Determination of specific rate constants of specific oligomers during polyester hydrolysis.

Aliphatic polyesters have great utility as temporary prosthetics and surgical aids, and in drug delivery systems. Knowledge of the mechanism and pathways of hydrolysis can form a basis for the design and selection of a controlled-release system. Because of the importance of hydrolysis to the properties of such a system, a technique was developed to accurately determine the specific rate constants and relevant kinetic parameters for the specific oligomers from the reaction mixture of polyesters undergoing hydrolysis. A detailed kinetic analysis of the acid hydrolysis of well-characterized oligomers of polyesters is presented. Several oligomers of poly(butylene tartrate)s were synthesized and their kinetic behavior was studied under acidic conditions. The oligomers and their degradation products were monitored by HPLC and identified by fast-atom bombardment mass spectrometry. From the rates of hydrolysis measured from pH 1 to 3.0 and at temperature of 75 degrees C, it becomes evident that the degradation of the oligomers obeys pseudo-first-order kinetics. The rate of hydrolysis among the homologous series of oligomers increases as the molecular weight increases. The hydrolysis was catalyzed by hydrogen ion; the catalytic rate constant increased predictably with the number of ester linkages present in the molecule. The reaction is first order with respect to the catalyst concentration and the number of ester linkages. Good agreement was obtained with a model in which the individual rate of bond cleavage depends only on the statistical factor. The technique described in this paper is unique for the determination of polyester hydrolysis pathways and isolation of any structural effects on the rates of hydrolysis.     

Influence of Age on August Levels of Pineal Immunoreactive Arginine Vasotocin in Rats

The present study was undertaken to evaluate carefully the influence of age on physiological levels of arginine vasotocin-like peptide in rat pineal glands. Glands were collected from male and female rats aged 13, 33, 53, and 73 days on August 4, 12, and 19, 1984. Individual extracts were assayed for arginine vasotocin (AVT) by radioimmunoassay. The results confirm our previous observation that rat pineal AVT immunoactivity (iAVT) increases significantly during August each year; and in this study, each group of rats reached the same peak level of iAVT (700-750 pg/gland) regardless of age or gender. Thus we do not confirm a previously reported decrease in AVT activity with age. In our studies thus far, season of the year is the physiological variable with the most significant influence on pineal AVT activity levels.     

Monoclonal antibody against human squamous-cell-carcinoma-associated antigen

Mouse monoclonal antibody (MAb) 3F8E3 (IgG3k) was developed against the head and neck cancer cell line LICR-LON-HN2. Subjected to indirect immunofluorescence, the MAb reacted exclusively with SCC cell lines and showed no reactivity with normal or transformed mouse and human non-SCC cell lines and hematopoietic cell lines. The radiolabelled MAb showed an affinity constant of 1.8 x 10(8) M-1 with HN2 cells and identified 2.07 x 10(4) sites/cell by Scatchard analysis. It identified 2 peptides from membrane extracts of HN2 cells by Western blotting. Avidin-biotin-complexed immunoperoxidase staining on cryostat sections of tumors from various tissues revealed that 3F8E3 reacted mainly with the membrane antigens of well differentiated SCC cells of oral cavity, larynx, esophagus, lung, uterine cervix, metastatic nodes of patients with oral cancer, and dysplastic cells in oral leukoplakia. The MAb did not react with poorly differentiated cells of Ca esophagus, adenocarcinoma of breast, stomach and colon, renal-cell carcinoma and soft-tissue sarcoma.     

Effects of Melatonin on the Growth of MtT/F4 Anterior Pituitary Tumor

In the present report, we have examined the anti-tumor potential of melatonin by utilizing the MtT/F4 anterior pituitary transplantable tumor. The tumor was obtained (Bogden Labs.) in cryopreserved condition and transplanted (in the left rear thigh), and allowed to grow for 8 weeks in adult Fischer 344 rats, maintained under uniform laboratory conditions of light (LD 14:10; lights on at 06:00 h), and temperature (21-23 degrees C). Subsequently, the tumor was dissected out, minced, and washed in Medium 199, and similarly transplanted into groups of adult Fischer 344 rats representing the final tumor recipient groups utilized for the evaluation of melatonin's anti-tumor effects. Melatonin (50 micrograms/0.1 ml/animal) was administered subcutaneously either early in the morning (at 08:00 h), or late in the afternoon (at 18:00 h), for 6 weeks, beginning the day after tumor transplantation. The matched controls were given equal volumes of physiological saline. A careful record of the appearance and growth of the tumor was maintained by examining the animals every morning. At the termination of the experimental schedule, the tumor masses were carefully dissected out, rinsed with normal saline, dried, and weighted on a sensitive Mettler balance. Our results showed that melatonin significantly increased the latency period of the tumor, irrespective of the time of drug administration. Analysis of the final tumor weights showed that afternoon, but not morning, injections of melatonin significantly reduced both the absolute (P less than 0.025) and relative (P less than 0.05) tumor weights in comparison to the saline-injected matched control. These results suggest that a) melatonin exhibits its anti-tumor efficacy on MtT/F4 tumor, by delaying the appearance of the tumor, and b) the anti-tumor potential of melatonin is greatly dependent on the time of administration of the drug within the daily light-dark cycle.