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Biomedical subjects

E Murillo

Publications and source records attributed to E Murillo.

15 recordsLinked to original sources
PubMed2001

New progesterone esters as 5alpha-reductase inhibitors.

The pharmacological activity of four new progesterone derivatives: 4-bromo-17alpha-(p-fluorobenzoyloxy)-4-pregnene-3,20-dione (7), 4-bromo-17alpha-(p-bromobenzoyloxy)-4-pregnene-3,20-dione (8), 4-bromo-17alpha-(p-chlorobenzoyloxy)-pregnene-3,20-dione (9) and 4-bromo-17alpha-(p-toluoyloxy)-4-pregnene-3,20-dione (10) was determined. These compounds were evaluated as 5alpha-reductase inhibitors on gonadectomized hamster seminal vesicles and flank organs. The pharmacological data of this study indicate that compounds 7 and 9 having at C-17 p-fluorobenzoyloxy and p-chlorobenzoyloxy ester functions respectively showed the highest antiandrogenic effect as measured by the reduction of the weight of the seminal vesicles. In the flank organ model, the same compounds 7 and 9 exhibited a smaller diameter, 1.8 and 1.0 mm, respectively, than the commercially available finasteride 3 (2.3 mm), thus indicating a higher inhibitory effect on 5alpha-reductase enzyme. Steroid 7 showed a higher inhibitory activity on the conversion of T to DHT (Fig. 3) than the presently used finasteride, thus indicating a higher antiandrogenic effect. The nonsubstituted benzoyloxy ester (compound 15) showed a lower antiandrogenic activity as measured in the seminal vesicles model than the p-substituted benzoyloxy compounds.

5-alpha Reductase Inhibitors↗
PubMed2000

Antiandrogenic effect of 16-substituted, non-substituted and D-homopregnane derivatives.

The pharmacological activities of 12 pregnane derivatives (4-15) were determined on gonadectomized male hamster flank organs and seminal vesicles as antiandrogens and as 5alpha-reductase inhibitors. The results from this study indicate that subcutaneous injection of testosterone for 3 d increased the diameter of the pigmented spot in the flank organs, whereas finasteride when injected with testosterone decreased the size of the spot significantly when steroids 4-15 were injected together with testosterone, the diameter of the flank organs of gonadectomized male hamsters, decreased significantly (p<0.005) compared to testosterone. Compound 11 was the most active steroid and reduced the diameter of the pigmented spot more than the other synthesized steroids or finasteride. Subcutaneous injections of testosterone to gonadectomized animals restore the seminal vesicle size lost upon castration. Injection of testosterone plus finasteride decreased significantly the weight of these glands (p<0.005). Steroids 5-15 when injected with testosterone decreased the weight of the seminal vesicles compared to testosterone. Finasteride is a good inhibitor of the conversion of testosterone to dihydrotestosterone (DHT) (low formation of DHT) measured as pmole of DHT/g of protein/h. Steroids 6-15 inhibited the conversion of testosterone to DHT as compared to testosterone however finasteride and 10 appeared to be the most effective compounds. Castration increases the protein content of the seminal vesicles (control) expressed as microg/mg of tissues. Testosterone tends to decrease it significantly, as did compounds 4, 5, 7, 9, and 15. We demonstrated that DHT as well as cyproterone acetate and steroids 5, 6, 8, 9, 11, and 14 at increasing non radioactive steroid concentration, inhibited the binding of [3H]DHT to cytosolic androgen receptor (AR), as indicated by its Ki values. However, 4, 7, 10, 12, and 13 did not have any inhibitory effect.

Androgen Antagonists↗
PubMed2000

Fungi test for evaluation of new antiandrogenic molecule.

Antiandrogens have high impact in medicine as they are compounds capable of decreasing the effect of benign prostatic hyperplasia, cancer, and other androgen-dependent diseases that affect a large percentage of the male population in the world. [figure: see text] Dihydrotestosterone, a 5 alpha-reductase metabolite of testosterone, has been implicated as the responsible factor of these androgen abnormalities. This fact indicates that the logical step in the treatment of these diseases is the inhibition of this enzyme activity using molecules that compete selectively with its natural substrates. The study of the pharmacological effect of antiandrogens requires specific animal models using a large number of laboratory animals. On basis of this concept, presently there is a tendency to eliminate studies with animals. In this paper we report a new method for antiandrogenic evaluation using microbial transformations.

Androgen Antagonists↗
PubMed2000

Antiandrogenic effect of new synthetic steroids.

