Milk excretion of ivermectin and moxidectin in dairy sheep: assessment of drug residues during cheese elaboration and ripening period

Ivermectin (IVM) and moxidectin (MXD) are broad-spectrum endectocide antiparasitic drugs extensively used in food-producing animals. The patterns of IVM and MXD excretion in milk were comparatively characterized following their subcutaneous administration (200 microg.kg(-1) of body weight) to lactating dairy sheep. The relationship between milk excretion and plasma disposition kinetics of both compounds was characterized. A pool of milk collected from all of the animals in each experimental group was used for cheese elaboration. IVM and MXD residual concentrations were assessed during the cheese-making process and ripening period. IVM and MXD concentrations were measured in plasma, milk, and milk product (whey, curd, and cheese) samples using an HPLC-based methodology with fluorescence detection. IVM and MXD were extensively distributed from the bloodstream to the mammary gland, and large quantities, particularly of MXD, were excreted in milk. Residual concentrations of both compounds were recovered in milk up to 30 (IVM) and 35 (MXD) days post-treatment. The total fraction of the administered dose excreted in milk for MXD was significantly higher than that of IVM. During cheese production, the highest residual concentrations of both molecules were measured in the curd. Thirty-four percent of the total drug residue measured in the pooled milk collected from treated sheep was lost during the cheese-making process. The lowest residual concentrations were measured in the whey. IVM and MXD concentrations in the elaborated cheese tended to increase during the ripening period, reaching the highest residual level at 40 days of cheese maturation. The long persistence of milk residual concentrations of MXD and IVM in lactating dairy sheep and the high concentrations found in cheese and other milk-related products should be seriously considered before recommendation of the extralabel use of these antiparasitic drugs in dairy animals.     

Compound K enhances insulin secretion with beneficial metabolic effects in db/db mice

Compound K (CK) is a final metabolite of panaxadiol ginsenosides. Although Panax ginseng is known to have antidiabetic activity, the active ingredient is not yet fully identified. In our preliminary studies, panaxadiol ginsenosides showed insulin secretion stimulating activity. Therefore, it would be interesting to know whether and how CK has antidiabetic activity. In in vitro studies using HIT-T15 cells and primary cultured islets, CK enhanced the insulin secretion in a concentration-dependent manner. This effect, however, was completely abolished in the presence of diazoxide (K+ channel opener) or nifedipine (Ca2+ channel blocker). Insulin secretion stimulating activity of a single oral CK administration was also confirmed with an oral glucose tolerance test (OGTT) using ICR mice. From these studies, we may conclude that CK lowered the plasma glucose level by stimulating insulin secretion and this action was presumably associated with an ATP-sensitive K+ channel. In a long-term study using C57BL/KsJ db/ db mice, CK treatment significantly decreased the fasting blood glucose levels in a dose-dependent fashion. OGTT revealed that CK improved glucose tolerance with increased insulin levels 30 min after the glucose challenge. Concurrently, CK treatment prevented the destruction of islets and preserved more insulin. Next, to gain insight into the extra-pancreatic molecular mechanism of CK, we performed a global gene expression profiling study in the liver and adipose tissues. According to DNA microarray analysis, CK shifted glucose metabolism from hepatic glucose production to hepatic glucose utilization in the liver and improved insulin sensitivity through enhancing plasma adiponectin levels, resulting in overexpression of genes for adipogenesis and glucose transporter in the adipose tissue. Taken together, we may suggest that CK could be developed as a therapeutic tool in type 2 diabetic patients with disability of insulin secretion and/or insulin resistance.     

