Screening of Phosphodiesterase-5 Inhibitors and Their Analogs in Dietary Supplements by Liquid Chromatography-Hybrid Ion Trap-Time of Flight Mass Spectrometry.

An accurate and reliable method based on ion trap-time of flight mass spectrometry (IT-TOF MS) was developed for screening phosphodiesterase-5 inhibitors, including sildenafil, vardenafil, and tadalafil, and their analogs in dietary supplements. Various parameters affecting liquid chromatographic separation and IT-TOF detection were investigated, and the optimal conditions were determined. The separation was achieved on a reversed-phase column under gradient elution using acetonitrile and water containing 0.2% acetic acid at a flow rate of 0.2 mL/min. The chromatographic eluents were directly ionized in the IT-TOF system equipped with an electrospray ion source operating in the positive ion mode. The proposed screening method was validated by assessing its linearity, precision, and accuracy. Sequential tandem MS was conducted to obtain structural information of the references, and the fragmentation mechanism of each reference was proposed for providing spectral insight for newly synthesized analogs. Structural information, including accurate masses of both parent and fragment ions, was incorporated into the MSn spectral library. The developed method was successfully applied for screening adulterated dietary supplement samples.

Phase II trial of epidermal growth factor ointment for patients with Erlotinib-related skin effects.

PURPOSE: The efficacy of erlotinib, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has been demonstrated in patients with non-small cell lung cancer (NSCLC) and pancreatic cancer (PC). In the present study, we evaluated the effect of epidermal growth factor (EGF) ointment on erlotinib-related skin effects (ERSEs). METHODS: This was an open-label, non-comparative, multicenter, phase II trial. The patients included those diagnosed with NSCLC or PC who were treated with erlotinib. The effectiveness of the ointment was defined as follows: (1) grade 2, 3, or 4 ERSEs downgraded to ≤ grade 1 or (2) grade 3 or 4 ERSEs downgraded to grade 2 and persisted for at least 2 weeks. RESULTS: Fifty-two patients from seven institutes in Korea were enrolled with informed consent. The final assessment included 46 patients (30 males, 16 females). According to the definition of effectiveness, the EGF ointment was effective in 36 (69.2%) intention to treat patients. There were no statistically significant differences in the effectiveness of the EGF ointment by gender (p = 0.465), age (p = 0.547), tumor type (p = 0.085), erlotinib dosage (p = 0.117), and number of prior chemotherapy sessions (p = 0.547). The grading for the average National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) rating of rash/acne and itching improved from 2.02 ± 0.83 to 1.13 ± 0.89 and 1.52 ± 0.84 to 0.67 ± 0.90, respectively (p < 0.001). The most common reason for discontinuing the study was progression of cancer (37%). CONCLUSIONS: Based on the results, the EGF ointment is effective for ERSEs, regardless of gender, age, type of tumor, and dosage of erlotinib. The EGF ointment evenly improved all kinds of symptoms of ERSEs. CLINICAL TRIAL REGISTRATION NO: ClinicalTrials.gov identifier: NCT01593995.

Purple grape juice supplementation in smokers and antioxidant status according to different types of GST polymorphisms.

DNA damages and antioxidant status was assessed after 8 weeks of purple grape juice supplementation in male smokers depending on the glutathione S-transferase polymorphisms. Ninety-five smokers consumed 480 ml of purple grape juice for 8 weeks. The blood samples were collected before and after supplementation to measure lymphocyte DNA damages, plasma antioxidants, conjugated diene, and the erythrocyte antioxidant enzymes. The diastolic pressure, lymphocyte DNA damage, and plasma conjugated diene were significantly decreased but the plasma γ-tocopherol was increased in GSTM1-null genotype, while increased blood glutathione and decreased lymphocyte DNA damage were observed in GSTM1-present genotype. In case of GSTT1 on the other hand, the decrease in diastolic pressure and lymphocyte DNA damage was observed in both null types and present types, but the erythrocyte catalase activity was decreased in GSTT1-null type and the plasma vitamin C level was increased in GSTT1-present type, suggesting that, the antioxidant effect of grape juice was greater in GSTT1-present type compared to GSTT1-null type. The intakes of 8-week purple grape juice affected diastolic blood pressures, DNA damage reductions and antioxidant status in smokers, mainly greater in GSTM1-null type and GSTT1-present type.

