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Biomedical subjects

C Moretti

Publications and source records attributed to C Moretti.

At least 73 records · Page 4Linked to original sources
PubMed1994

Isolation of bis-indole alkaloids with antileishmanial and antibacterial activities from Peschiera van heurkii (syn. Tabernaemontana van heurkii).

Extracts from leaves and stem bark of Peschiera van heurkii (Muell. Arg.) L. Allorge (syn. Tabernaemontana van heurkii Muell. Arg., Apocynaceae) have been assayed for antileishmanial and antibacterial activities. The activities were concentrated in the alkaloid fractions which yielded 20 indole and bisindole alkaloids. The strongest leishmanicidal and antibacterial activities were observed with the dimeric alkaloids conodurine (1), N-demethylconodurine (= gabunine) (2), and conoduramine (3). Weak toxicity towards macrophage host cells and strong activity against the intracellular amastigote form of Leishmania were observed for compounds 1 and 2. In vivo, 1 was less active than glucantime (= N-methylglucamine antimonate), the drug of reference, while 2 was devoid of activity at 100 mg/kg.

Alkaloids↗
PubMed1993

Evidence of functional alterations in sympathetic activity after myocardial infarction.

To assess whether the presence of areas of efferent sympathetic denervation might contribute to alterations in sympathetic and vagal neural regulatory activities observed after myocardial infarction, we attempted to correlate the changes in the spectral components of RR variability with the I-123 MIBG and Thallium-201 uptake defects. Ten patients with first and uncomplicated myocardial infarction were studied. Thallium-201 and I-123 MIBG scintigraphy as well as spectral analysis of heart rate variability were performed 7 days, 4, 12 and 30 months after the acute event. Regional abnormalities in I-123 MIBG uptake were more extensive than the perfusion defects indicated by Thallium-201 images and remained constant throughout the entire period of observation. In the early post-infarction period, spectral analysis of RR variability was characterized by a predominant LF (74 +/- 6 nu) and a smaller HF (16 +/- 3 nu) component indicating a sympathetic predominance. Thereafter, we observed a progressive reduction in LF and a gradual increase in HF which were consistent with a normalization of sympatho-vagal balance. These data indicate that after a myocardial infarction, the presence and persistence of areas of sympathetic functional denervation do not seem to play a major role in determining the changes in sympathetic and vagal neural regulatory activities directed to the heart.

3-Iodobenzylguanidine↗
PubMed1992

[Antimalarial effect of n-hentriacontanol isolated from Cuatresia sp (Solanaceae)].

The antimalarial activity of the fatty alcohol, n-hentriacontanol, isolated from the bolivian Solanaceae, Cuatresia sp, is investigated in vivo through a classical four-day suppressive test against Plasmodium berghei and P. vinckei in mice. This product markedly reduced the virulence of experimentally induced P. vinckei infection. n-Hentriacontanol belongs to a new class of antimalarial natural compounds to be exploited for therapeutic purposes.

Animals↗
PubMed1992

Expression of the growth hormone-releasing hormone gene and its peptide product in the rat ovary.

GH-releasing hormone (GHRH) is a potent cAMP-mediated agonist in the rat ovary, where it binds to a common vasoactive intestinal peptide/GHRH receptor and enhances the actions of FSH on granulosa cell maturation. A GHRH-like peptide has been detected by immunocytochemistry in the human ovary and by RIA in follicular fluid, suggesting local synthesis of the peptide. In rat ovarian poly(A)+ RNA, Northern blot hybridization analysis with a 32P-labeled 48-nucleotide (nt) rat GHRH oligonucleotide probe revealed the presence of one major and two minor mRNA species. The major ovarian GHRH mRNA (1750 nt) was much larger than that present in hypothalamus and placenta (750 nt), but was similar to that observed in the rat testis. Two well defined higher mol wt forms of 3.2 and 3.6 kilobases were also present and probably represent unprocessed precursors of the 1750-nt mRNA. Further evidence of GHRH gene expression in the ovary and testis was provided by reverse transcription polymerase chain reaction of ovarian mRNA and restriction enzyme analysis of the amplified product. In addition, immunoreactive (ir) GHRH was detected in ovarian extracts and in the incubation medium of cultured rat granulosa cells. Ovaries from PMSG-treated female rats, aged 22-27 days, contained 400 +/- 25 pg/g ir-GHRH. The GHRH content of the hypothalamus of the same animals was 2.9 +/- 0.1 ng/g. Cultured rat granulosa cells released 20 +/- 0.1 pg ir-GHRH/4 x 10(5) cells.3 h into the incubation medium. The GHRH immunoreactivity detected in ovarian extracts coeluted on gel filtration chromatography with authentic rGHRH (5.2 kilodaltons). A larger form of ir-GHRH (approximately 16.5 kilodaltons) was also present. These data demonstrate that the rat ovary contains a 1750-nt transcript that could arise from the GHRH gene by tissue-specific initiation, alternative splicing, or transcript termination. The translation product of this mRNA is the same similar size as the rat hypothalamic neuropeptide and may promote follicular maturation by autocrine or paracrine modulation of the stimulatory action of FSH on granulosa cell function.

