BACKGROUND: Adenosine A1 receptor (A1-AR) activation can lower plasma glucose in diabetic rats lacking insulin. We investigated the change in A1-AR gene expression in diabetic rats. METHODS: The incorporation of [U-(14)C]-glucose into glycogen was carried out to evaluate the effect of N(6)-cyclopentyladenosine (CPA) on glucose utilization in vitro. The plasma glucose concentration was assessed by the glucose oxidase method. The mRNA and protein levels of A1-AR in isolated liver were detected by Western blotting analysis and Northern blotting analysis, respectively. RESULTS: The effect of CPA, an agonist of A1-AR, on glycogen incorporation in hepatocytes isolated from streptozotocin-induced diabetic rats (STZ-diabetic rats) was more marked than that from the normal rats. However, similar glycogen synthesis was not modified by 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, in the isolated hepatocytes from both the normal and the STZ-diabetic rats. A change in response at the receptor level can thus be considered. The mean level of liver mRNA transcripts encoding A1-AR was increased in STZ-diabetic rats to about 250% of that in normal rats. Exogenous insulin at a dose sufficient to normalize the plasma glucose of STZ-diabetic rats reversed the mRNA level of A1-AR in the liver after a four-day treatment. Similar results were also observed in STZ-diabetic rats that received treatment with phlorizin for four days. Moreover, the protein level of A1-AR was higher in the liver of STZ-diabetic rats than that in the normal rats. Similar treatment with exogenous insulin or phlorizin reversed the elevated protein level of A1-AR in the liver of STZ-diabetic rats to near the normal level. Therefore, correction of hyperglycemia in STZ-diabetic rats can reverse the higher gene expression of A1-AR in liver. CONCLUSIONS: The obtained results suggest that an increase in plasma glucose is responsible for the higher gene expression of A1-AR in the liver of STZ-diabetic rats.

Adenosine↗

PubMedDate not supplied

Inferring systemic exposure from a pharmacokinetic screen: model-free and model-based approaches.

To infer patterns of average systemic exposure and to estimate individual exposures in phase III clinical trials of a new anxiolytic, two statistical methodologies were applied and compared: non-linear mixed-effect modelling, and a model-free approach based on quartiles of dose-normalized plasma concentrations of the drug. Although the model-based approach provides more quantitative insight about relationships between average exposure and demographic covariates, the model-free approach provides qualitatively similar results about average clearance and quantitatively similar results about individual exposures, and the model-free approach is easy and inexpensive to implement.

Adult↗

PubMedDate not supplied

The effect of wait time on T2 distributions from NMR experiments.

Nuclear magnetic resonance (NMR) relaxation curves for both T1 and T2 on two brine-saturated core plugs have been measured at 1 MHz. T2 distributions were extracted from Carr-Purcell-Meiboom-Gill (CPMG) measurements using different wait times between consecutive echo sequences. The analysis was performed with both a limited number of exponentials and a continuous B-spline basis. The distributions depend strongly on wait time. The distributions were generally restored to the true distributions when a wait time correction was applied.

Humans↗

PubMedDate not supplied

NMR characterization of hydrocarbon gas in porous media.

Laboratory investigations of nuclear magnetic resonance (NMR) relaxation properties of methane gas in bulk and in porous media are reported. Measurements were performed for methane alone and together with water in glass bead packs and Bentheimer sandstone. Results indicate that surface relaxation effects can be significant and that diffusion effects dominate observed T2 relaxation.

Gases↗

PubMedDate not supplied

Rapid hypertensinogenic effect of lead: studies in the spontaneously hypertensive rat.

Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile response of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na(+)-K(+)-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na(+)-K(+)-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.

Animals↗

PubMedDate not supplied

Review of four hundred cases with intrauterine loops.

Explore the source record for details and available documents.

Adult↗