Ferritin is known to be associated with insulin resistance (IR) and oxidative stress; however, recent studies have shown that there is an association between ferritin and anti-oxidative status. To date, the biphasic response of ferritin to oxidative stress has not been fully evaluated. Thus, we investigated the association between ferritin and IR and anti-oxidative status in obese and non-obese women.
We evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) and total anti-oxidant status (TAS) in a total of 111 healthy women between the ages of 32 and 68 years.
In all of the study subjects, ferritin levels were positively correlated with age (r = 0.38, P < 0.001), body mass index (r = 0.24, P = 0.01), TAS (r = 0.38, P < 0.001) and HOMA-IR (r = 0.20, P = 0.04). In the subgroup analysis, ferritin levels were correlated with age (r = 0.39, P < 0.001) and TAS (r = 0.43, P < 0.001) in the non-obese group and with insulin (r = 0.50, P = 0.02) and HOMA-IR (r = 0.52, P = 0.01) levels in the obese group. On stepwise multiple linear regression analysis, ferritin was found to be independently associated with TAS (B = 177.16, P < 0.0001) in the non-obese group and independently associated with HOMA-IR (B = 30.36, P = 0.01) in the obese group.
Our findings suggest ferritin is associated with IR in obese women and with anti-oxidative status in non-obese women. Further studies are warranted to elucidate the precise role of ferritin in obesity.
Ferritins; Obesity; Oxidative Stress
Though adiponectin has been associated with insulin resistance and cardiovascular risk factors, the relationship between adiponectin and polycystic ovary syndrome (PCOS) remains controversial. The aim of this study was to compare adiponectin level in women with PCOS and without PCOS, and to investigate the relationship between adiponectin level and metabolic variables including insulin resistance.
60 women with PCOS were enrolled along with a control group of 80 healthy women, matched for age and body mass index (BMI). We measured hormonal and metabolic parameters, as well as the plasma adiponectin concentration of each participant. We estimated the insulin sensitivity according to the quantitative insulin sensitivity check index (QUICKI).
The PCOS group displayed significantly lower level of adiponectin (P < 0.001) after adjustment for age, BMI, mean blood pressure, fasting glucose, fasting insulin, and several metabolic parameters. Adiponectin levels were positively correlated with QUICKI in the PCOS group (P < 0.001) and the control group (P = 0.03). Following step-wise multiple regression analysis, however, adiponectin level was positively correlated with QUICKI in the control group only (P = 0.03). In addition, adiponectin level was found to be independently associated with HDL-cholesterol level (P < 0.001) and BMI (P = 0.02) in the PCOS group and independently associated with HDL-cholesterol (P = 0.02) in the control group.
We report decreased adiponectin level in PCOS patients in relation to controls independently of insulin resistance or other metabolic factors. And adiponectin is associated with both lipid metabolism and obesity, which, in turn, is related to insulin resistance in PCOS. Further studies are needed to clarify the mechanism of adiponectin in PCOS.
Adiponectin; Polycystic Ovary Syndrome; Insulin Resistance
Pandemic influenza A (H1N1) virus has spread rapidly and prompt diagnosis is needed for successful treatment and prevention of transmission. We investigated clinical predictors, validated the use of previous criteria with laboratory tests, and evaluated the clinical criteria for H1N1 infection in the Korean population.
Materials and Methods
We analyzed clinical and laboratory evaluation data from outpatient clinics at Severance Hospital in Seoul, Korea between November 11 and December 5, 2009.
This analysis included a total of 828 patients. Of these, 372 (44.9%) patients were confirmed with H1N1 infection by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The most common and predictive symptom was cough (90.3%, OR 8.87, 95% CI 5.89-13.38) and about 40% of H1N1-positive patients were afebrile. The best predictive model of H1N1 infection was cough plus fever or myalgia. The sensitivities, specificities, positive predictive values, and negative predictive values of our suggested criteria were 73.9%, 69.5%, 66.4%, and 76.6%, respectively.
