The effect of denosumab in breast cancer patients receiving adjuvant aromatase inhibitors: 36-month results.

INTRODUCTION: Aromatase inhibitor (AI)-associated bone loss increases the risk of bone fracture and reduces patients' quality of life, making it a critical issue worldwide. We conducted a prospective non-randomized clinical trial (UMIN-CTR, UMIN 000016173) to assess the effect of denosumab on bone loss in patients treated with adjuvant AI and have previously reported the results at 12 and 24 months. This study aimed to present the results at 36 months of treatment with denosumab for osteopenia in breast cancer patients who were undergoing treatment with adjuvant AI; 36 months is the longest denosumab treatment period reported so far. MATERIALS AND METHODS: Patients received 60-mg denosumab subcutaneously every 6 months. Daily supplements containing 500-mg elemental calcium and at least 400 international units of vitamin D were highly recommended throughout the study period. The levels of bone mineral density (BMD) and bone turnover markers, serum tartrate-resistant acid phosphatase isoform 5b, and bone alkaline phosphatase were determined at baseline and 6, 12, 18, 24, and 36 months. RESULTS: At 36 months, the bone mineral density of the lumbar spine, right femoral neck, and left femoral neck were found to increase by 8.8% (95% confidence interval CI 7.6-10.1), 4.3% (95% CI 3.0-5.5), and 3.1% (95% CI 2.1-4.1), respectively. No non-traumatic clinical fractures occurred in patients receiving AI and denosumab. CONCLUSION: Twice-yearly administration of denosumab to the breast cancer patients treated with adjuvant AI, regardless of the skeletal site, resulted in consistent increases in BMD without severe adverse events at 36 months.

Correlation study between gastronomy culture and content of selenium towards prevalence of cardiovascular and diabetes in West Java, Indonesia.

BACKGROUND AND AIM: Selenium (Se) is an important element in the human body. Deficiency or excess of Se can cause harm to human health. A previous study showed an association of Se with cardiovascular and diabetes diseases. One of the food sources of Se is vegetables. In West Java, Indonesia, people consume fresh vegetables such as Garlic, Jengkol, and Petai. This research aims to study the correlation between the gastronomy culture of people in West Java, Se content in Garlic (Allium sativum), Jengkol (Archidendron pauciflorum) and Petai (Parkia speciosa) from several Regencys/cities in West Java, and the prevalence cardiovascular and diabetic diseases. METHOD: A cultural study was conducted based on a literature review. Cluster sampling was chosen for the sampling method. The prevalence of cardiovascular disease and diabetes in these regencies were obtained from the Ministry of Health of Indonesia. The measurement of Se content in a sample was conducted by the fluorometry method, based on the formation of the piazoselenol complex from the reaction between selenite ion and DAN (2,3-diaminonapthalene). RESULTS: People in West Java prefer to consume garlic, jengkol, and petai as a fresh vegetable as part of their culture. The highest content of Se in Allium sativum was found in Tasikmalaya City with a value of 69.20 ng/g. For Archidendron pauciflorum from Subang Regency values were 498 ng/g. Parkia speciosa found in the Bandung Barat Regency had a mean value 257.9 ng/g. There is a positive correlation between Se-concentration in Archidendron pauciflorum and the prevalence of diabetes while negative correlation with the prevalence of cardiovascular disease. In addition, no correlation was observed for Allium sativum and Parkia Specose might be due to a lower Se-concentration in these vegetables that in the Archidendron fauciflorum. CONCLUSION: Different areas have varying concentrations of Se in plants that grow in the region. The gastronomy culture and Se content may play a role to increase or decrease cardiovascular and diabetes prevalence in that area.

Recent advances in clinical studies of selenium supplementation in radiotherapy.

