ABSTRACT
The genotoxicity study of a synthetic progestin norethynodrel, was carried out on human lymphocytes chromosomes using sister chromatid exchanges (SCEs), replication index (RI) and chromosomal aberrations (CAs) as parameters. The study was carried out in the presence and absence of metabolic activation (S9 mix). Norethynodrel was studied at three different concentrations (20, 40 and 60 microg/ml of peripheral blood lymphocyte culture) and was found non-genotoxic in the absence of metabolic activation. But in the presence of S9 mix norethynodrel increased SCE (p<0.03) and CA (p<0.005) frequencies and inhibits lymphocyte proliferation (p<0.03) at 60 microg/ml. The results suggest a genotoxic and cytotoxic effect of norethynodrel in human lymphocytes in vitro in the presence of S9 mix.
Subject(s)
Animals , Cell Proliferation/drug effects , Chromosome Aberrations/chemically induced , DNA Replication/drug effects , Dose-Response Relationship, Drug , Humans , Lymphocytes/drug effects , Microsomes, Liver/metabolism , Mutagenicity Tests , Norethynodrel/toxicity , Rats , Rats, WistarABSTRACT
This paper presents the correlative changes of cancellous bone histomorphometry, biomechanical property and bone mineral contents of lumbar vertebrae in ovariectomized rats. Forty eight 10.5-month-old female SD rats were randomized to six groups: 1) Basal: at 10.5 mon. of age; 2) sham-1: sham-operated at 13 mon. of age; 3) OVX-1: ovariectomized at 13 mon. of age; 4) sham-2: sham-operated at 16 mon. of age; 5) OVX-2: ovariectomized at 16 mon. of age; and 6) OVX-2 + EE: ovariectomized and treated with 17 alpha-ethynylestradiol (100 micrograms.kg-1.d-1) starting at 13 mon. of age for 12 weeks. Double in vivo fluorochrome labeling was administered to all rats. At the end-point of study, the undecalcified longitudinal fourth lumbar vertebra (LV4) sections were cut and stained with Goldner's Trichrome for bone histomorphometric analyses. The mechanical properties of the compact fifth lumbar vertebra body (LV5) were measured with compression test, the LV5 bodies then were dried constantly with high temperature and digested with acid for testing of bone mineral content. A trend in trabecular bone volume (BV/TV), trabecular thickness (Tb.Th) of LV4, bone break load, break stress, elastic moduli and bone calcium content of LV5 to increase with the increase of age was revealed in the intact rats, but the highest value was at 13 mon. of age. A positive correlation was seen between histomophormetry and bone bio-mechanical properties in the intact rats. Compared with the data from the sham-operated rats, the BV/TV and Tb. Th significantly decreased and bone turnover rate significantly increased in OVX rats at 10 weeks, and the above parameters further decreased 22 weeks post OVX. Correspondingly, the bone break load, break stress, elastic moduli and bone calcium content significantly decreased with the increase of time post OVX was compared with those of sham-operated rats. A positive correlation between histomophormetry and bone biomechanical properties was also observed in OVX rats (r = 0.399, P = 0.018). Bone histomorphometry is good for predicting early physiological and pathological changes and bone biomechanical properties are good parameters for predicting corresponding function of bone such as fracture. Both of them are useful and needful in the animal studies on osteoporosis and related pharmacodynamic observations on new drugs.
Subject(s)
Animals , Female , Rats , Biomechanical Phenomena , Bone Density , Lumbar Vertebrae , Pathology , Norethynodrel , Therapeutic Uses , Osteoporosis , Drug Therapy , Pathology , Ovariectomy , Random Allocation , Rats, Sprague-DawleyABSTRACT
OBJETIVO: Avaliar o efeito da tibolona (Livial) na evoluçäo de miomas em mulheres na pós-menopausa. TIPO DO ESTUDO: Estudo prospectivo, aberto, multicêntrico e näo comparativo. PACIENTES E MÉTODO: Foram estudadas 12 pacientes menopausadas, portadoras de miomas uterinos dos tipos intramurais ou subserosos, com diâmetro médio de 3 cm, submetidas à terapêutica de reposiçäo hormonal com tibolona na dose de 2,5 mg, durante 48 semanas. Realizou-se ultra-sonografia transvaginal antes, e após 24 e 48 semanas do tratamento. RESULTADOS: Houve reduçäo significativa (p<0,05) no número total de miomas, declinando de 16 para 11 após 48 semanas. Näo ocorreu alteraçäo significativa no diâmetro médio dos nódulos miomatosos, assim como na espessura endometrial, que se traduziu clinicamente por ausência de sangramento durante o tratamento. CONCLUSÕES: a tibolona parece näo interferir com o crescimento do mioma uterino e dve ser considerada como boa opçäo para terapia de reposiçäo hormonal em pacientes na pós-menopausa portadoras dessa neoplasia benigna
Subject(s)
Humans , Female , Hormone Replacement Therapy , Leiomyoma , Norethynodrel/therapeutic use , Menopause , PostmenopauseABSTRACT
Two sensitive indirect atomic absorption spectrometric [AAS] procedures are described for the determination of five monoacetylenic compounds. The first procedure is based on the formation of the copper acetylides, dissolving the acetylides in dilute nitric acid solution, followed by AAS measurement of the copper content. 17, alpha-ethinylestradiol, lynoestrenol, norethynodrel, ethchlorvynol [placidly] and methylpentynol carbamate are determined with mean percentage accuracies; 99.5 +/- 0.425, 100.27 +/- 0.678, 100.09 +/- 1.27, 100.56 +/- 1.749 and 100.64 +/- 2.04, respectively. The second procedure depends on the precipitation of certain monoacetylenic compounds as silver acetylides, followed by extraction with an organic solvent and measurement by AAS, 17, alpha- ethinylestradiol, lynoestrenol, norethynodrel and methylpentynol carbamate are determined by this technique with mean percentage accuracies; 99.5 +/- 0.58, 100.0 +/- 0.9115, 99.8 +/- 0.558 and 99.4 +/- 0.538, respectively