A black soybean seed coat extract prevents obesity and glucose intolerance by up-regulating uncoupling proteins and down-regulating inflammatory cytokines in high-fat diet-fed mice

Black soybean seed coat extract (BE) is a polyphenol-rich food material consisting of 9.2% cyanidin 3-glucoside, 6.2% catechins, 39.8% procyanidins, and others. This study demonstrated that BE ameliorated obesity and glucose intolerance by up-regulating uncoupling proteins (UCPs) and down-regulating inflammatory cytokines in C57BL/6 mice fed a control or high-fat diet containing BE for 14 weeks. BE suppressed fat accumulation in mesenteric adipose tissue, reduced the plasma glucose level, and enhanced insulin sensitivity in the high-fat diet-fed mice. The gene and protein expression levels of UCP-1 in brown adipose tissue and UCP-2 in white adipose tissue were up-regulated by BE. Moreover, the gene expression levels of major inflammatory cytokines, tumor necrosis factor-α and monocyte chemoattractant protein-1 were remarkably decreased by BE in white adipose tissue. BE is a beneficial food material for the prevention of obesity and diabetes by enhancing energy expenditure and suppressing inflammation.     

Analysis of the temporal intake of cereal and dairy products in Irish adults: implications for developing food-based dietary guidelines

OBJECTIVES: To analyse the temporal distribution of the intake of cereal and dairy products in the Republic of Ireland. DESIGN: The North/South Ireland Food Consumption Survey established a database of habitual food and drink consumption using a 7-day food diary. The database also recorded the time and day of food consumption. Mean intakes of cereal and dairy products were calculated for time of the day and day of the week. RESULTS: At the weekend, the percentage of consumers decreased for nearly all cereal and dairy products. White bread, total cereals, full-fat milk and total dairy intakes were significantly lower at the weekend (P<0.01) compared with weekdays. Intakes of cereal and dairy products over time of the day showed clear mealtime or snacking patterns when the number of consumers was controlled for. White bread, wholemeal bread, total cereals, full-fat milk, reduced-fat milk and total dairy intakes showed mealtime peaks for morning, afternoon and evening. When examined by tertile of intake, tertile of percentage energy from fat and tertile of fibre intake, intakes of cereal and dairy products over time of the day and day of the week were similar to trends described above, regardless of the tertile. CONCLUSIONS: Temporal analysis of the intakes of cereal and dairy products did not reveal any unusual trends in this population. However, the significant methodological issues raised in this paper will be of benefit to other aspects of research in this area.     

The influence of cereal and dairy consumption on the Irish diet: implications for developing food-based dietary guidelines

OBJECTIVES: To estimate the intakes of cereal and dairy products and their contribution to nutrient intakes in men and women from the Republic of Ireland with a view to formulating food-based dietary guidelines. DESIGN: The North/South Ireland Food Consumption Survey established a database of habitual food and drink consumption using a 7-day food diary. From this database all cereal and dairy products from recipes and identifiable sources were identified and a new database was generated from which analysis of the role of cereal and dairy products in the diet was carried out. RESULTS: Almost 100% of the population consumed cereal and dairy products over the course of the survey week. In general, men consumed significantly more cereal and dairy products than did women (P<0.05). Cereal products made an important contribution to the mean daily intakes of energy (26%), protein (21%), fat (13%), carbohydrate (41%), fibre (45%), iron (43%) and folate (27%). Dairy products also contributed largely to the mean daily intakes of energy (11%), protein (14%), fat (17%), calcium (48%), phosphorus (24%) and vitamin A (27%). Analysis of nutrient intakes across tertiles of cereal and dairy consumption showed that high consumers of wholemeal bread, breakfast cereals, reduced-fat milk and yoghurt had lower fat and higher carbohydrate, fibre and micronutrient intakes than low consumers of these foods. CONCLUSIONS: Findings from the present study could be used to develop effective health strategies to implement changes in cereal and dairy consumption that could alter fat, fibre and micronutrient intakes in the diet.     

Kinetics of abamectin disposition in blood plasma and milk of lactating dairy sheep and suckling lambs

Abamectin (ABM) has been used worldwide as an anthelmintic drug in veterinary medicine and as an agricultural pesticide. Its pharmacokinetics and permeation into milk was evaluated in dairy sheep after subcutaneous administration. ABM elimination half-lives and mean residence times were 1.7 and 3.7 days for blood plasma and 1.9 and 3.8 days for milk, respectively. The ABM milk to plasma concentration ratio (0.89) primarily depends on milk fat content. Transfer of ABM residues to suckling lambs was evaluated by determination of ABM concentration time courses in lambs' plasma. Mean maximal concentration in lambs was 1.6 microg L(-1) at 3.3 days, and elimination half-life was 2.7 days. In ewes' plasma and milk, ABM was detected up to 23 days. Because of different pharmacokinetics, ABM exposure in lambs was almost 10% of the exposure in ewes, although the amount excreted in milk was only 1.0% of the dose.     