BACKGROUND: Radiotherapy is one of the most important and common therapies for cancer patients. Selenium has been shown to be capable of reducing the side effects of radiotherapy because selenoproteins have anti-oxidative functions against reactive oxygen species that are induced by the radiation. They also function in DNA-repair and cytokine control. PURPOSE: We explored the benefits and risks of selenium supplementation in radiotherapy in our previous review to establish guidelines. In the current study, we expanded the search to cover recent advances in clinical studies of selenium supplementation in radiotherapy. METHODS: We conducted an initial screening in the PubMed using the MeSH terms and keywords "selenium", "radiation", "therapy", and "radiotherapy" using the same methodology applied in our previous review. We identified 121 articles published between January 2013 and December 2019. We then identified eight articles (six studies) on selenium and radiotherapy by excluding 113 articles. RESULTS: In selenium supplementation studies, selenium doses of 300-500 µg/day with duration of 10 days to 6 months were used. Selenium supplementation improved the selenium nutritional conditions of the patients and reduced the side effects of radiotherapy. Selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. CONCLUSION: The results of our previous and current reviews showed that selenium supplementation offers specific benefits for several cancer types treated with radiotherapy. Here, we suggest a new guideline for selenium supplementation in radiotherapy. We recommend determining the selenium status of the patients before radiotherapy, and in cases of deficiency (<100 µg/L serum selenium level), selenium supplement can be beneficial.

Distribution of midwives in Mongolia: A secondary data analysis.

INTRODUCTION: Midwives are at the core of strengthening the health system, especially in the crucial period around pregnancy, childbirth, and the early weeks of life. In 2016, the national-level maternal mortality ratio in Mongolia was 48.6 deaths per 100,000 live births, but this was much higher (up to 212.9 deaths/100,000) in some rural provinces of the country. The wide variation in maternal mortality between urban and rural areas of Mongolia might be related to the distribution of midwives and equity of access to maternity care. OBJECTIVES: In the present study, we aimed to determine the distribution of midwives in each province of Mongolia and to examine inequality in the distribution of midwives nationwide. DESIGN: A secondary data analysis. METHODS: Data from the Centre of Health Development and the National Statistical Office of Mongolia were obtained and analysed. First, we assessed the distribution of midwives at provincial and regional levels, along with the association between these distributions and the maternal mortality ratio in 2016. We then calculated the inequality of these distributions using the Gini coefficient and examined trends for the years 2010-2016. We compared results for urban, suburban, and rural provinces. Rural areas are sparsely populated and enormous in size, so it may be difficult access to basic healthcare services. It was considered important, therefore, to assess the number of midwives per 1000 km2 as well as the commonly used indicator of per 10,000 population. RESULTS: When the land area in each province was taken into consideration rather than only the population, wider variations between urban, suburban, and rural provinces became apparent. Provinces varied according to the number of midwives per 10,000 population by a factor of three (range 2.0-6.2/midwives); while provinces varied according to the number of midwives per 1000 km2 by a factor of approximately 300 (range 0.2-61.2/midwives). The Gini coefficient for the number of midwives per 10,000 population in 2016, R = 0.201, revealed "relative" equality. This was slightly reduced from R = 0.305 in 2010 and indicated a shift toward equality. However, the Gini coefficient for the number of midwives per 1000 km2 area indicated "severe" inequality of R = 0.524 in 2016. This was increased from R = 0.466 in 2010, indicating that no improvement has been seen over these years. CONCLUSIONS: Our study suggests that two different measures of midwifery distribution should be used as indicators: number of midwives "per 10,000 population" and "per 1000 km2 area". In rural areas such as parts of Mongolia, geographical features and population density are important features of the local context. To deliver healthcare services in a timely manner and within a reasonable distance for pregnant women who need care, the indicator of per 1000 km2 area would be more suitable for rural and sparsely populated areas than the indicator of per 10,000 population, which is commonly used for urban and settled areas. Based on our findings, to reduce the wide gap in MMR between rural and urban areas, we recommend at least one midwife per 1000 km2 area in rural regions of Mongolia.

Predictive factors for the efficacy of denosumab in postmenopausal Japanese women with non-metastatic breast cancer receiving adjuvant aromatase inhibitors: a combined analysis of two prospective clinical trials.

