Various murine tumour sublines which differed considerably in their in vivo metastatic capacity were tested in vitro for their ability to invade normal tissue. For this purpose we developed two quantitative tests, a Boyden chamber endothelial cell invasion assay and a brain tissue microsphere invasion assay. The invasion of [75Se]methionine-prelabelled tumour cells into the normal tissues was followed by measuring the percentage of tumour-associated label in the brain microspheres or the endothelial monolayers after 12-48 h of co-cultivation. Clear and comparable differences existed in both assays between the amount of radiolabel found in the normal tissues after a co-cultivation with the different tumour lines. In three of the four tumour lines invasiveness correlated with metastatic capacity. The fourth line, a plastic adherent variant, was highly invasive but low metastatic. The ability of tumour cells to invade normal tissue, therefore, while necessary for the generation of metastases, is not in itself sufficient. Since both assays are independent of time-consuming histological sectioning and staining and allow a quantitative determination of invasive capacity of tumour cells grown as single cell suspensions they appear well suited for experimental manipulation and for screening of anti-invasive drugs.

Animals↗

PubMedDate not supplied

Penetration of ampicillin and sulbactam into human epididymis and testis.

Urologic refertilization microsurgery such as vaso-vasostomy or vaso-epididymostomy benefits from perioperative antibiotic prophylaxis. The ability of ampicillin and sulbactam to penetrate sufficiently into mixed epididymis or testis tissue was investigated in nine patients (bodyweights ranged from 58 kg to 92 kg, mean 77.3 kg) undergoing orchiectomy for testicular cancer or advanced prostatic cancer. Each patient received a single infusion of 3 g ampicillin/sulbactam (ratio 2:1) preoperatively for antibiotic prophylaxis. The concentrations of both components were determined in serum and in epididymis/testis tissue samples taken 30 min to 65 min after infusion. Ampicillin was determined by bioassay and sulbactam was determined by gas chromatography/ mass spectrometry. Mean tissue concentrations of ampicillin were 38.5 +/- 15.9 mg/kg. Mean tissue concentrations of sulbactam at the same time were 19.8 +/- 5.2 mg/kg. Comparison of the tissue/serum ratios for both agents showed no significant difference. These values indicate that both compounds achieve high concentrations in the scrotal organs. The concentrations exceed the MIC (minimal inhibitory concentration) values of important bacterial pathogens such as Staphylococcus aureus involved in postoperative wound infections. The combination of ampicillin and sulbactam may be effective for perioperative prophylaxis in reconstructive scrotal urologic surgery.

Adult↗

PubMedDate not supplied

Effect of perioperative antioxidant therapy on suboptimal islet transplantation in rats.

Islet transplantation success is limited by the posttransplant inflammatory response, and we are investigating the ability of antioxidants to neutralize this islet damage. We have shown that pyruvate can enhance the engraftment and functionality of a suboptimal islet mass in rats. The present study further investigated the effects of pyruvate, as well as the antioxidants vitamin E and vitamin C. In study A, 350 syngeneic islets were transplanted into the liver of chemically diabetic rats. Antioxidant treatment, or vehicle, was administered during the perioperative period and an intraperitoneal glucose tolerance test (IPGTT) was performed 2 months posttransplant. In study B, 500 syngeneic islets were transplanted under the kidney capsule of chemically diabetic rats. Antioxidant treatment was administered during the perioperative period. Islet-bearing kidney grafts were harvested 24, 48, and 96 hours posttransplant for histological study. Results revealed that pyruvate was the only significantly effective treatment in enhancing the engraftment and functionality of a suboptimal islet mass. Respectively, 56% and 80% of pyruvate-treated rats became normoglycemic after islet transplantation in study A and study B and had a normal insulin response to IPGTT. Histology results from the islet-bearing kidneys were inconclusive as to whether or not pyruvate has an antiapoptotic effect. We conclude that pyruvate, but not vitamin E or vitamin C, aids in the engraftment and functionality of a suboptimal islet mass with as much effectiveness as a full mass in this study. Further investigation into the mechanism of pyruvate protection is still warranted.

Animals↗