We present a hybrid method to inspect the phase stability of compounds having a CaCu5-type crystal structure. This is done using 2D stability plots using the Miedema parameters that are based on the ...work function and electron density of the constituent elements. Stable compounds are separated from unstable binary compounds, with a probability of 94%. For stable compounds, a linear relation is found, showing a constant ratio of charge transfer and electron density mismatch. DFT calculations show the same trend. Elements from the s,d,f-block are all reliably represented, elements from the p-block are still challenging.
•The phase stability of CaCu5-type compounds is modelled for s,d,f-block elements.•Using the Miedema parameters, one can separate stable and unstable compositions with a reliability of 94%.•The underlying mechanism depends on the atomic radius, the electron density and the work function of the constituent elements.•For CaCu5-type compounds, a linear relationship between the electronic factors was found and verified using DFT calculations.
Leptin-deficient ob/ob mice are hyperinsulinaemic and hyperglycaemic; however, the cause of hyperglycaemia remains largely unknown.
Glucose metabolism in vivo in 9-h fasted ob/ob mice and lean ...littermates was studied by infusing U-(13)C-glucose, 2-(13)C-glycerol, 1-(2)H-galactose and paracetamol for 6 h, applying mass isotopomer distribution analysis on blood glucose and urinary paracetamol-glucuronide.
When expressed on the basis of body weight, endogenous glucose production (109+/-23 vs 152+/-27 micromol.kg(-1).min(-1), obese versus lean mice, p<0.01) and de novo synthesis of glucose-6-phosphate (122+/-13 vs 160+/-6 micromol.kg(-1).min(-1), obese versus lean mice, p<0.001) were lower in ob/ob mice than in lean littermates. In contrast, glucose cycling was greatly increased in obese mice (56+/-13 vs 26+/-4 micromol.kg(-1).min(-1), obese versus lean mice, p<0.001). As a result, total hepatic glucose output remained unaffected (165+/-31 vs 178+/-28 micromol.kg(-1).min(-1), obese vs lean mice, NS). The metabolic clearance rate of glucose was significantly lower in obese mice (8+/-2 vs 18+/-2 ml.kg(-1).min(-1), obese versus lean mice, p<0.001). Hepatic mRNA levels of genes encoding for glucokinase and pyruvate kinase were markedly increased in ob/ob mice.
Unaffected total hepatic glucose output in the presence of hyperinsulinaemia reflects hepatic insulin resistance in ob/ob mice, which is associated with markedly increased rates of glucose cycling. Hyperglycaemia in ob/ob mice primarily results from a decreased metabolic clearance rate of glucose.
Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is known about which human ...sulfotransferase isoenzymes are involved. We have investigated the sulfation of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3'-diiodothyronine (3,3'-T2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively. In all cases, the substrate preference was 3,3'-T2 >> rT3 > T3 > T4. The apparent Km values of 3,3'-T2 and T3 at 50 micromol/L 3'-phosphoadenosine-5'-phosphosulfate (PAPS) were 1.02 and 54.9 micromol/L for liver cytosol, 0.64 and 27.8 micromol/L for kidney cytosol, 0.14 and 29.1 micromol/L for SULT1A1, and 33 and 112 micromol/L for SULT1A3, respectively. The apparent Km of PAPS (at 0.1 micromol/L 3,3'-T2) was 6.0 micromol/L for liver cytosol, 9.0 micromol/L for kidney cytosol, 0.65 micromol/L for SULT1A1, and 2.7 micromol/L for SULT1A3. The sulfation of 3,3'-T2 was inhibited by the other iodothyronines in a concentration-dependent manner. The inhibition profiles of the 3,3'-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 micromol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate similar substrate specificities for iodothyronine sulfation by native human liver and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney.
