Intraventricular insulin suppresses the acoustic startle response in rats.

We and others have previously reported that the hormone insulin alters brain noradrenergic function at the synaptic and molecular levels. In the present study, we examined the in vivo effect of insulin (administered chronically via osmotic minipumps at a dose of 5 mU/day into the third cerebral ventricle) on the acoustic startle response. Rats receiving chronic intraventricular insulin had a significantly reduced startle response relative to vehicle-treated controls (i.e., 47 +/- 21% of baseline control startle response). Because our previous findings suggest that on an acute basis, insulin may enhance endogenous noradrenergic activity by inhibiting norepinephrine reuptake, we speculate here that the chronic effect of insulin is similar to that of the noradrenergic reuptake blocker, desipramine, which has been reported to decrease baseline startle performance.

A Gsalpha mutant designed to inhibit receptor signaling through Gs.

Hormonal signals activate trimeric G proteins by substituting GTP for GDP bound to the G protein alpha subunit (Galpha), thereby generating two potential signaling molecules, Galpha-GTP and free Gbetagamma. The usefulness of dominant negative mutations for investigating Ras and other monomeric G proteins inspired us to create a functionally analogous dominant negative Galpha mutation. Here we describe a mutant alpha subunit designed to inhibit receptor-mediated hormonal activation of Gs, the stimulatory regulator of adenylyl cyclase. To construct this mutant, we introduced into the alpha subunit (alphas) of Gs three separate mutations chosen because they impair alphas function in complementary ways: the A366S mutant reduces affinity of alphas for binding GDP, whereas the G226A and E268A mutations impair the protein's ability to bind GTP and to assume an active conformation. The triple mutant robustly inhibits (by up to 80%) Gs-dependent hormonal stimulation of adenylyl cyclase in cultured cells. Inhibition is selective in that it does not affect cellular responses to expression of a constitutively active alphas mutant (alphas-R201C) or to agonists for receptors that activate Gq or Gi. This alphas triple mutant and cognate Galpha mutants should provide specific tools for dissection of G protein-mediated signals in cultured cells and transgenic animals.

Diagnostic testing during pregnancy: a descriptive analysis of utilisation data.

To describe patterns of diagnostic testing during the antenatal period and to assess the potential benefit of using Medicare claims data in monitoring testing practice, we examined the matched claims data (with identifying details removed) on approximately 10,000 women having a confinement for which a Medicare benefit was claimed between 1 July and 30 September 1990. The results showed that almost all the women included in the study sample had an ultrasound and blood group and antibody examination. A smaller proportion had serological tests for syphilis (77 per cent), rubella (51 per cent) and hepatitis B carriage (73 per cent). Two-thirds had urine microscopy and culture, and under half (40 per cent) had serum alpha-fetoprotein estimation. Few (18 per cent) had a claim processed for microscopy and culture of a genital swab and fewer than 8 per cent claimed for any other pathology tests. There were differences in the proportions having tests, depending on whether the clinician managing the confinement was a specialist obstetrician or a general practitioner, and depending on geographic area and age group. While the data do not represent all women having a confinement in New South Wales, the selective use of antenatal diagnostic tests found in this study is of considerable public health importance and analysis of claims data can provide useful information for health professionals.