Aromatase inhibitors (AIs) are the gold standard therapy for breast cancer in postmenopausal women. AI suppresses the conversion of androgens to estrogens; however, this results in osteopenia, osteoporosis, and bone fracture, thus reducing the patient's quality of life. The use of adjuvant denosumab reduces the risk of clinical fractures in postmenopausal patients with breast cancer receiving AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. In this study, we aimed to investigate the predictive factors for the efficacy of denosumab in postmenopausal patients with breast cancer treated with AI by analyzing the results of two prospective trials. The patients received 60 mg denosumab subcutaneously every 6 months. The primary endpoint was percentage change in lumbar spine bone mineral density (BMD) from baseline to month 12 in lumbar spine. Post hoc analysis and T tests were performed. A total of 205 patients were enrolled. At 12 and 24 months, the lumbar spine BMD increased by 5.6% [95% confidence interval (CI) 4.9-6.3] and 8.3% (95% CI 7.5-9.1), respectively. Subgroup analysis was conducted according to the time of AI therapy initiation, type of AI therapy, age, time since menopause, baseline body mass index, and BMD. The results showed that baseline lumbar and left femoral BMD was significantly associated with a percentage change in these sites, respectively. In addition, baseline left femoral BMD was also associated with a change in lumbar BMD. In conclusion, the baseline BMD in the lumbar spine was a predictive indicator for the efficacy of denosumab in this site and the baseline BMD in left femoral neck was a predictive indicator in lumbar spine and left femur.

Effects of denosumab on bone mineral density in Japanese women with osteoporosis treated with aromatase inhibitors for breast cancer.

Adjuvant aromatase inhibitor (AI) therapy, for hormone receptor-positive breast cancer, in postmenopausal women is associated with bone loss, leading to an increased risk of fractures. Denosumab, an antibody raised against the receptor activator of nuclear factor-κB ligand, has been proven to protect against AI-induced bone loss. Hence, we aimed to determine whether denosumab is effective in postmenopausal Japanese women with osteoporosis, treated with AI. We prospectively evaluated the bone mineral density (BMD) in the lumbar spine and the bilateral femoral neck in 102 postmenopausal women with clinical hormone receptor-positive breast cancer, stages I-IIIA, during a postoperative period of 12 months. The other inclusion criteria for this study were: women that should receive AIs as adjuvant therapy and those with evidence of osteoporosis (lumbar spine or bilateral femoral neck BMD, equivalent to T-score classification of ≤ - 2.5) upon enrollment. The patients received supplemental calcium, vitamin D, and 60 mg of subcutaneous denosumab every 6 months. The BMD of the lumber spine increased by 4.9 and 6.6% at 6 and 12 months, respectively. An increase in BMD was observed at the femoral neck, bilaterally. Hypocalcemia ≥ grade 2, osteonecrosis of the jaw, and non-traumatic clinical fracture were not observed in this study. Our findings revealed that biannual treatment with denosumab is associated with a great increase of BMD in Japanese women receiving adjuvant AI therapy, irrespective of their previous history of AI therapy.

Effect of denosumab on low bone mineral density in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: 24-month results.

BACKGROUND: Aromatase inhibitors (AI) have been established as the gold-standard therapy for postmenopausal patients. Worldwide, adjuvant denosumab at a dose of 60 mg twice per year reduces the risk of clinical fractures in postmenopausal patients with breast cancer who received AI. However, the efficacy of denosumab in the treatment of AI-associated bone loss had not been prospectively evaluated in Japan. Previously, we reported the 12-month effect of denosumab in Japanese patients for the first time; the primary endpoint was the change in the percentage of bone mineral density (BMD) of the lumbar spine from baseline to 12 months. METHODS: This secondary follow-up study prospectively evaluated the change in the percentage of BMD of the lumbar spine from baseline to 24 months. Postmenopausal women with early-stage, histologically confirmed, hormone receptor-positive, invasive breast cancer who were receiving or scheduled to receive AI were included. Denosumab was administered subcutaneously on day 1 of the study and then 6, 12, 18, and 24 months. The lumbar spine and bilateral femoral neck BMD was measured at baseline and 6, 12, 18, and 24 months. RESULTS: At 18 and 24 months, the lumbar spine BMD increased by 5.9 and 7.0%, respectively. The femoral neck BMD also increased. Grade ≥ 2 hypocalcemia, osteonecrosis of the jaw, and atypical femoral fractures did not occur. CONCLUSIONS: Our prospective study showed that semiannual treatment with denosumab was associated with continuously increased BMD in Japanese women receiving adjuvant AI therapy for up to 24 months, regardless of prior AI treatment.