Differential effects of powdered whole soy milk and its hydrolysate on antiobesity and antihyperlipidemic response to high-fat treatment in C57BL/6N mice

This study was performed to investigate the beneficial effects of powdered whole soy milk and its hydrolysate, compared to the processed soy milk and its hydrolysate, on the alteration of lipid metabolism and their possible effects on antiobesity in C57BL/6N mice fed a high-fat and -cholesterol diet. The mice were divided into a control group (20% casein) and four test groups for 5 weeks: soy milk (SM, 20% soy milk protein), soy milk hydrolysate (SMH, 20% hydrolyzed soy milk protein), whole soy milk (WSM, 20% whole soy milk protein), and whole soy milk hydrolysate (WSMH, 20% whole soy milk hydrolysate protein). The body weight and adipose tissue weights were significantly lowered in SMH, WSM, and WSMH groups compared to the control group despite providing an isoenergetic diet. Plasma lipid concentrations and hepatic fatty acid synthase (FAS) and glucose-6-phosphate dehydrogenase (G6PD) activities were significantly lowered in all soy milk groups; however, the hepatic lipid contents and malic enzyme (ME) activity were only significantly lowered in the WSM and WSMH groups, compared to the control group. Data suggest that powdered WSM or WSMH appears to be more beneficial than SM or SMH in overall antiobesity and antihyperlipidemic properties following in the order WSMH/WSM, SMH, SM, and casein.     

Plasmin system and microbial proteases in milk: characteristics,roles, and relationship

Proteolysis of milk proteins can be attributed to both native proteases and the proteases produced by psychrotrophic bacteria during storage of fresh raw milk. These proteases cause beneficial or detrimental changes, depending on the specific milk product. Plasmin, the major native protease in milk, is important for cheese ripening. Milk storage and cheese-making conditions can affect the level of plasmin in the casein and whey fractions of milk. A microbial protease from a psychrotrophic microorganism can indirectly increase plasmin levels in the casein curd. This relationship between the plasmin system and microbial proteases in milk provides a means to control levels of plasmin to benefit the quality of dairy products. This paper is a short review of both the plasmin system and microbial proteases, focusing on their characteristics and relationship and how the quality of dairy products is affected by their proteolysis of milk proteins.     

Effect of processing and storage on the stability of flaxseed lignan added to dairy products

This study investigated the effects of processing and storage on the stability of purified, flaxseed-derived secoisolariciresinol diglucoside (SDG) added to milk prior to the manufacture of different dairy products. We analyzed the effect of high-temperature pasteurization, fermentation, and milk renneting as well as storage on the stability of SDG added to milk, yogurt, and cheese. Also, the stability of SDG in whey-based drinks was studied. Added SDG was found to withstand the studied processes well. In edam cheese manufacture, most of the added SDG was retained in the whey fraction and 6% was found in the cheese curd. SDG was also relatively stable in edam cheese during ripening of 6 weeks at 9 degrees C and in yogurt during storage of 21 days at 4 degrees C. Up to 25% of added SDG was lost in whey-based drinks during storage of 6 months at 8 degrees C. We conclude that SDG can be successfully supplemented in dairy-based products.     

Dry rehydratable films for enumeration of coliforms and aerobic bacteria in dairy products: collaborative study

A collaborative study was conducted to compare proposed dry-film plating methods, using aerobic count plates and coliform count plates, to standard agar plating methods for quantifying aerobic bacteria and coliforms in dairy products. In this study, 5 food products (chocolate milk, pasteurized cheese, nonfat dry milk, evaporated milk, and vanilla ice cream), selected as representative dairy products, were analyzed by 11 collaborating laboratories. The results indicate that the dry-film plating methods are equivalent to or better than the agar plating methods. The aerobic count and coliform count dry-film plating methods have been adopted official first action.     

