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Biomedical subjects

A Dupont

Publications and source records attributed to A Dupont.

At least 163 records · Page 9Linked to original sources
PubMed1983

New hormonal treatment in cancer of the prostate: combined administration of an LHRH agonist and an antiandrogen.

At doses which have no or minimal inhibitory effect when administered alone, the LHRH agonist [D-Ser(TBU)6,des-Gly-NH10(2)] LHRH ethylamide (HOE-766) and the antiandrogen RU-23908 administered simultaneously cause a marked inhibition of ventral prostate and seminal vesicle weight after 5 months of treatment. The effect of the LHRH agonist is due to a blockage of the testicular steroidogenic pathway. The same LHRH agonist administered to adult men with cancer of the prostate causes a marked inhibition of serum testosterone and dihydrotestosterone to castration levels within 1-2 weeks. Administration of the pure antiandrogen to men with cancer of the prostate already receiving the LHRH agonist does not interfere with the LHRH agonist-induced blockage of androgen biosynthesis: Moreover, objective signs of remission of the disease were rapidly observed in 8 out of 10 patients. The ease of application of this new form of hormonal therapy which neutralizes androgens from all sources should facilitate its early administration and thus minimize the development of metastases and androgen-resistant cell clones.

Androgen Antagonists↗
PubMed1983

Effects of thyroid state on serotonin, 5-hydroxyindoleacetic acid and substance P contents in discrete brain nuclei of adult rats.

The effects of chemical thyroidectomy produced by propylthiouracil treatment or hyperthyroidism produced by daily injections of thyroxine on the content of serotonin, its metabolite 5-hydroxyindoleacetic acid and of substance P in discrete brain nuclei of adult rats have been studied. Brain nuclei were removed by punches of frozen brain slices. The serotonin and 5-hydroxyindoleacetic acid contents were measured by high performance liquid chromatography with electrochemical detection while substance P was assayed by radioimmunoassay. The serotonin level was significantly increased in 11 nuclei of the hypothyroid and in 12 nuclei of the hyperthyroid rats. The 5-hydroxyindoleacetic acid levels were higher in 16 nuclei of the hypothyroid and 7 nuclei of the hyperthyroid animals. The state of the thyroid gland in adult rats also affected the substance P system but less consistently than the serotonin pathway. Thus, the substance P content in the brain of propylthiouracil-treated animals increased significantly in 4 nuclei while it decreased in the septum lateralis and the striae terminalis. Following the chronic thyroxine injections, the substance P level was increased in the nucleus caudatus putamen and the tractus diagonalis and was decreased in the area ventralis tegmenti. We previously reported that neonatal thyroidectomy caused a general increase of the substance P and serotonin contents in many brain nuclei of young rats. It appears that the effects of chemical thyroidectomy on mature and immature rat brain are different for the substance P system, suggesting that thyroxine plays an important role in the maturation of substance P-containing neurons.

Animals↗
PubMed1983

Determination of 5-hydroxytryptophan, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in 20 rat brain nuclei using liquid chromatography with electrochemical detection.

High-performance liquid chromatography with electrochemical detection is utilized for the simultaneous determination of serotonin, its precursor 5-hydroxytryptophan, and its major metabolite 5-hydroxyindoleacetic acid in nervous tissue samples. Tissue preparation required only homogenization in acidic solution and centrifugation prior to application to the chromatograph. Detection limits in the low picogram range were obtained for those indoles separated. This assay was used in combination with a micropunch dissection technique of 20 discrete rat brain nuclei to measure serotonin, its precursor, and major metabolite. The specificity of the assay was checked with pharmacological experiments aimed to increase or decrease serotonin levels. Pargyline, a monoamine oxidase inhibitor, led to a marked increase in serotonin and a decrease of 5-hydroxyindoleacetic acid while p-chlorophenylalanine, by blocking the conversion of tryptophan to 5-hydroxytryptophan, selectively depleted 5-hydroxytryptophan, serotonin, and 5-hydroxyindoleacetic acid.