Lactobacillus plantarum IS-10506 probiotic administration increases amlodipine absorption in a rabbit model.

OBJECTIVE: Probiotics are beneficial in human health. In this study, we investigated the effect of probiotics on absorption of amlodipine, a dihydropyridine calcium antagonist used in the treatment of angina and hypertension, in a rabbit model. METHODS: Lactobacillus plantarum IS-10506 probiotic was administered for 14 days to male New Zealand rabbits. Blood samples were collected before and after probiotic supplementation. Amlodipine (10 mg) was then administered to all groups. Blood samples from a marginal vein were withdrawn at 5, 15, 30, 60, and 120 minutes to determine amlodipine concentrations in rabbit plasma. RESULTS: Amlodipine concentrations in the L. plantarum IS-10506 group were 4.95 ± 1.22, 8.71 ± 0.69, and 12.48 ± 2.53 ng/ml, and those in the control group were 1.69 ± 0.31, 3.89 ± 1.23, and 7.17 ± 1.85 ng/ml at 30, 60, and 120 minutes, respectively after administration of amlodipine. Amlodipine concentrations in the L. plantarum IS-10506 group were significantly higher than those in the control group at 30, 60, and 120 minutes after amlodipine administration. CONCLUSION: Our results suggested that supplementation of L. plantarum IS-10506 significantly increases amlodipine plasma concentrations in rabbits.

Effect of denosumab on bone mineral density in Japanese women with osteopenia treated with aromatase inhibitors for breast cancer: subgroup analyses of a Phase II study.

BACKGROUND: The aim of the study was to conduct subgroup analyses of therapeutic effects of 12-month denosumab therapy on the percentage change in bone mineral density (BMD) from baseline in the lumber spine and femoral neck. MATERIALS AND METHODS: We prospectively evaluated the BMD of the lumbar spine and femoral neck of 100 hormone receptor-positive, clinical stage I-IIIA postoperative postmenopausal breast cancer patients, for whom treatment with aromatase inhibitors (AIs) as adjuvant endocrine therapy was scheduled. The primary endpoint was the percent change in lumbar spine BMD from baseline to 12 months. Patient subgroups were analyzed according to baseline variables that are known risk factors for bone loss, including previous AI therapy, age, time since menopause, baseline body mass index (BMI), and baseline BMD T-score. RESULTS: At 12 months, lumbar spine BMD increased by 4.7%; the patients who were administered AI therapy prior to denosumab (n=70) demonstrated a 4.7% increase in BMD, and the patients who received denosumab at the start of AI therapy (n=30) demonstrated a 4.5% increase in BMD (p=0.8385). Additionally, 2.4% and 1.4% increases in BMD of the right and left femoral neck, respectively, were observed. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (<65, ≥65 years), time since menopause (≤5, >5 years), BMI (<25, ≥25 kg/m2), and T-score (≤-1.0, >-1.0) of the right femoral neck were as follows: (2.2%, 2.5%, p=0.7773), (2.6%, 0.9%, p=0.1726), (2.5%, 2.3%, p=0.7594), (2.1%, 2.4%, p=0.2034), (2.1%, 2.9%, p=0.2034), and (2.3%, 2.7%, p=0.6823), respectively. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (<65, ≥65 years), time since menopause (≤5, >5 years), BMI (<25, ≥25 kg/m2), and T-score (≤-1.0, >-1.0) of the left femoral neck were as follows: (1.0%, 1.5%, p=0.1972), (1.2%, 2.7%, p=0.2931), (1.4%, 1.3%, p=0.8817), (-0.1%, 1.6%, p=0.1766), (1.3%, 1.9%, p=0.6465), and (1.5%, 1.1%, p=0.6573), respectively. CONCLUSION: Twice-yearly treatment with denosumab was associated with increased BMD among Japanese women receiving adjuvant AI therapy, regardless of the baseline characteristics or skeletal site.

Effects of Selenium Supplementation on the Diabetic Condition Depend on the Baseline Selenium Status in KKAy Mice.