Dietary combination of conjugated linoleic acid (CLA) and pine nut oil prevents CLA-induced fatty liver in mice

Conjugated linoleic acid (CLA) strongly prevents fat accumulation in adipose tissue of mice, even if hepatic fat deposition and insulin resistance are concomitantly observed. This study investigated the possibility of maintaining the antiadiposity properties of CLA while preventing adverse effects such as liver steatosis and hyperinsulinemia. To this end, mice were divided into three groups and fed a standard diet (control) or a diet supplemented with 1% CLA (CLA) or a mixture of 1% CLA plus 7.5% pine nut oil (CLA + P). The combination of CLA + P preserved the CLA-mediated antiadiposity properties (70% fat reduction), preventing hepatic steatosis and a sharp increase in plasmatic insulin starting from the eighth week of CLA treatment. The assay of both fatty acid synthesis and oxidation in the CLA + P mice revealed a time-dependent biphasic behavior of the corresponding enzymatic activities. A sudden change in these metabolic events was indeed found at the eighth week. A strong correlation between the changes in key enzymes of lipid metabolism and in insulin levels apparently exists in CLA-fed mice. Furthermore, lower levels of lipids, in comparison to values found in CLA-fed mice, were observed in the liver and plasma of CLA + P-fed animals.     

Steam-dried ginseng berry fermented with Lactobacillus plantarum controls the increase of blood glucose and body weight in type 2 obese diabetic db/db mice

This study examined whether steam-dried ginseng berries fermented with Lactobacillus plantarum (FSGB) could improve the indices of type 2 diabetes mellitus (T2DM) in obese db/db mice. FSGB was shown to have an effect on body weight and blood glucose/serum parameters when administered at a dose of 0.5 g/kg. In the intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT), FSGB was clearly shown to improve insulin tolerance and glucose tolerance. Moreover, FSGB was shown to enhance immune activities by increasing the immune cell population, and glucose transpoter 1 (GLUT1) mRNA expression in L6 cells was up-regulated, suggesting that FSGB can increase glucose transport activity in target cells. These results indicate that steam- and dry-processed ginseng berries fermented with L. plantarum can be used to effectively control blood sugar metabolism via improving insulin and glucose tolerance and body weight gain in db/db mice.     

Disposition of doramectin milk residues in lactating dairy sheep

Doramectin (DRM) is a broad spectrum macrocyclic lactone antiparasitic drug not approved for use in dairy animals. However, DRM and other endectocide compounds are widely used extra-label to control endo- and ectoparasites in dairy sheep. The plasma disposition kinetics and the pattern of DRM excretion in milk were characterized following its subcutaneous administration to lactating dairy sheep. DRM concentration profiles were measured in plasma and milk samples after validation of a specific HPLC-based methodology. DRM was detected between 1 h and 30 days post-treatment. DRM concentrations of 0.48 ng.mL(-1) (plasma) and 1.03 ng.mL(-1) (milk) were measured at 30 days post-treatment. DRM was extensively distributed from the bloodstream to the mammary gland, and large concentrations were excreted in milk. The peak concentrations and total amount of DRM recovered in milk (expressed as area under the concentration versus time curve) were 3-fold higher than those measured in plasma; 2.44% of the total DRM dose was excreted in milk. The long persistence of DRM milk residues should be seriously considered before its extra-label use in dairy animals is recommended.     