Cough was the most common independent symptom in patients with laboratory-confirmed H1N1 infection, and while not perfect, the combination of cough plus fever or myalgia is suggested as clinical diagnostic criteria. Health care providers in Korea should suspect a cough without fever to be an early symptom of H1N1 infection.
Influenza A virus (H1N1 subtype); criteria; diagnosis
AIM: To investigate whether nonalcoholic fatty liver disease (NAFLD) affects coronary artery disease (CAD) and identify candidate mediators.
METHODS: Patients who underwent coronary angiography were consecutively recruited. The patients were classified into four groups by coronary artery stenosis: A, insignificant; B, one-vessel disease; C, two-vessel disease; and D, three-vessel disease. Abdominal ultrasonography was performed to determine the presence of a fatty liver and categorize by grade: 0, no evidence; 1, mild; 2, moderate; and 3, severe. We measured not only known CAD risk factors, but also serum insulin, HOMA-index, adiponectin, interleukin-6, tumor necrosis factor-α and high-sensitivity C-reactive protein levels.
RESULTS: Of the 134 patients who met the inclusion criteria, 82 (61.2%) had ultrasonographically diagnosed NAFLD. Among the 46 patients with CAD, 37 (80.4%) had evidence of a fatty liver. The two groups (A vs B-D) were significantly different in terms of age, total cholesterol, triglycerides, low-density lipoprotein levels and fatty liver. Coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner (P = 0.025). In binary logistic regression, NAFLD was a significant independent predictor of CAD (P = 0.03, OR = 1.685; 95%CI: 1.051-2.702). Among the candidate mediators, the serum adiponectin level showed a trend toward lowering based on CAD progression (P = 0.071).
CONCLUSION: NAFLD is an independent risk factor for CAD in a grade-dependent manner. Moreover, adiponectin might be related to the pathogenesis of NAFLD.
Nonalcoholic fatty liver disease; Coronary artery disease; Coronary angiography; Adiponectin; Insulin resistance
Epigallocatechin gallate (EGCG), the major polyphenol in green tea, acutely stimulates production of nitric oxide (NO) from vascular endothelium to reduce hypertension, and improve endothelial dysfunction in SHR rats. Herein, we explored additional mechanisms whereby EGCG may mediate beneficial cardiovascular actions. When compared with vehicle-treated controls, EGCG treatment (2.5 μM, 8 h) of human aortic endothelial cells (HAEC) caused a ~3-fold increase in hemeoxygenase-1 (HO-1) mRNA and protein with comparable increases in HO-1 activity. This was unaffected by pre-treatment of cells with wortmannin, LY294002, PD98059, or L-NAME (PI 3-kinase, MEK, and NO synthase inhibitors, respectively). Pre-treatment of HAEC with SB203580 (p38 MAPK inhibitor) or siRNA knockdown of p38 MAPK completely blocked EGCG-stimulated induction of HO-1. EGCG treatment also inhibited TNF-α-stimulated expression of VCAM-1 and decreased adhesion of monocytes to HAEC. siRNA knockdown of HO-1, p38 MAPK, or Nrf-2 blocked these inhibitory actions of EGCG. In HAEC transiently transfected with a human HO-1 promoter luciferase reporter (or an isolated Nrf-2 responsive region), luciferase activity increased in response to EGCG. This was inhibitable by SB203580 pre-treatment. EGCG-stimulated expression of HO-1 and Nrf-2 was blocked by siRNA knockdown of Nrf-2 or p38 MAPK. Finally, liver from mice chronically treated with EGCG had increased HO-1 and decreased VCAM-1 expression. Thus, in vascular endothelium, EGCG requires p38 MAPK to increase expression of Nrf-2 that drives expression of HO-1 resulting in increased HO-1 activity. Increased HO-1 expression may underlie anti-inflammatory actions of EGCG in vascular endothelium that may help mediate beneficial cardiovascular actions of green tea.