Oxidative stress in obesity leads to insulin resistance in type 2 diabetes. Some selenoproteins possess antioxidant properties, suggesting that selenium (Se) may protect against type 2 diabetes; however, evidence from epidemiological studies is contradictory. We hypothesized that Se status before supplementation (baseline) contributes to the supplementation outcome. This study aimed to clarify the influence of baseline Se status on the effect of Se supplementation on the diabetic condition. Six-week-old KKAy mice were fed a diet without supplemental Se or with 0.1 ppm Se in the form of L-selenomethionine (SeM) for 2 weeks to create low-Se and sufficient-Se baseline statuses, respectively. For the next 4 weeks, low-Se mice were given a SeM (0.5 ppm Se)-supplemented diet, and sufficient-Se mice were given either a SeM (0.5 ppm Se)- or sodium selenite (0.5 ppm Se)-supplemented diet; control groups continued on baseline diets. Serum Se concentrations, glutathione peroxidase (GPx) activities, adiponectin levels, glucose tolerance, and insulin sensitivity were analyzed. All mice became diabetic during the 2-week baseline induction period. At the end of the supplementation period, Se-receiving groups demonstrated significantly higher Se concentrations and GPx activities than their respective controls. Sufficient-Se mice receiving SeM had lower blood glucose levels and better insulin sensitivity than control and sodium selenite-receiving mice, whereas low-Se mice receiving SeM showed no such improvements compared with their controls. Our results suggest that Se supplementation in the form of SeM may help prevent type 2 diabetes aggravation in people taking the 55 µg/day Se recommended dietary allowance.

Effect of denosumab administration on low bone mineral density (T-score -1.0 to -2.5) in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer.

Although adjuvant aromatase inhibitor (AI) therapy is widely used in postmenopausal women with hormone receptor-positive breast cancer, it is known to be associated with bone loss and increased fracture risk. Denosumab, a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand, has been shown to protect against AI-induced bone loss. However, the efficacy of denosumab in the treatment of AI-associated bone loss has not been prospectively evaluated in Japan. We prospectively monitored bone mineral density (BMD) of the lumbar spine and bilateral femoral necks in 100 postmenopausal women with hormone receptor-positive postoperative breast cancer of clinical stage I-IIIA in whom treatment with AI as adjuvant endocrine therapy was planned or had been ongoing. Study participants received supplemental calcium and vitamin D every day and denosumab (60 mg) subcutaneously every 6 months. At enrollment, patients were required to have evidence of low bone mass without meeting the criteria for osteoporosis. The primary endpoint was percentage change from baseline in lumbar spine BMD at month 12. At 6 and 12 months, lumbar spine BMD increased by 3.3 and 4.7%, respectively. BMD of the femoral necks also increased. Hypocalcemia of grade ≥2, osteonecrosis of the jaw, and non-traumatic clinical fracture did not occur. In conclusion, semi-annual treatment with denosumab was associated with increased BMD in Japanese women receiving adjuvant AI therapy, regardless of prior AI treatment.

Catechin Isolated from Garcinia celebica Leaves Inhibit Plasmodium falciparum Growth through the Induction of Oxidative Stress.

BACKGROUND: Resistance of antimalarial drugs to Plasmodium falciparum has become a major concern in malaria eradication. Although it is also affected by several socioeconomic factors, a new antiplasmodial agent is needed for a global malaria control program. OBJECTIVE: In this study, we attempted to uncover the antiplasmodial properties of Garcinia celebica, an Indonesian medicinal plant, along with the responsible compound and its possible mechanism. MATERIALS AND METHODS: The G. celebica leaves were ethanol extracted and fractionated based on their polarity using n-hexane, ethyl acetate, and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant P. falciparum at 100 µg/ml for 72 h. The active compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. RESULTS: The IC50 of (+)-catechin, the characterized compound, against P. falciparum was 198 µM in 24 h and experiment. The isolated catechin inhibited P. falciparum growth in both trophozoite and schizont stages. An additional experiment also suggests that the antiplasmodial property of catechin occurs through the induction of the oxidative stress to P. falciparum. CONCLUSION: This result shows that the potential of catechin and its antimalarial properties should be explored further. SUMMARY: Garcinia celebica leaf extract and fractions inhibit Plasmodium falciparum growthCatechin, the active compound of Garcinia celebica leaf extract, inhibits Plasmodium falciparum growth in a time- and dose-dependent manner Abbreviations used: RBC: Red Blood Cells; IC50: Inhibition Concentrattino 50; MeOH: Methanol; RPMI: Roswell Park Memorial Institute; EI: Electron Ionization.

