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A Isidori

Publications and source records attributed to A Isidori.

At least 19 recordsLinked to original sources
PubMed2000

All-trans retinoic acid significantly reduces the incidence of early hemorrhagic death during induction therapy of acute promyelocytic leukemia.

Early hemorrhagic death (within the first 10 d of treatment [EHD]) is reported as the main cause of death during induction therapy for acute promyelocytic leukemia (APL). In order to evaluate possible differences in the incidence of EHD during induction regimens based on all-trans retinoic acid (ATRA), we retrospectively analyzed a consecutive series of 86 APL patients, diagnosed and treated at our Institution from 1982. Forty-three patients received combination chemotherapy with anthracyclines and cytosine arabinoside (January 1982 to December 1991), while induction of the remaining 43 was based on ATRA alone or on a combination of ATRA and anthracyclines (January 1992 to October 1996). There were significantly less induction deaths in the ATRA group [9 (chemotherapy group-CT) vs. 2 (ATRA group-RA) overall and 8(CT) vs. 1(RA) of EHD; p = 0.01]. Hemostatic evaluations showed an earlier reduction of D-dimer in the ATRA group. No cases of morphological resistance were observed in the ATRA group after induction. In addition, the number of relapses occurring in the first 24 months from the achievement of complete remission (CR) was significantly lower in the ATRA group (15 vs. 7; p = 0.01), with a disease free survival at 2 yr of 67% vs. 31%. In conclusion, ATRA appears to be able to significantly reduce the incidence of EHD, increasing the number of possible long-term remissions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Alpha-interferon improves survival and remission duration in P-190BCR-ABL positive adult acute lymphoblastic leukemia.

Treatment of P190BCR-ABL+ acute lymphoblastic leukemia (ALL) patients remains problematic: one possibility is to use biologic response modifiers such as alpha-interferon (alpha-IFN), which is known to be active in chronic myeloid leukemia (CML). We used alpha-IFN to treat 10 adult P190BCR-ABL+ ALL patients (eight newly diagnosed; two in first relapse). All received a remission induction chemotherapy (modified L-20 protocol). Patients achieving morphological, immunological and cytogenetic complete remission (CR) were then submitted to a rotational consolidation regimen lasting 6 months. When no HLA-identical donor was available, patients aged <55 years underwent stem cell harvest followed by autologous transplantation; patients aged >/=55 years received standard maintenance treatment for 6 months. In the second year, maintenance treatment (all ages) was based on cycles of alpha-IFN (3 MU three times a week for 6 weeks) alternated with methotrexate/6-mercaptopurine continuously for up to 2 years from first demonstration of CR. Thereafter, patients maintaining CR had the same schedule of alpha-IFN (6 weeks on, 6 off). Eight patients (6/8 first diagnosis, 2/2 relapsed) obtained morphological, immunological and cytogenetic CR with persistent molecular positivity. Two with an HLA-identical donor had allogeneic bone marrow transplantation. Six proceeded with chemotherapy: one experienced early relapse, three were autotransplanted, and two received maintenance. Five patients then received alpha-IFN as scheduled. All five are in continuous morphological and cytogenetic CR, with a longer mean duration of maintained morphological CR (mean 46 months; range: 20-88) than in previous reports of Ph+ ALL patients treated with chemotherapy regimens (excluding allogeneic BMT). alpha-IFN thus appears effective in this poor-risk subset of patients. This well-tolerated IFN-containing maintenance treatment could be considered to reinforce intensified programs based on autologous stem cell transplantation as an alternative to allogeneic transplantation in P190BCR-ABL+ ALL patients (and by extension for Ph+ ALL patients) lacking an HLA-matched donor. Leukemia (2000) 14, 22-27.

Adult↗
PubMed2000

Second chronic phase before transplantation is crucial for improving survival of blastic phase chronic myeloid leukaemia.

