The aim of this work was to investigate the feasibility of cross-linker free polyelectrolyte 1 complex formation at the nanoscale between carrageenan (CAR) and protamine (PROT). 2 The properties of CAR/PROT nanoparticles (NPs) were dependent on the carrageenan type: 3 kappa (KC), iota (IC) and lambda (LC), concentration of components, addition of divalent 4 cations, weight mixing ratio (WMR) of constituents and mode of component addition. In the 5 case of 0.1% w/v solutions, IC-based NPs had the smallest particle sizes (100-150 nm) and 6 low polydispersity indices (0.1-0.4). A decrease in the solution concentration from 0.1% to 7 0.05% w/v enabled the formation of KC/PROT NPs. All carrageenans exhibited the ability to 8 form NPs with surface charge ranging from -190 to 40 mV. The inclusion of divalent cations 9 caused an increase in the particle size and zeta potential. Infrared analysis confirmed the 10 presence of a complex between CAR and PROT and showed that IC chains undergo 11 structural changes when forming NPs. Colloidal stability of NPs was related to the initial 12 surface charge of particles and was time-and pH-dependent. IC was found to be the most 13 suitable type of CAR when forming nanoplexes with PROT. 14 15
Quantitative transplantation assays of a syngeneic murine adenocarcinoma have been used to investigate the effects of stress hormones and tumor take probability. Cortisol, injected intraperitoneally one hour before and 3 hours after tumor cells, caused a dose dependent reduction of TD50 (number of tumor cells required for 50% takes) by factors of from 4 at a total dose 4 microng/g to 68 at 400 microng/g. ACTH, given at 0.2 I.U. daily for 9 days spanning the time of tumor cell injection, reduced the TD50 2.5-fold, indicating that the peak gluco-corticoid level achieved, rather than its duration, was of greater significance. Adrenaline, while much less effective than cortisol, produced an 8-fold reduction in TD50 at its maximum tolerable dose. The effect of cortisol simulated that of whole body irradiation (WBI), and while both these agents depress immune reactivity, evidence is presented to suggest that immunological mechanisms are not responsible for their effect. WBI constitutes a systemic stress, and the demonstration that surgical trauma (laparotomy) could also reduce the TD50 for this tumor suggested that both might act via endogenous glucocorticoids. However, the failure of prior total adrenalectomy of mice to abrogate the effect of either WBI or laparotomy indicated that stress hormones were not essential intermediaries. It is concluded that both stress hormones, especially glucocorticoids, and stressful procedures acting independently of stress hormones, can facilitate tumor transplantation.
These findings, correlated with measurements of cyclic AMP in the lungs of normal and stressed rats, suggest that changes in the resistance of the host to tumour growth involve changes in cyclic nucleotide metabolism in the target tissues (tumour bed); possible mechanisms of action of cyclic nucleotides in this respect are discussed.
Summary.-Acute inflammatory reactions were induced in rats by the intravenous injection of cellulose sulphate (CS) or The mechanisms which may be responsible for the nonspecific growth promoting effects of inflammatory reactions induced by various types of tissue injury on tumour induction and growth are discussed.
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