST2 concentrations were 23.8 ng/mL (interquartile range (IQR), 19.0-28.7), 26.6 ng/mL (IQR, 21.0-30.9), and 21.9 ng/mL (IQR, 17.3-26.5) for the entire cohort, men, and women, respectively. sST2 levels were significantly higher in men than in women (P<0.0001). The 97.5th percentile upper reference limits for sST2 were 43.8 ng/mL, 49.6 ng/mL, and 35.4 ng/mL for the cohort, men, and women, respectively. Gender-specific upper reference limits were similar to limits reported by other studies. CONCLUSIONS: We suggest that gender-specific reference intervals should be used for the Korean population, as application of a single cut-off value of 35 ng/mL may be overcautious of the possibility of false positivity, especially in men.
Cohort Studies ; Enzyme-Linked Immunosorbent Assay ; Female ; Heart Failure ; Humans ; Male ; Methods

PURPOSE: The aim of this study is to evaluate the incidence of hyperkalemia and the contributing factors of nonoliguric hyperkalemia in low birth weight infants within 48 hours after birth. METHODS: The incidence of nonoliguric hyperkalemia and difference of clinical features between hyperkalemia (>6.7 mEq/L) and normokalemia (< or =6.7 mEq/L) groups were determined by reviewing medical records of 196 low birth weight infants who were born in Hanyang university hospital between Oct. 2001. and Jul. 2004. We analized the serum level of sodium, potassium, fluid intake, urine output, pH of blood gas and others. RESULTS: Among 196 infants, 17 infants was hyperkalemia developed in 48 hours after birth. In that cases, 10 infants were showed EKG abnormalities, such as ventricular tachycardia. In all cases, birth weight, gestational age, Apgar score, usage of surfactant, urine output, BUN and creatinine were significant. In A group gestational age, urine output, BUN, creatinin were significant, in B group BUN, creatinine were significant, in C group BUN were significant between hyperkalemia and normokalemia. Six infants with hyperkalemia died as a result of hyperkalemia induced cardiac arrhythmia. CONCLUSION: Hyperkalemia frequently occurred extremely premature infants. But hyperkalemia also be developed in low birth weight infants who were not suffered from asphyxia or tissue damage. Serum potassium level should be monitored to avoid life threatening cardiac arrhythmia in low birth weight infant.
Apgar Score ; Arrhythmias, Cardiac ; Asphyxia ; Birth Weight ; Creatinine ; Electrocardiography ; Gestational Age ; Humans ; Hydrogen-Ion Concentration ; Hyperkalemia* ; Incidence ; Infant* ; Infant, Extremely Premature ; Infant, Low Birth Weight* ; Infant, Newborn ; Medical Records ; Parturition ; Potassium ; Sodium ; Tachycardia, Ventricular

BACKGROUND: The associations of vitamin D deficiency with various clinical conditions highlighted the importance of vitamin D testing. Currently, clinicians measure only the total 25-hydroxyvitamin D [25(OH)D] concentration, regardless of its bioavailability. We aimed to determine the effect of vitamin D-binding protein (VDBP) on 25(OH)D bioavailability. METHODS: Serum samples were collected from 60 healthy controls, 50 pregnant women, and 50 patients in intensive care units (ICUs). Total 25(OH)D was quantified by liquid chromatography with tandem mass spectrometry, and VDBP levels were determined by using an ELISA kit (R&D Systems, USA). The bioavailable 25(OH)D levels were calculated by using total 25(OH)D, VDBP, and albumin concentrations. RESULTS: In comparison with healthy controls, the total 25(OH)D concentration was significantly lower in ICU patients (median, 11.65 vs 18.25 ng/mL; P<0.00001), but no significant difference was noted between pregnant women (18.25 ng/mL) and healthy controls. The VDBP level was significantly lower in ICU patients (95.58 vs 167.18 µg/mL, P=0.0002) and higher in pregnant women (225.01 vs 167.18 µg/mL, P=0.008) compared with healthy controls. Nonetheless, the calculated bioavailable 25(OH)D levels of ICU patients and pregnant women were significantly lower than those of healthy controls (1.97 and 1.93 ng/mL vs 2.56 ng/mL; P=0.0073 and 0.0027). CONCLUSIONS: A single marker of the total 25(OH)D level is not sufficient to accurately evaluate vitamin D status, especially in pregnant women. In cases where VDBP concentrations may be altered, VDBP measurements and bioavailable 25(OH)D calculations may help to determine vitamin D status accurately.
Adult ; Aged ; Chromatography, High Pressure Liquid ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Pregnancy ; Pregnant Women ; Serum Albumin/analysis ; Tandem Mass Spectrometry ; Vitamin D/*blood ; Vitamin D-Binding Protein/*blood