Because successful outcome after transplantation seems to depend in acute myeloid leukaemia (AML) and in chronic phase chronic myeloid leukaemia (CML) on disease status at the time of transplantation, we investigated whether FLAN (fludarabine, cytosine arabinoside, mitoxantrone) induction before allogeneic stem cell transplantation (allo-SCT) may be useful in blastic phase (BP)-CML. Twenty patients with BP-CML were studied: 10 patients received FLAN induction chemotherapy before proceeding to early allo-SCT, whereas 10 patients were submitted to bone marrow transplantation (BMT) without remission induction. Eight out of 10 (80%) patients achieved second chronic phase after one course of therapy with FLAN and seven patients (six in second chronic phase and one with partial response) were then submitted to allo-SCT. Of the six patients transplanted in the second chronic phase, all achieved molecular remission, four are still in second chronic phase, with intervals ranging from 10 to 54 months, whereas one patient died from infection having relapsed 14 months after SCT and one died of transplant-related complications in the second chronic phase. Mean durations of second chronic phase and survival after allo-SCT were both significantly longer than in the group of 10 BP-CML patients submitted to allo-SCT without FLAN remission induction treatment [22.4 (range 1-61) vs. 3.5 months (range 1-10) with FLAN and 22.7 (range 2-61) vs. 6.4 (range 1-16) months without FLAN]. We conclude that FLAN induction therapy followed by early allo-SCT appears to be effective in the treatment of BP-CML and could provide a curative possibility for BP-CML patients.

Adult↗
PubMed1999

Body-fat distribution and responsiveness of the pituitary-adrenal axis to corticotropin-releasing-hormone stimulation in sedentary and exercising women.

Excess upper-body (android) fat is considered an health hazard. Exercise training is known to have the potential to modify body composition and to induce a preferential loss of abdominal fat. We studied and compared the composition of whole body and major body regions using dual-energy X-ray absorptiometry (DEXA) in 21 exercising (3-4 hours of intense physical activity/day) and 21 sedentary eumenorrhoic women of similar ages, body mass index (BMI), waist-to-hip ratio (WHR) and age of menarche. In a small number of women in each group (6 out of 21), the ACTH and cortisol response to CRH test and the 24-h urinary cortisol excretion was evaluated. Exercising women had 10% higher total and leg lean mass (p<0.05), and 38% lower total fat mass (p<0.01) than sedentary women. Furthermore, the proportion of android fat was 22% lower in exercising than sedentary women (p<0.01), while the proportion of lower-body (gynoid fat) was unchanged. BMI and WHR were not different between the two groups, while the android/gynoid fat ratios were 16% lower in exercising than in sedentary women (p<0.01). In the exercising women, ACTH and cortisol plasma levels, as well as the 24-h urinary cortisol excretion, were significantly (p<0.01) higher than in the sedentary women studied. In these subjects, a direct relationship between the peak delta percentage increases of ACTH and cortisol after the CRH test and the proportion of android fat was found (r=0.60, p<0.05 and r=0.69, p<0.02, respectively). These results demonstrate that in women who practise intense exercise there are significant differences in body fat distribution in comparison to sedentary women, with a marked less amount of android fat, and suggest that this difference may be related to a reduced response of the pituitary-adrenal axis to CRH.

Absorptiometry, Photon↗
PubMed1999

Use of peripheral blood stem cells for autologous transplantation in acute myeloid leukemia patients allows faster engraftment and equivalent disease-free survival compared with bone marrow cells.

We compared the feasibility and efficacy of autologous bone marrow (ABMT) and peripheral blood progenitor cell transplantation (PBSCT) performed after an identical induction/consolidation in adults with acute myeloid leukemia (AML). From January 1993 to June 1996 91 consecutive AML patients were enrolled in a program consisting of anthracycline-based induction and high-dose cytarabine consolidation (NOVIA). Until May 1994 ABMT was performed; from June 1994, if PBSC collection was adequate, PBSCT was performed. Out of 88 evaluable patients, 73 obtained a complete remission (CR) and 15 were resistant. Allogeneic bone marrow transplantation was performed in 16 patients. Forty-four (50%) were given autologous stem cell transplantation. ABMT was performed in 21 cases; twenty-nine patients were given G-CSF mobilization after NOVIA administration. An adequate number of PBSC was obtained in 23/29 (79%) cases, which were then re-infused. Median times to both neutrophil and platelet recovery from transplant were significantly shorter for the PBSC group (17 vs 36 days to 500 PMN/microl, P < 0.01; 20 vs 150 days to 20000 platelets/microl, P < 0.02; 37 vs 279 days to 50000 platelets/microl, P < 0.03), as were days of hospitalization after the reinfusion (18 vs 33, P < 0.03) and median days to transfusion independence. Toxicity was not significant in either group. After a minimum follow-up for live patients of 24 months (longer than the mean time for relapse observed for the PBSC series - 14 months) the percentage of relapses was similar: 11 of 21 (52.4%) and 12 of 23 (52.1%) in the ABMT and PBSC groups, respectively. Our results indicate that autologous PBSC transplantation, performed after an intensive chemotherapy regimen, is not inferior to ABMT in terms of disease-free survival and allows faster recovery times and reduced need for transfusion support.