Epigallocatechin gallate (EGCG); hemeoxygenase-1; p38 kinase; nuclear factor-E2-related factor-2; endothelium
Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3%) patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing −1774 del and/or −24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR = 7.17, 95% CI = 1.79–28.67, P = 0.005). Creatinine elevation was observed in 9 patients (9.2%). Body weight ≥40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR = 8.48, 95% CI = 1.7–43.57, P = 0.010 and OR = 14.17, 95% CI = 1.34–150.35, P = 0.028). Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox.
The dried flower buds of Magnolia sp. are widely used as herbal medicines because of their anti-inflammatory, anti-malarial and anti-platelet activities. Here, we found that veraguensin and galgravin, lignan compounds derived from Magnolia sp., dose-dependently inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblastic cells. These compounds also inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells and bone marrow macrophages. In the RANKL-induced signaling pathway, veraguensin and galgravin reduced p38 phosphorylation and suppressed the expression of c-Fos, a key transcription factor for osteoclastogenesis. Veraguensin and galgravin also inhibited osteoclastic pit formation, which was accompanied by decreased mature osteoclast viability. In conclusion, these results indicate that veraguensin and galgravin can inhibit bone resorption and may offer novel compounds for the development of drugs to treat bone-destructive diseases such as osteoporosis.
Veraguensin.; Galgravin; RANKL; Osteoclast; p38; c-Fos
Recent literature suggests that Staphylococcal enterotoxin specific IgE may be a risk factor for asthma.
To investigate the associations between Staphylococcal enterotoxin sensitization and asthma.
A systematic review and meta-analysis was performed for relevant case-control or population-based studies, published in the peer-reviewed journals until February 2013. Data were extracted on study designs, subjects, definitions and the prevalence of Staphylococcal enterotoxin sensitization.
A total of 683 studies were initially identified, of which 7 studies finally met the inclusion criteria (5 case-control and 2 population-based studies). All the included studies reported higher prevalence of the sensitization in asthmatics than in controls, despite clinical and methodological heterogeneity. In a meta-analysis, the pooled odds ratio of the sensitization for asthma was 2.95 (95% confidence intervals 2.28-3.82).
Staphylococcal enterotoxin sensitization was significantly associated with asthma. The mechanisms of associations warrant further elucidation.
Asthma; Staphylococcus; Meta-analysis
Insulin resistance, decreased response of peripheral tissue to normal insulin levels, is known to be related to cardiometabolic diseases. Cardiopulmonary fitness is also considered to be related to these comorbidities. Therefore, we investigated the relationship between insulin resistance and cardiopulmonary fitness by performing a 3-minute step test in a Korean non-diabetes mellitus (DM) population.
A total of 118 non-DM subjects were enrolled during their routine health check-up. Insulin resistance was measured by calculating homeostatic model assessment-insulin resistance (HOMA-IR), and a 3-minute step test was performed to measure cardiopulmonary fitness.
Post-60 seconds exercise heart rate after 3-minute test (R60 heart rate) was correlated with age (r = -0.21, P = 0.02), education (r = 0.17, P = 0.04), body mass index (r = 0.23, P = 0.01), waist circumference (r = 0.28, P < 0.01), fasting insulin (r = 0.28, P < 0.01), HOMA-IR (r = 0.25, P < 0.01), low density lipoprotein-cholesterol (r = 0.28, P < 0.01), high sensitivity C-reactive protein levels (r = 0.22, P = 0.02), and baseline heart rate (r = 0.56, P < 0.01). In a step-wise multiple regression analysis, baseline heart rate (β = 0.79, P < 0.001), HOMA-IR (β = 0.65, P = 0.02), and systolic blood pressure (β = 0.15, P = 0.03) were identified as explanatory variables for R60 heart rates.
Our results suggested that cardiopulmonary fitness was associated with insulin resistance in non-DM patients of a university hospital in Korea. Further studies are needed to elucidate the underlying mechanisms.