The clinical impact of the sum of the maximum standardized uptake value on the pretreatment with F-FDG-PET/CT in small-cell lung cancer.

OBJECTIVES: The aim of this study was to investigate the clinical significance of the sum of the maximum standardized uptake value (sumSUVmax) on pretreatment positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in newly diagnosed small-cell lung cancer (SCLC). METHODS: We retrospectively analyzed 145 SCLC patients from March 2005 to June 2013 who underwent pretreatment (18)F-FDG-PET/CT. The sumSUVmax was assessed in all malignant lesions up to a maximum of 5 lesions and a maximum of 2 lesions per organ according to RECIST 1.1. RESULTS: A significant difference was found between the low and high sumSUVmax groups (low vs. high sumSUVmax, 91.5 vs. 77.3%; p = 0.018) in the response rate (RR) following frontline platinum-based chemotherapy. The group with low sumSUVmax showed significantly better overall survival (OS; p < 0.001) as well as better progression-free survival (PFS; p < 0.001) compared with the group with high sumSUVmax. Moreover, multivariate analysis revealed that a high sumSUVmax alone was an independent poor prognostic factor for OS (hazard ratio 2.676; 95% confidence interval, 1.674-4.277; p < 0.001). CONCLUSIONS: This study showed that the sumSUVmax adopted from RECIST 1.1 on pretreatment (18)F-FDG PET/CT was significantly correlated with response to treatment, OS, and PFS in patients with SCLC.

Dietary patterns and weight status associated with behavioural problems in young children.

OBJECTIVE: To investigate the associations of behavioural problems with dietary patterns and weight status in young children. DESIGN: We assessed poor social skills and behavioural problems with a seventy-six-item Preschool and Kindergarten Behavior Scale (PKBS) and found three dietary patterns ('Korean healthy', 'animal foods' and 'sweets') in food/food group intake data assessed by an FFQ and analysed using factor analysis. Multiple logistic regression analyses were used to assess the association of diet and weight status with behaviour. SETTING: Pre-schools in the metropolitan areas of Korea. SUBJECTS: A total of 1458 children (mean age 5·2 (sd 0·9) years) from the Practical Approach for Better Maternal and Child Nutrition and Health Study conducted from 2001 to 2005. RESULTS: The 'Korean healthy' pattern showed a significant inverse association with poor social skills in the second highest quartile group (OR = 0·42; 95 % CI 0·21, 0·82) compared with the lowest quartile group for boys. For girls, the 'sweets' pattern was associated with a greater risk of poor social skills (OR = 3·41; 95 % CI 1·29, 9·01 at Q4 v. Q1) and problem behaviours (OR = 2·80; 95 % CI 1·05, 7·43 at Q4 v. Q1). Regarding weight status, both underweight and overweight boys had a higher risk of poor social skills than normal-weight boys. CONCLUSIONS: Dietary patterns and weight status are important indicators for the behaviour of young children. Healthy and unhealthy dietary patterns, underweight and overweight status, and gender differences should thus be considered for further studies.

Sociodemographic and lifestyle factors are associated with the use of dietary supplements in a Korean population.

OBJECTIVE: The use of dietary supplements has been increasing rapidly in Korea over the last decade. The aim of this study was to investigate associations between the pattern of dietary supplement use and the sociodemographic/lifestyle characteristics of Korean consumers. METHODS: Participants were asked to complete a self-administered questionnaire on their sociodemographic and lifestyle characteristics, perceived health status, and regular dietary supplement use. RESULTS: A total of 697 men and 832 women completed the questionnaire. Of the respondents, 44.3% of the men and 53.2% of the women used some kind of dietary supplement regularly. Dietary supplement users were more likely to be women (P < 0.001), to be older than 50 years (P < 0.001), to have a higher household income (P = 0.003), to engage in moderate or vigorous physical activity (P < 0.032), to perceive themselves as healthy (P = 0.026), and to have received a diagnosis of a chronic disease (P < 0.001). In addition, the type of dietary supplements used varied with respect to sociodemographic and lifestyle factors. Among dietary supplement users, men preferred ginseng, and older respondents were more likely to use carbohydrate supplements and less likely to use lipid supplements. Those who had a lower BMI, were ex-smokers, or were nondrinkers preferred either vitamins or minerals. Those who were highly physical active or were nondrinkers tended to prefer either vitamin/mineral complexes or carbohydrate supplements. CONCLUSIONS: The use of dietary supplements was related to sociodemographic and lifestyle factors in a Korean population.