Acute Disease↗
PubMed1999

All-trans retinoic acid at low concentration directly stimulates normal adult megakaryocytopoiesis in the presence of thrombopoietin or combined cytokines.

In order to investigate the direct effects of retinoids on normal adult hematopoietic progenitors, purified CD34+ cells were seeded in serum-free cultures in the presence of pharmacological (10(-6)) M or physiological (10(-12)) M concentrations of all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA) plus combinations of specific cytokines. 10(-6) M ATRA and 9-cis RA significantly decreased the number of granulomacrophagic, erythroid and megakaryocytic (CFU-meg) progenitors. On the other hand, 10(-12) M ATRA significantly promoted the growth of CFU-meg, in the presence either of thrombopoietin or of IL-3+ GM-CSF, and induced a reproducible stimulation of the immature CD34+DR- subset. In conclusion, our findings suggest that retinoic acids probably play a direct role in normal adult hematopoietic development at both physiological and pharmacological concentrations. The stimulatory effect on megakaryocytopoiesis should be considered in the perspective of a potential use of low-dose ATRA, combined with thrombopoietin or other cytokines, in pathological conditions where the megakaryocytic compartment is impaired and the stimulation of megakaryocytopoiesis is requested.

Adult↗
PubMed1999

Aspirin inhibits androgen response to chorionic gonadotropin in humans.

Eicosanoids play an important role in the regulation of the hypothalamic-pituitary axis; less clear is their role in testicular steroidogenesis. To evaluate the involvement of cyclooxygenase metabolites, such as prostaglandins, in the regulation of human testicular steroidogenesis, we examined the effects of a prostaglandin-blocker, aspirin, on plasma testosterone, pregnenolone, progesterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol response to human chorionic gonadotropin (hCG) in normal male volunteers in a placebo-controlled, single-blinded study. To test the efficacy of aspirin, seminal prostaglandin E(2) levels were also determined. hCG stimulation increased peripheral levels of testosterone, 17OH-progesterone, androstenedione, dehydroepiandrosterone, and 17beta-estradiol, without affecting circulating pregnenolone and progesterone values. Aspirin significantly lowered seminal prostaglandin E(2) levels, whereas it did not modify steroid concentrations not exposed to exogenous hCG. Moreover, the drug significantly reduced the response of testosterone, 17OH-progesterone, androstenedione, and dehydroepiandrosterone to hCG, as assessed by the mean integrated area under the curve, whereas it did not influence 17beta-estradiol response. In conclusion, aspirin treatment inhibits androgen response to chorionic gonadotropin stimulation in normal humans. The action of aspirin is probably mediated via an effective arachidonate cyclooxygenase block.

Administration, Oral↗
PubMed1999

Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels.

Leptin circulates in plasma at concentrations that parallel the amount of fat reserves. In obese males, androgen levels decline in proportion to the degree of obesity. Recently, we have shown that in rodent Leydig cells leptin inhibits hCG-stimulated testosterone (T) production via a functional leptin receptor isoform; others have found that leptin inhibits basal and hCG-induced T secretion by testis from adult rats. In this study, we further investigated the relationship linking leptin and androgens in men. Basal and hCG-stimulated leptin and sex hormone levels were studied in a large group of men ranging from normal weight to very obese (body mass index, 21.8-55.7). Initial cross-sectional studies showed that circulating leptin and fat mass (FM) were inversely related with total and free T (r = -0.51 and r = -0.38, P < 0.01 and P < 0.05, respectively). Multiple regression analysis indicated that the correlation between leptin or FM and T was not lost after controlling for SHBG and/or LH and/or estradiol (E2) levels and that leptin was the best hormonal predictor of the lower androgen levels in obesity. Dynamic studies showed that in obese men the area under the curve of T and free T to LH/hCG stimulation (5000 IU i.m.) was 30-40% lower than in controls and inversely correlated with leptin levels (r = -0.45 and r = -0.40, P < 0.01 and P < 0.05, respectively). Also, LH/hCG-stimulation caused higher increases in 17-OH-progesterone to T ratio in obese men than in controls, whereas no differences were observed between groups either in stimulated E2 levels or in the E2/T ratio. In all subjects, the percentage increases from baseline in the 17-OH-progesterone to T ratio were directly correlated with leptin levels or FM (r = 0.40 and r = 0.45, P < 0.01), but not with E2 or other hormonal variables. In conclusion, our studies, together with previous in vitro findings, indicate that excess of circulating leptin may be an important contributor to the development of reduced androgens in male obesity.

17-alpha-Hydroxyprogesterone↗
PubMed1999

[The use of dynamic Doppler color ultrasonography of the penis in the study of erectile dysfunction].

INTRODUCTION: We investigated the diagnostic accuracy of dynamic color Doppler sonography (D-CDS) in men with erectile dysfunctions (ED). Terminal microcirculation alterations and their correlation with erectile response after drug testing were investigated with power Doppler energy. MATERIAL AND METHODS: 134 impotent patients were submitted to CDS during flaccidity: 8 of them (6%) had sparse hyperechoic spots inside the corpora. A standardized intracavernous injection of 10 micrograms alprostadil (PGE1) was followed by audiovisual sexual stimulation. If rigid erection was not achieved after 20 minutes, patients were randomized to redosing of either 10 micrograms PGE1 (phase 2a) or 10 micrograms PGE1 plus 1 mg phentolamine (phase 2b), with reassessment of power Doppler recordings after 20 minutes (peak systolic velocities and the resistive index, RI). RESULTS: A rigid erection (RI > .90) was achieved in 26% of patients after the first injection. As for the remaining patients, the RI was improved in 12% after phase 2a and in 34% after phase 2b (p < .05), with no differences in mean peak systolic velocities. Power Doppler showed two/three orders of distal branches of helicine arterioles with regular morphology, in most of the latter subjects. A negative correlation (r = .68, p < .001) was found between penile fibrosis and the degree of rigidity achieved after the first injection. CONCLUSIONS: Penile sonography in the flaccid state can show calcificic plaques and/or fibrosis of the corpora. Redosing of PGE1 plus phentolamine during D-CDS is a safe procedure and improves diagnostic accuracy in erectile dysfunctions, with significantly fewer non-responders than redosing of PGE1 alone. Power Doppler energy shows altered morphology of helicine arterioles otherwise missed at color Doppler and is thus recommended to make an accurate diagnosis in some men with erectile dysfunctions.

Erectile Dysfunction↗
PubMed1998

Galanin stimulates steroidogenesis in rat Leydig cells.

The present study was designed to evaluate whether galanin could play a role in the regulation of testicular steroidogenesis. To this purpose, using purified rat Leydig cells, we examined the effects of galanin on basal and hCG- or LHRH-induced testosterone production and the interference of a specific galanin receptor antagonist, galantide, on galanin activity. Moreover, since it has been shown that galanin-induced stimulation of LHRH secretion appears to involve the release of prostaglandin E2 (PGE2) as intracellular mediator, we evaluated also the effect of galanin on Leydig cells PGE2 output and the interference of indomethacin, a cycloxygenase blocker, on its activity. Furthermore, the effect of nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, was also examined. Data obtained indicate that galanin amplified testosterone response to hCG or LHRH whilst galantide prevented its potentiating activity. Moreover, galanin stimulated PGE2 output though this fatty acid is not involved in galanin activity on Leydig cells as indomethacin failed to affect its amplification of testosterone production. The possible involvement of leukotrienes should also be excluded as NDGA did not modify galanin action. In summary, the present study indicates that galanin potentiates acute gonadotropin or LHRH steroidogenic action on Leydig cells and that this activity is specific and receptor-mediated as it is prevented by a specific receptor antagonist.