Chronic myelogenous leukaemia (CML) is a myeloproliferative neoplasm that is almost always characterised by the presence of t(9;22)(q34;q11.2). Approximately 5% to 10% of CML patients lack cytogenetic evidence of t(9;22)(q34;q11.2) but have the breakpoint cluster region (BCR)/ABL1 fusion, as revealed by fl uorescence in situ hybridisation (FISH) or the reverse transcription-polymerase chain reaction (RT-PCR). We present a case of Philadelphia-negative CML with a cryptic insertion of BCR at 9q34. A 22-year-old woman incidentally presented with marked leucocytosis and anaemia. Her complete blood count results were as follows: white blood cells, 238.61x10(9)/L; haemoglobin, 9.6 g/dL; platelets, 395x10(9)/L. A peripheral blood smear showed leucocytosis with neutrophilia, basophilia, left-shifted neutrophils, and circulating blasts comprising 2% of the total leucocytes. The bone marrow showed a striking increase in megakaryocytes and granulocytic precursors. The myeloid/erythroid ratio was 7.4:1, and blasts comprised up to 1.8% of all nucleated cells. Bone marrow sections revealed active megakaryopoiesis and granulopoiesis with 100% cellularity. Chromosomal analysis revealed a normal karyotype. However, interphase FISH using a dual-colour BCR/ABL1 fusion probe showed an atypical pattern consisting of one red, two green, and one fusion (1R2G1F) signal in 97.5% of the 200 analysed cells. Metaphase FISH revealed a single BCR/ABL1 fusion signal on chromosome 9. RT-PCR was positive for BCR/ABL1 (b3a2). Quantitative PCR revealed a normalised copy number of 15.32. The patient started her treatment with imatinib, reached a complete molecular response eight months afterwards, and has been coping well without any adverse events.
Blood Cell Count ; Bone Marrow ; Chromosomes, Human, Pair 9 ; Cytogenetics ; Female ; Humans ; Interphase ; Karyotype ; Leukocytes ; Megakaryocytes ; Metaphase ; Neutrophils ; Polymerase Chain Reaction ; Strikes, Employee ; Young Adult ; Imatinib Mesylate

BACKGROUND: JEOL BioMajesty JCA-BM6010/C (JCA-BM6010/C, JEOL Ltd., Japan) is a recently developed ultra-compact automated clinical chemistry analyzer with a throughput of 1,200 tests per hour. Here, we present the first performance evaluation of JCA-BM6010/C. METHODS: We evaluated the precision, linearity, correlation, accuracy, and carryover of 11 analytes (ALP, ALT, AST, calcium, creatinine, GGT, glucose, LDH, total bilirubin, total protein, and uric acid) using the JEOL closed reagent (JEOL Ltd.) according to the guidelines of the Clinical Laboratory Standards Institute. Linearity was further evaluated for ALT, AST, and GGT using open reagents by Sekisui (Japan). The performance of JCA-BM6010/C was compared to that of the Roche-Hitachi Cobas 8000 c702 chemistry autoanalyzer (Cobas 8000, Roche Diagnostics, Switzerland). Its performance using open reagents from Denka Seiken (Japan), Roche, and Sekisui was also evaluated. RESULTS: The total coefficients of variation (CV) for all analytes were 1.0–2.7%. Linearity was observed for all analytes over the entire tested analytical range (R²≥0.99). The results of JCA-BM6010/C strongly correlated (r≥0.988) with those of Cobas 8000 for all evaluated analytes except LDH (r=0.963), as well as for all open reagents. Recovery rates for creatinine, glucose, calcium, and uric acid were 96.6–101.5% and 98.7–109.3% with the JEOL exclusive and open reagents, respectively. Sample carryover was less than 0.34%. CONCLUSIONS: JCA-BM6010/C showed acceptable performance in the precision, linearity, correlation, accuracy, and sample carryover analyses and in the method comparison. Therefore, it could be a useful routine laboratory medical analyzer.
Bilirubin ; Calcium ; Chemistry ; Chemistry, Clinical* ; Creatinine ; Glucose ; Indicators and Reagents ; Methods ; Uric Acid

