Temporal relationship between progestin and luteinizing hormone concentrations in pseudopregnant rats treated with prostaglandin-F2 alpha

The temporal changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and luteinizing hormone (LH) concentrations in pseudopregnant (PSP) rats after treatment with a single subcutaneous Silastic-PVP tube containing 600 micrograms PGF2 alpha were correlated. Progesterone levels fell and LH levels rose significantly 2h after initiation of treatment, while 20 alpha-DHP levels were found to increase significantly 12h after treatment. Since the changes in delta 4P and LH concentrations occurred concurrently, it seems that the increase in LH levels could have been due to a direct effect of PGF2 alpha on the ovary causing a reduction in delta 4P and thus a negative feedback effect on LH release. Alternatively, PGF2 alpha might exert a direct effect on LH secretion at the hypothalamic-pituitary level.     

Role of simple anionic ligands in deep decontamination of liquid radioactive waste

The influence of the NO₉^-, SO₄^2–, HCO₃^–, and Ac^– anions on the efficiency of the sorption of bivalent metals by sulfonic cation exchangers was studied. The main method was elution of the Mg²⁺, Ca²⁺, and Co²⁺ cations with individual solutions of the corresponding sodium salts and their mixed solutions with sodium nitrate from the Dowex-50 ion-exchange resin at fixed temperatures. The exchange efficiency is influenced both by neutral complexes of the metal cations mainly with inorganic acid ligands and by the single-charged species. The latter species affect the efficiency of the ion-exchange waste reprocessing considerably more strongly. An increase in the temperature of the solution being treated leads to a significant shift of the peak position toward larger retention volumes, which indicates that it is appropriate to perform the water treatment on sulfonic cation exchangers at elevated temperatures. The first formation constant of the single-charged cobalt dihydrogen phosphate complex species at an ionic strength of 0 M was obtained: logK₁(CoH₂PO₄⁺) = 1.36.     

Proadrenomedullin N-terminal 20 peptide: minimal active region to regulate nicotinic receptors

Proadrenomedullin N-terminal 20 peptide (PAMP-[1-20]; ARLDVASEFRKKWNKWALSR-amide) is a potent hypotensive and catecholamine release-inhibitory peptide released from chromaffin cells. We studied the mechanism of PAMP action and how its function is linked to structure. We tested human PAMP-[1-20] on catecholamine secretion in PC12 pheochromocytoma cells and found it to be a potent, dose-dependent (IC50 approximately 350 nmol/L) secretory inhibitor. Inhibition was specific for nicotinic cholinergic stimulation since PAMP-[1-20] failed to inhibit release by agents that bypass the nicotinic receptor. Nicotinic cationic (22Na+,45Ca2+) signal transduction was disrupted by this peptide, and potencies for inhibition of 22Na+ uptake and catecholamine secretion were comparable. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. N- and C-terminal PAMP truncation peptides indicated a role for the C-terminal amide and refined the minimal active region to the C-terminal 8 amino acids (WNKWALSR-amide), a region likely to be alpha-helical. PAMP also blocked (EC50 approximately 270 nmol/L) nicotinic cholinergic agonist desensitization of catecholamine release, as well as desensitization of nicotinic signal transduction (22Na+ uptake). Thus, PAMP may exert both inhibitory and facilitatory effects on nicotinic signaling, depending on the prior state of nicotinic stimulation. PAMP may therefore contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release.     

Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts

Genital human papillomavirus infection is one of the most common sexually transmitted diseases. Imiquimod is a new agent, an immune-response modifier, that has been demonstrated to have potent in vivo antiviral and antitumor effects in animal models. The present prospective, multicenter, double-blind, randomized, vehicle-controlled trial evaluated the efficacy and safety of daily patient-applied imiquimod for up to 16 weeks for the treatment of external genital warts. Wart recurrence was investigated during a 12-week treatment-free follow-up period. In the intent-to-treat analysis, baseline warts cleared from 49 of 94 (52%) patients treated with 5% imiquimod cream, 13 of 90 (14%) patients treated with 1% imiquimod cream, and 3 of 95 (4%) vehicle-treated patients; the differences between the groups treated with vehicle and imiquimod were significant (P < 0.0001). For subjects who completed the follow-up period, recurrence rates after a complete response were 19% (9 of 48 patients) in the 5% imiquimod cream group, 17% (2 of 12) in the 1% imiquimod cream group, and 0% (0 of 3) in the vehicle-treated group. There were no systemic reactions, although local skin reactions (generally of mild or moderate severity) were common, particularly in the 5% imiquimod cream group. Local reactions caused two patients to discontinue treatment. The most frequently reported local skin reactions were erythema, excoriation or flaking, and erosion. Patient-applied 5% imiquimod cream is effective for the treatment of external genital warts and has a favorable safety profile.     

Evidence for inhibition of monoamine oxidase in vivo in rat brain by 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline

7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (DCTQ) (50 mg/kg i.p.) antagonized the inactivation of MAO by pargyline as measured by direct enzyme assays in brain homogenates and by accumulation of hypothalamic catecholamines. These findings lend credence to the earlier interpretation that changes in brain concentrations of biogenic amines and their metabolites in DCTQ-treated rats were due at least in part to MAO inhibition.