In vivo profile of the anticoagulant effect of 17ß-amino-1,3,5(10)estratrien-3-ol.

The anticoagulant activity of 17ß-amino-1,3,5(10)estratrien-3-ol (AE(2)) was established for the first time. Experiment 1: mice groups were treated with a single subcutaneous (s.c.) AE(2) injection (0.5, 1, 2, 4, and 8 mg/100 g BW) or vehicle (propylenglycol; 0.5 ml/100 g). After 24 h, AE(2) produced dose-dependent blood clotting time increases related to control, Emax=+121% (P<0.01) finishing the sixth day. Experiment 2: four groups received a single s.c. administration of AE(2) (4 or 8 mg/100g BW) or 17ß-estradiol (E(2); 3mg/100g BW) or vehicle. After 24 and 48 h post-administration, the times of blood clotting, prothrombin, thrombin, and activated partial thromboplastin and fibrinogen concentrations were assessed. Both AE(2) doses increased blood clotting and fibrinogen similarly, blood clotting time: 64, 94%; fibrinogen: 71, 107% (P<0.01). Prothrombin, activated partial thromboplastin and thrombin times, increased 13-15%, 27-55%, and 15-29%, respectively (P<0.01). Meanwhile E(2) decreased blood clotting 20% (P<0.01) and thrombin 23% (P<0.01) after 48 h. Experiment 3: for five consecutive days, mice received AE(2) or E(2) (0.1, 1, 10, 100, and 1000 µg/kg/day), or vehicle. Blood clotting time was assessed at 1, 2, 3, 4, 5, 8, and 11 days after treatment. AE(2) at all doses were anticoagulant for 2-3 days after administration whereas E(2) was procoagulant for 8-11 days. These opposite effects were: AE(2) Emax=+29%; E(2) Emax=-30%; (P<0.01). AE(2) is the parent compound of the 17ß-aminoestrogens, with the largest and longest anticoagulant effect until now reported.

Electronic structure evaluation through quantum chemical descriptors of 17ß-aminoestrogens with an anticoagulant effect.

17ß-aminoestrogens have been experimentally studied due to their anticoagulant effect, shown both in in vitro and in vivo assays; this is a non-typical behavior for steroids. The anticoagulant effect of these aminoestrogens has been related to the aromaticity of the A-ring of the steroid molecule; as well as to the length of the amino-alcohol side-chain at C17, which might have an influence on the biological activity of these compounds. The study of the electronic structure of 17ß-aminoestrogens using quantum chemical descriptors could provide significant information and may contribute to a better understanding of structure-activity relationships in these molecules. In this work, we present a density functional theory (DFT) study at the B3LYP level of theory for selected 17ß-aminoestrogens compounds, with the main purpose of characterizing their electronic and physicochemical properties and relating them to their anticoagulant effect, using quantum chemical descriptors such as: atomic charges, bond order, electrostatic potential isosurface analysis, hardness, electrophilicity and aromaticity indexes. The results obtained from these quantum chemical descriptors, led us to characterize the physicochemical properties, reactive sites and substituent influence on electronic structure, as well as to identify additional quantum chemical descriptors that could be associated with the anticoagulant effect of 17ß-aminoestrogens.

Potential prescription patterns and errors in elderly adult patients attending public primary health care centers in Mexico City.

INTRODUCTION: Six out of every 10 elderly persons live in developing countries. OBJECTIVE: To analyze and assess the drug prescription patterns and errors in elderly outpatients attending public health care centers in Mexico City, Mexico. MATERIALS AND METHODS: A descriptive and retrospective study was conducted in 2007. Fourteen hundred prescriptions were analyzed. Prescriptions of ambulatory adults aged >70 years who were residents of Mexico City for at least two years were included. Prescription errors were divided into two groups: (1) administrative and legal, and (2) pharmacotherapeutic. In group 2, we analyzed drug dose strength, administration route, frequency of drug administration, treatment length, potential drug-drug interactions, and contraindications. Variables were classified as correct or incorrect based on clinical literature. Variables for each drug were dichotomized as correct (0) or incorrect (1). A Prescription Index (PI) was calculated by considering each drug on the prescription. SPSS statistical software was used to process the collected data (95% confidence interval; p <0.05). RESULTS: The drug prescription pattern in elderly outpatients shows that 12 drugs account for 70.72% (2880) of prescribed drugs. The most prescribed drugs presented potential pharmacotherapeutic errors (as defined in the present study). Acetylsalicylic acid-captopril was the most common potential interaction (not clinically assessed). Potential prescription error was high (53% of total prescriptions). Most of the prescription errors were due to omissions of dosage, administration route, and length of treatment and may potentially cause harm to the elderly outpatients. CONCLUSIONS: A high number of potential prescription errors were found, mainly due to omissions. The drug prescription pattern of the study population is mainly constituted by 12 drugs. The results indicate that prescription quality depends on the number of prescribed drugs per prescription (p < 0.000).