5-Hydroxytryptophan↗
PubMed1983

New hormonal therapy in prostate cancer: combined use of a pure antiandrogen and an LHRH agonist.

Treatment with an LHRH agonist (HOE-766) alone causes an almost complete blockage of testicular testosterone formation in rat and man. In order to neutralize androgens of adrenal origin, a pure antiandrogen (RU-23908) was given in combination with the LHRH agonist in the rat. At doses where each drug has no or minimal effect alone, prostate and seminal vesicle weight were reduced to 9 and 15% of control after 5 months of combined treatment, respectively. Among the species studied, man is the most sensitive to the inhibitory effect of treatment with LHRH agonists on testicular steroidogenesis. Near castration levels of serum testosterone and 5 alpha-dihydrotestosterone are obtained within 1-2 weeks of daily subcutaneous administration of the LHRH agonist [D-Ser(tbu)6, des-Gly-NH2(10)]LHRH ethylamide (HOE-766) in adult men with cancer of prostate. The decrease in serum androgen levels is accompanied by objective remission of the cancer in approximately 75% of cases. In a preliminary study where the LHRH agonist was administered in combination with the pure antiandrogen RU-23908, it was shown that the antiandrogen does not interfere with the LHRH-induced inhibition of serum androgen levels. The ease of application of this new form of hormonal therapy should permit its use at early stages of the disease and thus reduce the development of metastases and androgen-resistant cell clones.

Androgen Antagonists↗
PubMed1983

[New approach in the treatment of prostatic cancer: combined use of a LHRH agonist and an androgen antagonist].

Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high doses of estrogens. These two approaches cause a temporary improvement in 60 to 70% of advanced prostatic cancer. However, castration is not always well accepted and high doses of estrogens are frequently accompanied by lethal cardiovascular side effects. Following our observation that treatment with LHRH agonists causes a blockage in the biosynthesis of testosterone by the testis accompanied by a marked reduction in prostatic weight in the rat, the possibility was opened for a new approach in the treatment of prostatic cancer. Fortunately, among all species studied, man is the most sensitive to the inhibitory effect of LHRH agonists on testicular androgen biosynthesis and near-medical castration can be easily achieved without secondary effects other than those related to low androgen levels. Following long-term studies in the rat which have shown that the inhibitory effect of LHRH agonists is markedly potentiated by simultaneous administration of a pure antiandrogen, a study using the LHRH agonist [D-Ser(TBU)6, des-Gly-NH2(10)] LHRH ethylamide (HOE-766) and the pure antiandrogen RU-23908 was performed in men with advanced prostatic cancer. The combined treatment with the LHRH agonist and the antiandrogen in 37 patients not previously treated caused a positive objective response in 97% of cases while, previously, partial hormonal treatment achieved through castration or high doses of estrogens caused a positive response in 60 to 70% of patients. The serum levels of prostatic acid phosphatase (PAP) were decreased to 40% of control as early as four days after starting combined hormonal therapy. By contrast, in patients previously treated with estrogens or castrated, complete neutralization of adrenal androgens by the antiandrogen led to a much lower rate of positive response ranging from 25 to 55%. In patients previously treated, there is thus a predominance of tumor cells insensitive to androgens. An additional important finding in this study is that the administration of the antiandrogen prevents the flare-up of the disease frequently observed when LHRH agonists are administered alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid Phosphatase↗
PubMed1982

Effect of chronic estradiol treatment on dopamine concentrations in discrete brain nuclei of hypophysectomized female rats.

We investigated the effect of chronic estradiol treatment on dopamine concentrations in 14 discrete brain nuclei of hypophysectomized rats. Estrogen treatment reduced dopamine concentrations in nigrostriatal and mesolimbic dopaminergic systems of hypophysectomized and ovariectomized rats compared to hypophysectomized controls while the opposite was observed in tuberoinfundibular nuclei. However, hypophysectomized rats had significantly higher dopamine concentrations compared to ovariectomized animals is nigrostriatal and mesolimbic nuclei while lower levels were found in tuberoinfundibular structures. Thus, estradiol treatment has an effect on brain dopamine concentrations independently of the pituitary. Furthermore, this steroid treatment corrects the effects produced by hypophysectomy on brain dopamine concentrations.