苹果酸对泌乳早期奶牛泌乳性能和代谢产物的影响

选用28头经产奶牛,根据泌乳期、上一泌乳期305d的产奶量和预产期,采用随机区组设计分为4组,研究苹果酸(07、0、140和210g/d)对泌乳早期奶牛采食量、泌乳性能、血液代谢产物和尿酮浓度的影响。结果表明:日粮添加苹果酸对奶牛的采食量、乳脂率、乳蛋白率、乳糖率和乳干物质率无显著影响,140g/d组和210g/d组产奶量和饲料转化效率显著高于对照组(P<0.05)。添加苹果酸后,140g/d组和210g/d组血浆葡萄糖浓度显著高于对照组(P<0.05),而血浆游离脂肪酸和β-羟丁酸浓度显著低于对照组(P<0.05);140g/d组和210g/d组尿酮浓度显著低于对照组和70g/d组(P<0.05)。根据试验结果,苹果酸适宜添加量为140g/d。     

Laboratory and on-farm studies on the bioaccumulation and elimination of dioxins from a contaminated mineral supplement fed to dairy cows

A dioxin-contaminated mineral supplement was used to study the bioaccumulation and elimination of dioxins in two dairy cows. The supplement was mixed into the total maintenance ration and fed to the cows for 40 days after which unfortified diets were fed for 40 additional days. Dioxins and coplanar polychlorinated biphenyls (PCBs) were measured twice a week in the milk and in selected tissues of the cows, one at death (day 10 of withdrawal) and one at slaughter (day 40 of withdrawal). The dioxins and PCBs were readily transferred into the milk, and at steady state, total toxic equivalents were concentrated 6-fold into the milk fat from the diet. Bioaccumulation was inversely related to chlorination number. The elimination of dioxins and PCBs in milk was biphasic. With the exception of 1,2,3,4,6,7,8-heptachlorodioxin and both octachlorinated congeners, dioxin and furan half-lives in milk were approximately 3-5 days for the alpha-phase and 35-50 days for the beta-phase. PCB-169 had a longer half-life: 11 (alpha) and 200 days (beta). When milk and feed samples from Minnesota farms that had used similar contaminated mineral supplements were analyzed, no elevated dioxin levels were found in milk. It appeared that although the dioxins from the mineral supplements have the potential to bioaccumulate, dilution into the total diet was sufficient to prevent a significant rise in the dioxin concentrations in the milk at these farms.     

Diverse Mechanisms of Antidiabetic Effects of the Different Procyanidin Oligomer Types of Two Different Cinnamon Species on db/db Mice

The procyanidin oligomers are thought to be responsible for the antidiabetic activity of cinnamon. To investigate the hypoglycemic effects of different procyanidin oligomer types, the procyanidin oligomer-rich extracts were prepared from two different cinnamon species. Using high-performance liquid chromatography with purified procyanidin oligomers as reference compounds, we found that the Cinnamomum cassia extract (CC-E) and Cinnamomum tamala extract (CT-E) were rich in B- and A-type procyanidin oligomers, respectively. In the experiment, 8-week-old diabetic (db/db) mice were gavaged with CC-E and CT-E (both 200 mg/kg per day) for 4 weeks. Both CC-E and CT-E exhibited antidiabetic effects. Moreover, histopathological studies of the pancreas, liver, and adipose tissue showed that CC-E promoted lipid accumulation in the adipose tissue and liver, whereas CT-E mainly improved the insulin concentration in the blood and pancreas.     

Calcium, nutrient and food intake of Greek Orthodox Christian monks during a fasting and non-fasting week

OBJECTIVE: To assess the Ca, nutrient and food intake of Greek Orthodox Christian monks during a vegetarian-type fasting week, compared with their normal diet. DESIGN: Dietary data collection (using 7 d weighed food records), anthropometric and blood pressure measurements, as well as serum glucose and lipid analyses, were performed during Palm Sunday week (fasting) and the week following Pentecost Sunday (non-fasting). Mean daily nutrient and food (g/d) intakes were calculated from the food records. SETTING: The study took place in two monasteries in the Municipality of Heraklion, Crete. SUBJECTS: The study involved ten healthy monks aged 254 (sd 10June 2005. RESULTS: Nutrient and food intake profiles were more favourable during the fasting week, when participants had lower intakes of total and saturated fat and trans-fatty acids, and higher intakes of dietary fibre, Fe, folate, legumes and fish/seafood. Ca intake was lower when participants fasted, whereas consumption of dairy products, meat and eggs increased significantly in the non-fasting week. Systolic blood pressure was significantly higher, whereas blood lipid levels were more favourable during the fasting week. CONCLUSIONS: The periodic vegetarianism recommended by the Greek Orthodox Church contributes to the favourable profiles of several biomarkers of health among this sample of monks. The fasting rituals described are an important component of the traditional diet of Crete and should be emphasised in nutrition education programmes promoting this Mediterranean eating pattern.     