Objectives Low-back and shoulder complaints were examined in relation to self-reported and objectively assessed exposure to work-related pushing and pulling. Methods Workers from several companies ...(eg, nursing homes and flower auctions) with pushing and pulling tasks and, as reference, workers without physically demanding tasks were invited to participate. Altogether 829 workers initially received a questionnaire, of whom 459 responded both initially and after 1 year of follow-up. Initially, self-reported exposure to pushing and pulling was assessed by questionnaire. Furthermore, a representative sample of 131 workers was observed at work using TRAC (task recording and analysis on computer) to assess exposure to pushing and pulling objectively. For exposure to pushing and pulling, the workers were classified into a reference group and medium and high exposure groups. Initially and in the follow-up, the 12-month prevalence of low-back and shoulder complaints was assessed. Complaints reported in the follow-up were separately used as dependent variables to calculate prevalence rate ratios (PR) in a Cox's proportional hazard regression analysis. Results The adjusted PR values were not significant for low-back complaints. For shoulder complaints, both the medium and high exposure groups showed significant adjusted PR values for self-reported exposure and observed duration of pushing and pulling when compared with the reference group (PR range 2.18-4.86). For the observed frequency of pushing and pulling, only the medium exposure group showed a significant PR, of 3.95. Conclusions The findings suggest a rather strong relationship between pushing and pulling and shoulder complaints. The evidence for a relationship between pushing and pulling and low-back complaints is limited.
In order to accurately determine a small fraction of a ferromagnetic phase in a paramagnetic matrix, the difference in ferromagnetic and paramagnetic responses to an applied magnetic field has been ...analyzed. The fraction was examined by field-dependent magnetization measurement at different temperatures as well as by thermo-magnetic measurements at constant magnetic fields. The method was successfully applied for the determination of small martensite fractions in a cold-rolled twinning-induced plasticity austenitic steel at three different thickness reductions.
Very low density lipoprotein overproduction is the major metabolic characteristic in familial combined hyperlipidemia (FCHL). Peripheral handling of free fatty acids (FFAs) in vitro may be impaired ...in FCHL by decreased action of acylation-stimulating protein (ASP), which is identical to the immunologically inactive complement component 3a (C3adesArg). Because decreased FFA uptake by impaired complement component 3 (C3) response (as the precursor for ASP) may result in enhanced FFA flux to the liver in FCHL, we have evaluated postprandial C3 changes in vivo in FCHL patients. Accordingly, 10 untreated FCHL patients and 10 matched control subjects underwent an oral fat loading test. Fasting plasma C3 and ASP levels were higher in FCHL patients (1.33+/-0.09 g/L and 70.53+/-4.37 mmol/L, respectively) than in control subjects (0.91+/-0.03 g/L and 43.21+/-8.96 mmol/L, respectively; P=0.01 and P<0.05). In control subjects, C3 concentrations increased significantly after 4 hours (to 1.03+/-0.04 g/L). In FCHL, plasma C3 was unchanged after 4 hours. The earliest postprandial C3 rise in FCHL patients occurred after 8 hours (1.64+/-0.12 g/L). The maximal apolipoprotein B-48 concentration was reached after 6 hours in FCHL patients and control subjects. Postprandial FFA and hydroxybutyric acid (as a marker of hepatic FFA oxidation) were significantly higher in FCHL patients than in control subjects, and the early postprandial C3 rise was negatively correlated with the postprandial FFA and hydroxybutyric acid concentrations. The present data suggest an impaired postprandial plasma C3 response in FCHL patients, most likely as a result of a delayed response by C3, as the precursor for the biologically active ASP, acting on FFA metabolism. Therefore, an impaired postprandial C3 response may be associated with impaired peripheral postprandial FFA uptake and, consequently, lead to increased hepatic FFA flux and very low density lipoprotein overproduction.
The aetiology of insulin resistance is still an enigma. Mouse models are frequently employed to study the underlying pathology. The most commonly used methods to monitor insulin resistance are the ...HOMA-IR, glucose or insulin tolerance tests and the hyperinsulinemic euglycaemic clamp (HIEC). Unfortunately, these tests disturb steady state glucose metabolism. Here we describe a method in which blood glucose kinetics can be determined in fasted mice without noticeably perturbing glucose homeostasis. The method involves an intraperitoneal injection of a trace amount of 6,6-(2)H2glucose and can be performed repeatedly in individual mice. The validity and performance of this novel method was tested in mice fed on chow or high-fat diet for a period of five weeks. After administering the mice with 6,6-(2)H2glucose, decay of the glucose label was followed in small volumes of blood collected by tail tip bleeding during a 90-minute period. The total amount of blood collected was less than 120 μL. This novel approach confirmed in detail the well-known increase in insulin resistance induced by a high-fat diet. The mice showed reduced glucose clearance rate, and reduced hepatic and peripheral insulin sensitivity. To compensate for this insulin resistance, β-cell function was slightly increased. We conclude that this refinement of existing methods enables detailed information of glucose homeostasis in mice. Insulin resistance can be accurately determined while mechanistic insight is obtained in underlying pathology. In addition, this novel approach reduces the number of mice needed for longitudinal studies of insulin sensitivity and glucose metabolism.