Factors associated with child malnutrition in mountainous ethnic minority communities in Lao PDR.

BACKGROUND: Although in many low- and middle-income countries undernutrition is steadily decreasing, nutritional challenges persist in remote communities, such as those in mountainous areas of Lao PDR. Isolated, with limited access to food and to health care and other public services, local diets are low in both quantity and diversity. Data needed to guide policy and planning are lacking. OBJECTIVES: The study aimed to identify the extent of malnutrition and associated factors among children aged 12-47 months in remote mountainous communities in Lao PDR. METHODS: A cross-sectional survey was conducted in Nong district, Savannakhet province, covering 173 households, involving heads of households, mothers and their children aged 12-47 months. RESULTS: The prevalence of undernutrition was very high among the 173 children studied: 72.8% were stunted, 50.3% underweight and 10.4% wasted. Key factors showing significant positive associations with nutritional status were assets (mobile phone or electric rice mill), collection of non-timber forest products, and household dietary diversity. Negative associations were found with experience of malaria and consuming high amounts of white roots and tubers. Immediate causes of malnutrition were prevalent; half the children had insufficient consumption of all micro- and macronutrients. Diseases were highly prevalent; 30% had recently experienced fever. The households in these villages were quite homogeneous. All scored high on causes of malnutrition; 90% of households experienced food insecurity, nearly all lived below the poverty line, and almost two-thirds of household heads and nearly all mothers had had no education. CONCLUSION: This study identified multiple factors influencing child malnutrition, including low household food diversity, food insecurity, and poor feeding practices among ethnic minority people living in a difficult environment with limited resources. Child undernutrition in these poor communities is complex. Interventions are needed in different sectors, including agricultural production, knowledge on feeding and health services.

Combination chemotherapy with irinotecan and cisplatin in elderly patients (>or= 65 years) with extensive-disease small-cell lung cancer.

INTRODUCTION: Combination chemotherapy with irinotecan and cisplatin is one of the standard treatments for patients with small-cell lung cancer (SCLC). In elderly patients, however, its efficacy and toxicity has not been well documented. In this Phase II study, we assessed the efficacy and toxicity of combination chemotherapy with irinotecan and cisplatin and examined whether advanced age compromises it in elderly patients with previously untreated extensive-disease small-cell lung cancer (ED-SCLC). METHODS: In this study, 46 previously untreated elderly patients (65 years or older) with ED-SCLC were given combination chemotherapy consisting of irinotecan 60 mg/m(2) on days 1, 8 and 15 and cisplatin 60 mg/m(2) on day 1. The treatment was repeated every 4 weeks until patients completed the maximum six cycles. RESULTS: Patients consisted of 37 men and 9 women, whose median age was 70 years (range 65-81 years). A complete response and a partial response were observed in 19.6% (9/46) and 56.5% (26/46), respectively. The overall response rate was 76.1% (95% C.I; 63.8-88.4%). The overall median survival was 10.4 months (range 7.6-13.2 months). The median progression-free survival was 8.32 months (range 6.8-9.8 months). Major toxicities included neutropenia (grade 3-4, 58.7%), leukopenia (grade 3-4, 49.9%), infection (grade 3-4, 39.1%) and diarrhea (grade 3-4, 30.4%). Incidence of febrile neutropenia was significantly higher in patients with ECOG performance status 2-3 compared with ECOG performance status 0-1 (70.4% vs. 5.2%; p<0.001). There were two treatment related deaths in patients ECOG performance status 3. CONCLUSIONS: Our results indicate that combination chemotherapy with irinotecan and cisplatin is an effective treatment for elderly patients with ED-SCLC who have good ECOG performance status and physicians should be aware of the mortality and morbidity due to myelosuppression following this treatment in elderly ED-SCLC patients with poor ECOG performance status.

Effects of glutathione s-transferase (GST) M1 and T1 polymorphisms on antioxidant vitamins and oxidative stress-related parameters in Korean subclinical hypertensive subjects after kale juice (Brassica oleracea acephala) supplementation.

