Cocktails of Mycotoxins,Phytoestrogens, and Other Secondary Metabolites in Diets of Dairy Cows in Austria: Inferences from Diet Composition and Geo-Climatic Factors

Dairy production is a pivotal economic sector of Austrian and European agriculture. Dietary toxins and endocrine disruptors of natural origin such as mycotoxins and phytoestrogens can affect animal health, reproduction, and productivity. This study characterized the profile of a wide spectrum of fungal, plant, and unspecific secondary metabolites, including regulated, emerging, and modified mycotoxins, phytoestrogens, and cyanogenic glucosides, in complete diets of lactating cows from 100 Austrian dairy farms. To achieve this, a validated multi-metabolite liquid chromatography/electrospray ionization–tandem mass spectrometric (LC/ESI–MS/MS) method was employed, detecting 155 of >800 tested metabolites. Additionally, the most influential dietary and geo-climatic factors related to the dietary mycotoxin contamination of Austrian dairy cattle were recognized. We evidenced that the diets of Austrian dairy cows presented ubiquitous contamination with mixtures of mycotoxins and phytoestrogens. Metabolites derived from Fusarium spp. presented the highest concentrations, were the most recurrent, and had the highest diversity among the detected fungal compounds. Zearalenone, deoxynivalenol, and fumonisin B1 were the most frequently occurring mycotoxins considered in the EU legislation, with detection frequencies >70%. Among the investigated dietary factors, inclusion of maize silage (MS) and straw in the diets was the most influential factor in contamination with Fusarium-derived and other fungal toxins and metabolites, and temperature was the most influential among the geo-climatic factors.     

单克隆抗体—表阿霉素免疫偶合物的制备和体外活性

用双功能试剂己二酰肼制备腙键连接的聚谷氨酸—表阿霉素,通过控制交联条件,所得产物克服了大分子自身交联的缺点,交联率较高。聚谷氨酸的载药量与分子量呈正比,平均每8～11个谷氨酸单体连接1分子表阿霉素。分子量为14300的聚谷氨酸做载体其载药量为1:11,与单抗交联所得的偶合物McAb:PGA:PAR为1:2:22。偶合物较好地保留了抗体活性,体外细胞毒性较游离药物略有下降,但表现出单抗介导的靶细胞选择性杀伤作用。本研究用腙键交联法成功地制备了药/抗比高且体外有效的免疫偶合物,为进一步制备细胞靶向的肿瘤化疗制剂奠定了基础。     

固相萃取GC-FID和GC-MS分析血浆中碱性药物

报道了用X-5固相萃取分离、毛细管GC-FID和GC-MS定性定量分析人血浆中34种碱性药物的方法。在优化的提取条件下,大部分药物的最低检测浓度在0.5～2.0μg·ml^-1之间,线性范围、定量精密度等满足临床中毒分析的要求。     

The Impact of Migraine on Health Status

Problems.-What is the effect of migraine on health status, defined as the patient's physical, psychological, and social functioning? And, suppose that the health status of migraine sufferers appears to be impaired, to what extent is this a consequence of migraine-associated comorbidity rather than of migraine itself? Methods.-A group of 846 migraineurs, selected from the general population following IHS criteria, and a control group were surveyed with the Medical Outcomes Study 36-item Short-Form Health Survey, Nottingham Health Profile, EuroQol instrument, end the COOP/WONCA charts. Questions on demographic characteristics and comorbidity were included. Results.-The health status of migraineurs appeared to be significantly impaired in comparison to the control group. Because statistical significance is distinct from relevance, effect size estimators were employed. Although the direction of the differences indicated consistently a worse health status of the migraineurs, regardless of the instrument used, the sizes of the differences were small to medium. Self-reported comorbidity, especially depression, was more prevalent in the migraine group. However, this offered only a partial explanation for the impaired health status of the migraine group. Conclusions.-Migraine has an independent moderately deteriorating effect on the daily functioning of individuals.     

Effect of thyroid hormone on protein turnover in cultured cardiac myocytes

Since systemic actions of thyroid hormone increase cardiac work, direct effects of T3 on myocardial protein turnover may be obscured in the intact animal. For this reason, the effects of T3 on synthesis and degradation of cellular protein were measured in replicate cultures of cardiac myocytes obtained from chick embryos. During the first 3 days of exposure, 10(-8) M T3 increased the fractional rate of protein synthesis 10% to 16% and the fractional rate of cell growth 20% to 40% with no change in protein degradation. During the fourth and fifth days of 10(-8) M T3 exposure, fractional synthesis rates in T3 cultures increased 15% to 19% but fractional degradation rates also increased 17% to 29% so that growth rates in T3 cultures fell to control levels. Similar changes in myocardial protein turnover have occurred in response to T3 treatment in intact animals. T3 treatment caused a disproportionately large increase in the rate of myosin heavy chain turnover when compared to total cellular protein and actin. This may be related to the change in amounts of myocardial isomyosins occurring in response to thyroid hormone treatment.     

