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This paper describes the voltammetric behavior of primaquine as a previous support to the further understanding of the delivery and action mechanisms of its respective synthesized prodrugs. There are few papers describing the drug behavior and most of the time no correlation between oxidation process and pH is done. Our results showed that primaquine oxidation is a one-step reaction involving two electrons with the charge transfer process being strongly pH-dependent in acid medium and pH-independent in a weak basic medium, with the neutral form being easily oxidized. This leads to the conclusion that quinoline nitrogen ring neutralization is a determinant step to the formation of the oxidized primaquine form. The existence of a relationship between the primaquine dissociation equilibrium and its electrooxidation process is shown. This work points the importance of voltammetric methodology as a tool for further studies on quantitative relationship studies between chemical structure and biological activity (QSAR) for electroactive drugs.

The newly developed DNA-biosensor is a very promising tool for the investigation and study of the action of drugs specifically designed to interact with DNA. In this work the electrochemical reduction of nitroimidazole drugs was studied in the presence of DNA immobilized onto the surface of a glassy carbon electrode. This enabled preconcentration of the drug onto the electrode surface, which was then electrochemically reduced to the corresponding hydroxylamine which followed by reoxidation give the nitroso compound and subsequently an azoxycompound. Moreover, as the target of the nitroimidazole action was the DNA, the damage caused to DNA on the electrode surface by a reduction product of this drug could be detected in situ.

Monoamines (MA) such as dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) are now generally regarded as widely distributed and essential endogenous mediators contributing to the integration of reproductive physiology. MA measured in the hypothalamus tissue of male and female rats aged 1 to 90 days showed its own characteristic development pattern. Significant differences were observed at 5, 15, and 90 days of age in NE mean levels and at all ages except for 3 days of age in 5-HT mean levels. In contrast, no sex differences were seen in DA mean levels.

Publisher Summary The electrochemical reduction of nitroimidazoles follows a complex mechanism and in theory the nitro group is able to receive up to six electrons to form the corresponding amine. Under anaerobic and low oxygen pressure conditions metronidazole follows a reduction mechanism similar to that of nitrobenzene. Electrochemical reduction of nitroimidazole derivatives shows two reduction waves in aqueous acid media, the first involving four electrons and corresponding to the reduction of the nitro group to form the intermediate hydroxylamine (-NHOH) and the second involving two electrons and corresponding to the reduction of the hydroxylamine to amine (-NH2). Using three different electrode materials (bare glassy carbon electrode, mercury thin film electrode, and DNA biosensor), it has been verified that hydroxylamine formation involves four electrons and is pH dependent. This chapter shows that the DNA biosensor developed provides a new perspective to the research and study of the mechanism of action of nitroimidazoles with DNA.

Proceedings de 2 Conferencias simultâneas: "International Conference on Natural Antioxidants and Lipid Peroxidation in Atherosclerosis and Cancer (ALPAC)" e "International Conference on Quality and Safety Aspects and Nutrition in Europe'95 (QSFNE), 22-25 Agosto 1995, Helsinquia, Finlândia.

Meal-fed (3 h) rats had a decreased food intake, body weight and carcass fat compared with rats fed ad libitum. On refeeding a chow meal containing [1-14C]triolein, the production of 14CO2 was lower (45%) and the accumulation of carcass [14C]lipid higher (37%) in the meal-fed rats. There was higher lipoprotein lipase activity and greater accumulation of [14C]lipid in the epididymal and subcutaneous adipose-tissue depots of the meal-fed rats. In contrast, heparin-releasable lipoprotein lipase was not increased in perfused hearts of meal-fed rats on refeeding. Return of meal-fed rats to feeding ad libitum reversed these changes before the restoration of body weight or carcass fat. Evidence is presented that decreased dietary intake rather than meal pattern is an important determinant of the alterations in adipose lipid metabolism in the meal-fed rat in response to a meal.

The effect of chlormadinone acetate (CA) on mammary growth and lactation was studied in the New Zealand white rabbit. Mammary development studies were performed in 5-month males castrated prepuberally. All rabbits were treated for 28 days. Ten μg estrone (E) produced good ductal development without alveolar growth (mean mammary area = 376 mm2). CA alone did not stimulate mammary growth. Administration of 0.5 mg CA plus 10 Mg E produced optimal ductal and alveolar development (mean mammary area = 765 mm2). By contrast, a larger dose of CA (2.5 mg) combined with 10 μg E resulted in a much smaller mammary response (mean mammary area = 284 mm2). Administration of 100 ng or 2.5 mg CA from day 10 to 25 of lactation neither inhibited nor facilitated milk production in lactating rabbits. It is concluded that prolonged administration of CA when combined with estrogen stimulates mammary growth at moderate doses (0.5 mg) and inhibits it at large doses (2.5 mg). CA has no clear effect on milk production and/or remova...

The synthesis, elemental and spectrometric analysis of isoniazid conjugates with polyethylene glycol) (PEG) were obtained. In the first part of the work, acyl isoniazid, hydroxymethyl isoniazid, and modified poly(ethylene glycol) were synthesized. These compounds were characterized by FTIR, by elemental analysis, and by NMR. To obtain antituberculosis macromolecular prodrugs with sustained delivery, the modified PEG were used as carriers by linking, via end group, either isoniazid or its hydroxymethyl derivative.