BACKGROUND/OBJECTIVES: Glutathione s-transferase (GST) is involved in the formation of a multigene family comprising phase II detoxification enzymes, involved in the detoxification of reactive oxygen species. This study evaluated whether daily supplementation with kale juice could modulate levels of plasma antioxidant vitamins and oxidative stress-related parameters. We further examined whether this modulation was affected by combined GSTM1 and T1 polymorphisms. SUBJECTS/METHODS: Totally, 84 subclinical hypertensive patients having systolic blood pressure (BP) over 130 mmHg or diastolic BP over 85 mmHg, received 300 mL of kale juice daily for 6 weeks. Blood samples were drawn before start of study and after completion of 6 weeks. RESULTS: After supplementation, we observed significant decrease in DNA damage and increase in erythrocyte catalase activity in all genotypes. Plasma level of vitamin C was significantly increased in the wild/null and double null genotypes. The plasma levels of ß-carotene, erythrocyte glutathione peroxidase activity, and nitric oxide were increased only in the wild/null genotype after kale juice supplementation. CONCLUSIONS: The effect of kale juice was significantly greater in the GSTM1 null genotype and wild/null genotype groups, suggesting possibility of personalized nutritional prescriptions based on personal genetics.

Combined effects of swim training and ginseng supplementation on exercise performance time, ROS, lymphocyte proliferation, and DNA damage following exhaustive exercise stress.

The purpose of this study was to analyze the combined effects of regular exercise and ginseng supplementation on peritoneal exudate ROS (reactive oxygen species), lymphocyte proliferation by splenocytes, and DNA damage following exhaustive exercise stress. Thirty-six female BALB/c mice were randomly divided into control (UT, n = 12), trained (TR, n = 12), and ginseng supplemented and trained (GT, n = 12) groups. Each group was divided into two equal subgroups where mice were studied at rest (UTre, TRre, and GTre) or immediately after exhaustive exercise stress (UTex, TRex, and GTex). Animals were bred in the animal facility, where they were housed at 22-24 degrees C and relative humidity (RH) 50-60% in a controlled environment with a 12-hour photoperiod, and provided food and water ad libitum. The trained mice underwent 10 weeks of endurance swim training (5 times/week) in water at 27-30 degrees C for 60 minutes. The analytical items examined were weight, proliferative activity, the production of ROS from peritoneal exudate cells, and DNA damage following exhaustive exercise stress (2 h exercise stress). Significant level was set at p < 0.05. The results obtained showed that the trained group had a significantly lower mean body weight than the untrained group (p < 0.05). However, there was no significant difference between UT and GT. Swim training increased swim survival time in TRex and GTex, and TRex showed the highest swim survival time. With regard to mitogenic activities of splenocytes in response to exhaustive exercise stress, all groups showed much lower lymphocyte proliferative activity when stimulated with media (Med), concanavalin A (ConA), or lipopolysaccharide (LPS) after exhaustive exercise stress. However, GTex had a higher proliferative activity than the other groups. Trained and ginseng-supplemented groups showed lower peritoneal ROS responses and lymphocyte DNA damage levels after exhaustive exercise. These findings suggest that the combined effect of swim training and ginseng supplementation sustain lymphocyte function in the presence of reduced ROS production and DNA damage following acute exercise stress.

Comparison of lymphocyte DNA damage levels and total antioxidant capacity in Korean and American diet.

BACKGROUND/OBJECTIVE: This study aims to measure the in vitro antioxidant capacity of Korean diet (KD) with American diet (AD) as a control group and to examine the ex vivo DNA damage reduction effect on human lymphocytes. MATERIALS/METHODS: The KD applied in this study is the standard one-week meals for Koreans (2,000 kcal/day) suggested by 2010 Dietary Reference Intakes for Koreans. The AD, which is the control group, is a one-week menu (2,000 kcal/day) that consists of foods that Americans would commonly take in according to the National Health and Nutrition Examination Survey. The antioxidant capacity of each menu was measured by means of the total phenolic assay and 3 in vitro antioxidant activity assays (2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, trolox equivalent antioxidant capacity (TEAC), Oxygen radical absorbance capacity (ORACROO·)), while the extent of ex vivo lymphocyte DNA damage was measured by means of the comet assay. RESULTS: When measured by means of TEAC assay, the in vitro antioxidant capacity of the KD of the day was higher than that of the AD (P < 0.05) while there was no significant difference in total phenolic contents and DPPH and ORAC assays. The ex vivo lymphocyte DNA damage protective effect of the KD was significantly higher than that of the AD (P < 0.01). As for the one-week menu combining the menus for 7 days, the total phenolic assay (P < 0.05) and in vitro antioxidant capacity (P < 0.001, DPPH; P < 0.01, TEAC) of the KD menu were significantly higher than those of the AD menu. Likewise, the ex vivo DNA damage reduction rate of the Korean seven-day menu was significantly higher than that of the American menu (P < 0.01). CONCLUSION: This study demonstrates that the high antioxidant capacity and DNA damage protective effect of KD, which consists generally of various plant foods, are higher than those of typical AD.