Animals↗
PubMed1998

Rapid decline of fertility in a case of adrenoleukodystrophy.

Adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN) is a group of genetically determined peroxisomal disorders associated with progressive central demyelination, primary adrenal cortical insufficiency (Addison's disease) and, frequently, primary hypogonadism. Recently, testicular dysfunction was described in ALD/AMN patients but no information on sperm characteristics was provided. In this paper we studied the reproductive function of a patient with adult cerebral ALD, focusing our attention on sperm characteristics. At the time of diagnosis the patient was 22 years old, had high plasma C26 and C24 very-long-chain fatty acid (VLCFA) concentrations and adrenal insufficiency. Plasma testosterone concentration was in the normal range. The patient was prescribed a low-fat diet and 'Lorenzo's oil', which led to normalization of plasma VLCFA concentrations within 3 months of therapy. Semen analysis showed normal sperm count, gross morphological alterations and reduced motility. Electron microscopy analysis of sperm cells showed pathological changes in the head, the plasma membrane and the nucleus in 60% of the spermatozoa examined. However, isolated motile spermatozoa showed normal molecular dynamics of phospholipid bilayer surface and physiological responsiveness to progesterone. At the 12 months follow-up, the patient became azoospermic and testicular histology showed arrested maturation. To our knowledge, this is the first description of sperm alterations in a post-pubertal ALD patient, in which severe impairment of spermatogenesis and rapid progression to azoospermia occurred despite normalization of plasma VLCFA concentrations.

Adrenoleukodystrophy↗
PubMed1998

Analysis of Yq microdeletions in infertile males by PCR and DNA hybridization techniques.

Defects in spermatogenesis have been found associated with deletions of different portions of Y chromosome long arm (Yq), suggesting the presence of the azoospermia factor in the control of spermatogenesis. We studied 67 men with idiopathic azoospermia and severe oligozoospermia, cytogenetically normal, for the presence of microdeletions on Yq chromosome. By using polymerase chain reaction (PCR) and Southern blotting techniques we analysed the AZFa, AZFb and AZFc loci on Yq, where deletions have been associated with defects in spermatogenesis. Deletions of a portion of the Y chromosome were detected in five patients. Four of these patients shared deletions in distal Yq11 interval 6, including the DAZ gene, while one patient lacked loci in the proximal Yq11. Testicular histology of two patients bearing distal Yq11 deletions showed two different spermatogenic defects including Sertoli cell-only (SCO) syndrome and maturation arrest, while the patient with microdeletions in the proximal Yq11 showed a SCO phenotype.

Blotting, Southern↗
PubMed1997

Stimulatory action of endothelin-1 on rat Leydig cells: involvement of endothelin-A subtype receptor and phospholipase A2-arachidonate metabolism system.

In a previous report we have observed that endothelin-1 (ET-1) is able to stimulate testosterone (T) production by rat Leydig cells revealing an interaction with human chorionic gonadotropin (hCG). The present study was designed to further characterize the stimulatory action of ET on testicular steroidogenesis, to evaluate which subtype of ET receptors is involved in this activity and to examine the role of phospholipase A2 (PLA2)-arachidonate metabolism system in ET-1 transduction mechanism. To this purpose we investigated: i) the interaction of ET-1 with another secretagogue of T, like luteinizing hormone releasing hormone (LHRH); ii) the interference of ET(A) and ET(B) receptor antagonists (BQ-123 and BQ-788, respectively) and of inhibitors of PLA2 (quinacrine) and arachidonate lipoxygenase pathway (nordihydroguaiaretic acid:NDGA) on ET-1-induced T and PGE2 secretion from purified rat Leydig cells. Data obtained indicate that ET-1 amplified T and PGE2 response to LHRH and this secretagogue in turn potentiated testicular steroidogenesis stimulated by endothelin. The ET(A) antagonist, BQ-123, inhibited in a dose-related fashion ET-1-induced T production whereas ET(B) antagonist, BQ-788, failed to affect T response to the peptide. Furthermore, ET(A) antagonist inhibited the stimulatory effect of ET-1 on hCG- or LHRH-induced T secretion and it was able to exert a dose-dependent inhibition of ET-1-stimulated PGE2 output. Moreover, a PLA2 inhibitor quinacrine inhibited the stimulatory action of ET-1 on T production and suppressed basal and ET-1-induced PGE2 release whilst a lipoxygenase blocker NDGA did not modify T response to the peptide. Taken together these findings i) indicate additivity of effects between ET-1 and LHRH in stimulating T and PGE2 production; ii) confirm that ET(A) subtype receptors mediate the stimulatory action of ET-1 on rat Leydig cells; iii) strongly suggest that PLA2-arachidonate metabolism system is involved in endothelin transduction mechanism.