Protective effects of sodium selenite supplementation against irradiation-induced damage in non-cancerous human esophageal cells.

The administration of radioprotective compounds is one approach to preventing radiation damage in non-cancerous tissues. Therefore, radioprotective compounds are crucial in clinical radiotherapy. Selenium is a radioprotective compound that has been used in previous clinical studies of radiotherapy. However, evidence regarding the effectiveness of selenium in radiotherapy and the mechanisms underlying the selenium-induced reduction of the side effects of radiotherapy remains insufficient. To further investigate the effectiveness of selenium in radiotherapy, the present study examined the protective effects of sodium selenite supplementation administered prior to X-ray radiation treatment in CHEK-1 non-cancerous human esophageal cells. Sodium selenite supplementation increased glutathione peroxidase 1 (GPx-1) activity in a dose- and time-dependent manner. The sodium selenite dose that induced the highest GPx-1 activity was determined to be 50 nM for 72 h prior to radiotherapy. The half-maximal inhibitory concentration of sodium selenite in CHEK-1 cells was 3.6 µM. Sodium selenite supplementation increased the survival rate of the cells in a dose-dependent manner and enhanced the degree of cell viability at 72 h post-irradiation (P<0.05). Combined treatment with 50 nM sodium selenite and 2 gray (Gy) X-ray irradiation decreased the number of sub-G1 cells from 5.9 to 4.2% (P<0.05) and increased the proportion of G1 cells from 58.8 to 62.1%, compared with 2 Gy X-ray irradiation alone; however, this difference was not statistically significant (P=1.00). Western blot analysis revealed that treatment with 2 Gy X-ray irradiation significantly increased the expression levels of cleaved poly (ADP-ribose) polymerase (PARP; P<0.05). In addition, combined treatment with 50 nM sodium selenite and 2 Gy X-ray irradiation reduced the expression levels of cleaved PARP protein, compared with 2 Gy X-ray irradiation alone; however, this reduction was not statistically significant (P=0.423). These results suggest that 50 nM sodium selenite supplementation administered for 72 h prior to irradiation may protect CHEK-1 cells from irradiation-induced damage by inhibiting irradiation-induced apoptosis. Therefore, sodium selenite is a potential radioprotective compound for non-cancerous cells in clinical radiotherapy.

A STUDY OF THE ASSOCIATION BETWEEN SELENIUM AND CARDIOVASCULAR DISEASE IN LAMPUNG, INDONESIA.

Selenium deficient areas have been associated with a higher prevalence of cardiovascular disease in some countries. In this study, we investigated the correlation between cardiovascular disease prevalence and selenium concentration in paddy soil and rice grains, the main staple food in Lampung, Indonesia. Paddy soil and rice samples (n(s) = 35) from eight regencies (n(d) = 8) in Lampung were analyzed for selenium content. The prevalences of heart disease, stroke, and hypertension in those regencies were obtained from the Ministry of Health of Indonesia. The Shapiro-Wilk's test was used to examine the data distribution. The Pearson's correlation was used to examine the correlation between cardiovascular disease prevalence and selenium concentration in the paddy soil and rice grains. Heart disease prevalence was negatively correlated with the selenium concentration in the paddy soil (r = -0.77, p = 0.02) and rice grain (r = -0.71, p = 0.05). A negative correlation was seen for stroke prevalence and selenium concentration in paddy soil (r = -0.76, p = 0.02). Hypertension prevalence was negatively correlated with the selenium concentration in the rice grains (r = -0.83, p = 0.01). These findings suggest that the selenium concentration in paddy soil and rice grains in the Lampung area may play a role in the fact the area has the lowest cardiovascular disease prevalence in Indonesia. Keywords: selenium, cardiovascular diseases, paddy soil, rice grain, Indonesia

Effect of probiotic L. plantarum IS-10506 and zinc supplementation on humoral immune response and zinc status of Indonesian pre-school children.