These results indicate that castration decreased the flank organ diameter and the weight of the seminal vesicles, whereas daily injection of testosterone restores them. However injections of finasteride together with testosterone inhibited the diameter of the flank organs, the weight of the seminal vesicles, and the conversion of testosterone to dihydrotestosterone. The four compounds tested inhibited flank organ diameter size and the weight of the seminal vesicles as compared to the testosterone-treated animals. On the other hand, none of these compounds suppressed the conversion of testosterone to dihydrotestosterone. These results suggest that the synthesized steroids compete with androgen receptors.

Androgen Antagonists↗
PubMed1999

Comparative study of the clinical efficacy of two different coumarin dosages in the management of arm lymphedema after treatment for breast cancer.

In a randomized, double-blind, parallel group study, we compared the clinical efficacy of coumarin 90 mg/day (Group A) with 135 mg/day (Group B) in 77 women (age 35-65 years) with lymphedema of the upper limb secondary to surgery and irradiation for treatment of breast cancer. During 12 months of coumarin therapy, the arm volume of lymphedema and a clinical score (degree of arm edema, heaviness, hardness, and neuralgia/dysesthesia) were determined. In both groups, the volume of arm lymphedema decreased (14.9% in Group A and 13.2% in Group B) (N.S.), the overall clinical score improved (12.9 +/- 4.3 to 5.7 +/- 3.5 in Group A and from 11.7 +/- 3.7 to 4.7 +/- 3.9 in Group B) (N.S.), and the overall efficacy of coumarin was similarly good or excellent (71.9% in Group A and 68.6% in Group B) (N.S.). Only mild to moderate side effects of drug therapy were recorded. Coumarin prevents a spontaneous trend toward an increase in arm lymphedema after treatment of breast cancer, decreases the severity of local symptoms, and overall improves the quality of life. No difference was found between the apparent benefits of coumarin at 90 mg/day compared with 135 mg/day.

Arm↗
PubMed1999

Steroidal antiandrogens and 5alpha-reductase inhibitors.

The purpose of this work is to synthesize a pregnane derivative with a high antiandrogenic effect or a high inhibitory activity for the enzyme 5 alpha-reductase type 2. Benign prostatic hyperplasia and prostate cancer are androgen dependent diseases which afflict a large percentage of the male population. Dihydrotestosterone 3, a 5 alpha-reductase metabolite of testosterone 2 has been implicated as a causative factor in the progression of these diseases, largely through the clinical evaluation of males who are genetically deficient of steroid 5 alpha-reductase enzyme. As a result of this study, the inhibition of this enzyme has become a pharmacological strategy for the design and synthesis of new drugs. The advent of finasteride 22 "figure 5" a 5 alpha-reductase inhibitor, has greatly alleviated the symptoms associated with benign prostatic hyperplasia. On the other hand, the discovery of cyproterone acetate 4 "figure 2" alone or in combination with the antiandrogens flutamide 14 "figure 3" or bicalutamide 21 has greatly reduced the misery of prostate cancer. Prostate cancer kills about 40,000 men in the USA and approximately 400,000 prostatectomies are performed each year. In our laboratory we have recently synthesized ten new progesterone derivatives 17 alpha-acyloyloxy-6-halo (chloro, bromo) 16 beta-methyl-4, 6-pregnadiene-3, 20-diones (54a-54e and 55a-55e), "figure 10". These steroids were evaluated as antiandrogens and exhibited a much higher activity than the commercially available cyproterone acetate 4. The same compounds were also evaluated as 5 alpha-reductase inhibitors and showed a slightly higher inhibitory activity than that of finasteride 22, the drug of choice today for the treatment of benign prostatic hyperplasia In another study we synthesized several new 4-halo (bromo and chloro) 17 alpha-benzoyloxy and also 4-halo-17 alpha-acetoxy progesterone derivatives (58-63) "figure 13". These compounds were prepared from the commercially available 17 alpha-acetoxy progesterone 56. The pharmacological evaluation of these steroids "figure 14" indicated that the 17 alpha-benzoyloxy derivatives (4-chloro and bromo) 62 and 63 were very potent antiandrogens. On the other hand, the 4-halo (bromo and chloro) 17 alpha-acetoxy (58, 59) and the 17 alpha-benzoyloxy-4-chloro analog 63 showed a very high inhibitory activity for the enzyme 5 alpha-reductase type 2 "figure 15".

Adrenergic Antagonists↗
PubMed1997

UFT in combination as adjuvant therapy for breast cancer. Grupo Oncologico de Sevilla Seville, Spain.