Animals↗
PubMed1997

Pituitary adenylate cyclase-activating polypeptide regulates rat Leydig cell function in vitro.

The present study was designed to evaluate the effects of both pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 on testosterone, cAMP and prostaglandin E2 (PGE2) production by purified rat Leyding cells. Because PACAP-38 shares homology with vasoactive intestinal peptide (VIP), the effects of VIP and both PACAP and VIP receptor antagonists on testicular steroidogenesis were also examined. PACAP-38 potentiated testosterone response to a low effective dose of human chorionic gonadotropin (hCG), while PACAP-27 was without effect. Furthermore, PACAP-38 amplified testosterone response to a wide concentration range of hCG until the submaximal dose. VIP evoked a dose-dependent increase of both basal and hCG-induced testosterone production. PACAP potentiation of steroidogenesis was nullified in the presence of a PACAP antagonist, but was not modified by a VIP antagonist. Moreover, while VIP antagonist blunted testosterone response to VIP, PACAP antagonist was without effect. Increasing concentrations of PACAP-38 evoked a dose-response enhancement of both cAMP and PGE2 production. However, this fatty acid is not involved in PACAP activity, as a prostaglandin blocker indomethacin did not modify the effect of PACAP on steroidogenesis. Taken together these findings: (i) demonstrate that PACAP-38 is able to activate both cAMP- and phosphatidylinositol-dependent mechanisms in Leydig cells; (ii) indicate that the peptide exerts an amplificatory action on testicular steroidogenesis stimulated by hCG and that this activity is receptor-mediated, as it is prevented by a PACAP receptor antagonist; (iii) predict the existence of specific PACAP receptors (type 1 binding sites) on Leydig cells.

Animals↗
PubMed1996

Anxiety-induced failure in erectile response to intracorporeal prostaglandin-E1 in non-organic male impotence: a new diagnostic approach.

Intracavernous injection (ICI) of prostaglandin-E1 (PGE1) is used widely as the first diagnostic test in the study of erectile dysfunction. However, a lack of full erection after a maximal dose is frequent. As well as vascular incompetence, this may be due to stress-induced changes, related to the ICI procedure. The aim of this study was to investigate the influence of emotional disturbances on erectile response to ICI in impotent patients. Initially, 24 young men with non-organic impotence (age 34.6 +/- 1.5 years; mean +/- SEM) were selected and randomized single-blind to pharmacoerection with PGE1 alone (20 micrograms/mL) or a mixture (cocktail) containing 20 micrograms PGE1 plus an alpha-adrenergic receptor blocker, phentolamine (Phe, 0.5 mg/mL). Additional studies were also performed double-blind on 10 men with non-organic impotence (age 37.6 +/- 1.2 years) utilizing higher PGE1 dosages for ICI (25 micrograms/mL alone or in combination with Phe, 0.5 mg/mL). After a 7-day interval, all subjects were crossed-over to receive the alternative treatment. The presence of emotional disturbances was assessed in all patients by the administration of rapid tests (Stai-X1 and Stai-X1r for state-anxiety before and after ICI, respectively; Stai-X2 for trait-anxiety; Zung-test for depression) at the first and at the remaining (Stai-X1 and Stai-X1r) ICI sessions. ICI with 20 and 25 micrograms/mL PGE1 led to a comparable percentage of patients who reported a valid-for-intromission (VFI) erection (63 and 60%, respectively). In contrast, use of the cocktails significantly increased the percentage of subjects with a VFI (87 and 90% of the total number of patients tested, respectively; p < 0.05). Moreover, a strong inverse correlation between state-anxiety scores (Stai-X1) and the erectile response to ICI with 20 and 25 micrograms PGE1 was found (r = -0.69, p < 0.001); such a correlation was not present in patients who underwent ICI with the cocktails. Two cases of prolonged erection occurred (one after 20 micrograms PGE1 and the other after 20 micrograms PGE1 plus Phe) which were reversed promptly by the intracavernous injection of metharaminol. It is concluded that the lack of a full erectile response after ICI with PGE1 can be related to the presence of a high 'state-anxiety' in the patients. In such patients, a VFI erectile response can be induced by the administration of a cocktail test-dose.