A 90-day randomized, double-blind, placebo-controlled, pre-post trial was conducted in four groups of Indonesian children aged 12-24 months: placebo, probiotic, zinc, and a combination of probiotic and zinc (n=12 per group). Microencapsulated Lactobacillus plantarum IS-10506 of dadih origin was supplemented at a dose of 10(10)CFU/day as a probiotic. Zinc was supplemented as 20mg zinc sulfate monohydrate (8mg zinc elemental). Blood and stool samples were collected at baseline and at the end of the study period. Fecal sIgA was assessed by ELISA and serum zinc concentrations by ICP-MS. Fecal sIgA increased significantly in the probiotic group (30.33±3.32µg/g; p<0.01) and in the combination probiotic and zinc group (27.55±2.28µg/g; p<0.027), as compared with the placebo group (13.58±2.26µg/g). Changes in serum zinc concentrations in the combination probiotic and zinc group showed the highest elevation at the end of the study period. A combination of probiotic L. plantarum IS-10506 at a dose of 10(10)CFU/day and 8mg of elemental zinc supplementation showed a potential ability to improve the zinc status of pre-school children. Taken together, supplementation with the probiotic L. plantarum IS-10506 and zinc for 90 days resulted in a significantly increased humoral immune response, as well as improved zinc status, in young children.

Antiplasmodial properties of kaempferol-3-O-rhamnoside isolated from the leaves of Schima wallichii against chloroquine-resistant Plasmodium falciparum.

Previous intervention studies have shown that the most effective agents used in the treatment of malaria were isolated from natural sources. Plants consumed by non-human primates serve as potential drug sources for human disease management due to the similarities in anatomy, physiology and disease characteristics. The present study investigated the antiplasmodial properties of the primate-consumed plant, Schima wallichii (S. wallichii) Korth. (family Theaceae), which has already been reported to have several biological activities. The ethanol extract of S. wallichii was fractionated based on polarity using n-hexane, ethyl acetate and water. The antiplasmodial activity was tested in vitro against chloroquine-resistant Plasmodium falciparum (P. falciparum) at 100 µg/ml for 72 h. The major compound of the most active ethyl acetate fraction was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested against chloroquine-resistant P. falciparum in culture to evaluate its antiplasmodial activity. The ethanol extract of S. wallichii at 100 µg/ml exhibited a significant parasite shrinkage after 24 h of treatment. The ethyl acetate fraction at 100 µg/ml was the most active fraction against chloroquine-resistant P. falciparum. Based on the structural characterization, the major compound isolated from the ethyl acetate fraction was kaempferol-3-O-rhamnoside, which showed promising antiplasmodial activity against chloroquine-resistant P. falciparum with an IC50 of 106 µM after 24 h of treatment. The present study has provided a basis for the further investigation of kaempferol-3-O-rhamnoside as an active compound for potential antimalarial therapeutics.

Updates on clinical studies of selenium supplementation in radiotherapy.

To establish guidelines for the selenium supplementation in radiotherapy we assessed the benefits and risks of selenium supplementation in radiotherapy. Clinical studies on the use of selenium in radiotherapy were searched in the PubMed electronic database in January 2013. Sixteen clinical studies were identified among the 167 articles selected in the initial search. Ten articles were observational studies, and the other 6 articles reported studies on the effects of selenium supplementation in patients with cancer who underwent radiotherapy. The studies were conducted worldwide including European, American and Asian countries between 1987 and 2012. Plasma, serum or whole blood selenium levels were common parameters used to assess the effects of radiotherapy and the selenium supplementation status. Selenium supplementation improved the general conditions of the patients, improved their quality of life and reduced the side effects of radiotherapy. At the dose of selenium used in these studies (200-500 µg/day), selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported. Selenium supplementation may offer specific benefits for several types of cancer patients who undergo radiotherapy. Because high-dose selenium and long-term supplementation may be unsafe due to selenium toxicity, more evidence-based information and additional research are needed to ensure the therapeutic benefits of selenium supplementation.