Insulin Resistance; Physical Fitness; Exercise Test
To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum).
Patients and methods
This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints.
Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007).
This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.
Primary CNS lymphoma (PCNSL) is a very uncommon disease in children, and usually treated by chemotherapy, combined with focal or craniospinal radiotherapy (RT). However, adverse effects of RT are a concern. We evaluated the outcomes of childhood PCNSL, treated with systemic and intrathecal chemotherapy, but without RT. For fifteen years, six patients among 175 of non-Hodgkin lymphoma were diagnosed as PCNSL in Seoul National University Children's Hospital and we analyzed their medical records retrospectively. Their male:female ratio was 5:1, and median age was 10.1 yr. The primary sites were the sellar area in three patients, parietal area in one, cerebellum in one, and multiple areas in one. Their pathologic diagnoses were diffuse large B-cell lymphoma in three patients, Burkitt lymphoma in two, and undifferentiated B-cell lymphoma in one. Five were treated with the LMB96 treatment protocol, and one was treated with the CCG-106B protocol. None had RT as a first-line treatment. One patient had a local relapse and received RT and salvage chemotherapy, without success. No patient had treatment-related mortality. Their estimated 5-yr event-free and overall survival rates were both 83.3%. In conclusion, PCNSL is a rare disease in childhood, but successfully treated by chemotherapy without RT.
Primary CNS Lymphoma; Children; Irradiation
In folk medicine, the aerial part of Crytotaenia japonica Hassk. (CJ), is applied for treatment of the common cold, cough, urinary problems, pneumonia, and skin rashes. In this paper, the in vitro and in vivo anti-inflammatory activity of CJ methanol extract was tested using lipopolysaccharide (LPS)-induced inflammatory models.
We measured nitric oxide (NO), inducible NO synthase (iNOS), and inflammatory cytokine levels from LPS-stimulated mouse peritoneal macrophages. Also, several cellular signaling molecules which regulate the expressions of these inflammatory markers were examined. Finally, we tested whether oral administration of CJ methanol extract might affect the serum cytokine levels in LPS-injected mice.
CJ methanol extract reduced NO release via iNOS protein inhibition. The extract was also shown to decrease the secretions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12. Analysis of signaling molecules showed that CJ inhibited the phosphorylation of STAT1, p38, JNK and ERK1/2 as well as IκBα degradation. Finally, CJ decreased the serum levels of TNF-α and IL-6 in LPS-injected mice.
Our results demonstrated the anti-inflammatory activity of CJ methanol extract and its possible underlying mechanisms that involve modulation of IκBα, MAPK, and STAT1 activities.
Cryptotaenia japonica Hassk.; Inflammation; Macrophages; iNOS; Cytokines; Signaling
Carcinoembryonic antigen (CEA) is a tumor marker overexpressed in adenocarcinoma that has proinflammatory properties. Recent studies have reported that CEA is positively associated with carotid atherosclerosis and metabolic syndrome. Because visceral obesity is a known risk factor for cardiometabolic diseases, CEA may also be associated with visceral adiposity. Therefore, we investigated the relationship between serum CEA concentration and visceral obesity in female Korean nonsmokers.
A total of 270 Korean female nonsmokers were enrolled during their routine health check-ups. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. Serum CEA levels were measured by using a chemiluminescence immunoassay analyzer.
Serum CEA levels correlated with visceral fat area, fasting glucose, and triglyceride levels after adjusting for age and BMI. The mean visceral fat area increased significantly with the increasing CEA tirtiles. In a step-wise multiple regression analysis, age (β = 0.26, p<0.01) and visceral fat area (β = 0.19, p = 0.03) were identified as explanatory variables for serum CEA level.
This study suggested that CEA may be a mediator that links metabolic disturbance and tumorigenesis in visceral obesity. Further studies are required to better understand the clinical and pathophysiological significance of our findings.
The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines.
Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines.
Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity.
This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.
Carcinoma, renal cell; Cyclooxygenase 2; Prognosis
Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15±5.08 kg/m2. Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00–33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS.
Peripheral blood stem cell (PBSC) mobilization, which uses plerixafor (AMD 3100), a newly developed specific inhibitor of the CXCR4 receptor, in combination with granulocyte-colony stimulating factor(G-CSF), has been shown to enhance the stem cell mobilization in adult patients, but pediatric data are scarce. We documented our experience with this drug in 6 Korean pediatric patients who had failed in chemomobilization, using G-CSF, alone. All patients were mobilized CD34+ cells (median, 11.08 × 106/kg: range, 6.34-28.97 × 106/kg) successfully within 2 to 3 cycles of apheresis, without complications. A total of 7 autologous transplantations were performed, including 1 tandem transplantation. However, 2 patients with brain tumors showed severe pulmonary complications, including spontaneous pneumomediastinum. This is the first study of PBSC mobilization with plerixafor in Asian pediatric patients. Furthermore our study suggests that mobilization with plerixafor may be effective in Korean pediatric patients, who have previously been heavily treated and have failed PBSC mobilization with classical chemomobilization, using G-CSF. However, further studies are needed to examine the possible complications of autologous transplantation, using a mobilized plerixafor product in children.
Plerixafor; Hematopoietic Stem Cell Mobilization; Pediatrics; Complications; Interstitial Lung Diseases
To examine trends in the prevalence of type 2 diabetes and related conditions in Asian Americans compared with non-Hispanic whites.
RESEARCH DESIGN AND METHODS
We analyzed data from the National Health Interview Survey (NHIS) from 1997 to 2008 to construct a nationally representative sample of 230,503 U.S. adults aged ≥18 years. Of these adults, 11,056 identified themselves as Asian Americans and 219,447 as non-Hispanic whites.
The age- and sex-adjusted prevalence of type 2 diabetes was higher in Asian Americans than in whites throughout the study period (4.3–8.2% vs. 3.8–6.0%), and there was a significant upward trend in both ethnic groups (P < 0.01). BMI also was increased in both groups, but age- and sex-adjusted BMI was consistently lower in Asian Americans. In fully adjusted logistic regression models, Asian Americans remained 30–50% more likely to have diabetes than their white counterparts. In addition, Asian Indians had the highest odds of prevalent type 2 diabetes, followed by Filipinos, other Asians, and Chinese.
Compared with their white counterparts, Asian Americans have a significantly higher risk for type 2 diabetes, despite having substantially lower BMI. Additional investigation of this disparity is warranted, with the aim of tailoring optimal diabetes prevention strategies to Asian Americans.
Age-related macular degeneration (AMD) is the major cause of blindness among persons aged 60 years and older. The current approved therapies for AMD are exclusively limited to inhibiting vascular endothelial growth factor. However, substantial improvement in vision occurs in only one-third of patients treated with vascular endothelial growth factor antagonists, and one-sixth of treated patients still progress to legal blindness. Therefore, more specific targets are needed to treat AMD. Our goal was to find secretory proteins that change in number in the aqueous humor and that cause exudative AMD disease.
The number of molecules changed in the aqueous humor of patients with AMD compared to the control group was determined using antibody array analysis. The levels of angiopoietin-2 and insulin-like growth factor binding protein-related protein 7 were measured using enzyme-linked immunosorbent assay. The levels of T-cell cytokine receptor (TCCR/WSX-1) were determined using western blot. Potential TCCR/WSX-1-mediated effects on tube formation as well as phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells were determined.
We found that the numbers of several molecules were changed in the aqueous humor of patients with AMD compared to the control group. Among them, angiopoietin-2 was reduced by 20% and TCCR/WSX-1 was increased twofold. Moreover, exogenous TCCR protein induced tube formation and phosphorylation of extracellular signal-regulated kinase in human umbilical vein endothelial cells.
