Physiological Activities of Policosanol Extracted from Sugarcane Wax

Policosanol extracted from sugarcane wax is a generic term used for total fatty alcohols obtained from esterification of fatty acids. It has been approved as a health functional food by the Ministry of Food and Drug Safety of Korea in 2006. Policosanol is well-known to aid in lowering blood cholesterol level. Recently, several studies have reported the physiological activities of policosanol, such as anti-inflammatory effects, antioxidant effects, and lowering of the incidence of ageing-related diseases, for example, hypertension, stroke, among others. This review describes the physiological activities of policosanol and its applications in the field of health functional foods.

Neonatal Meningoencephalitis caused by Herpes Simplex Virus Type 2 / 소아감염

Despite its rare occurrence, early diagnosis and appropriate treatment for neonatal herpes simplex virus infection are mandatory due to its high morbidity and mortality. In Korea, there has been no epidemiologic data on neonatal herpes simplex virus infection, and even case reports are rare. We observed a 16-day-old neonate who presented with fever and seizures. We diagnosed her with meningoencephalitis caused by herpes simplex virus type 2 based on the polymerase chain reaction test, and treated her with intravenous acyclovir and anticonvulsants. The seroprevalence of herpes simplex virus type 2 sharply increases in women in their 30s, and the average age for childbirth has increased to older than 30 years of age in Korea; we therefore expect that the incidence of neonatal herpes simplex virus type 2 infection will rise in Korea, and more attention should be directed to neonatal herpes simplex virus type 2 infection. We report this newborn patient's case along with a literature review.

Artemisinin attenuates platelet-derived growth factor BB-induced migration of vascular smooth muscle cells

BACKGROUND/OBJECTIVES: Artemisinin (AT), an active compound in Arternisia annua, is well known as an anti-malaria drug. It is also known to have several effects including anti-oxidant, anti-inflammation, and anti-cancer activities. To date, the effect of AT on vascular disorders has not been studied. In this study, we investigated the effects of AT on the migration and proliferation of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor BB (PDGF-BB). MATERIALS/METHODS: Aortic smooth muscle cells were isolated from Sprague-Dawley rats. PDGF-BB stimulated VSMC migration was measured by the scratch wound healing assay and the Boyden chamber assay. Cell viability was determined by using an EZ-Cytox Cell Viability Assay Kit. The production of reactive oxygen species (ROS) in PDGF-BB stimulated VSMC was measured through H2DCF-DA staining. We also determined the expression levels of signal proteins relevant to ROS, including measures of extracellular signal-regulated kinase (ERK) 1/2 measured by western blot analysis and matrix metalloproteinase (MMP) 9 measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: AT (10 microM and 30 microM) significantly reduced the proliferation and migration of PDGF-BB stimulated VSMC in a dose-dependent manner. The production of ROS, normally induced by PDGF-BB, is reduced by treatment with AT at both concentrations. PDGF-BB stimulated VSMC treated with AT (10 microM and 30 microM) have reduced phosphorylation of ERK1/2 and inhibited MMP9 expression compared to untreated PDGF-BB stimulated VSMC. CONCLUSIONS: We suggest, based on these results, that AT may exert an anti-atherosclerotic effect on PDGF-BB stimulated VSMCs by inhibiting their proliferation and migration through down-regulation of ERK1/2 and MMP9 phosphorylation.

Blockade of VEGFR-1 and VEGFR-2 Enhances Paclitaxel Sensitivity in Gastric Cancer Cells

PURPOSE: Hypoxia-inducible factor-1alpha (HIF-1alpha) increases transcription of the vascular endothelial growth factor (VEGF) gene. Inhibition of VEGF abolishes VEGF mediated induction of HIF-1alpha. Recent reports suggested that HIF-1alpha also mediated the induction of class III beta-tubulin (TUBB3) in hypoxia. TUBB3 confers resistance to taxanes. Inhibition of VEGF may decrease the expression of HIF-1alpha and TUBB3. This study was undertaken to investigate the roles of vascular endothelial growth factor receptor (VEGFR) in gastric cancer cell behavior and to identify methods to overcome paclitaxel resistance in vitro. MATERIALS AND METHODS: The protein expression levels of HIF-1alpha and TUBB3 were measured in human gastric cancer cell lines (AGS) under normoxic and hypoxic conditions. The relationship between TUBB3 and paclitaxel resistance was assessed with small interfering TUBB3 RNA. AGS cells were treated with anti-VEGFR-1, anti-VEGFR-2, placental growth factor (PlGF), bevacizuamb, and paclitaxel. RESULTS: Hypoxia induced paclitaxel resistance was decreased by knockdown of TUBB3. Induction of HIF-1alpha and TUBB3 in AGS is VEGFR-1 mediated and PlGF dependent. Hypoxia-dependent upregulation of HIF-1alpha and TUBB3 was reduced in response to paclitaxel treatment. Expressions of HIF-1alpha and TUBB3 were most decreased when AGS cells were treated with a combination of paclitaxel and anti-VEGFR-1. AGS cell cytotoxicity was most increased in response to paclitaxel, anti-VEGFR-1, and anti-VEGFR-2. CONCLUSION: We suggest that blockade of VEGFR-1 and VEGFR-2 enhances paclitaxel sensitivity in TUBB3-expressing gastric cancer cells.

Clinical Prognostic Factors for Locally Advanced Esophageal Squamous Carcinoma Treated after Definitive Chemoradiotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Locally advanced esophageal cancers are generally treated with neoadjuvant chemoradiotherapy, followed by surgery in operable candidates. However, even if the patients were diagnosed as operable disease, surgery could not be performed on patients with poor condition or other comorbidity. In this case, definitive chemoradiotherapy (dCRT) is the other option for localized esophageal cancer. Therefore, the purpose of this study was to evaluate the efficacy and clinical prognostic factors for dCRT in locally advanced esophageal cancer. MATERIALS AND METHODS: We conducted a review of patients who received dCRT for locally advanced squamous esophageal cancer from 2004 to 2010, focusing on stages III and IVa. All patients received at least two cycles of platinum-based chemotherapy during radiation, and all tumor burdens were included in the radiation field. The treatment results were analyzed for patterns of failure and prognostic factors associated with survival. RESULTS: In total, 63 patients were enrolled in this study. The overall response rate was 84.1%. Relief from dysphagia after dCRT was achieved in 48 patients. The most frequent failure was local recurrence. The median overall survival (OS) was 23.0 months, and the 2-year survival rate was 45.4%. Similar results were observed for elderly study patients. Significant prognostic factors for OS were duration of smoking, high grade of dysphagia (score of 3 or 4), and shorter duration of progression-free and dysphagia-free survival. Maintenance chemotherapy after dCRT did not influence OS. However, "good risk" patients receiving maintenance chemotherapy showed better OS than those who did not receive maintenance chemotherapy (30.4 months vs. 12.0 months, p=0.002). CONCLUSION: dCRT has a major role in improving survival and palliation of dysphagia in inoperable advanced esophageal cancer, even in elderly patients. Maintenance chemotherapy after dCRT may be effective in prolonging survival in "good risk" patients.

Evaluation of the Nanopia P-FDP Reagent Kit for Use in the STA-R EVOLUTION Automated Blood Coagulation Analyzer / 임상검사와정도관리

BACKGROUND: In this study on fibrinogen/fibrin degradation products (FDPs), we evaluated the performance of a quantitative immunoturbidimetric assay (ITA) using the new Nanopia P-FDP reagent kit (Sekisui Medical Co., Japan) in comparison with a semiquantitative latex agglutination assay (LA) currently performed using the FDP PLASMA kit (Diagnostica Stago SAS, France). METHODS: The quantitative Nanopia P-FDP method using the STA-R EVOLUTION automated coagulation analyzer (Diagnostica Stago SAS) was evaluated with respect to precision, linearity, carryover, and reference interval. The correlations were measured for each of the 145 samples by using the Nanopia P-FDP method and the semiquantitative FDP PLASMA method. RESULTS: The coefficients of variation with regard to precision in low and high control concentrations were 2.97% and 5.77%, respectively. The correlation coefficient of linearity (r) was 0.990 in the measurement range of 2.4-122.8 microg/mL. The level of carryover was 0.83%, while the reference interval range was 0.22-4.32 microg/mL. The results of FDP assay showed an acceptable accord in 115 samples (79%) among the 145 samples by both LA method and ITA method. Seventeen samples (12%) showed relatively lower FDP values in the LA method than those in the ITA method. Thirteen cases (9%) showed relatively higher FDP values in the LA method than those in the ITA method. CONCLUSIONS: The quantitative Nanopia P-FDP method showed good precision, linearity, carryover, reference interval, and an acceptable concordance rate with the semiquantitative FDP PLASMA method. Thus, the Nanopia P-FDP reagent using the STA-R EVOLUTION automated coagulation analyzer can replace the FDP PLASMA reagent for the quantitative analysis of FDPs.