The temporal pattern of the contribution of fat to energy and of food groups to fat at various eating locations: implications for developing food-based dietary guidelines

OBJECTIVES: To examine the temporal pattern of the number of eating occasions that occurred at home, at work and outside the home, and to examine the contribution of fat to energy and the contribution of 26 food groups to fat at home and outside the home. DESIGN AND SETTING: Food intake data were collected using a 7-day food diary from a random sample of 18-64-year-old adults from the Republic of Ireland (n=958). Respondents recorded the day, time and location of every eating occasion. RESULTS: The number of eating occasions was constant across the days of the week for meals consumed at home, whereas the number of eating occasions increased at weekends for meals outside the home. The contribution of fat to energy approximated the 35% recommendation at home from Monday to Friday, but increased above this on Saturday and Sunday. The contribution of fat to energy outside the home was always above the recommendation. The food groups that contributed most to fat were similar at home and outside the home. These included butter and full-fat spreads, fresh meat, meat products, meat dishes, biscuits, cakes and pastries, whole milk, and chips and processed potatoes. CONCLUSION: The contribution of fat to energy was above the recommendations when eating outside the home, regardless of day of the week. A number of food groups have been identified that contributed most to fat intake outside the home and these might be targeted in developing public health nutrition strategies to reduce fat intake.     

早稻乳熟初期高温热害气象指标试验研究

以杂交稻品种淦鑫203为试验材料,于乳熟初期在人工气候箱中进行日最高气温34~39℃高温控制试验,以同期自然温度为对照,采用主成分分析和聚类分析法,对各组材料结实率、秕谷率、千粒重和单株产量4个与早稻乳熟初期高温热害密切相关的因子进行分析,以探讨早稻乳熟初期高温热害气象等级指标。结果表明,早稻乳熟初期高温热害气象指标可分为轻、中、重3个等级,日最高气温达35℃持续5d或36℃持续4d或37℃持续3~4d或≥38℃持续3d,为轻度高温热害;日最高气温达35℃持续6~8d或36~37℃持续5d或≥38℃持续4~5d,为中度高温热害;日最高气温达35℃持续8d以上或≥36℃持续6d及以上,为重度高温热害。本文建立的高温热害指标不仅考虑了高温强度和持续时间,且综合考虑了它们之间的相互配置,每个灾害等级均有各自的临界日最高气温和对应的持续时间,对高温热害的识别性更敏感。研究结果可为早稻高温热害监测预警、风险评估及区划等提供科学依据。     

Hypoglycemic effects of a phenolic acid fraction of rice bran and ferulic acid in C57BL/KsJ-db/db mice

Rice bran contains many phenolic acids, the most abundant of which is the antioxidant, ferulic acid (FA). We evaluated the hypoglycemic effects of a phenolic acid fraction (the ethyl acetate fraction, EAE) of rice bran and of FA in C57BL/KsJ db/db mice. Type 2 diabetic mice were allocated to a control group, an EAE group, or an FA group. Animals were fed a modified AIN-76 diet, and EAE or FA was administered orally for 17 days. There was no significant difference in body weight gain between groups. Administration of EAE and FA significantly decreased blood glucose levels and increased plasma insulin levels. EAE or FA groups had significantly elevated hepatic glycogen synthesis and glucokinase activity compared with the control group. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations were significantly decreased by EAE and FA administration. These findings suggest that EAE and FA may be beneficial for treatment of type 2 diabetes because they regulate blood glucose levels by elevating glucokinase activity and production of glycogen in the liver.