4-hydroxy-3-methoxycinnamic acid regulates orexigenic peptides and hepatic glucose homeostasis through phosphorylation of FoxO1

4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) is known to have numerous beneficial health effects, including anti-obesity and anti-hyperglycemic properties. However, the molecular networks that modulate the beneficial FA-induced metabolic effects have not been well elucidated. In this study, we explored the molecular mechanisms mediating the beneficial metabolic effects of FA. In mice, FA protected against high-fat diet-induced weight gain, reduced food intake and exhibited an overall improved metabolic phenotype. The food intake suppression by FA was accompanied by a specific reduction in hypothalamic orexigenic neuropeptides, including agouti-related protein and neuropeptide Y, with no significant changes in the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-regulated transcript. FA treatment also inhibited fat accumulation in the liver and white adipose tissue and suppressed the expression of gluconeogenic genes, including phosphoenolpyruvate carboxylase and glucose-6-phosphatase. Furthermore, we show that FA phosphorylated and inactivated the transcription factor FoxO1, which positively regulates the expression of gluconeogenic and orexigenic genes, providing evidence that FA might exert its beneficial metabolic effects through inhibition of FoxO1 function in the periphery and the hypothalamus.

Revision Superficial Temporal Artery-Middle Cerebral Artery Bypass Surgery for Recurrent Acute Ischemic Stroke Due to Delayed Occlusion of the Bypass Graft

Intravenous thrombolysis (IVT) and endovascular treatment (EVT) are currently the main treatments for reperfusion in acute ischemic stroke. Although the EVT recanalization rate has increased, unsuccessful recanalization is still observed in 10-30% cases. Superficial temporal artery-middle cerebral artery (STA-MCA) bypass is considered a rescue therapy in such cases, but in most centers it is not usually performed for acute ischemic stroke. Graft occlusion is rare following STA-MCA bypass, but it might lead to recurrent ischemic stroke. We hereby report on a patient with right MCA infarction and in whom EVT failed due to complete proximal internal carotid artery occlusion. He underwent an emergency STA-MCA bypass, resulting in a full recovery of his motor weakness. However, six months later, the patient experienced recurrent acute ischemic stroke due to bypass graft occlusion. His EVT failed again but revision bypass surgery, using STA remnant branch, was successful with full motor weakness recovery. We recommend a revision bypass surgery as a feasible therapeutic option for recurrent cerebral infarction caused by delayed STA graft occlusion.

Water Extracts of Anthriscus sylvestris Leaf induces Apoptosis in FaDu Human Hypopharynx Squamous Carcinoma Cells

Anthriscus sylvestris (L.) Hoffm. is a perennial herb found widely distributed in various regions of Korea, Europe, and New Zealand. The root of A. sylvestris have been extensively used in the treatment for antitussive, antipyretic, cough remedy in Oriental medicine, but the physiologically active function of the leaf of A. sylvestris is as yet unknown. In this study, we investigated the anti-cancer activity and the mechanism of cell death of water extracts of leaf of Anthriscus sylvestris (WELAS), on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that WELAS treatment inhibited cell viability in a concentration- and time-dependent manner. In addition, the treatment of WELAS markedly induced apoptosis in FaDu cells, as determined by the viability assay, DAPI stain and FACS analysis. WELAS also increased the proteolytic cleavage of procaspase-3, -9 and PARP (poly(ADP-ribose) polymerase). In addition, exposure to WELAS decreased the expression of Bcl-2 (an anti-apoptotic factor), but increased the expression of Bax (a pro-apoptotic factor), suggesting that mitochondria-dependent apoptotic pathways are mediated in WELAS-induced apoptosis. Taken together, these results indicate that water extracts of leaf of A. sylvestris inhibits cell growth and induces apoptosis via the mitochondrial-dependent apoptotic pathway in FaDu human hypopharyngeal squamous carcinoma cells. Therefore, we propose that the water extracts of leaf of A. sylvestris is a novel chemotherapeutic drug, having growth inhibitory properties and induction of apoptosis in human oral cancer cells.

Effect of probiotic 379D as an alternative to antibiotics for feed supplementation in broiler chickens / 동물의과학연구지

Antibiotics have been used to prevent disease, promote growth rate, and improve feed efficiency. However, the use of antibiotics in livestock has been restricted worldwide due to problems such as bacterial resistance. Therefore, probiotics among alternatives to antibiotics have gained attention in the livestock feed industry these days. This study was conducted to investigate the effects of dietary supplementation with probiotic 379D on safety, growth rate, and feed efficiency. In this study, bacterial strain 379D was isolated from soil and identified as a Bacillus sp. according to 16S rRNA sequence analysis. In an in vitro test, in-gel activity assay and antimicrobial susceptibility test were conducted to evaluate 379D. In an in vivo study, 379D was administered at concentrations of 0.1% and 1% to broiler chickens for 28 days. The results of in-gel activity assay and antimicrobial susceptibility test showed that strain 379D had broad spectrum antimicrobial activity. Furthermore, no adverse 379D-related effects were observed in 0.1% and 1% groups. Feed efficiency was higher in the 379D-treated groups than in the control group. In conclusion, 379D is expected to be used as a safe alternative to antibiotics in a feed supplement and will improve feed efficiency in broiler chickens.

The Relationship between Arterial Carbon Dioxide Tension and Oxygenator Exhausted Carbon Dioxide Tension during Cardiopulmonary Bypass

BACKGROUND: The neurologic deficit is one of the most serious complications after cardiopulmonary bypass (CPB). This complication has reported to be closely associated with arterial partial pressure of carbon dioxide tension (PaCO2). The traditional way to measure PaCO2 is by intermittent arterial gas analysis during CPB. We tested the relationship between PaCO2 and CPB exhausted partial pressure of carbon dioxide tension (exPCO2) which can be monitored continuously during CPB. METHODS: The total 46 patients who underwent cardiac surgery under CPB were studied. Capnography sampling line was connected to CPB exhausted port to monitor exPCO2. We sampled arterial blood from CPB for gas analysis at cooling, stable hypothermia, and rewarming phase and recorded exPCO2 simultaneously at each phase. RESULTS: We found out that exPCO2 was associated with temperature corrected PaCO2 (cPaCO2) at all 3 phases(r = 0.73, 0.70, 0.84, P < 0.05) and with temperature uncorrected PaCO2 (ucPaCO2) at cooling (r = 0.64, P < 0.05) and rewarming phases (r = 0.81, P < 0.05). CONCLUSIONS: We concluded that exPCO2 could be used to monitor either ucPaCO2 or cPaCO2 at cooling and rewarming phase and cPaCO2 at hypothermia during CPB.

Effects of Physiological Factors and Lifestyles on Bone Mineral Density in Postmenopausal Women

This study was performed to assess the effects of physiological factors and lifestyles on bone mineral density (BMD) in 64 postmenopausal women. Sixty four subjects were selected out of 223 postmenopausal women in Seoul and Kyunggido. The BMD of the lumbar spine (L2 -> L4) and femoral neck were measured dual energy X-ray absorptiometry (DEXA). Subjects were assigned to one of three groups such as normal (T-score > -1, n = 20), osteopenia (-2.5 L4), femoral neck were 0.84 g/cm2, 0.71 g/cm2 respectively. Years after menopause and age of last delivery of the osteoporosis and osteopenia group were significantly longer than the normal group (p < 0.05). The hours of exercise and outdoor activity of the normal group were longer than the osteoporosis and osteopenia group, but there were no significant differences among the three groups. The BMDs of these two sites were positively correlated with weight, BMI, hip and body fat and negatively correlated with LBM, TBW. These results show there are no consistent effects on bone mineral density, adjusting for age and BMI, of physiological factors and lifestyles in postmenopausal women. Therefore. this study confirmed that one of the most effective ways to minimize bone loss in postmenopausal women would be to maintain an adequate body weight.

Intravenous Anesthesia in Spinal Muscular Atrophy: A case report / 대한마취과학회지

Spinal muscular atrophy (SMA) is a rare lower motor neuron disease in which anesthetic management is often difficult, because the patients usually have muscle weakness and hypersensitivity to muscle relaxants. We describe the anesthesia for a 8 year-old girl with type II SMA who presented for a lower lid epiblepharon repair. We chose to use intravenous anesthesia based on propofol and remifentanil without any muscle relaxants. The peri-operative course was completely uneventful. We consider that intravenous anesthesia without muscle relaxants could be a good anesthetic choice for a patient with SMA undering general anesthesia.