Introduction
In the field of healthcare, empowering patients who have a chronic disease is defined as increasing their knowledge and skills, in order to enable them to define their treatment goals ...and take personal responsibility for their medical treatment. Our goal was to explore the nature of empowerment for employees who have a chronic disease and who experience work-related problems.
Methods
We used an explorative qualitative approach to document, from a professional perspective, the experiences of patients who participated in an empowerment training program. The researcher and the three instructors identified several themes which appeared to be important to many participants. These themes were fine-tuned and illustrated using brief case histories.
Results
We identified seven themes and characterized them in terms of employee tasks. These included: (1) developing a realistic understanding of one’s abilities, (2) standing up for oneself in a self-confident way, (3) maintaining social relations based on mutual understanding with supervisors and colleagues, (4) collecting and assimilating knowledge of one’s options, rights and duties, (5) consulting others and negotiating with regard to work accommodations, (6) planning one’s job so as to provide personal satisfaction, and (7) maintaining a social life outside work. Not every employee is faced with all of these tasks, but most have to deal with several.
Conclusion
Empowerment presupposes that employees with a chronic disease can act to solve problems at the workplace. The experiences during a comprehensive empowerment training illustrate that a process of reflection on personal emotions and a cognitive process of exploration and identification of bottlenecks at work may precede these actions. Our primary contribution is the aforementioned list of seven common tasks that many workers have to perform. Disseminating the list can support employees who have a chronic disease and may also be useful for their managers, HRM staff, occupational health and other healthcare workers.
Effects of acute inhibition of glucose-6-phosphatase activity by the chlorogenic acid derivative S4048 on hepatic carbohydrate fluxes were examined in isolated rat hepatocytes and in vivo in rats. ...Fluxes were calculated using tracer dilution techniques and mass isotopomer distribution analysis in plasma glucose and urinary paracetamol-glucuronide after infusion of U-(13)Cglucose, 2-(13)Cglycerol, 1-(2)Hgalactose, and paracetamol. In hepatocytes, glucose-6-phosphate (Glc-6-P) content, net glycogen synthesis, and lactate production from glucose and dihydroxyacetone increased strongly in the presence of S4048 (10 microm). In livers of S4048-treated rats (0.5 mg kg(-1)min(-)); 8 h) Glc-6-P content increased strongly (+440%), and massive glycogen accumulation (+1260%) was observed in periportal areas. Total glucose production was diminished by 50%. The gluconeogenic flux to Glc-6-P was unaffected (i.e. 33.3 +/- 2.0 versus 33.2 +/- 2.9 micromol kg(-1)min(-1)in control and S4048-treated rats, respectively). Newly synthesized Glc-6-P was redistributed from glucose production (62 +/- 1 versus 38 +/- 1%; p < 0.001) to glycogen synthesis (35 +/- 5% versus 65 +/- 5%; p < 0.005) by S4048. This was associated with a strong inhibition (-82%) of the flux through glucokinase and an increase (+83%) of the flux through glycogen synthase, while the flux through glycogen phosphorylase remained unaffected. In livers from S4048-treated rats, mRNA levels of genes encoding Glc-6-P hydrolase (approximately 9-fold), Glc-6-P translocase (approximately 4-fold), glycogen synthase (approximately 7-fold) and L-type pyruvate kinase (approximately 4-fold) were increased, whereas glucokinase expression was almost abolished. In accordance with unaltered gluconeogenic flux, expression of the gene encoding phosphoenolpyruvate carboxykinase was unaffected in the S4048-treated rats. Thus, acute inhibition of glucose-6-phosphatase activity by S4048 elicited 1) a repartitioning of newly synthesized Glc-6-P from glucose production into glycogen synthesis without affecting the gluconeogenic flux to Glc-6-P and 2) a cellular response aimed at maintaining cellular Glc-6-P homeostasis.
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