Tetsuo Hayashi

CHANGES IN MUSCARINIC CHOLINERGIC, PCP, GABAA, D1, AND 5-HT2A RECEPTOR BINDING, BUT NOT IN BENZODIAZEPINE RECEPTOR BINDING IN THE BRAINS OF AGED RATS

We used in vitro quantitative autoradiography to investigate changes in neurotransmitter receptor binding, including muscarinic cholinergic, PCP, GABAA, benzodiazepine, D1 and 5-HT2A receptor, in the brains of aged rats, compared with such binding in young rats. Scatchard analysis revealed that the maximal number of binding sites for [3H]quinuclidinyl benzilate (QNB) in the caudate/putamen and accumbens was significantly decreased in aged rats compared with young rats, while its affinity remained unchanged. The specific binding of [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) for the ion channels coupled with N-methyl-D-aspartate receptors in the caudate/putamen and hippocampus was significantly decreased in aged rats compared with young rats. The [3H]muscimol binding in aged rats was decreased in all brain regions examined compared with that in young rats, whereas [3H]flunitrazepam binding was not changed in any brain regions. The [3H]SCH23390 binding for dopamine D1 receptors was significantly increased in the parietal cortex, but decreased in the caudate/putamen and accumbens of aged rats compared with that in young rats. The [3H]ketanserin binding for 5-HT2A receptors in the cortex and accumbens was significantly decreased in aged rats compared with young rats. These results suggest that uneven changes in receptors for various neurotransmitters throughout the brain may be responsible for the decline of brain function in aged rats.

Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier

We investigated the tissue distribution of vancomycin (VCM) incorporated in fibrin glue (FG) in a rat model. One VCM-loaded FG Dacron graft (VCM-FG, VCM 0.6 mg/ graft) was implanted in the subcutaneous tissue of the anterior abdominal wall of each rat. VCM was injected intravenously at an equal dose (0.6 mg/rat) after implantation of one control graft (without VCM-FG). After the implantation and the iv injection of an equal dose of VCM (0.6 mg/rat), the tissue distribution of VCM for up to 24 h was determined through analysis of the implanted VCM-FG grafts, which released VCM over a 24 h period. The area under the VCM concentration-time curve (AUC) of the tissue was 89.58 micrograms.h/g after the implantation of the VCM-FG graft, and 7.40 micrograms.h/g after the iv injection of VCM, respectively. The targeting index of the tissue, defined as the ratio of AUC after the implantation of the VCM-FG graft to that after VCM iv injection, was 12.11. None of the six VCM-FG Dacron grafts after implantation became infected following inoculation with S. aureus ATCC 25923 (0.1 mL 10(8) CFU/mL). These results suggest that this VCM-FG Dacron graft delivery may be useful in preventing local infection by enhancing the delivery of VCM to the local areas of the implanted site in rats.

The development of levofloxacin-bonded albumin Dacron graft.

The highly porous Dacron graft fabricated from polyester filaments is generally considered to be one of the most suitable synthetic vascular prostheses in arterial reconstructive surgery. To prevent blood leakage through the pores during an operation, several sealing materials such as albumin (ALB), collagen and gelatin have been employed. As vascular graft infection is a disastrous complication on vascular surgery, great effort must be taken to avoid it. To reduce the systemic effect while maintaining an increase in local resistance to graft infection, it seems reasonable that an antibiotic-loaded graft prolongs the release of antibiotics from the graft at the operated site. Common skin microorganisms, such as Staphylococcus aureus and Staphylococcus epidermidis, have been associated with graft-related infection. Levofloxacin(LVFX) was used as a model drug since it shows a broad protective spectrum against Gram-positive and Gram-negative bacteria, particularly staphylococci. To control the release rate of LVFX, ALB was bonded to the Dacron graft. In vitro and in vivo studies demonstrated that the release rate of LVFX decreased in the presence of ALB. One LVFX-ALB disk (diameter : 1.2 cm) was implanted in the skin pocket made in a rat, and inoculated with Staphylococcus aureus or Staphylococcus epidermidis (0.1 ml of 108 CFU/ml). While all control grafts were infected at the time of removal, all LVFX-ALB Dacron grafts resisted infection, thus demonstrating their effectiveness. These studies suggest that LVFX controlled-releasing Dacron delivery system can decrease graft infection at the operated site.