Néstor J. Aparicio

Effect of the Phosphodiesterase Inhibitor Pentoxyfylline on Human Sperm Motility

Einfluß des Phosphodiesterase‐Inhibitors Pentoxyphyllin auf die Motilität menschlicher Spermatozoen

Pentoxifylline (BL 191) by Oral Administration in the Treatment of Asthenozoospermia

Pentoxyphyllin (BL 191) in der Behandlung der Asthenozoospermie bei oraler Applikation

Luteinizing Hormone-Releasing Hormone in the Treatment of Anovulatory Infertility

: Fifteen infertile, anovulatory women, ages 20 to 37, were treated with synthetic luteinizing hormone-releasing hormone (LH-RH) to stimulate follicular maturation and/or ovulation. Thirteen of the patients had been treated unsuccessfully with other therapeutic regimens. To obtain follicular maturation, LH-RH was given intramuscularly in daily doses of 25 mu-g for 7 days and 50 mu-g for the next 7 days, or 100 mu-g for 3 days and 150 mu-g for the next 3 days. Both regimens were begun on the 4th day of a spontaneous or induced cycle. Follicular maturation (evaluated by the cervical mucus scale) occurred in three of seven cycles treated withe the first regimen and three of five treated with the second regimen. To induce ovulation, LH-RH was given in intravenous infusion (50 to 500 mu-g), intramuscularly (100 mu-g), or in a combination of both methods. The drug was administered after follicular maturation with LH-RH, clomiphene citrate, or human menopausal gonadotropin had been achieved; it was also given during four cycles in which spontaneous follicular maturation had occurred. Ovulation occurred in 10 of 25 treated cycles. Five pregnancies resulted, three in the first post-treatment cycle.

Plasma levels of norepinephrine during the periovulatory period in normal women

Abstract Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day −8 to day −4, and every 8 hours from day −3 to day +2; estradiol (E 2 ), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E 2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E 2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E 2 peak. These values remained high until 16 hours before the LH peak and decreased gradually, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge.

Release of Prolactin During Pregnancy: Effect of Sulpiride

The aim of this trial was to study the prolactin-releasing capacity of the pituitary during pregnancy by means of an acute stimulation with sulpiride. Thirty women with normal pregnancies were included in the study (first trimester, nine women; second trimester, eleven women thir trimester, ten women). Each woman received an intramusclar injection of 100 mg of sulpiride sulfate between 8 and 9 A.M. Three similar groups received injections of a saline solution. Blood samples were obtained before and 30 and 60 minutes after the injection. In each sample the prolactin concentration was determined by radioimmunoassay. Basal prolactin levels increased during pregnancy. Significant responses to sulpiride were observed during the three stages of pregnancy, and the levels in the second and third trimesters were higher than those in the firsttrimester. The prolactin-releasing capacity of the pituitary, as judged by the response to sulpiride, seems to be maintained during pregnancy.

Response of Luteinizing Hormone and Follicle-Stimulating Hormone to Different Doses of Synthetic Luteinizing Hormone-Releasing Hormone by Intramuscular Administration in Normal and Oligospermic Men: Preliminary Report

The response of LH and FSH levels to intramuscularly administered synthetic LH-RH was studied in two healthy volunteers and three oligospermic patients. Four tests with 50, 100, 250, and 500 mug of LH-RH, respectively, were carried out on each subject at 8 am; the interval between tests was one week. The serum levels of LH and FSH were determined by radioimmunoassay (double-antibody method) before each injection, and 60, 120, 180, and 240 minutes after each injection. No differences in the basal values of either hormone were observed. In both oligospermic and normal men, maximal responses were obtained with doses between 100 and 250 mug. With 500 mug, levels decreased rather than increased. Maximal peaks occurred between 60 and 180 minutes after injection. In the two normal subjects, the responses of LH and FSH were similar. Two of the three oligospermic patients showed discordant responses. From the results, we can assume that LH-RH doses between 100 and 250 mug should be used as a basis for chronic treatment.

