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Biomedical subjects

F Tejada

Publications and source records attributed to F Tejada.

At least 19 recordsLinked to original sources
PubMed2001

Aminoglutethimide, a steroidogenesis inhibitor, abolishes hormonal induction of ornithine decarboxylase in steroidogenic tissues: evidence for its role as cAMP-dependent protein kinase inhibitor.

Aminoglutethimide (AMG), a potent inhibitor of steroidogenesis used in the treatment of breast cancer and some adrenal pathologies, abolished the induction of ornithine decarboxylase (ODC) elicited by peptide hormones and by dibutyryl-cAMP in steroidogenic tissues. This effect seems to be related to an inhibition of cAMP-dependent protein kinase (IC50 = 287 microM) rather than blockade of the steroidogenic pathway. This inhibition may explain some of the effects observed in AMG treatment which cannot be ascribed to its direct effect on the cytochrome P450scc complex or aromatase. Taking into account that ODC, the rate-limiting enzyme in polyamine synthesis, is elevated in many types of cancer and that overexpression of this enzyme is associated with cell transformation, one may speculate that the inhibitory action of AMG on protein kinase A represents a positive colateral effect of this drug in cancer therapy.

Adrenal Glands↗
PubMed2001

Ambulatory blood pressure after renal transplantation.

Renal transplantation has been a usual medical practice in developed countries for several decades. A large number of studies report the excellent results obtained with such a practice. The survival of the graft, although able to be improved, is excellent and gives a great deal of hope to patients with renal insufficiency. The high level of investigation into immunosuppressor drugs offers, almost continuously, more efficient and better tolerated products. Paradoxically, the usual problems of patients with a renal transplant are not immunological but cardiovascular. Elevated serum cholesterol levels, obesity, diabetes and other cardiovascular risk factors (CVRFs) are usual in these patients, arterial hypertension (AHT) being the most frequent. Nephrologists are increasingly using ambulatory blood pressure monitoring (ABPM) on a daily basis. In the last 10 years, we have obtained highly valuable and interesting results with this technique which have allowed us to study and understand with greater precision the relationship of AHT to the kidney. Here we analyse and review the most relevant aspects of ABPM in the different stages of kidney disease, with special emphasis on renal transplantation.

Blood Pressure↗
PubMed1999

Postnatal exposure to androgens alters renal ornithine decarboxylase ontogeny and abolishes renal sexual dimorphism in mice.

The mouse kidney presents marked sexual dimorphism, manifested not only in renal size but also in the subcellular structure and enzyme activity. Ornithine decarboxylase (ODC), a key enzyme in the biosynthetic pathway of polyamines, is induced in the kidney by androgens, and its activity is higher in the kidney of male mice. The renal differences between male and female mice are not manifested during the first weeks of life and start to be expressed after weaning, simultaneously with the increase in plasma testosterone concentration. Treatment of newborn mice before postnatal day 21 with a single dose of testosterone propionate (TP, 200 microg/animal) did not increase renal ODC activity or renal size. From day 21 the same treatment elicited significant increases in renal ODC, especially in females where the basal activity of control animals was much lower than in males. The repeated injection of TP during the first 10 days of life (200 microg/animal, days 1, 4, 7 and 10) promoted an early increase in renal ODC activity but abolished the physiological rise observed in male mice at puberty and adulthood. This treatment dramatically reduced the secretion of the sexual hormones, testosterone, estradiol and progesterone, by the gonads, and diminished renal size as well as ODC and beta-glucuronidase activities in male mice. Stanozolol produced effects similar to those of TP, while the nonsteroidal antiandrogen, flutamide, did not apparently affect the normal development of the male or female kidney. The results indicate that: (a) kidney sexual dimorphism is not congenital; (b) neonatal androgens are not required to induce the sexual dimorphism of the mouse kidney; (c) the neonatal kidney is unresponsive to testosterone; (d) the premature and repeated exposure to supraphysiological levels of testosterone may accelerate the ontogeny of renal ODC but can abolish later testosterone secretion and hence alter the sexual characteristics of the male kidney, and (e) the postnatal treatment with androgens does not affect the response of the adult kidney to exogenous androgens. One can conclude that the postnatal manipulation of androgens may accelerate the development of the mechanisms of androgen responsiveness in some tissues but it may alter neural structures, probably the GnRH pulse generator, that control testosterone secretion.

Aging↗
PubMed1998

Interference of the antihormone RU486 in the determination of testosterone and estradiol by enzyme-immunoassay.

The antihormone RU486 (mifepristone, 11beta-(4-dimethylaminophenyl)-17beta-hydroxy-17alpha-(prop- 1-ynyl)-estra-4,9-dien-3-one) is currently used in many endocrinological studies and in clinical practice as a contraceptive agent. The results presented here indicate that the synthetic steroid RU486 may interfere in determinations of testosterone and estradiol when using some commercial kits. Although the cross reactivity is low (0.30% for testosterone and 0.16% for estradiol), in animal experiments RU486 doses higher than 5 mg/kg may produce false positive results in the estimation of plasma testosterone (specially in castrated male or female mice) or estradiol concentrations, even in samples obtained 48 h after the administration of this antihormone.

Animals↗
PubMed1998

Hypokalemia alters sex hormone and gonadotropin levels: evidence that FSH may be required for luteinization.

Hypokalemia produced different effects on steroid sex hormone concentrations in plasma and ovary in the mouse. Estradiol levels were slightly increased, whereas circulating progesterone was markedly decreased in all estrous periods. The preovulatory surge of gonadotropins and the secondary surge of follicle-stimulating hormone (FSH) at estrus were also decreased, but basal levels of both gonadotropins were unaffected. Supplementation with luteinizing hormone (LH), FSH, or gonadotropin-releasing hormone (GnRH) at proestrus rapidly normalized plasma and ovarian progesterone levels at this stage of the estrous cycle. Plasma progesterone levels at diestrus were restored only by combined treatment, at the periovulatory stage, with LH and FSH or GnRH but not by LH or FSH alone. The results demonstrate a lack of steroidogenic activity in the corpus luteum of the potassium-deficient mice and, furthermore, that FSH plays an important role in luteinization in the hypokalemic mice. We conclude that alteration of the transcellular potassium gradient may affect the regulation of the periovulatory surge of gonadotropins and progesterone secretion, probably by altering the release of GnRH from the hypothalamus. In addition, the results suggest that FSH may play a certain role as a luteotropic hormone in mice.

Animals↗
PubMed1996

Cytomegalovirus preemptive therapy with ganciclovir in renal transplant patients treated with OKT3.

In an attempt to decrease the prevalence and severity of cytomegalovirus (CMV) disease, preemptive therapy with ganciclovir was administered to all renal transplant patients treated with OKT3 between February 1993 and December 1994 (26 patients). The results were compared with those of a historical group treated with OKT3 but not with ganciclovir (29 patients). Both groups were similar in age, sex, number of previous transplants, number of rejections, serological status of donor and recipient and OKT3 dose. Ganciclovir was administered during the period of treatment with OKT3. Only 2 (7.7%) treated patients developed CMV disease versus 11 (37.9%) of the control group (p = 0.01). In the control group the intensity of the disease was severe in 7 (63.6%) cases, whereas in the treated patients it was always of slight intensity (p = 0.01). In conclusion, preemptive therapy with ganciclovir during treatment with OKT3 decreases the prevalence and severity of CMV disease.

Acyclovir↗
PubMed1995

Cytomegaloviraemia and T cell subpopulations in renal transplant patients.

We studied 54 consecutive recipients of renal transplants to evaluate their immunological responses to cytomegalovirus (CMV) infection. Forty-three (79.6%) patients developed CMV infection, and all of them subsequently recovered. Fourteen of these infected patients (32.6%) developed viraemia during the infectious process, four of whom then manifested the disease. The number of lymphocytes and their main subpopulations was normal before the appearance of CMV infection. During the infection there was a significant growth (P < 0.001) in the CD8+DR+ subset, corresponding to activated T suppressor/cytotoxic lymphocytes, whereas the natural killer measured subsets remained within normal limits during the whole infectious process. As all viraemic patients recovering from the infection developed CD8+DR+ activation, we conclude that this recovery is associated with the immunological activation.

Adult↗
PubMed1993

Potassium regulates plasma testosterone and renal ornithine decarboxylase in mice.

Potassium deficiency produced different effects in the kidney of male or female mice. While in female, potassium deficiency caused a marked renal hypertrophy with no significant changes in testosterone-regulated enzymes, such as ornithine decarboxylase and beta-glucuronidase, in the male the same treatment provoked a marked fall of these enzymes owing to a dramatic decrease in plasma testosterone. Potassium replenishment restored plasma testosterone and renal enzymatic activities. These results show for the first time, that potassium modulates circulating testosterone and suggest that this cation could exert an important regulatory role in controlling androgen actions.

