[Changes in menstrual flow induced by copper intrauterine devices].
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Biomedical subjects
Publications and source records attributed to A Gallegos.
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In 1973 the Mexican government changed its official position on family planning from one of neurtality to one of support. Prior to that time, family planning activities had been limited to the commercial sector and two private programs. As a result of the new policy, all major official health programs began organizing family planning activities. While about the same number of couples were served by the private programs in 1976 as in 1973, the commercial sector grew at over 10 percent per year and official coverage expanded around fivefold. It is estimated that the proportion of eligible women protected by contraception doubled and that the birth rate fell from 43-44 in 1973 to 37-40 by the end of 1976.
Three affected siblings with the hermaphrodism are described. The propositi showed the following characteristics: male phenotype and gender role, hypospadias, bilateral scrotal ovotestes with palpable nodules, and absence of müllerian structures. The X chromatin was positive and the Y chromatin was negative in the 3 affected subjects. Their karyotype in peripheral blood lymphocytes and in gonadal fibroblasts was 46,XX and no Y chromosome fluorescence was observed. Plasma FSH was elevated in the 2 older patients and plasma LH was elevated only in the oldest. Plasma testosterone was low and plasma estradiol high in the 3 siblings; plasma progesterone was elevated in 2, but normal in 1 sibling. Since some of the clinical characteristics of these 3 affected siblings are not the most common features in the majority of sporadic cases of true hermaphrodism, it is suggested that the presence of all of them may be the first clue for the clinical suspicion of the familial type of true hermaphrodism.
In this work, is studied the application, within a quantum similarity framework, of the recently described Kinetic Energy Density Function in the evaluation of the antimalarial activity. First, this new type of Density Function is briefly presented from its theoretical foundations, and its inclusion in the molecular quantum similarity is discussed afterward. The application of Kinetic Energy-based Quantum Similarity Measures to QSAR is tested with 2 molecular sets composed of artemisinin derivatives, in which the 50% inhibition of synthesis and reduction of hidrofolate (IC50) in different Plasmodium falciparum clones are analyzed. Satisfactory correlations are obtained for all antimalarial activities in all studied molecular sets. Molecular Quantum Similarity analysis provides a consistent, unbiased, and homogeneous set of molecular descriptors and is a feasible alternative to the use of classical physicochemical descriptors.
We have found that analogues of phosphatidylinositol modified at the 3'-myo-inositol position prevent phosphorylation by phosphatidylinositol 3-kinase (PI3-kinase) inhibit the anchorage-independent growth of HT-29 human colon adenocarcinoma cells as colonies in soft agarose but have no effect on monolayer growth on a plastic surface. Examination of an incomplete differential display library revealed 3 genes whose expression was increased and 11 genes whose expression was decreased or absent in HT-29 cells growing as colonies compared to monolayer growth. One of the cDNAs corresponding to an mRNA that was expressed only in cells growing as a monolayer was a 126 bp fragment that had 98% identity with a fragment of mRNA for human p55PIK PI3-kinase regulatory subunit. The down regulation of p55PIK gene expression in HT-29 cells growing as colonies was confirmed by RT-PCR using p55PIK-specific oligonucleotide primers. RT-PCR and Northern hybridisation were used to show that the expression of the p110 catalytic subunit and the p85 regulatory subunit of PI3-kinase were also down regulated in HT-29 cells growing as colonies. We measured a decrease of approximately 25% in total PI3-kinase activity of the HT-29 cells grown in soft agarose compared to HT-29 cells grown as monolayer. The results suggest that p110 PI3-kinase activity may be limiting in cells showing anchorage independent-growth which could explain their increased sensitivity, compared to cells in monolayer culture, to inhibitors of PI3-kinase signalling.
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Progesterone -6,7-3H (P*) was incubated in minces of human secretory and proliferative endometrium in absence as well as in presence of 10 and 100 micrograms/ml of unlabelled progesterone (P), in Eagle's Culture Medium throughout 72h. The following metabolites of P* were found in culture media: 1. C-21 derivatives of P* reduced at C-5, and C-20 positions. Also, a 3 beta-hydroxy-5 alpha pregnane-20-One conjugated to a glucuronic acid moiety was identified. 2. Concentrations of water-soluble derivative accounted for 21% and 29% of the recovered radioactivity in proliferative and secretory endometria, respectively. 3. After beta-glucuronidase cleavage, 80% to 95% of the water soluble derivatives were released as free steroids. 4. Approximately 60% corresponded to 3 beta -hydroxy- 5 alpha pregnane-20-one of the pooled water extracts. 5. Alson, 17% and 13% as well as 9% and 8% recoveries under 10 and 100 micrograms/P were observed in proliferative and secretory endometria, respectively. Glucuronidation seems to be a compensatory route to metabolize P and P* in human endometrium as might also occur in other species.