The influence of pentoxyfylline [1-(5-oxohexyl-) 3,7-dimethylxanthine] (BL 191) on the insulin secretion induced by glibenclamide and by arginine/glucose in the perfused pancreas

SummaryPharmacodynamic characteristics of pentoxyfylline (BL 191) related to insulin secretion by the isolated perfused rat pancreas are studied.The results obtained show that: 1) BL 191 (5 mM) is capable of stimulating insulin secretion, even in the presence of another stimulator; 2) BL 191 increases both phases of the secretion produced by constant arginine 20 mM/glucose 5 mM perfusion; 3) BL 191 significantly increases and turns biphasic the monophasic insulin secretion pattern produced by 1 µg/ml glibenclamide; 4) the effects mentioned in points 2) and 3) are inhibited if the phosphodiesterase activator imidazole (300 mg/100 ml) is present in the perfusion medium; 5) the phosphodiesterase inhibitor theophylline has the same effects as BL 191, except for its inability to stimulate insulin release in the absence of another stimulator; 6) somatostatin (100 ng/ml) significantly inhibits insulin secretion produced by arginine/glucose or glibenclamide, as well as by arginine, glucose plus theophylline or BL 191, and by glibenclamide plus theophylline or BL 191; in both cases the inhibitory effect of somatostatin is reduced by the presence of BL 191 or theophylline.

Bromocriptine in the Treatment of Hyperolactinemic Amenorrhea

Thirty women with secondary amenorrhea and hyperprolactinemia were studied; galactorrhea was present in 25 of them, and 18 were infertile. Serum prolactin (PRL) levels were high in all cases, between 26 and 120 ng/ml. All women were treated with bromocriptine in increasing doses from 2.5 to 5.0 or 7.5 mg daily, according to the response obtained, for 4 months. In 27 patients a PRL determination was performed during treatment; values returned to normal (up to 20 ng/ml) in 23 women and remained high in 4. Galactorrhea disappeared in 21 of 25 women. Ovulatory menses were re-established in 17 patients (56.6%). Seven women became pregnant (38.8%), one of them after bromocriptine and clomiphene were given simultaneously in the same cycle. According to our results and a literature review the following conclusions may be drawn: (1) bromocriptine is a useful therapeutic tool for re-establishing menstruation and inducing ovulation in patients with the hyperprolactinemic-amenorrhea syndrome; (2) the association of bromocriptine and clomiphene could be the next step in the treatment of patients who fail to ovulate with bromocriptine alone.

Serum Levels of Prolactin in Basal Conditions and after Administration of 2-Bromo-5α-Ergocryptine in Normal and Galactorrheic Subjects

Serum levels of prolactin were measured basally and after the oral administration of 2.5mg of 2-bromo-5α-ergocryptine to healthy male (n=4) and female (n=5) subjects; to women with spontaneous galactorrhea and normal, biphasic cycles (n=3); to galactorrheic women with spontaneous bleeding but no indirect signs of ovulation (n=9); to galactorrheic-amenorrheic women with no evidence of pituitary adenoma (n=19); and to galactorrheic-amenorrheic women with roentgenologic signs of pituitary adenoma (n=4). The drug was given between 8:00 and 9:00 A.M.; blood samples were obtained before and 60, 120, 180, and 240 minutes and 24 hours after the administration of 2-bromo-5α-ergocryptine. Serum levels of prolactin were measured by radioimmunoassay with a double-antibody technique. The mean basal prolactin level in normal men was 12.5±1.0ng/ml; in normal women (7th to 9th days of the cycle) it was 16.2±4.0ng/ml. After drug administration serum levels of prolactin decreased progressively and systematically; minimal values were found at 180 to 240 minutes. The lowest maximal percentage of inhibition in normal subjects was 56%. Basal prolactin levels in galactorrheic women tended to be higher in relation to the severity of the pathophysiologic involvement. The highest levels were found in patients with demonstrable tumors. The drug-induced percentage reduction of these prolactin levels was lower in galactorrheic women than in normal women; paradoxical increases in prolactin levels occurred in some cases. The wide variability of the results obtained in the galactorrheic groups would restrict the practical application of this testing procedure.

PLASMA LEVELS OF NOREPINEPHRINE DURING THE PERIOVULATORY PERIOD IN NORMAL WOMEN

Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day -8 to day -4, and every 8 hours from day -3 to day +2; estradiol (E2), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E2 peak. These values remained high until 16 hours before the LH peak and decreased gradually, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge.