Safety and toxicological evaluation of a synthetic vitamin K2, menaquinone-7

Menaquinone-7 (MK-7) is part of a family of vitamin K that are essential co-factors for the enzyme γ-glutamyl carboxylase, which is involved in the activation of γ-carboxy glutamate (Gla) proteins in the body. Gla proteins are important for normal blood coagulation and normality of bones and arteries. The objective of this study was to examine the potential toxicity of synthetic MK-7 in BomTac:NMRI mice and in Sprague-Dawley rats. In an acute oral toxicity test, mice were administered a single oral dose of 2000 mg/kg body weight (limit dose) and no toxicity was observed during the 14-day observation period. In the subchronic oral toxicity test in rats, animals were administered MK-7 for 90 days by gavage at the following doses: 0 (vehicle control, corn oil), 2.5, 5, and 10 mg/kg body weight/day. All generated data, including clinical observations, ophthalmology, clinical pathology, gross necropsy, and histopathology, revealed no compound-related toxicity in rats. Any statistically significant findings in clinical pathology parameters and/or organ weights noted were considered to be within normal biological variability. Therefore, under the conditions of this experiment, the median lethal dose (LD50) of MK-7 after a single oral administration in mice was determined to be greater than the limit dose level of 2000 mg/kg body weight. The no observed adverse effect level (NOAEL) of MK-7, when administered orally to rats for 90 days, was considered to be equal to 10 mg/kg body weight/day, the highest dose tested, based on lack of toxicity during the 90-day study period

High prevalence of vitamin D insufficiency and its association with obesity and metabolic syndrome among Malay adults in Kuala Lumpur, Malaysia

Background: Vitamin D status, as indicated by 25-hydroxyvitamin D is inversely associated with adiposity, glucose homeostasis, lipid profiles, and blood pressure along with its classic role in calcium homeostasis and bone metabolism. It is also shown to be inversely associated with metabolic syndrome and cardiovascular diseases in western populations. However, evidence from the Asian population is limited. Therefore, we aim to study the prevalence of vitamin D insufficiency (< 50 nmol/L) and the association of 25-hydroxyvitamin D with metabolic risk factors among an existing Malay cohort in Kuala Lumpur. Methods: This is an analytical cross sectional study. A total of 380 subjects were sampled and their vitamins D status (25-hydroxyvitamin D), fasting blood glucose, full lipid profile were assessed using venous blood. Systolic and diastolic blood pressure, weight, height and waist circumference were measured following standard protocols. Socio-demographic data such as sex, age, smoking status etc were also collected. Data was analysed using t-test, chi-square test, General Linear Model and multiple logistic regression. Results: Females made up 58 of the sample. The mean age of respondents was 48.5 (SD 5.2) years. Females had significantly lower mean Vitamin D levels (36.2; 95 CI: 34.5, 38.0 nmol/L) compared to males (56.2; 95 CI: 53.2, 59.2 nmol/L). Approximately 41 and 87 of males and females respectively had insufficient (< 50 nmol/L) levels of 25-hydroxyvitamin D (p < 0.001). The prevalence of Metabolic Syndrome for the whole sample was 38.4 (95 CI: 33.5, 43.3). In the multivariate model (adjusted for age, sex, abdominal obesity, HDL-cholesterol, diastolic blood pressure), insufficient Vitamin D status was significantly associated with 1-year age increments (OR: 0.93; 95 CI: 0.88, 0.98), being female (OR: 8.68; 95 CI: 5.08, 14.83) and abdominal obesity (OR: 2.57; 95 CI: 1.51, 4.39). Respondents with insufficient vitamin D were found to have higher odds of having Metabolic Syndrome (OR: 1.73; 95 CI: 1.02, 2.92) after adjusting for age and sex. Conclusions: Our results highlight the high prevalence of vitamin D insufficiency among Malay adults in Kuala Lumpur. Vitamin D insufficiency is independently associated with younger age, female sex and greater abdominal obesity. Vitamin D insufficiency is also associated with Metabolic Syndrome

Behavioural responses to unexpected changes in reward quality

Successive negative contrast (SNC) effects are changes in anticipatory or consummatory behaviour when animals unexpectedly receive a lower value reward than they have received previously. SNC effects are often assumed to reflect frustration and appear to be influenced by background affective state. However, alternative explanations of SNC, such as the functional-search hypothesis, do not necessarily imply an aversive affective state. We tested 18 dogs in a SNC paradigm using a patch foraging task. Dogs were tested in two conditions, once with the low value reward in all of five trials (unshifted) and once when reward value was altered between high and low (shifted). Following a reward downshift, subjects showed a SNC effect by switching significantly more often between patches compared to the unshifted condition. However, approach latency, foraging time and quantity consumed did not differ between conditions, suggesting non-affective functional search behaviour rather than frustration. There was no relationship between strength of SNC and anxiety-related behaviours as measured in a novel object test and a personality questionnaire (C-BARQ). However, associations with the C-BARQ scores for Trainability and Stranger directed aggression suggest a possible link with behavioural flexibility and coping style. While reward quality clearly affects incentive motivation, the relationship between SNC, frustration and background affective state requires further exploration

High nitrogen contribution by Gunnera magellanica

Chronosequences at the forefront of retreating glaciers provide information about colonization rates of bare surfaces. In the northern hemisphere, forest development can take centuries, with rates often limited by low nutrient availability. By contrast, in front of the retreating Pia Glacier (Tierra del Fuego, Chile), a Nothofagus forest is in place after only 34 yr of development, while total soil nitrogen (N) increased from near zero to 1.5%, suggesting a strong input of this nutrient. We measured N-fixation rates, carbon fluxes, leaf N and phosphorus contents and leaf δ15N in the dominant plants, including the herb Gunnera magellanica, which is endosymbiotically associated with a cyanobacterium, in order to investigate the role of N-fixing and mycorrhizal symbionts in N-budgets during successional transition. G. magellanica presented some of the highest nitrogenase activities yet reported (potential maximal contribution of 300 kg N ha−1 yr−1). Foliar δ15N results support the framework of a highly efficient N-uptake and transfer system based on mycorrhizas, with c. 80% of N taken up by the mycorrhizas potentially transferred to the host plant. Our results suggest the symbiosis of G. magellanica with cyanobacteria, and trees and shrubs with mycorrhizas, to be the key processes driving this rapid successioncyanobacteriaMinisterio de Economía y Competitividad (España)Depto. de Farmacología, Farmacognosia y BotánicaFac. de FarmaciaTRUEpu