Lymphocyte DNA damage and plasma antioxidant status in Korean subclinical hypertensive patients by glutathione S-transferase polymorphism.

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of xenobiotics by conjugating substances with glutathione. The aim of this study is to assess the antioxidative status and the degree of DNA damage in the subclinical hypertensive patients in Korea using glutathione S-transferase polymorphisms. SUBJECTS/METHODS: We examined whether DNA damage and antioxidative status show a difference between GSTM1 or GSTT1 genotype in 227 newly diagnosed, untreated (systolic blood pressure (BP) ≥ 130 mmHg or diastolic BP ≥ 85 mmHg) subclinical hypertensive patients and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). From the blood of the subjects, the degree of the DNA damage in lymphocyte, the activities of erythrocyte superoxide dismutase, the catalase, and the glutathione peroxidase, the level of glutathione, plasma total radical-trapping antioxidant potential (TRAP), anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. RESULTS: Of the 227 subjects studied, 68.3% were GSTM1 null genotype and 66.5% were GSTT1 null genotype. GSTM1 null genotype had an increased risk of hypertension (OR: 2.104, CI: 1.38-3.35), but no significant association in GSTT1 null genotype (OR 0.982, CI: 0.62-1.55). No difference in erythrocyte activities of superoxide dismutase, catalase, or glutathione peroxidase, and plasma TRAP, CD, lipid profiles, and GSH levels were observed between GSTM1 or GSTT1 genotype. Plasma levels of α-tocopherol increased significantly in GSTT1 wild genotype (P < 0.05); however, plasma level of ß-carotene increased significantly in GSTT1 null genotype (P < 0.01). DNA damage assessed by the Comet assay was significantly higher in GSTM1 null genotype than wild genotype (P < 0.05). CONCLUSIONS: These results confirm the association between GSTM1 null genotype and risk of hypertension as they suggest that GSTM1 null genotype leads to an increased oxidative stress compared with wild genotype.

Relationships between milk consumption and academic performance, learning motivation and strategy, and personality in Korean adolescents.

BACKGROUND/OBJECTIVES: A healthy diet has been reported to be associated with physical development, cognition and academic performance, and personality during adolescence. This study was performed to investigate the relationships among milk consumption and academic performance, learning motivation and strategies, and personality among Korean adolescents. SUBJECTS/METHODS: The study was divided into two parts. The first part was a survey on the relationship between milk consumption and academic performance, in which intakes of milk and milk products and academic scores were examined in percentiles among 630 middle and high school students residing in small and medium-sized cities in 2009. The second part was a survey on the relationships between milk consumption and learning motivation and strategy as well as personality, in which milk consumption habits were collected and Learning Motivation and Strategy Test (L-MOST) for adolescents and Total Personality Inventory for Adolescents (TPI-A) were conducted in 262 high school students in 2011. RESULTS: In the 2009 survey, milk and milk product intakes of subjects were divided into a low intake group (LM: ≤ 60.2 g/day), medium intake group (MM: 60.3-150.9 g/day), and high intake group (HM: ≥ 151.0 g/day). Academic performance of each group was expressed as a percentile, and performance in Korean, social science, and mathematics was significantly higher in the HM group (P < 0.05). In the 2011 survey, the group with a higher frequency of everyday milk consumption showed significantly higher "learning strategy total," "testing technique," and "resources management technique" scores (P < 0.05) in all subjects. However, when subjects were divided by gender, milk intake frequency, learning strategy total, class participation technique, and testing technique showed significantly positive correlations (P < 0.05) in boys, whereas no correlation was observed in girls. Correlations between milk intake frequency and each item of the personality test were only detected in boys, and milk intake frequency showed positive correlations with "total agreeability", "organization", "responsibility", "conscientiousness", and "intellectual curiosity" (P < 0.05). CONCLUSION: Intakes of milk and milk products were correlated with academic performance (Korean, social science, and mathematics) in Korean adolescents. In male high school students, particularly, higher milk intake frequency was positively correlated with learning motivation and strategy as well as some items of the personality inventory.

Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products.

This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea.

Soy isoflavone supplementation alleviates oxidative stress and improves systolic blood pressure in male spontaneously hypertensive rats.

The aim of this study was to investigate the protective effect of isoflavone against hypertension, via the mitigation of oxidative stress and prevention of nitric oxide (NO, a potent vasodilator) reduction, in spontaneously hypertensive rats (SHR). The 8 wk-old male SHR were divided into two groups, and fed a casein-based high fat diet (120 g fat, 1 g cholesterol/kg diet) for 30 d, either with or without 10 g of soy powder (containing 31.2% of isoflavones)/kg. During the 30-d study period, tail systolic blood pressures (BP) in the control SHR group increased, from 162.4 +/- 2.3 to 177.9 +/- 5.4 mmHg (p<0.05), while the isoflavone-supplemented group benefited from a clear antihypertensive effect (160.1 +/- 1.8 to 160.2 +/- 4.9 mmHg). The serum NO and total radical trapping antioxidant potential (TRAP) were elevated in the isoflavone group. The isoflavone group also experienced a significant decrease in oxidative DNA damage in leukocytes, using comet assay. DNA damage correlated positively with incremental BP during the study, and systolic BP at the end of the study (p<0.01). Our results indicate that soy isoflavone has an antihypertensive effect, possibly through the amelioration of oxidative stress, and the augmentation of NO production, in SHR.

The effect of glutathione S-transferase M1 and T1 polymorphisms on blood pressure, blood glucose, and lipid profiles following the supplementation of kale (Brassica oleracea acephala) juice in South Korean subclinical hypertensive patients.

BACKGROUND/OBJECTIVES: Glutathione S-transferase (GST) forms a multigene family of phase II detoxification enzymes which are involved in the detoxification of reactive oxygen species. This study examines whether daily supplementation of kale juice can modulate blood pressure (BP), levels of lipid profiles, and blood glucose, and whether this modulation could be affected by the GSTM1 and GSTT1 polymorphisms. SUBJECTS/METHODS: 84 subclinical hypertensive patients showing systolic BP over 130 mmHg or diastolic BP over 85 mmHg received 300 ml/day of kale juice for 6 weeks, and blood samples were collected on 0-week and 6-week in order to evaluate plasma lipid profiles (total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol) and blood glucose. RESULTS: Systolic and diastolic blood pressure was significantly decreased in all patients regardless of their GSTM1 or GSTT1 polymorphisms after kale juice supplementation. Blood glucose level was decreased only in the GSTM1-present genotype, and plasma lipid profiles showed no difference in both the GSTM1-null and GSTM1-present genotypes. In the case of GSTT1, on the other hand, plasma HDL-C was increased and LDL-C was decreased only in the GSTT1-present type, while blood glucose was decreased only in the GSTT1-null genotype. CONCLUSIONS: These findings suggest that the supplementation of kale juice affected blood pressure, lipid profiles, and blood glucose in subclinical hypertensive patients depending on their GST genetic polymorphisms, and the improvement of lipid profiles was mainly greater in the GSTT1-present genotype and the decrease of blood glucose was greater in the GSTM1-present or GSTT1-null genotypes.

A prospective multicentre study to evaluate the efficacy and tolerability of osmotic release oral system (OROS) hydromorphone in opioid-naive cancer patients: Results of the Korean South West Oncology Group study.

