Toxicity of vancomycin on corneal endothelium in rabbits

PURPOSE: To evaluate the toxic effect of vancomycin on the corneal endothelium related to concentrations of vancomycin. METHODS: The toxic effect is assessed with a weighing method that gives a measure of endothelial function. Thirty-three rabbit corneas were divided into four groups. Three groups of seven corneas each were exposed to concentrations of 1.0 mg/ml, 3.0 mg/ml and 5.0 mg/ml vancomycin, respectively. The fourth group of twelve corneas served as a control group. RESULTS: The corneas exposed to 1.0 mg/ml vancomycin showed no significant weight increase, while the corneas exposed to 3.0 mg/ml and 5.0 mg/ml showed a significant weight increase as compared to the control corneas. The weight increase was significantly larger in the group of corneas exposed to 5.0 mg/ml as compared to 3.0 mg/ml. CONCLUSIONS: In the interval of tested concentrations there is a dose response relationship between vancomycin concentrations and endothelial toxicity. This experiment shows that vancomycin in the concentration of 1.0 mg/ml is non-toxic to the endothelium, while 3.0 mg/ml and 5.0 mg/ml increasingly impair endothelial function.     

Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells

One of the key limiting factors in the treatment of advanced stage human epithelial malignancies is the lack of new, selective molecular targets for antineoplastic therapy. A substantial subset of human breast, ovarian, endometrial, colorectal, and prostatic cancers express elevated levels of fatty acid synthase, the major enzyme required for endogenous fatty acid biosynthesis, and carcinoma lines are growth inhibited by cerulenin, a noncompetitive inhibitor of fatty acid synthase. We have shown previously that the difference in fatty acid biosynthesis between cancer and normal cells is an exploitable target for metabolic inhibitors in the in vitro setting and in vivo in a human ovarian carcinoma xenograft in nude mice. Here, we report that cerulenin treatment of human breast cancer cells inhibits fatty acid synthesis within 6 h after exposure, that loss of clonogenic capacity occurs within the same interval, and that DNA fragmentation and morphological changes characteristic of apoptosis ensue.     

Lipolytic response of rat adipocytes to epinephrine: effect of age and cell size

Isolated fat cells from 3, 12 and 28 month old rats were compared intheir lipolytic response to various doses of L-epinephrine. With increasing age a progressive decline in the response occurred when comparing rats with unmatched mean adipocyte diameters. However, this apparently age-related decrease was no longer evident if the diameters were matched since the 28 month old animals had a lipolytic response less than the 3 month old rats but greater than the 12 month olds. Body weight differences between these ages may account for these observations. The biphasic dose response curve to hormone stimulation in the 3 and 12 month olds was monophasic at 28 months. Within each age group the initial lag in glycerol release decreased and the lipolytic response increased as mean cell size increased. The rate of hormone stimulated glycerol release varied inversely with incubations of 3,700 to 25,000 cells/ml and aging had no effect on this parameter. DNA content per fat cell remained constant with age.     

The evolutionary relationship among Caucasian MS patients and controls

Previous observations suggest that the mitochondrial (mt)DNA may confer susceptibility to multiple sclerosis (MS). However, the proportion of affected individuals and the range of contributing mtDNA abnormalities are unknown. To help clarify this question, we analyzed the first hypervariable D-loop sequences of the mtDNA in a group of randomly selected Caucasian MS patients, in MS patients with prominent optic neuritis (PON) and in controls. Phylogenetic analysis of these D-loop sequences revealed that individuals in both groups of patients are generally scattered in the Caucasian phylogeny. However, a small cluster of unrelated MS patients identified by this analysis suggests that a maternal lineage with MS relevant mtDNA sequences may exist, and merits a more comprehensive study.     

Effect of electrical stimulation post mortem of bovine muscle on the binding of glycolytic enzymes. Functional and structural implications

The extent of binding of glycolytic enzymes to the particulate fraction of homogenates was measured in bovine psoas muscle before and after electrical stimulation. In association with an accelerated glycolytic rate on stimulation, there was a significant increase in the binding of certain glycolytic enzymes, the most notable of which were phosphofructokinase, aldolase, glyceraldehyde 3-phosphate dehydrogenase and pyruvate kinase. From the known association of glycolytic enzymes with the I-band of muscle it is proposed that electrical stimulation of anaerobic muscle increases enzyme binding to actin filaments. Calculations of the extent of enzyme binding suggest that significant amounts of enzyme protein, particularly aldolase and glyceraldehyde 3-phosphate dehydrogenase, are associated with the actin filaments. The results also imply that kinetic parameters derived from considerations of the enzyme activity in the soluble state may not have direct application to the situation in the muscle fibre, particularly during accelerated glycolysis.