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Biomedical subjects

G Argentieri

Publications and source records attributed to G Argentieri.

7 recordsLinked to original sources
PubMed2001

The effect of 1,3-diaryl-[1H]-pyrazole-4-acetamides on glucose utilization in ob/ob mice.

This article provides evidence of a new class of compounds, 1,3-diaryl-[1H]-pyrazole-4-acetamides, initially identified from their ability to increase glucose transport in an adipocyte and muscle cell line and ultimately demonstrating dramatic glucose lowering in ob/ob mice, a diabetic animal model. The lead compound, 1, possessed some behavioral-like effects which were removed by structural variation during the course of this investigation. Specifically, 11g (R1 = meta-CF(3), Ar2 = 4'biphenyl, R3 = diethylamide) illustrated the potency of this series with ED(50) values for glucose lowering in ob/ob mice of 3.0 mg/kg/day. Concomitant with its effect on glucose lowering, 11g also caused a 50% reduction in insulin levels consistent with an agent that increases whole body insulin sensitivity. 11g showed favorable pharmacokinetic data with acceptable absorption, negligible metabolism, and good duration of action. 11g demonstrated no appreciable adipogenic effect through PPAR gamma agonism, a characteristic of the thiazolidinediones (TZD), and so represents a potentially new class of agents for the treatment of diabetes.

Acetamides↗
PubMed2000

Effects of pioglitazone on promoting energy storage, not expenditure, in brown adipose tissue of obese fa/fa Zucker rats: comparison to CL 316,243.

Recent advances in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) include the use of thiazolidinediones (TZDs), agents that enhance insulin action, in part, through an activation of adipose tissue peroxisome proliferator-activated receptor gamma. Current evidence also indicates that these agents upregulate uncoupling protein 1 (UCP1) gene expression in brown adipocytes and increase interscapular brown adipose tissue (IBAT) mass in rodents, suggestive of a thermogenic component to their mechanism of action. In the present study, the TZD pioglitazone (PIO) and the beta3-adrenoceptor agonist CL 316,243 (CL), were used to determine whether the antidiabetic effects of PIO, like those of CL, may, in part, be mediated by an increase in either IBAT thermogenesis or whole-body energy expenditure. Treatment of obese, insulin resistant fa/fa Zucker rats with PIO for 10 days resulted in a 2- to 3-fold increase in IBAT mass, due largely to an increase in adipocyte size and number, and increased fatty acid biosynthesis. However, unlike the effects of CL, the PIO-induced IBAT changes were not associated with an increase in UCP1 expression or whole-body energy expenditure. In contrast to CL, PIO substantially increased body weight gains over the 10-day treatment period by increasing feeding efficiency. These data suggest that, unlike CL, the actions of PIO in the obese Zucker rat does not include increased energy expenditure, but rather strengthens its role as an adipogenic and lipogenic agent, which promotes energy storage.

Adipose Tissue, Brown↗
PubMed1995

The comparative histology of porcine and guinea pig skin with respect to iontophoretic drug delivery.

The anatomy of pig skin, neonatal pig skin, and hairless guinea pig skin was investigated with respect to iontophoretic drug transport. Fixed sections of skin were stained with hematoxylin and eosin, and the morphology of the skin appendages was examined. Quantitative measurements of the hair follicle density, diameter and lumen area were obtained, and the effective surface areas available for low resistance iontophoretic transport were calculated. The clustering and density of the follicles of neonatal porcine skin and hairless guinea pig skin suggest that linear mass transport may dominate iontophoretic flux. In contrast, the morphology and density of the hair follicles of porcine skin suggests that a radial mass transport mechanism may dominate iontophoretic transdermal drug delivery.

Administration, Cutaneous↗