Adrenergic alpha-Antagonists↗
PubMed1996

Aspirin inhibition of naloxone-induced luteinizing hormone secretion in man.

It is well known that endogenous opioid peptides exert a tonic inhibitory control on GnRH release, leading to the inhibition of LH secretion, whereas eicosanoids, particularly prostaglandin E2(PGE2), stimulate GnRH output. Furthermore, in vitro studies suggest the existence of an interaction between these two regulatory systems in animals. The present work was designed to evaluate the acute effect of the prostaglandin blocker aspirin on plasma LH response to the opiate antagonist naloxone or GnRH in normal volunteers in a placebo-controlled, single-blind study. To exclude a hypothetical action of aspirin directly at the testis level, plasma testosterone concentrations were monitored during basal sampling after acetylsalicylic acid ingestion, whereas the efficacy of the drug as a prostaglandin blocker was tested by the determination of seminal PGE2 levels. Aspirin pretreatment significantly lowered seminal PGE2 levels (from 86 +/- 5 before to 11 +/- 2 micrograms/mL [corrected] after drug administration; P < 0.001) without affecting testosterone concentrations. Moreover, the drug induced a significant reduction of LH response to naloxone, assessed as the mean integrated area under the curve, from 1666.5 +/- 116 to 1197.5 +/- 98 mUI/mL per min (P < 0.05), whereas it did not influence GnRH-induced LH release. We conclude that the effective cycloxygenase blockade inhibits the stimulatory activity of naloxone on LH release, suggesting that the inhibitory tone of opioids on GnRH secretion may be caused by the block of hypothalamic prostaglandin biosynthesis with consequent inhibition of PGE2-induced GnRH secretion.

Adult↗
PubMed1996

[Azoospermia and genetic mutations: implications for the methods of in vitro fertilization].

Much evidence suggests the fundamental role of the Y chromosome during spermatogenesis. Especially, a gene on the long arm (localized in a portion of the chromosome called Yq11), the AZF (azoospermic factor), is necessary for the achievement and the maintenance of the spermatogenetic process. In fact mutations and deletions in this part of the chromosome inevitably cause severe oligozoospermia or azoospermia. Furthermore other genes on the short arm seem to have a role during spermatogenesis: they are called ZFY (zink finger Y, which encodes a DNA binding protein) and TSPY (expressed in the spermatids nuclei); but the function of these genes is still uncertain, since at this moment no deletions or mutations have been found at this level. Further genes only recently cloned include the CREM (cAMP-responsive element modulator), whose mutation causes azoospermia with a spermatidic arrest in the mouse, and the complex c-kit/Steel-factor. The latter is essential for spermatogonial proliferation and differentiation, so that an alteration at this level can determine spermatogonial arrest or the absence of germinal cells with the presence of Sertoli cells only (Sertoli cells only syndrome). In contrast with AZF, both the CREM gene and c-kit/Steel-factor genes are autosomal (chromosome 10 for the CREM, 4 for c-kit, 1 for Steel-factor, respectively). Several genes may be involved in the spermatogenetic process, but their role, excepting for AZF, is still unclear.

Animals↗