Animals↗
PubMed1986

Postoperative whole lung irradiation with or without adriamycin in osteogenic sarcoma.

Thirty-six patients with histologically proven osteogenic sarcoma of the extremities, treated between September 1975 and April 1978, are the subject of this report. The primary tumor was treated with radical surgery. Patients received 2000 cGy whole lung irradiation postoperatively in an attempt to control micrometastases to the lung. Twenty-nine of the patients were given Adriamycin (60 mg/m2 IV every 6 weeks for a total dose of 550 mg/m2) in addition to the irradiation. The median, disease-free interval was 118 days for the seven patients treated with lung irradiation only. The median overall survival for these patients is 241 days, with one patient alive with disease. All patients developed lung metastasis. For the 29 patients treated with postoperative lung irradiation and Adriamycin, the median disease-free interval was 372 days, and the median overall survival is 843 days. Nineteen of the patients recurred (65.5%). The differences are statistically significant (p less than or equal to 0.003, median disease-free survival and p less than or equal to 0.03, median survival). This study supports the role of whole lung irradiation plus Adriamycin, in the control of micrometastases in osteogenic sarcoma of the extremities and suggests that additional clinical trials are warranted.

Adolescent↗
PubMed1984

Local control of osteogenic sarcoma by radiation and chemotherapy.

Sixteen patients with osteogenic sarcoma of limbs were treated with high dose methotrexate followed by leucovorin rescue, adriamycin and radiotherapy to the primary tumor. A post-treatment surgical biopsy was performed in 15 of the 16 patients. In 12 of 15 patients (80%), the follow-up biopsy was negative for active tumor. Complications of treatment were myelosuppression (16 cases), moist desquamation (13 cases), soft tissue necrosis (2 cases) local infection (2 cases), fibrosis (9 cases) and bone fracture (4 cases). The mean survival time in this group of patients was 712 days.

Adolescent↗
PubMed1982

Combination chemotherapy of the epipodophyllotoxin derivatives, teniposide and etoposide. A pharmacodynamic rationale?

Previous studies in vitro on the influence of extracellular protein binding of Teniposide (VM26) and Etoposide (VP16-213) on subsequent cellular uptake by experimental murine tumor cells [Cancer Res 38:2549 (1978); Drug Metab Rev 8:119 (1978)] suggested that a timed-sequential combination of VM26 and VP16-213 may increase the bioavailability of VP16-213. This was studied clinically in six cancer patients with ascites (five ovarian, one rectal) whereby VM26 (20 mg/m2) was given i.p. 2 h prior to VP16-213 (100 mg/m2; i.p.) In some patients, this regimen was administered i.v. The i.v. regimen was found to be more toxic (myelosuppression, nausea, vomiting) than i.p. regimen at same doses of drugs. Several patients remained stable to disease during 1-2 courses of therapy (3 weeks per course), one patient had partial remission, and has been stable in her disease for more than 4 months. In two patients, plasma and ascites fluid was analyzed for VP16-213 and VM26 by a new reverse-phase high performance liquid chromatography method. Both VM26 and VP16-213 could be eluted isocratically (28% v/v acetonitrile in water) from a c18 column with retention times of 6.6 and 13.3 min, respectively. Subsequent pharmacokinetic analysis of one patient suggests that protein binding displacement of VP16-213 in plasma and perhaps ascites fluid increased the pharmacokinetic volume of distribution (28 l) and reduced the elimination half-life (12 h). The data suggests that VP16-213 is distributed more widely in the body and is represented by a single compartment pharmacokinetic model. Analysis of VM26 in ascites and plasma suggests that the so-called "deep pharmacokinetic compartment" represents ascites equivalent space and that the plasma concentration represents VM26 as free and protein-bound drug in kinetic distinguishable compartments. Determinants of drug action are potentially composed of a multiplicity of physiological, biochemical, and other factors. The potential for manipulating the pharmacodynamic properties of drugs to achieve greater therapeutic potential needs further study.

Adult↗
PubMed1981

Penile angiosarcoma presenting in bladder.

A case of angiosarcoma of the right corpus cavernosum with direct extension to the bladder, prostate, and seminal vesicles and metastasis to brain, liver, and cheek is presented, and the literature is reviewed.

Brain Neoplasms↗