Human skin biotransform naturally occurring steroid hormones. 4-14C progesterone skin fate might involve C-19 derivates formation. In vitro incubation of 4-14C-progesterone with defammation. human abdominal skin minces for 5 days periods, predominantly yield: 1) Metabolites reduced at C-20 and C-5 positions of 4-14C progesterone. 2) 4-pregnen-17 01-20-one (0.85%). 3) 4-Androsten-17-01-3-one isolated as an acetylated derivative (0.29%). 4) A metabolite that behaves like 4-androsten-3, 17-diol. The metabolites identity was established through repeated cocrystallizations with known purified carriers in different organic solvents 17 -hydroxy-progesterone was found at greater concentrations in the group of polar metabolites. These metabolites are of biochemical interest but can not be assessed until the effects of these compounds on human skin are known.
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The microbial product wortmannin has previously been shown to be a potent inhibitor of phosphatidylinositol-3-kinase. In view of the potential role of this enzyme in transduction of mitogenic signals, we determined the cytotoxic activity of wortmannin against several human tumor cell lines in vitro. The most sensitive lines included GC3 colon carcinoma, IGROV1 ovarian carcinoma, and CCRF-CEM leukemia (IC-50s ranging from 0.7-2.1 microM). The cytotoxicity of wortmannin was decreased approximately 10-fold by serum-free conditions. Wortmannin was generally less active in low passage human breast cancer cell lines that overexpress either epidermal growth factor receptor or Her2/neu. Wortmannin was also tested for in vivo antitumor activity against seven murine tumor and ten human tumor xenograft models. Activity (> 60% inhibition of tumor growth) was observed in only the C3H mammary carcinoma and the human BxPC-3 pancreatic carcinoma xenograft. In vivo antitumor activity did not correlate with in vitro sensitivity to wortmannin cytotoxicity.
Murine NIH 3T3 cells were stably transfected with human NQO1 (DT-diaphorase) cDNA and clonal cell lines with up to 15-fold elevated DT-diaphorase activity were obtained. These cell lines showed no significant increase in cell growth inhibition by the quinone anticancer drugs mitomycin C, diaziquone and menadione, when compared to vector alone transfected control cells. There was a small increase in sensitivity to doxorubicin. The relative increase in DT-diaphorase activity in the transfected cells compared to the control cell lines is similar to the increase of DT-diaphorase activity found in some human tumors compared to their paired normal tissue. The results of this study, and other evidence, suggests that DT-diaphorase may not, as suggested by others, be a clinically useful target for the bioreductive activation of anticancer drugs.
Thioredoxin and thioredoxin reductase are redox proteins that have been implicated in the control of cell proliferation and transformation. We report the levels and activity of these proteins and their mRNAs in human primary tumors and tumor cell lines. Half of human primary colorectal carcinomas (5/10) examined had increased thioredoxin mRNA, of 3- to over 100-fold, compared to adjacent normal colonic mucosa from the same subject. Thioredoxin reductase protein and activity were increased an average of 2-fold in human colorectal tumors compared to normal mucosa. A number of human hematologic and solid tumor cell lines were studied and showed a 10-fold range of thioredoxin mRNA and a 23-fold range of thioredoxin reductase mRNA. Increased proliferation and hypoxia are factors that might contribute to the increased expression in solid tumors. We found that serum stimulation of growth arrested MCF-7 breast cancer cells caused a 59% increase in thioredoxin mRNA and a 62% increase in thioredoxin reductase mRNA by 24 hours. Exposure of HT-20 colon cancer cells to hypoxia resulted in a 14-fold increase in thioredoxin mRNA by 16 hours, and a transient 4-fold increase in thioredoxin reductase mRNA at 1 hour that had returned to control levels by 8 hours. Cancer cells were found to release thioredoxin into the medium at rates between 1 to 2 pmole/10(6) cells/3 hours. The rate of secretion was not, however, related to cellular-levels of thioredoxin. The results of the study show that the expression of thioredoxin and thioredoxin reductase are increased several fold in some human solid tumors compared to normal tissue. Secretion of thioredoxin, which is known to have a direct growth stimulating activity, by human tumor cells might lead to the stimulation of cancer cell growth.
Selenium (Se) is an essential trace element and has been reported to decrease the incidence of some human cancers. We have investigated the effects of Se on thioredoxin reductase, a selenocysteine containing flavoenzyme, in HT-29 human colon cancer cells grown in serum-free medium. Sodium selenite and other Se containing compounds produced a time and concentration dependent increase in intracellular thioredoxin reductase activity and protein levels. Selenite was the most active of the Se compounds examined: 1 microM selenite produced a 28-fold increase in thioredoxin reductase activity by 1 day and 10 microM selenite over a 60-fold increase by 5 days. The activity of a related non-selenocysteine containing flavoenzyme glutathione reductase was not increased by selenite. Selenite, but not the other Se containing compounds inhibited cell growth at concentrations above 2 microM. The results show that Se can produce large increases in cell thioredoxin reductase activity.