Intravenous KITENIN shRNA Injection Suppresses Hepatic Metastasis and Recurrence of Colon Cancer in an Orthotopic Mouse Model

KITENIN (KAI1 C-terminal interacting tetraspanin) promotes invasion and metastasis in mouse colon cancer models. In the present study, we evaluated the effects of KITENIN knockdown by intravenous administration of short hairpin RNAs (shRNAs) in an orthotopic mouse colon cancer model, simulating a primary or adjuvant treatment setting. We established orthotopic models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). In the primary therapy model, treatment with KITENIN shRNA substantially delayed tumor growth (P = 0.028) and reduced the incidence of hepatic metastasis (P = 0.046). In the adjuvant therapy model, KITENIN shRNA significantly reduced the extent of tumor recurrence (P = 0.044). Mice treated with KITENIN shRNA showed a better survival tendency than the control mice (P = 0.074). Our results suggest that shRNA targeting KITENIN has the potential to be an effective tool for the treatment of colon cancer in both adjuvant and metastatic setting.

Survival Prediction in Terminally Ill Cancer Patients: Laboratory Variables and Prospective Validation of The Palliative Prognostic Index / 대한내과학회지

BACKGROUND/AIMS: The palliative prognostic index (PPI) was designed to predict life expectancy based on clinical symptoms. In this study, a PPI was constructed and used with other biological parameters to predict 3-week survival in patients with advanced cancer. METHODS: The study included 222 patients. The PPI was constructed with five variables (performance status, oral intake, edema, dyspnea at rest, and delirium). PPI scores were grouped as follows: 4 (group 1); > 4 and 6 (group 3). At admission, seven biological variables (white blood cell count, lymphocyte, C-reactive protein [CRP], bilirubin, albumin, creatinine, and lactate dehydrogenase) were measured. RESULTS: The overall survival duration was 50 days in group 1, 22 days in group 2, and 14 days in groups 3. Using the PPI, a survival of 6 and increases in serum bilirubin and CRP levels. Furthermore, the 3-week survival rate in patients with hepatopancreatobiliary cancer was more accurately predicted using a combination of the PPI, CRP, and serum bilirubin levels. CONCLUSIONS: Although a PPI has limitations, it can be quickly applied to determine survival duration in patients admitted to hospice and accurately predicts 3-week survival. Furthermore, bilirubin and CRP are useful factors for predicting 3-week survival in patients with gastrointestinal cancer, including hepatopancreatobiliary cancer.

Efficacy and Tolerability of OROS Hydromorphone in Strong Opioid-Naive Patients: An Open Label, Prospective Study / 대한내과학회지

BACKGROUND/AIMS: OROS hydromorphone is a synthetic opioid agent. While clinical studies have tested its effectiveness at controlling cancer-associated pain in patients who have received other strong opioids, no clinical studies have tested its effectiveness at managing cancer pain in strong opioid-naive patients. We performed the present study to evaluate the efficacy and tolerability of OROS hydromorphone in strong opioid-naive cancer patients. METHODS: We administered OROS hydromorphone to patients who had not received strong opioids during the previous month. The starting dose was 8 mg/day. The dose was increased every 2 days in patients who experienced more than four episodes of breakthrough pain per day (more than four times in patients being treated with short-acting opioids). We evaluated the efficacy, safety and tolerability of ORS hydromorphone. We also evaluated patient satisfaction and investigators' global assessments. RESULTS: We enrolled 23 patients to the study. The decrease in the numeric rating scale (NRS) was 59%. NRS variation had decreased markedly during the previous 24 h. All patients achieved stable pain control. The side effects were similar to those of other strong opioids. In total, 26% of patients were very satisfied with the treatment and 47% satisfied, and 74% of the investigators deemed OROS hydromorphone to be very effective or effective at controlling cancer pain. CONCLUSIONS: OROS hydromorphone is an osmotically driven, controlled-release preparation that is very effective and safe when administered once daily to strong opioid-naive cancer patients.

Airway Responsiveness to Inhaled Aspirin is Influenced by Airway Hyperresponsiveness in Asthmatic Patients