Our study suggests that TCCR/WSX-1 is closely associated with angiogenesis and could serve as a novel therapeutic target in patients with AMD.
To investigate the effectiveness of GnRH antagonist multiple-dose protocol (MDP) with oral contraceptive pill (OCP) pretreatment in poor responders undergoing IVF/ICSI, compared with GnRH antagonist MDP without OCP pretreatment and GnRH agonist low-dose long protocol (LP).
A total of 120 poor responders were randomized into three groups according to controlled ovarian stimulation (COS) options; GnRH antagonist MDP after OCP pretreatment (group 1), GnRH antagonist MDP without OCP pretreatment (group 2) or GnRH agonist luteal low-dose LP without OCP pretreatment (group 3). Patients allocated in group 1 were pretreated with OCP for 21days in the cycle preceding COS, and ovarian stimulation using recombinant human FSH (rhFSH) was started 5 days after discontinuation of OCP.
There were no differences in patients' characteristics among three groups. Total dose and days of rhFSH used for COS were significantly higher in group 3 than in group 1 or 2. The numbers of mature oocytes, fertilized oocytes and grade I, II embryos were significantly lower in group 2 than in group 1 or 3. There were no significant differences in the clinical pregnancy rate and implantation rate among three groups.
GnRH antagonist MDP with OCP pretreatment is at least as effective as GnRH agonist low-dose LP in poor responders and can benefit the poor responders by reducing the amount and duration of FSH required for follicular maturation.
Gonadotropin-releasing hormone; Antagonist; Agonist; Oral Contraceptives; Poor Responders; In vitro fertilization; Intracytoplasmic sperm injection; Human
Amoxicillin, an antibiotic that is widely prescribed for various infections, is associated with a very low rate of drug-induced liver injury; hepatitis and cholestasis are rare complications. Here we present a case of a 39-year-old woman who was diagnosed with abdominal actinomycosis and received amoxicillin treatment. The patient displayed hepatocellular and bile-duct injury, in addition to elevated levels of liver enzymes. The patient was diagnosed with amoxicillin-induced cholestatic hepatitis. When amoxicillin was discontinued, the patient's symptoms improved and her liver enzyme levels reduced to near to the normal range.
Drug-induced liver injury; Amoxicillin; Cholestatic hepatitis
We compared the outcomes of patients with Burkitt lymphoma and French-American-British (FAB) L3 acute lymphoblastic leukemia treated using Lymphoma Malignancy B (LMB) or other treatment protocols.
Thirty-eight patients diagnosed between July 1996 and December 2007 were treated using LMB 96, and 22 patients diagnosed between January 1991 and May 1998 (defined as the early period) were treated using the D-COMP or CCG-106B protocols. We retrospectively reviewed their medical records and analyzed cumulative survival according to the treatment period by using Kaplan-Meier analysis.
There were no intergroup differences in the distribution of age, disease stage, or risk group. The median follow-up period of the 33 live patients in the LMB group was 72 months (range, 36-170 months). Overall survival (OS) and event-free survival (EFS) of patients treated using LMB 96 were 86.8%±5.5% and 81.6%±6.3%, respectively, whereas OS and EFS of patients treated in the early period were 72.7%±9.6% and 68.2%±9.9%, respectively. In the LMB 96 group, OS of cases showing non-complete response (N=8) was 62.5%±17.1%, and OS of relapsed or primary refractory cases (N=6) was 33.3%±19.3%. Central nervous system (CNS) disease, high lactate dehydrogenase levels at diagnosis, and treatment response were significant prognostic factors.
Survival outcome has drastically improved over the last 2 decades with short-term, dose-intensive chemotherapy. However, CNS involvement or poor response to chemotherapy was worse prognostic factors; therefore, future studies addressing this therapeutic challenge are warranted.
