Forty rats were given a choice between 0.1% sodium saccharin and water. Based on their intakes, three groups of six rats representing high, intermediate, and low saccharin preferences were selected. These rats were reduced to 80% of their free-feeding weights. Ethanol was established as a reinforcer by use of a food-induced drinking procedure. Between-group differences were assessed based on response rates across acquisition sessions (0, 1, 2, 4, 5.7, 8%, w/v), a fixed-ratio series (1, 2, 4, 8, 1), and a concentration series (8, 5.7, 4, 2, 2, 4, 5.7, 8, 11.3, 16, 22.6, 32, 8%, w/v). In 29 of 32 conditions which were analyzed, the mean number of responses for ethanol was higher for the high saccharin preference group than for the low, and in 25 of 32 conditions, the intermediate group fell between the high and the low. However, there was considerable variability within groups across all conditions, such that mean between-group differences were not significant. This variability may be reduced by considering diet preferences in addition to saccharin preference. Nonetheless, these results offer limited support for the increasing body of evidence indicating a relationship between the factors mediating ethanol self-administration and those involving ingestion of palatable foods and fluids.

Animals↗

PubMedDate not supplied

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.

Acoustic Stimulation↗

PubMedDate not supplied

Exacerbation of acetazolamide teratogenesis by amiloride and its analogs active against Na+/H+ exchangers and Na+ channels.

Postaxial forelimb ectrodactyly induced by acetazolamide given on Day 9.5 of murine gestation is thought to be mediated by reduced intracellular pH (pHi) within the limb bud. Coadministration of amiloride increases the incidence and severity of acetazolamide-induced forelimb malformations and further reduces limb bud pHi. These findings were hypothesized to be attributable to the action of amiloride as an inhibitor of Na+/H+ exchangers (NHEs), plasma membrane-localized proteins involved in the maintenance of cellular pH homeostasis. Here, we explored this hypothesis further by coadministering with acetazolamide, amiloride, or analogs known to preferentially inhibit NHEs 5-(N-methyl-N-isobutyl)-amiloride, 5-(N, N-hexamethylene)-amiloride, 5-(N, N-dimethyl)-amiloride, and 5-(N-ethyl-N-isopropyl)-amiloride or amiloride-sensitive Na+ channels (benzamil). The coadministration of either amiloride, benzamil, 5-(N, N-dimethyl)-amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, or 5-(N-methyl-N-isobutyl)-amiloride all dose responsively increased the frequency and severity of forelimb malformations compared to acetazolamide alone. None of the analogs given alone induced forelimb ectrodactyly. The data are consistent with the original hypothesis that the exacerbation of acetazolamide teratogenesis is due to NHE inhibition. Surprisingly, benzamil was the most potent potentiator of acetazolamide teratogenesis. This result strongly suggests that amiloride-sensitive Na+ channels are also present within the murine embryo and are likely to play a role in pHi homeostasis.

Abnormalities, Drug-Induced↗

PubMedDate not supplied

Genetic modification of cultured skin substitutes by transduction of human keratinocytes and fibroblasts with platelet-derived growth factor-A.

Gene therapy promises the potential for improved treatment of cutaneous wounds. This study evaluated whether genetically modified cultured skin substitutes can act as vehicles for gene therapy in an athymic mouse model of wound healing. Human keratinocytes and fibroblasts were genetically engineered by retroviral transduction to overexpress human platelet-derived growth factor-A chain. Three types of skin substitutes were prepared from collagen-glycosaminoglycan substrates populated with fibroblasts and keratinocytes: HF-/HK-, containing both unmodified fibroblasts and keratinocytes; HF-/HK+, containing unmodified fibroblasts and modified keratinocytes; and HF+/HK-, containing modified fibroblasts and unmodified keratinocytes. Skin substitutes were cultured for two weeks before grafting to full-thickness wounds on athymic mice. The modified skin substitutes secreted significantly elevated levels of platelet-derived growth factor throughout the culture period. Expression of retroviral platelet-derived growth factor-A mRNA was maintained after grafting to mice, and was detected in all HF-/HK+ grafts and one HF+/HK- graft at two weeks after surgery. Although no differences were seen between control and modified grafts, the results suggest that genetically modified cultured skin substitutes can be a feasible mechanism for cutaneous gene therapy. The cultured skin model used for these studies has advantages over other skin analogs containing only epidermal cells; because it contains both fibroblasts and keratinocytes, it therefore offers greater opportunities for genetic modification and potential modulation of wound healing.

Animals↗

PubMedDate not supplied

The reliability of radiologists' quality assessment of MR pelvic scans.

The purpose of this study was to test the reliability of radiologists' subjective assessment of the quality of MR scans of the pelvis. A four-grade ordinal subjective scale, based on the degree of artifact and contrast between pelvic organs, was developed in a pilot study by two MR radiologists. Forty pelvic scans were graded "blindly" in random order by the same two "practiced" MR radiologists, and an objective measurement of scan artifact was obtained for each scan. Twenty-eight pelvic scans were also graded by two "unpracticed" radiologists not involved in the development of the scale. For the practiced radiologists, the interobserver percentage agreement was 80% (weighted kappa of 0.78) and the intraobserver percentage agreement was 75% (weighted kappa of 0.73). For the unpracticed radiologists the percentage agreement was 61% and the weighted kappa was 0.55. The correlation between the subjective and objective measurement was only 0.27. In conclusion, the objective measurement of scan artifact showed poor correlation with the radiologists' subjective assessment of scan quality. The subjective assessment demonstrated satisfactory reliability and, therefore, could be considered as an additional outcome measurement for scan quality in clinical trials or as a relevant measure of quality assurance.

Artifacts↗

PubMedDate not supplied

Murine embryonal carcinoma cells express class I MHC-like antigens.

Previous work has concluded that murine embryonal carcinoma (EC) cells, the oncogenic stem cells of teratocarcinomas, do not express class-I, H-2K or D/L gene encoded products. Experiments using cell-mediated lysis, serological and molecular biological approaches show that EC cells do express some major histocompatibility complex (MHC) class I or class I-like molecules.

Animals↗

PubMedDate not supplied

Resistance of Haemophilus influenzae type b to ampicillin mediated by ROB-1 beta-lactamase.

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Ampicillin Resistance↗