Afferent Pathways↗
PubMed1982

[Congenital fibromatosis. Anatomical and clinical study on three observations (author's transl)].

Three congenital fibromatosis are studied. Six years later, the subcutaneous and skeletal lesions of the first patient have disappeared with no recurrence. Regression was also observed in the second one, a generalized fibromatosis with skeletal, subcutaneous and almost certainly pulmonary and laryngeal lesions. The last case is now progressing (vertebral lesion) with a vascular invasion, the prognostic of which is unknown. A review is made about microscopical appearance, origin and difficulties in diagnosis.

Diagnosis, Differential↗
PubMed1982

3H-mepyramine binding in various regions of rat brain following chronic treatment with different classes of antidepressant drugs.

1. The possible role of the histamine system in the mechanism of action of the antidepressant drugs was proposed. 2. We studied the 3H-mepyramine binding to histamine H1-receptor following chronic treatment with different classes of antidepressant products which possess diverse pharmacological action at the synaptic level. 3. Administration of chlorimipramine in clinical dosage caused a complete disappearance of the 3H-mepyramine affinity for its receptor in the occipital cortex. The number of H1-receptors was decreased in the hypothalamus, the posterior hippocampus and the occipital cortex following chronic desipramine treatment. Nomifensine administration increased the Bmax in the anterior hippocampus while iprindole treatment have not affected the H1-receptor in the rat brain. 4. We conclude that the modification of H1-receptors is not a general property of antidepressants indicating that is not causally related to their main therapeutic action.

Aminopyridines↗
PubMed1982

Distribution of dopamine in 35 subregions of the rat caudate-putamen: a high performance liquid chromatography with electrochemical detection analysis.

Topographical variations in the endogenous content of dopamine were studied in the rat caudate-putamen. For this purpose, a high performance liquid chromatography with electrochemical detection procedure for the determination of norepinephrine, epinephrine and dopamine in nervous tissue samples is described. Tissue preparation required only homogenization in acidic solution and centrifugation prior to application to the chromatograph. Detection limits in the low picogram range were found for the catecholamines separated. This assay was used in combination with a micropunch dissection technique. The performance of this analytical technique is illustrated by the detailed mapping of dopamine content in 35 subregions of the rat caudate-putamen. The distribution of dopamine varies along the major axis of the nucleus.

Animals↗
PubMed1982

Effects of estradiol on intact and denervated striatal dopamine receptors and on dopamine levels: a biochemical and behavioral study.

The present study describes the effect of chronic estrogen treatment on striatal dopamine levels and dopamine receptors, as well as on apomorphine-induced circling, a behavioral model reflecting dopaminergic activity in the rat striatum. Although estradiol itself does not show any affinity for the striatal dopamine receptor, its administration for 2 weeks in adult ovariectomized rats leads to a small increase in [3H]spiroperidol, [3H]haloperidol, and [3H]apomorphine binding in the striatum; this increase is associated with a greater number of binding sites. In order to dissociate possible pre- and post-synaptic effects of estrogens, these studies were next performed in animals bearing an unilateral 6-hydroxydopamine lesion of the substantia nigra. The apomorphine-induced circling behavior of rats bearing such a lesion was not affected by estrogen treatment. Estradiol treatment induced an increase of [3H]spiroperidol binding in both the intact and lesioned striatum, thus suggesting an estrogenic effect on a population of postsynaptic receptors. Chronic estradiol treatment reduced the concentration of dopamine in the striatum while the turnover of this amine measured using alpha-methyl-p-tyrosine remained unchanged. The present results show that estradiol exerts effects at the striatal level on both dopamine metabolism and receptor levels.

Animals↗