Breast cancer quality of life evaluation in Mexican Women at La Raza Hospital, Mexico City: A preliminary approach.

Breast cancer (BC) is the second leading cause of death among Mexican women over 40 years of age. This study aimed to identify and examine the effects of cancer stage and surgical treatment on the quality of life (QOL) of Mexican women with early stage breast cancer (ESBC) treated with either modified radical mastectomy (MRM) or breast conservative surgery (BCS), plus adjuvant chemotherapy. The QLQ-C30 and QLQ BR-23 questionnaires were used to assess QOL. Sociodemographic characteristics and clinical factors of 102 women with early BC were also evaluated; analysis of variance (ANOVA) was performed and a statistical significance of p < 0.05 was assumed. Most women were of reproductive age. Meaningful differences in QOL as a result of surgical treatment, in women receiving BCS compared with those receiving MRM, were limited to body image. We conclude that MRM and BCS are essentially equivalent choices in terms of QOL, with the exception of the impact on body image. In general, women who received BCS had a better perceived QOL.

The costs of breast cancer in a Mexican public health institution.

Breast cancer (BC) is the second leading cause of death as a result of neoplasia in Mexico. This study aimed to identify the direct and indirect costs of treating female outpatients diagnosed with BC at a Mexican public hospital. A cross-sectional, observational, analytical study was conducted. A total of 506 medical records were analyzed and 102 were included in the cost analysis. The micro-costing process was used to estimate treatment costs. A 17-item questionnaire was used to obtain information on direct and indirect costs. Of the 102 women with BC included in the study, 92.2% (94) were at Stage II, and only 7.8% at Stage I. Total direct costs over six months for the 82 women who had modified radical mastectomy (MRM) surgury were US$733,821.15. Total direct costs for the 15 patients with conservative surgery (CS) were US$138,190.39. We found that the total economic burden in the study population was much higher for patients with MRM than for patients with CS.

Changes on hemostatic parameters induced by 17beta-estradiol, ethinylestradiol, and the 17beta-aminoestrogen pentolame in the male Wistar rat.

Oral contraceptives containing estrogens increases the incidence of thromboembolic events. In contrast, administration of 17beta-aminoestrogens prolonged blood clotting time (BCT) in rodents. We studied the effect of estradiol (E(2)), ethinylestradiol (EE) and pentolame on some screening hemostatic tests. BCT was evaluated 24, 48, 72 and 96 h post-treatment. Rats received subcutaneously (s.c.) for five consecutive days E(2) (0.1-1000 microg), EE (1-1000 microg), pentolame (0.1-1000 microg), or vehicle (propyleneglycol 0.3 ml). At 48 h post-treatment E(2) (1000 microg) diminished BCT (32%, P<0.01), in contrast pentolame (1000 microg) augmented BCT by 41% (P<0.01). After 72 h, E(2) showed procoagulant effects with 10, 100 and 1000 microg doses (-45, -30, and -21%, respectively). Significant effects on BCT of EE were observed 72 h after with 1000 microg (-12%, P<0.05). Animals were treated s.c. for two consecutive days with E(2) (3mg/100g), pentolame (4 mg), or vehicle (0.1 ml). BCT, bleeding time (BT), platelet aggregation (PA), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen concentration were determined. E(2) produced a significant diminution on BCT (-20%) after 72 h whereas pentolame increased BCT from 24 to 96 h (62%, maximal response at 48 h). APTT and PT coagulation times of the groups treated with E(2) and pentolame were lengthened (33 and 29%; 16 and 24%, respectively; P<0.05). Fibrinogen concentration increased (115%, P<0.01) only in the pentolame-treated group. Pentolame and E(2) produced any effects on BT and PA compared with control groups, indicating that platelet function was not modified. Our results indicate that E(2), EE and pentolame affects the plasmatic phase of the hemostatic mechanism.