PURPOSE: This study was undertaken to investigate the spectrum and the prognosis of neonate with cardiovascular malformation delivered from diabetic mothers. METHODS: From January 2004 to December 2008, 70 neonates born to diabetic mothers who were delivered at Dongsan Medical Center, Keimyung University, and received echocardiographic study between 3rd and 14th days of life to identify the presence of cardiac anomaly were included. Cases combined with chromosomal anomaly were excluded. And follow up results (rate of cardiac operation and mortality) were assessed. RESULTS: Among 67 neonates, 22 cases (32.8%) had combined cardiovascular malformation. They were interventricular septal hypertrophy (10 cases), atrial septal defect (7 cases), significant patent ductus arteriosus (5 cases), ventricular septal defect (2 cases) and tetralogy of Fallot (1 case). Among them, 20 neonates (29.9%) were preterm babies, and 21 neonates (31.3%) were large babies. On follow up echocardiograpic examination between 2 and 12 months of life, all but 2 infants (received cardiac operation due to VSD or Tetralogy of Fallot) was improved spontaneously. And combined extracardiac anomalies were tracheoesophageal fistula (2 cases), imperforated anus (1 case) and corpus callosum agenesis (1 case). Only one preterm baby was dead due to necrotizing enterocolitis, but did not have cardiac disease. CONCLUSION: Pre-existing maternal diabetes was associated with the development of neonatal cardiac anomalies, but the prognosis was good in this study.
Agenesis of Corpus Callosum ; Anal Canal ; Ductus Arteriosus, Patent ; Echocardiography ; Enterocolitis, Necrotizing ; Follow-Up Studies ; Heart Diseases ; Heart Septal Defects, Atrial ; Heart Septal Defects, Ventricular ; Humans ; Hypertrophy ; Infant ; Infant, Newborn ; Mothers ; Prognosis ; Tetralogy of Fallot ; Tracheoesophageal Fistula

PURPOSE: Intrauterine growth retardatation(IUGR) is very important because of high mortality and morbidity in the neonatal period. We studied the intrauterine growth retardation pattern in neonates with congenital heart disease(CHD). METHODS: One hundred seventeen cases with CHD(acyanotic, 73 cases; cyanotic, 44 cases) who had no other congenital malformation or maternal diseases that might affect fetal growth were enrolled in this study along with 120 control cases without CHD. We analyzed birth weight, crown-heel length and neonatal ponderal index. RESULTS:The proportion of IUGR infants was 17 out of 237 cases(7.2%). Compared to a normal control group(5/120, 4.2%), the CHD group had more IUGR(12/117, 10.3%)(P=0.006). Low birth weight(LBW) was higher in the CHD group(26/117, 22.2% vs 15/120, 12.5%; P=0.048). Among the CHD group, acyanotic CHD had often more than cyanotic CHD(21/73, 28.8% vs 5/44, 11.4%; P= 0.028). The proportion of IUGR among the LBW was 12 out of 41 cases(16.3%) in total. But, there were no significant difference in the proportion of IUGR among the LBW(10/26, 38.5% vs 2/15, 13.3 %; P=0.089), the proportion of IUGR among the prematurity(3/25, 12.0% vs 2/25, 8.0%; P=0.637) and abnormal neonatal ponderal index(5/12, vs 3/5; P=0.490). The proportion of short crown-heel length was high in the CHD group(7/117, 6.0% vs 1/120, 0.8%; P=0.028). CONCLUSION: Neonates with CHD had greater incidence of LBW, short crown-heel length and IUGR compared to normal neonates. Moreover, symmetrical IUGR was more common in IUGR neonates with CHD. Therefore, intrauterine development might be more influenced by intrinsic fetal factors than hemodynamic alteration of the circulation in CHD with IUGR.
Birth Weight ; Fetal Development ; Fetal Growth Retardation ; Heart ; Heart Defects, Congenital* ; Hemodynamics ; Humans ; Incidence ; Infant ; Infant, Newborn* ; Mortality ; Parturition