人白血病HL60细胞的分化状态对细胞凋亡的影响

用细胞培养和流式细胞术等方法,研究人白血病HL60细胞诱导分化后,对三尖杉酯碱(Har)和喜树碱(Cam)诱导细胞凋亡的影响。结果表明,12-豆蔻酰及13-乙酸佛波酯以16nmol·L^-1浓度处理HL60细胞24h,细胞向单核/巨噬细胞方向分化,阻断于G_{1期;分化细胞抗Har和Cam诱导的细胞凋亡,但其c-myc基因的表达无变化。1.4%二甲基亚砜处理HL60细胞48h,细胞向粒细胞方向分化,阻断于G1期;分化细胞抗Cam,而不抗Har诱导的细胞凋亡;分化细胞的c-myc基因表达明显下降。结果提示,人白血病HL60细胞的分化状态,明显影响三尖杉酯碱和喜树碱诱导的细胞凋亡,但可能与c-myc基因的表达变化无关。}     

Lack of precision in neonatal death classifications based on the underlying causes of death stated on death certificates

Large-scale analyses of causes of neonatal deaths are usually based on death-certificate information. A new computer-based method has been introduced to define the cause of stillbirths and neonatal deaths in large amounts of material and to classify them according to two different models [Wigglesworth and Neonatal and Intrauterine death Classification according to (a)Etiology (NICE)]. The method is based on a combination of detailed information from health care registries and the death-certificate information. The present study aimed to compare these two classification models with a previously published method based solely on death certificate information [International Collaborative Effort (ICE)]. The study population comprised 2378 neonatal deaths in Sweden between 1987 and 1992. Cross-tabulation was made between the ICE classification and the other two classification models. In addition, case examples are presented in detail, exemplifying how classification errors arose. The ICE classification gives a rather low precision, notably for two important causes of death: asphyxia and immaturity. Among 328 infants dying from asphyxia according to computerized Wigglesworth classification, ICE classified 59% as asphyxia and 22% were labelled immaturity. When ICE classified the deaths as due to asphyxia, this was verified in only 50%. Among 792 infants dying from immaturity according to computerized Wigglesworth classification, 64% were classified as such by ICE. The findings cast doubts on the results of studies based exclusively on death-certificate information. Whenever possible in the analysis of neonatal deaths, death-certificate information should be supplemented with more detailed data. The computer-based method introduced here makes such analyses possible for large databases.     

Effect of estradiol and progesterone on the low-dose endotoxin-induced glomerular inflammatory response of the female rat.

PROBLEM: Is the endotoxin-induced glomerular inflammatory response of the female rat under ovarian control? METHOD OF STUDY: Ovariectomized rats (OVX), with or without progesterone (OVX-P) or estradiol (OVX-E) treatment, as well as rats in the follicular or luteal phase of the ovulatory cycle were infused with endotoxin or saline and sacrificed 3 days later. Cryostat kidney sections were immunohistologically stained for the presence of neutrophils and monocytes (MØ) and the expression of adhesion molecules. RESULTS: After endotoxin, the glomerular number of neutrophils and the number of MAC-1 positive cells were increased in luteal-phase and in OVX-P rats, and the number of glomerular MØ was increased in luteal-phase, OVX, OVX-E, and OVX-P rats. Endotoxin increased ICAM-1 expression in all groups of rats, except in follicular-phase rats. The glomerular number of LFA-1– and VLA-4-positive cells following endotoxin were only increased in OVX rats. CONCLUSIONS: It is concluded that endotoxin-induced monocyte infiltration and ICAM-1 expression are inhibited by a factor produced during the follicular phase, probably by developing follicles. Infiltration of neutrophils and expression of MAC-1, LFA-1, VLA-4 seem to be under control of progesterone or estradiol.     

Extracellular matrix molecules and their potential contribution to the function of transplanted pancreatic islets

Extracellular matrix (ECM) molecules are responsible for structural and biochemical support, as well as for regulation of molecular signalling and tissue repair in many organ structures, including the pancreas. In pancreatic islets, collagen type IV and VI, and laminins are the most abundant molecules, but other ECM molecules are also present. The ECM interacts with specific combinations of integrin α/β heterodimers on islet cells and guides many cellular processes. More specifically, some ECM molecules are involved in beta cell survival, function and insulin production, while others can fine tune the susceptibility of islet cells to cytokines. Further, some ECM induce release of growth factors to facilitate tissue repair. During enzymatic isolation of islets for transplantation, the ECM is damaged, impacting islet function. However, restoration of the ECM in human islets (for example by adding ECM to the interior of immunoprotective capsules) has been shown to enhance islet function. Here, we provide current insight into the role of ECM molecules in islet function and discuss the clinical potential of ECM manipulation to enhance pancreatic islet function and survival.