Between 1989 and 1993, 409 evaluable patients with breast cancer have been treated with tegafur and uracil (UFT) in an adjuvant setting in two different trials. Data from both trials were reviewed in December 1995 after a mean follow-up of 5.09 +/- 1.1 years (range, 2.9 to 7.1 years). The aim of the first trial was to demonstrate the activity of UFT 400 mg/day for 6 months plus prednimustine 60 mg/m2 for 7 consecutive days, every 28 days in 6 cycles given orally (arm B). This scheme was compared with 6 cycles of cyclophosphamide 600 mg/m2, plus methotrexate 40 mg/m2, plus fluorouracil 600 mg/m2, every 4 weeks (arm A). In this study, 187 premenopausal women were evaluable, 96 in arm A and 91 in arm B, all of whom had positive axillary nodes. Although there were more younger patients in arm A than in arm B, prognostic factors were similar in both groups. Disease-free survival and overall survival were similar in both arms. However, some concern is raised by the low disease-free survival rate. The toxicity was mild (mainly nausea and vomiting and alopecia) and slightly worse in arm A. We believe that oral administration could be a useful alternative to the parenteral route. In the second trial, 222 evaluable patients received 20 mg/day of tamoxifen (Nolvadex) for 1 year (arm A), or the same dose of tamoxifen plus UFT 400 mg/day for 6 months. All patients were postmenopausal, and the characteristics of the tumors were the same as those in patients in the first trial. In arm A there were 109 patients and in arm B, 113. The groups were well balanced. The overall survival and the disease-free survival rates were equal in both arms, but were longer in arm B in the subset of patients with five or more axillary-involved nodes. The toxicity was negligible in both arms. We conclude that UFT/tamoxifen might be useful in postmenopausal patients with five or more involved nodes who are unable to follow a more aggressive schedule because of their age or low performance status.

Administration, Oral↗
PubMed1993

[The nutritional evaluation of cooking fats and oils].

Fatty acids content of locally obtained margarines, shortenings and cooking oils from businesses in Panama were determined by gas chromatographic method. The results found show that all of these oils have a high nutritional value, because of their high unsaturated fatty acid content. The soya oil group is characterized by its high content of linolenic acid (w3), for this reason they are preferably recommended as edible oils. Margarines were classified as "saturated" (high in palmitic acid) and "unsaturated" (high in linoleic acid). Saturated margarines are not very recommendable as edible fats since the high palmitic acid content is a hypercholesterolemic agent. The majority of the shortenings are also rich in palmitic acid.

Chromatography, Gas↗
PubMed1992

[Hypercholesterolemic effect of canthaxanthin and astaxanthin in rats].

Three groups of male Wistar rats (130-140 g) were fed 30 days with a synthetic diets containing 0.1% of beta-carotene, canthaxanthin and astaxanthin respectively. Another group was fed with a synthetic diet without carotenoids. The results shows that the beta-carotene does not induce change in plasma cholesterol (49, 7 +/- 3.6 mg/dl), but canthaxanthin and astaxanthin induce a significant increase in cholesterol concentration (92.1 +/- 3.6 and 66.5 +/- 5.1 mg/dl). This increase is noted mainly in the HDL fraction of the lipoproteins. Canthaxanthin has more affinity than astaxanthin for the liver, principal site of lipoproteins catabolism. The hypercholesterolemic effect of these xanthophylls is not related to reported mechanisms of carotenoids in mammalian, because beta-carotene does not induce changes in plasma cholesterol.

Animals↗
PubMed1988

Epirubicin in rectal cancer.

Taking into account previous results with epirubicin in colorectal cancer, in January, 1985, an oriented Phase II trial was started in patients with measurable rectal cancer, previously untreated with chemotherapy. Ten patients were treated with 80 mg/m2 every 3 weeks, and another 10 patients with 100 mg/m2 every 3 weeks. One patient from the 80 mg/m2 group and 3 from the 100 mg/m2 group reached partial remission for 4, 9+, 15 and 72+ weeks. Median survival for all patients was 16 months. Hematological toxicity was not a limiting factor. Anemia was significantly more frequent in the higher dose group; clinical cardiotoxicity was not observed. The incidences of nausea/vomiting and mucositis were low. Considering the low toxicity and the responses observed, additional studies seem to be indicated with an increase in the epirubicin dose.

Adult↗
PubMedDate not supplied

[Treatment of acute lymphoblastic leukemia in low risk adults].

Forty five adult patients with low risk acute lymphoblastic leukemia were treated with prednisone, vincristine and adriamycin. 91 per cent (41 patients) obtained complete remission with a mean survival was of 39 months. The side effects of treatment were minimal and less patient had to delay his chemotherapy. This regimen of treatment is a good option for adults patients with low risk acute lymphoblastic leukemia, in consequence of: a) high value of complete remission and its duration. b) the mean survival obtained and the probability of cure. c) the absence of severe side effects and without necessity of support therapy or hospitalization.

Adolescent↗
PubMedDate not supplied

[Cerebellar abscess].

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Brain Abscess↗