Low-density lipoprotein protects Vibrio vulnificus-induced lethality through blocking lipopolysaccharide action

Lipoprotein plays a role in the host defense against bacterial infection, and its serum level has been demonstrated to be an important prognosis factor of survival. We have previously demonstrated that LDL directly inactivates the hemolytic activity of Vibrio vulnificus cytolysin (VVC) in vitro. The object of this study was therefore to examine whether the LDL-mediated inactivation of VVC leads to protection against lethal infection of V. vulnificus in vivo, using wild and VVC-deficient V. vulnificus strains. Unexpectedly, we found that LDL protects mouse lethality induced by VVC-deficient as well as wild V. vulnificus strain. We also demonstrated that LDL blocks V. vulnificus LPS-induced lethality in mice. These results suggest that LDL preferentially act on endotoxin rather than exotoxin in the protection against V. vulnificus-induced mice lethality.

An inhibitory compound against the interaction between Galpha(s) and the third intracellular loop region of serotonin receptor subtype 6 (5-HT(6)) disrupts the signaling pathway of 5-HT(6)

Serotonin receptor subtype 6 (5-HT(6)) is a neurotransmitter receptor, which is involved in various brain functions such as memory and mood. It mediates signaling via the interaction with a stimulatory G-protein. Especially, the third intracellular loop (iL3) of 5-HT(6) and the alpha subunit of stimulatory G protein (Galpha(s)) are responsible for the signaling process of 5-HT(6). Chemical compounds that could inhibit the interaction between the iL3 region of 5-HT(6) and Galpha(s) were screened from a chemical library consisted of 5,600 synthetic compounds. One of the identified compounds bound to Galpha(s) and effectively blocked the interaction between Galpha(s) and the iL3 region of 5-HT(6). The identified compound was further shown to reduce the serotonin-induced accumulation of cAMP in 293T cells transformed with 5-HT(6) cDNA. It also lowered the Ca2+ efflux induced by serotonin in cells expressing 5-HT(6) and chimeric Galpha(s5/q). These results indicate that the interaction between the iL3 of 5-HT(6) and Galpha(s) can be exploited for screening of regulatory compounds against the signaling pathway of 5-HT(6).

A Study on Nutrient Intakes and Serum Levels of Copper, Zinc and Manganese in Korean Postmenopausal Women with Different Bone Mineral Density

The purpose of this study was to investigate the relationships among nutrient intakes, BMD, serum copper, zinc and manganese contents in Korean postmenopausal women residing in Seoul and Kyunggi-do. Nutrient intakes analyses and anthropometric measurements were performed for 64 postmenopausal women. Also, fasting blood samples were collected. The BMDs of the lumbar spine (L2-L4) and femoral neck were measured by dual energy X-ray absorptiometry (DEXA). Subjects were classified into three groups: osteoporosis (T-score -1, n = 20). The results are summarized as follows: the mean age, height and weight were 62.1 yrs, 153.8 cm, and 56.1 kg, respectively, with no significant difference among three groups. On the other hand, the mean BMI (23.7 g/m2) of normal group was significantly higher than those of other two groups. The mean energy intake was 1,395.3 kcal (77.5% of Dietary referance intakes for koreans (KDRIs)). The average daily intakes of vitamin B2, calcium and zinc did not reach KDRIs. The mean intakes of iron, copper, zinc and manganese were 10.9 mg, 1.6 mg, 7.8 mg and 5.1 mg respectively, with no significant difference among three groups. The mean serum levels of copper, zinc and manganese were 96.4 mg/dl, 91.5 mg/dl and 39.5 ng/dl, respectively with no significant differences among three groups. The BMD of lumbar spine showed a significantly negative correlation intakes of animal protein, fat and iron intakes after adjusting for age, BMI. However, the BMD of lumbar spine was not significantly correlated with animal iron intakes after adjusting for animal protein, and fat intakes, indicating animal food intake is a possible confounding factor. Proper intakes of vitamin B 2 , vitamin C are required to protect osteoporosis in postmenopausal women. These results suggest that excessive animal food intakes may have adverse effect on bone mineral density. Further studies are necessary to elucidate the role of serum minerals in BMD.