BACKGROUND: Osmotic release oral system (OROS) hydromorphone is a potent, long-acting opioid analgesic, effective and safe for controlling cancer pain in patients who have received other strong opioids. To date, few studies have examined the efficacy of hydromorphone for pain relief in opioid-naive cancer patients. OBJECTIVES: A prospective, open-label, multicentre trial was conducted to determine the efficacy and tolerability of OROS hydromorphone as a single and front-line opioid therapy for patients experiencing moderate to severe cancer pain. METHODS: OROS hydromorphone was administered to patients who had not previously received strong, long-acting opioids. The baseline evaluation (visit 1) was followed by two evaluations (visits 2 and 3) performed two and 14 weeks later, respectively. The starting dose of OROS hydromorphone was 4 mg/day and was increased every two days when pain control was insufficient. Immediate-release hydromorphone was the only accepted alternative strong opioid for relief of breakthrough pain. The efficacy, safety and tolerability of OROS hydromorphone, including the effects on quality of life, and patients' and investigators' global impressions on pain relief were evaluated. The primary end point was pain intensity difference (PID) at visit 2 relative to visit 1 (expressed as %PID). RESULTS: A total of 107 patients were enrolled in the present study. An improvement in pain intensity of >50% (≥50% PID) was observed in 51.0% of the full analysis set and 58.6% of the per-protocol set. The mean pain score, measured using a numerical rating scale, was significantly reduced after two weeks of treatment, and most adverse events were manageable. Quality of life also improved, and >70% of patients and investigators were satisfied with the treatment. CONCLUSIONS: OROS hydromorphone provided effective pain relief and improved quality of life in opioid-naive cancer patients. As a single and front-line treatment, OROS hydromorphone delivered rapid pain control.

Clusterin mRNA expression in apoptotic and activated rat thymocytes.

Clusterin is a 75-80 kDa heterodimeric glycoprotein, that is produced in most tissues but which exact biological role is still not clear. Particularly, its role in protection or promotion of apoptosis is heavily disputed, since data supporting both views have been reported in several independent studies. To clarify this issue, and also to determine whether clusterin expression itself might be affected by apoptosis, in the present study, rat thymocytes were treated with dexamethasone, -a synthetic glucocorticoid that elicits apoptosis in thymocytes-, and clusterin mRNA expression was analyzed by semi-quantitative RT-PCR before and after induction of apoptosis. Interestingly, neither the treatment with dexamethasone in vitro nor triggering of apoptosis in vivo up- regulated clusterin expression, opposing the view that clusterin is involved in apoptotic processes. On the other hand, a new clusterin mRNA isoform was detected and isolated, whose expression was restricted to freshly isolated thymocytes. This novel isoform lacks the post-translational proteolytic cleavage site and is therefore predicted to encode a monomeric protein. The biological function under normal circumstances, however, will need further investigations for clarification. While apoptosis could not modulate clusterin expression, activation of thymocytes with concanavalin A and interleukin-2 resulted in up-regulation of clusterin mRNA level, indicating that clusterin expression is rather under the control of cell activation-mediated rather than apoptosis-induced signals.

Daily grape juice consumption reduces oxidative DNA damage and plasma free radical levels in healthy Koreans.

Grape contains flavonoids with antioxidant properties which are believed to be protective against various types of cancer. This antioxidative protection is possibly provided by the effective scavenging of reactive oxygen species (ROS), thus defending cellular DNA from oxidative damage and potential mutations. This study of healthy adults tested whether a daily regimen of grape juice supplementation could reduce cellular DNA damage in peripheral lymphocytes and reduce the amount of free radicals released. Sixty-seven healthy volunteers (16 women and 51 men) aged 19-57 years were given 480 ml of grape juice daily for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The DNA damage was determined by using the single cell gel (comet) assay with alkaline electrophoresis and was quantified by measuring tail length (TL). Levels of free radicals were determined by reading the lucigenin-perborate ROS generating source, using the Ultra-Weak Chemiluminescence Analyzer System. Grape juice consumption resulted in a significant decrease in lymphocyte DNA damage expressed by TL (before supplementation: 88.75 +/- 1.55 microm versus after supplementation: 70.25 +/- 1.31 microm; P=0.000 by paired t-test). Additionally, grape juice consumption for 8 weeks reduced the ROS/photon count by 15%, compared to the beginning of the study. The preventive effect of grape juice against DNA damage was simultaneously shown in both sexes. These results indicate that the consumption of grape juice may increase plasma antioxidant capacity, resulting in reduced DNA damage in peripheral lymphocytes achieved at least partially by a reduced release of ROS. Our findings support the hypothesis that polyphenolic compounds contained in grape juice exert cancer-protective effects on lymphocytes, limiting oxidative DNA damage possibly via a decrease in free radical levels.