Phosphodiesterase inhibitory properties of losartan. Design and synthesis of new lead compounds

In order to define more precisely the risk of hypoglycaemia in GH-deficient children and to clarify the role of growth hormone (GH) in glucose homeostasis, a 24-h fast was monitored in 10 GH-deficient children aged 1.1-6.5 y. Asymptomatic hypoglycaemia (blood glucose < or = 2.6 mmol/l) occurred in 9/10 children, 2 of whom prematurely interrupted the test. Blood glucose profile was not reproducible between children and had no correlation with age (p = 0.48). Gluconeogenesis was considered as non-altered as read from the normal plasma lactate and pyruvate concentrations throughout the test. Plasma ketone body concentrations increased during the test, but were lower than expected with respect to the decrease of blood glucose. This suggests insufficient ketogenesis which could exacerbate hypoglycaemia in GH-deficient children if brain glucose utilization were not alleviated by ketone body oxidization, as is normally the case. The positive glucose response after glucagon stimulation in 6/10 patients indicated normal hepatic glycogen content. However, these responses were unexpected following the prolonged fast and its concomitant hypoglycaemia, and would therefore tend to suggest a defect in glycogenolysis. These results confirm the tendency to hypoglycaemia, even after infancy, in GH-deficient children. These hypoglycaemias may occur by different types of malfunctioning, such as insufficient ketogenesis or a defect in glycogenolysis. These hypotheses require confirmation by a more systematic study of the metabolic and hormonal changes that occur during fasting in both GH-deficient and normal children.     

Modeling of metastable phase formation diagrams for sputtered thin films

A method to model the metastable phase formation in the Cu–W system based on the critical surface diffusion distance has been developed. The driver for the formation of a second phase is the critical diffusion distance which is dependent on the solubility of W in Cu and on the solubility of Cu in W. Based on comparative theoretical and experimental data, we can describe the relationship between the solubilities and the critical diffusion distances in order to model the metastable phase formation. Metastable phase formation diagrams for Cu–W and Cu–V thin films are predicted and validated by combinatorial magnetron sputtering experiments. The correlative experimental and theoretical research strategy adopted here enables us to efficiently describe the relationship between the solubilities and the critical diffusion distances in order to model the metastable phase formation during magnetron sputtering.     

Inhibition of eotaxin-mediated human eosinophil activation and migration by the selective cyclic nucleotide phosphodiesterase type 4 inhibitor rolipram

Epidemiological studies suggest that moderate consumption of alcoholic beverages may be beneficial for bone in postmenopausal women. To investigate prospectively these uncontrolled observations, female rats were divided in four groups of 10 animals each and treated with 1) ovariectomy (OVX) and 2.5% ethanol diet (OVX-ETOH group), 2) OVX and control diet (OVX-C group), 3) sham surgery and 2.5% ethanol diet (SHAM-ETOH group), or 3) sham surgery and control diet (SHAM-C group). Three weeks after surgery, bone histomorphometry revealed that the OVX-C group, as expected, had lower trabecular bone volume and higher parameters of bone formation and resorption than the SHAM-C group (p < 0.01). Intake of ethanol did not change these parameters in the SHAM rats, but in the OVX rats it was associated with sharp reduction in parameters of bone resorption (p < 0.01) without a concomitant effect on parameters of bone formation. The cytokines are believed to contribute to accelerated bone resorption during the early postmenopausal period. Indeed, the peripheral blood monocytic cells (PBMC) from the OVX-C rats produced higher amounts of TNF-alpha than the PBMC from the SHAM-C rats (p < 0.05) and administration of ethanol prevented this increase in OVX rats but had no effect in SHAM rats. In summary, short-term intake of moderate doses of ethanol was associated with markedly different effects in rats with and without ovarian function. Although ethanol had no significant effect on the bone tissue and TNF-alpha production of the SHAM rats, it was associated with markedly lower parameters of bone resorption and less TNF-alpha production in the OVX animals. This suggests that exposure to low-dose ethanol may protect from osteopenia following cessation of ovarian function.