Prediction of Future Occurrence and Probability of Developing Breast Cancer over Lifespan in Korean Women / 한국유방암학회지

PURPOSE: Although female breast cancer remains relatively rare in Korea, its incidence and mortality have been rising quite rapidly. In this study, we estimated the probability of developing breast cancer, and examined the trend of its incidence using the proportion of cases with breast cancer among the total female cancer cases in the Korean Central Cancer Registry. METHODS: The probability of developing breast cancer was estimated for Korean women using a method based on the cumulative risk. The number of future breast cancer cases for the year 2020 was estimated by extrapolating the secular trend of the proportions of those with breast cancer between 1995 and 2002, using a logistic regression model. RESULTS: With an expected average life span of 84 years, Korean female has a 2.36% chance of developing breast cancer during her lifetime. The predicted expected age-adjusted proportions of breast cancer among the total female cancer cases were 19.5, 24.3, 29.9 and 36.1% for the years 2005, 2010, 2015 and 2020, respectively. The predicted expected crude proportions for the same years were 17.4, 19.7, 21.7 and 23.4%, respectively. The expected number of breast cancer cases to the 2020 would be 19,791, which is at least five times than that in 1996. CONCLUSION: Based on our results, female breast cancer in Korea will increase further and cumulative rate of breast cancer is highest at 40s and 50s. Lifestyle modification and prevention strategy especially for younger or high risk women might be essential to reduce breast cancer incidence.

A Study of Nutrient Intake and Serum Levels of Osteocalcin, Ca, P, and Mg and Their Correlation to Bone Mineral Density in Korean Postmenopausal Women Residing in Rural Areas / 대한지역사회영양학회지

Postmenopausal women lose more bone mass than men as a result of estrogen deprivation. The resultant low bone mineral density (BMD) is a major risk factor in the development of osteoporosis. Calcium, phosphorus and magnesium are main components of bone. The purpose of this study is to investigate nutrient intake and serum osteocalcin, Ca, P and Mg and their correlation to bone mineral density in Korean postmenopausal women residing in rural areas. We conducted 24 hour dietary recalls, anthropometric measurements and blood analysis on 60 postmenopausal women. The BMD of the lumbar spine (L2-->L4) and the femoral neck were measured by dual energy X-ray absorptiometry (DEXA). Subjects were assigned to one of three groups:normal (T-score> -1, n=20), osteopenia (-2.5> T-score< or = -1, n=23), and osteoporosis ( T-score< or = -2.5, n=17). The mean age, height, weight and BMI were 62.37 yr, 154.36 cm, 55.28 kg and 23.18 kg/m2 respectively. The mean daily energy and protein intakes were 76.35% and 87.41% of RDA for Koreans. The mean intakes of calcium, phosphorus, and magnesium were 463.62 mg (66.23% of RDA), 955.32 mg (136.47% of RDA), 345.87 mg respectively. The mean serum levels of calcium, phosphorus and magnesium were 8.76 mg/dl, 3.80 mg/dl, and 2.10 mg/dl, respectively, and there were no significant differences among the three groups. However, the BMD of the femoral neck showed a significantly negative correlation with serum magnesium (p<0.05). To summarize the results, most nutrient intakes (especially calcium) in postmenopausal women did not reach the RDA values for Koreans. Also, increase of serum magnesium levels may be related to bone loss.

A Study on Nutritional Status, Maternal Factors, and Lifestyles according to BMD in Rural Postmenopausal Women / 대한지역사회영양학회지

Osteoporosis and other related conditions pose a growing public health problem, especially in postmenopausal women. The main purpose of the study was to investigate the correlations among BMD, maternal factors, and life styles, and intake of nutrients in postmenopausal women. One hundred participants in Kyungge-do were divided into three groups according to their BMD measurements measured by DXA. Dietary analysis, anthropometric measurements, and questionares were administered to these women. The percentage of the osteoporosis, osteopenia(Osteopinia), and normal groups were 32%, 48%, and 20% respectively. The average age was significantly the highest in the osteoporosis group. The average age at menopause was 47.2. Osteoporosis group's age at menopause was significantly the lowest. The sleeping hours of the osteoporosis and osteopenia group were significantly longer than the normal group. The intake of vitamin B2 was positively correlated with the BMD of femoral neck. The BMD of these two sites was positively correlated with weight, BMI, waist, and hip size and negatively correlated with the length of the menstrual cycle, duration after menopause, the age at the last delivery, and sleeping hours. Spinal BMD positively correlated with hours of outdoor activity. Therefore, maternal factors, lifestyles, and intake of nutrients contribute to BMD.