Reduced serum selenium concentration in miscarriage incidence of Indonesian subjects.

Selenium is an essential nutrient for human health, and maternal selenium concentration has been reported to be associated with pregnancy outcome. To further investigate the possible role of selenium (Se) in miscarriage, we conducted a case-control study to evaluate the correlations among selenium status, glutathione peroxidase activity, and spontaneous abortion. A total of 46 subjects with normal pregnancies and 25 subjects with spontaneous abortion were recruited, and their serum selenium concentrations and serum glutathione peroxidase activities were analyzed. The total serum selenium concentrations in subjects with normal pregnancies were significantly higher than those of subjects with spontaneous abortion; however, the glutathione peroxidase activities were similar in both groups. We further separated the subjects into smoking and nonsmoking groups, and the logistic regression analysis suggested that total serum selenium concentration, but not serum glutathione peroxidase activity or smoking, was significantly correlated with the incidence of miscarriage. The present study thus reaffirms that low serum selenium levels are associated with miscarriage and that selenium plays an important role in pregnancy maintenance.

[Selenium supplementation trials for cancer prevention and the subsequent risk of type 2 diabetes mellitus: selenium and vitamin E cancer prevention trial and after].

The essential trace element selenium has long been considered to exhibit cancer-preventive, antidiabetic and insulin-mimetic properties. However, recent epidemiological studies have indicated that supranutritional selenium intake and high plasma selenium levels are not necessarily preventive against cancer, and are possible risk factors for developing type 2 diabetes mellitus. The results of the SELECT, Selenium and Vitamin E Cancer Prevention Trial, in which it is hypothesized that the supplementations with selenium and/or vitamin E decrease the prostate cancer incidence among healthy men in the U.S., showed that the supplementation did not prevent the development of prostate cancer and that the incidence of newly diagnosed type 2 diabetes mellitus increased among the selenium-supplemented participants. The Nutritional Prevention of Cancer (NPC) trial showed a decreased risk of prostate cancer among participants taking 200 µg of selenium daily for 7.7 years. However, the results of the NPC trial also showed an increased risk of type 2 diabetes mellitus in the participants with plasma selenium levels in the top tertile at the start of the study. Recently, the association of serum selenium with adipocytokines, such as TNF-α, VCAM-1, leptin, FABP-4, and MCP-1, has been observed. Selenoprotein P has been reported to associated with adiponectin, which suggests new roles of selenoprotein P in cellular energy metabolism, possibly leading to the increased risk of type 2 diabetes mellitus and also the development of cancer. Further studies are required to elucidate the relationship between selenium and adipocytokines and the role of selenoprotein P in the development of type 2 diabetes mellitus and cancer at high levels of selenium.

Association between selenium nutritional status and metabolic risk factors in men with visceral obesity.

BACKGROUND AND AIM: Previous evidence has suggested an association between selenium and cardiovascular disease, which is main outcome of metabolic syndrome. The aim of this study was to examine possible correlation between selenium nutritional status and metabolic risk factors in men with visceral obesity. METHODS: Plasma samples were collected from 123 Indonesian men with visceral obesity. Their metabolic risk factors and selenium nutritional status were analyzed. The eligible subjects (n=78) were stratified according to the International Diabetes Federation: obese, obese plus one component, and obese plus two components or more. Obese plus two components or more were diagnostic criteria of metabolic syndrome. Pearson's correlation was performed to examine the correlation in each group. RESULTS: In the obese group, selenium positively correlated with high-density lipoprotein (HDL) cholesterol (r=0.390, P<0.05) and with fatty acid binding protein-4 (FABP4) (r=0.474, P<0.05); glutathione peroxidase-3 (GPx3) activity was inversely correlated with FABP4 (r=-467, P<0.05). In the obese plus one component group, GPx3 activity positively correlated with HDL cholesterol (r=0.413, P<0.05). In the metabolic syndrome group, selenium negatively correlated with monocytes chemoattractant protein (MCP)-1 (r=-0.429, P<0.05). CONCLUSIONS: These results show that the association between selenium nutritional status and metabolic risk factors is limited to particular group of obese men with or without metabolic syndrome.