BACKGROUND/AIMS: Many patients with aspirin-induced asthma have severe methacholine airway hyperresponsiveness (AHR), suggesting a relationship between aspirin and methacholine in airway response. This study was performed to determine whether methacholine AHR affects the response of asthmatics to inhaled aspirin. METHODS: The clinical records of 207 asthmatic patients who underwent inhalation challenges with both aspirin and methacholine were reviewed retrospectively. An oral aspirin challenge was performed in patients with a negative inhalation response. The bronchial reactivity index (BRindex) was calculated from the percent decrease in lung function divided by the last dose of the stimulus. RESULTS: Forty-one (20.9%) and 14 (7.1%) patients showed a positive response to aspirin following an inhalation and oral challenge, respectively. Only 24.3 and 14.3% of the responders had a history of aspirin intolerance, respectively. The methacholine BRindex was significantly higher in the inhalation responders (1.46 +/- 0.02) than in the oral responders (1.36 +/- 0.03, p < 0.01) and in non-responders (n = 141, 1.37 +/- 0.01, p < 0.001). The aspirin BRindex was significantly correlated with the methacholine BRindex (r = 0.270, p < 0.001). Three of four patients who received the oral challenge, despite a positive inhalation test, showed negative responses to the oral challenge. Two of these patients had severe AHR. CONCLUSIONS: A considerable number of asthmatic patients with no history of aspirin intolerance responded to the inhalation aspirin challenge. The airway response to aspirin was significantly correlated with methacholine-AHR, and a false-positive response to aspirin inhalation test seemed to occur primarily in patients with severe AHR.

Toxic Epidermal Necrolysis after Rituximab Therapy for Immune Thrombocytopenic Purpura

Rituximab is a chimeric monoclonal antibody that specifically targets the CD20 molecule on the B cell surface. Although rituximab was originally introduced for the treatment of lymphoid neoplasms such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), it is now emerging as an effective and relatively safe therapeutic option for the patients with refractory immune thrombocytopenic purpura (ITP). We report here on a case of life-threatening toxic epidermal necrolysis (TEN) that was related with the use of rituximab in a patient with refractory ITP. The patient developed extensive erythematous papules and bullous lesions on his whole body associated with fever and visual disturbance during the second cycle of rituximab. The rituximab was discontinued and high dose intravenous immunoglobuline and steroid were administrated. Four weeks later, he fully recovered without any sequelae. A review of the literature reveals this to be the first reported case of TEN associated with rituximab injection in Korea.

Prevention of bone loss with vitamin D3 supplementation, hormone replacement therapy and combination therapy in postmenopausal women

BACKGROUND: The positive effects of hormone replacement therapy (HRT) on the skeleton in postmenopausal women are well defined. However, the effects of vitamin D supplementation on BMD in postmenopausal women are controversial. But many women, who are contraindicated to HRT or afraid of side effects of HRT or are already on HRT regimen, take calcium plus vitamin D supplement for prevention of osteoporosis. Therefore, this study was designed to examine the effect of vitamin D supplementation on BMD in postmenopausal women and to determine whether vitamin D supplementation can give additional benefit to HRT. METHODS: Subjects were 109 postmenopausal women out of total 213, who visited the Sacred Heart Hostpital, Chuncheon and had follow up BMD study one year after druing January, 1996 to May, 1999. The study group was as follows: No treatment (n=31) ; Vit D (n=11) ; HRT (n=50) ; HRT+Vit D (n=17). We compared and analyzed the changes of BMD in the region of lumbar spine (L2-4) and femur (femoral neck, trochanter, Ward's triangle). SPSSWIN 7.5 was used for statistical procedure. RESULTS: Subject had a mean age of 54.4+/-5.7 years, mean menopausal age of 48.4+/-2.4 years, mean postmenopausal duration of 6.1+/-4.1 years, and mean body mass index of 24.1+/-2.8 kg/m2. No correlation was observed between general characteristics (age, menopausal age, postmenopausal duration, and body mass index) and changing rate of BMD. Lumbar BMD had increased by 1.83% in the Vit D group, by 1.95% in the HRT group and by 3.15% in the HRT+Vit D group, whereas it had decreased by 1.99% in the no treatment group. The increase of femoral neck BMD in the Vit D group was 1.5%, in the HRT group 0.66% and in the HRT+Vit D group 2.09%, but the loss in the no treatment group was 1.65%. The changes of trochanteric BMD were as follows: No treatment group (-2.49%), Vit D group (0.04%), HRT group (1.48%), and HRT+Vit D group (1.81%). In Ward's triangle BMD the changes were as follows : No treatment group (-4.09%), Vit D group (1.17%), HRT group (-0.01%), HRT+Vit D group (0.16%). In the Vit D group, except for the trochanteric area (P>0.05), there was a significant increase in BMD of L2-4, femoral neck, and Ward's triangle (P<0.05), whereas in the HRT group and HRT+Vit D group significant increases were observed in all areas (P<0.05). But there was no significance among Vit D group, HRT group and HRT+Vit D group. CONCLUSION: This study confirmed the beneficial effect of HRT on lumbar and femoral BMD. It also showed that low dose Vitamin D supplementation had effect in the prevention of osteoporosis in postmenopausal women. In the HRT+Vit D group, BMD had increased more than HRT alone, but does not give any benefit additional to that of HRT alone.