ABSTRACT
The study was undertaken to provide evidence that the salivary concentration of free testosterone (FT) well correlates with the serum level of unbound testosterone in men. Recent articles demonstrate that the results obtained by the use of especially automatic systems are incorrect. Anew luminescence enzyme immunoassay has been now put into practice. Its high analytical (6.2 pmol/l) and functional (17.3 pmol/l) sensitivities allow the quantification of minor salivary concentrations. In healthy males, the morning salivary concentration was 369 pl/lmo (median) with a range of 263-544 pmol/l, which is statistically higher than that in males with androgen deficiency (215 pl/lmol/I (median) with a range of 51-249 pmol/l. Once-weekly remeasurement of salivary FT during 5 weeks showed the high stability of results over time with a variation coefficient of 9% (range 5-23%). The study indicated that FT in the morning salivary sample well correlates with the calculated FR in the blood of both healthy males (R = 0.754; p = 0.001) and patients with androgen deficiency (R = 0.889; p = 0.0001).
ABSTRACT
Of all steroidal hormones, dehydroepiandrosterone (DHEA) and its sulphate form, DHEAS, are synthesized by the adrenal glands in the biggest quantities. In this review the authors consider the ways of the synthesis of the neurosteroids, possible mechanisms of the regulation of these processes, and their dynamics under stressful conditions. The paper presents analysis of experimental and clinical data on the role of DHEAS in the manifestation of different cerebral functions. The authors pay special attention to the results of substitutive therapy with DHEA(S) in patients with such CNS functional disorders, as Alzheimer's disease, depression, age-relative memory and sleep disturbances, etc.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Central Nervous System Diseases/drug therapy , Dehydroepiandrosterone/therapeutic use , Animals , Brain/drug effects , Brain/physiopathology , Central Nervous System Diseases/physiopathology , Humans , Memory/drug effects , Memory/physiologyABSTRACT
The adrenal glands synthesize dehydroepiandrosterone (DHEA) and its sulphate form (DHEAS) more intensively than they do other steroid hormones. Researchers are interested in these hormones for several reasons. Firstly, for some years they have been trying to find the reason for DHEA and DHEAS to be synthesized and present in the organism in such high concentrations. Secondly, their attention have been attracted by age-dependent regression of DHEA, which is strictly determined. Thirdly, despite longstanding efforts of scientists, the physiological role and spectrum of the biological activity of DHEA is still unclear. Evidence of that DHEA and DHEAS can be synthesized in situ in the brain tissue, received in rat experiments, urged researchers to clarify the role of these neurosteroids in the CNS. The presented review covers ways of neurosteroid synthesis, possible mechanisms of the regulation of these processes, and their dynamics under the condition of stress. The authors analyze experimental and clinical observations undertaken with a goal to clarify a possible role of DHEA in the manifestation of various brain functions. Special attention is payed to ambiguous results of modern studies, dedicated to replacement therapy of various disorders of CNS functioning (Alzheimer's disease, depression, age-specific memory impairment, sleep disturbance etc.) with DHEAS.
Subject(s)
Brain/metabolism , Dehydroepiandrosterone/physiology , Adult , Dehydroepiandrosterone/blood , Female , Humans , Male , Neuroglia/metabolismABSTRACT
The paper summarizes the current knowledge concerning various aspects of neurosteroid metabolism and mode of action. These steroid compounds including dehydroepiandrosterone, pregnenolone, and their sulfates, as well as progesterone and its tetrahydro metabolites, are synthesized de novo in glial cells of different brain structures both in humans and in animals. Biological effects of neurosteroids and their fundamental and clinical aspects are reviewed.
Subject(s)
Brain/metabolism , Dehydroepiandrosterone/physiology , Neuroglia/metabolism , Pregnenolone/physiology , Progesterone/physiology , Aging/metabolism , Animals , Dehydroepiandrosterone/metabolism , Dementia/metabolism , Depression/metabolism , Humans , Memory/physiology , Pregnenolone/metabolism , Progesterone/metabolismABSTRACT
The requirements for activity in a tumour-photosensitizing drug are outlined. A series of metallo tetrasulphonatophthalocyanines are shown to be inactive in an in vivo assay of tumour photosensitization; however, some less water-soluble compounds (hydroxylated derivatives of octaethylchlorin and octaethylbacteriochlorin) are shown to possess promising activity.
Subject(s)
Neoplasms/drug therapy , Photochemotherapy , Porphyrins/pharmacology , Radiation-Sensitizing Agents/pharmacology , Animals , Cell Line , Porphyrins/chemical synthesis , Structure-Activity Relationship , Tumor Cells, Cultured/drug effectsABSTRACT
The oligomeric composition of HpD, Photofrin II and other hematoporphyrin derivatives useful for the diagnosis and therapy of tumors has been studied. Gel chromatographic procedures were used that excluded porphyrin aggregation. Photofrin and hematoporphyrin derivatives were shown to contain different quantities of monomer, dimer and other oligomeric porphyrins.
Subject(s)
Hematoporphyrins/analysis , Chromatography, Gel , Chromatography, Thin Layer , Drug Stability , Polymers , SolutionsABSTRACT
The photosensitized luminescence of singlet molecular oxygen has been studied in aqueous and alcoholic solutions of hematoporphyrin IX (HP) and di- and oligomeric components of "hematoporphyrin derivative" (photofrin II) which is known to be used as a drug in photodynamic tumor therapy. The quantum yields of 1O2 generation (gamma delta) by these compounds have been determined. It was found that the highest gamma delta values are characteristic of alcoholic and micellar detergent aqueous solutions. In detergent-free aqueous solutions containing mainly associated porphyrin molecules, gamma delta is much lower (5-30%), polymeric photofrin components being considerably less active than HP. Both localization of porphyrins in hydrophobic loci and high photosensitizing activity in lipid phase are supposed to play the key role in tumor photodestruction.