The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia

OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP).DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements.SETTING: The Leiden University Medical Center.SUBJECTS: Postmenopausal women with type III HLP (aged ≤ 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L-1.MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels.RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L-1 and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L-1, respectively (both P &lt; 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P &lt; 0.05).CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.</p

The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia

OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP).DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements.SETTING: The Leiden University Medical Center.SUBJECTS: Postmenopausal women with type III HLP (aged ≤ 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L-1.MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels.RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L-1 and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L-1, respectively (both P &lt; 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P &lt; 0.05).CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.</p

The age-related slow increase in amyloid pathology in APP.V717I mice activates microglia, but does not alter hippocampal neurogenesis

In Alzheimer's disease, the hippocampus is characterized by abundant deposition of amyloid peptides (amyloid β [Aβ]) and neuroinflammation. Adult hippocampal neurogenesis (AHN) is a form of plasticity that contributes to cognition and can be influenced by either or both pathology and neuroinflammation. Their interaction has been studied before in rapidly progressing transgenic mouse models with strong overexpression of amyloid precursor protein (APP) and/or presenilin 1. So far, changes in AHN and neuroinflammation remain poorly characterized in slower progressing models at advanced age, which approach more closely sporadic Alzheimer's disease. Here, we analyzed 10- to 26-month-old APP.V717I mice for possible correlations between Aβ pathology, microglia, and AHN. The age-related increase in amyloid pathology was closely paralleled by microglial CD68 upregulation, which was largely absent in age-matched wild-type littermates. Notably, aging reduced the AHN marker doublecortin, but not calretinin, to a similar extent in wild-type and APP.V717I mice between 10 and 26 months. This demonstrates that AHN is influenced by advanced age in the APP.V717I mouse model, but not by Aβ and microglial activation

Анализ составляющих теплового баланса системы "прокатный стан - прокатываемая полоса" и пути снижения энергозатрат в процессе сортовой прокатки

Выполнен анализ составляющих теплового баланса системы «прокатный стан – прокатываемая полоса». Рассмотрены основные направления решения температурной задачи сортовой прокатки. Предложен ряд мероприятий, позволяющих снизить расход энергоресурсов на прокатку и уменьшить расходную часть теплового баланса системы «прокатный стан – прокатываемая полоса»

Morphological effects of vegetation on the tidal-fluvial transition in Holocene estuaries

Vegetation enhances bank stability and sedimentation to such an extent that it can modify river patterns, but how these processes manifest themselves in full-scale estuarine settings is poorly understood. On the one hand, tidal flats accrete faster in the presence of vegetation, reducing the flood storage and ebb dominance over time. On the other hand flow-focusing effects of a tidal floodplain elevated by mud and vegetation could lead to channel concentration and incision. Here we study isolated and combined effects of mud and tidal marsh vegetation on estuary dimensions. A 2-D hydromorphodynamic estuary model was developed, which was coupled to a vegetation model and used to simulate 100 years of morphological development. Vegetation settlement, growth and mortality were determined by the hydromorphodynamics. Eco-engineering effects of vegetation on the physical system are here limited to hydraulic resistance, which affects erosion and sedimentation pattern through the flow field. We investigated how vegetation, combined with mud, affects the average elevation of tidal flats and controls the system-scale planform. Modelling with vegetation only results in a pattern with the largest vegetation extent in the mixed-energy zone of the estuary, which is generally shallower. Here vegetation can cover more than 50 % of the estuary width while it remains below 10 %–20 % in the outer, tide-dominated zone. This modelled distribution of vegetation along the estuary shows general agreement with trends in natural estuaries observed by aerial image analysis. Without mud, the modelled vegetation has a limited effect on morphology, again peaking in the mixed-energy zone. Numerical modelling with mud only shows that the presence of mud leads to stabilisation and accretion of the intertidal area and a slight infill of the mixed-energy zone. Combined modelling of mud and vegetation leads to mutual enhancement with mud causing new colonisation areas and vegetation stabilising the mud. This occurs in particular in a zone previously described as the bedload convergence zone. While vegetation focusses the flow into the channels such that mud sedimentation in intertidal side channels is prevented on a timescale of decades, the filling of intertidal area and the resulting reduction in tidal prism may cause the infilling of estuaries over centuries

Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158 --> Cys) homozygotes is associated with hyperinsulinemia

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of apolipoprotein E2 (apoE2, Arg158-->Cys). Only a small percentage (< 5%) of these apoE2 homozygotes develops hyperlipidemia, indicating that additional environmental and genetic factors contribute to the expression of type III HLP. In the present study, first, the prevalence of type III HLP among apoE2 homozygotes was estimated in a Dutch population sample of 8888 participants. Second, 68 normocholesterolemic and 162 hypercholesterolemic apoE2 homozygotes (type III HLP patients) were collected to investigate additional factors influencing type III HLP expression. In the Dutch population sample, apoE2 homozygosity occurred with a frequency of 0.6% (57 of 8888 individuals). Among the 57 E2/2 subjects, 10 type III HLP patients were identified (prevalence 18%). Comparison of normocholesterolemic E2/2 subjects and type III HLP patients showed that the latter had a significantly increased body mass index (25.6 +/- 4.0 versus 26.9 +/- 3.8 kg/m(2), respectively; P=0.03) and prevalence of hyperinsulinemia (26% versus 63%, respectively; P<0.001). Multiple linear regression analysis

Isolation and characterisation of plant defensins from seeds of Asteraceae, Fabaceae, Hippocastanaceae and Saxifragaceae

AbstractFrom seeds of Aesculus hippocastanum, Clitoria ternatea, Dahlia merckii and Heuchera sanguinea five antifungal proteins were isolated and shown to be homologous to plant defensins previously characterised from radish seeds and γ-thionins from Poaceae seeds. Based on the spectrum of their antimicriobial activity and the morphological distortions they induce on fungi the peptides can be divided into two classes. The peptides did not inhibit any of three different α-amylases

Distinct actions of the fermented beverage kefir on host behaviour, immunity and microbiome gut-brain modules in the mouse

peer-reviewedBackground Mounting evidence suggests a role for the gut microbiota in modulating brain physiology and behaviour, through bi-directional communication, along the gut-brain axis. As such, the gut microbiota represents a potential therapeutic target for influencing centrally mediated events and host behaviour. It is thus notable that the fermented milk beverage kefir has recently been shown to modulate the composition of the gut microbiota in mice. It is unclear whether kefirs have differential effects on microbiota-gut-brain axis and whether they can modulate host behaviour per se. Methods To address this, two distinct kefirs (Fr1 and UK4), or unfermented milk control, were administered to mice that underwent a battery of tests to characterise their behavioural phenotype. In addition, shotgun metagenomic sequencing of ileal, caecal and faecal matter was performed, as was faecal metabolome analysis. Finally, systemic immunity measures and gut serotonin levels were assessed. Statistical analyses were performed by ANOVA followed by Dunnett's post hoc test or Kruskal-Wallis test followed by Mann-Whitney U test. Results Fr1 ameliorated the stress-induced decrease in serotonergic signalling in the colon and reward-seeking behaviour in the saccharin preference test. On the other hand, UK4 decreased repetitive behaviour and ameliorated stress-induced deficits in reward-seeking behaviour. Furthermore, UK4 increased fear-dependent contextual memory, yet decreased milk gavage-induced improvements in long-term spatial learning. In the peripheral immune system, UK4 increased the prevalence of Treg cells and interleukin 10 levels, whereas Fr1 ameliorated the milk gavage stress-induced elevation in neutrophil levels and CXCL1 levels. Analysis of the gut microbiota revealed that both kefirs significantly changed the composition and functional capacity of the host microbiota, where specific bacterial species were changed in a kefir-dependent manner. Furthermore, both kefirs increased the capacity of the gut microbiota to produce GABA, which was linked to an increased prevalence in Lactobacillus reuteri. Conclusions Altogether, these data show that kefir can signal through the microbiota-gut-immune-brain axis and modulate host behaviour. In addition, different kefirs may direct the microbiota toward distinct immunological and behavioural modulatory effects. These results indicate that kefir can positively modulate specific aspects of the microbiota-gut-brain axis and support the broadening of the definition of psychobiotic to include kefir fermented foods. Video abstract