Burkitt lymphoma; L3 lymphocytic leukemia; Treatment outcome; Prognosis
Osteoclasts are multinucleated cells that play a crucial role in bone resorption, and are formed by the fusion of mononuclear osteoclasts derived from osteoclast precursors of the macrophage lineage. Compounds that specifically target functional osteoclasts would be ideal candidates for anti-resorptive agents for clinical applications. In the present study, we investigated the effects of luteolin, a flavonoid, on the regulation of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, functions and signaling pathway. Addition of luteolin to a coculture system of mouse bone marrow cells and ST2 cells in the presence of 10−8 M 1α,25(OH)2D3 caused significant inhibition of osteoclastogenesis. Luteolin had no effects on the 1α,25(OH)2D3-induced expressions of RANKL, osteoprotegerin and macrophage colony-stimulating factor mRNAs. Next, we examined the direct effects of luteolin on osteoclast precursors using bone marrow macrophages and RAW264.7 cells. Luteolin completely inhibited RANKL-induced osteoclast formation. Moreover, luteolin inhibited the bone resorption by mature osteoclasts accompanied by the disruption of their actin rings, and these effects were reversely induced by the disruption of the actin rings in mature osteoclasts. Finally, we found that luteolin inhibited RANKL-induced osteoclastogenesis through the suppression of ATF2, downstream of p38 MAPK and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) expression, respectively. Taken together, the present results indicate that naturally occurring luteolin has inhibitory activities toward both osteoclast differentiation and functions through inhibition of RANKL-induced signaling pathway as well as actin ring disruption, respectively.
Luteolin; RANKL; Osteoclast; ATF2; NFATc1
The purpose of this study was to assess the safety issues concerning anesthetic management of video-assisted thoracoscopic surgery (VATS) in pediatric patients.
The medical records of 52 pediatric patients undergoing VATS using general anesthesia and one-lung ventilation (OLV) were reviewed. OLV was achieved with a Fogarty catheter (n = 23) or endobronchial intubation (n = 7) in patients < 10 years of age (group Y, n = 30), and using a double-lumen tube (n = 19) or a univent (n = 3) in children aged between 10 and 16 years of age (group O, n = 22). Hypoxemia, hypercarbia, the difference between ETCO2 and PaCO2, and the effect of CO2 insufflation were assessed.
A decrease in SpO2 less than 90% was observed in 40% of the group Y, compared to none of the group O (P < 0.05). A hypercarbia (ETCO2 > 50 mmHg) was observed more frequently in group Y (40%) than in group O (0%; P < 0.05). The difference between the ETCO2 and PaCO2 was 10.4 ± 8.9 mmHg in group Y and 4.6 ± 3.9 mmHg in group O (P < 0.05). Hypercarbia and acidosis occurred more frequently in patients with CO2 insufflation than those without insufflation in group Y.
Although the anesthesia for VATS in pediatric patients was successfully accomplished, the infants and younger children presented with more intra-operative problems when compared with older children. The anesthetic management for VATS in infants and younger children requires careful and vigilant monitoring.
Children; One lung ventilation; Video-assisted thoracoscopic surgery
Identification of prognostic factors and risk-based post-remission therapy was proposed to improve the outcomes of acute myeloid leukemia (AML) and a mutation of FLT3 has been reported to be a risk factor, especially for pediatric patients. Recently, FLT3 expression level was implicated to have prognostic significance in adults, but little is known for childhood AML. To define the prognostic significance, transcript level of FLT3 was analyzed in 52 pediatric AML patients. The median copy number of FLT3 was 4.6×103 (40-5.9×107 copies)/1.0×106 GAPDH copy, and the relapse free survival of patients with high transcript level of FLT3 (>106 copy number) (0%) was significantly lower than that of the others (53.2%). High transcript level of FLT3 was associated with a markedly high risk of relapse. The development of new therapeutic scheme such as a frontline allogeneic stem cell transplantation or administration of FLT3 inhibitor is needed to improve outcomes.
FLT3; Transcript Level; Leukemia, Myeloid, Acute; Pediatric Age