Animals↗
PubMed1991

Gonadotropin-induced expression of receptors for growth hormone releasing factor in cultured granulosa cells.

The hypothalamic neuropeptide, GRF, is formed in the ovary and acts via specific receptors in granulosa cells to enhance cAMP production and steroidogenic responses to the pituitary gonadotropin, FSH. Granulosa cells cultured without hormonal treatment displayed low levels of binding sites for GRF and the related neuropeptide, vasoactive intestinal peptide. However, treatment with increasing concentrations (50-500 ng/ml) of FSH caused dose-dependent increases in cAMP production and expression of binding sites measured with radioiodinated [His1, Nle27]human GRF(1-32)NH2, with no change in binding affinity. The maximum increase in GRF binding sites (2.2-fold) was elicited by 250 ng/ml FSH after 72 h incubation. GRF binding sites were also increased by agents that elevate intracellular cAMP, including choleragen, vasoactive intestinal peptide, dibutyryl cAMP, and forskolin. Low doses of forskolin that did not alone increase [125I] [His1, Nle27] human GRF(1-32)NH2 binding potentiated the action of FSH on GRF binding sites, but the effects of maximal stimulatory doses of both agents were not additive. These findings demonstrate that FSH promotes the expression of GRF receptors in maturing granulosa cells through cAMP-dependent mechanisms. Since GRF enhances the actions of FSH on cAMP production and granulosa cell differentiation, and GRF receptors are increased by the cAMP-mediated actions of FSH, locally produced GRF could exert a positive autoregulatory action to accelerate follicular maturation by amplifying the granulosa cell response to FSH.

Animals↗
PubMed1990

Neurotransmitter, opiodergic system, steroid-hormone interaction and involvement in the replacement therapy of sexual disorders.

Dopamine (DA) and serotonin (5-HT) are the neurotransmitters most directly involved in sexual activity. DA plays a stimulatory role while 5-HT has an inhibitory effect. The two monoaminergic systems modulate the secretion of many hormones (GnRH, LH, testosterone, prolactin and endorphins) involved in sexual functional capacity. Furthermore, hormones influence synthesis and storage of brain neurotransmitters. Impotence can often be associated to clinical depression and altered neurotransmitter function. Moreover, stress represents an unbalance between various neurotransmitter systems and can induce impotence especially when disorders of the endorphinic system are present. Replacement therapy is based upon the understanding of these basic concepts. Impotence due to an underlying depressive illness must be treated with dopaminergic antidepressant drugs; while in stressful conditions a good response to the naloxone test is the preliminary criterion to subsequent naltrexone treatment. When a hormonal deficiency has been proved, the hormone replacement therapy is of course highly effective (gonadotropins in hypogonadotropic syndromes, testosterone in aging, etc.). Finally, idiopathic impotence could be treated by DA agonist and/or 5-HT antagonist drugs either alone or better yet in association with psychotherapy.

Adult↗
PubMed1990

Immunohistochemical localization of growth hormone-releasing hormone in human gonads.

Human gonads were examined for the presence of ir growth hormone-releasing-hormone. We demonstrated the presence of immunostainable cells both in ovarian and in testicular tissue using a non-crossreactive anti-GRH antiserum and the immunoperoxidase detection technique. In ovaries from ovulating women, GRH immunoreactivity was localized in the corpora lutea; granulosa cells, theca cells and cells of primary follicles did not stain. In premenopausal ovaries, staining was detectable in scattered luteinized stromal cells. In testes from post-puberal men GRH immunoreactivity was localized in the Leydig cells; cells of the germinal epithelium did not stain. These results demonstrate the presence of GRH in human gonads and suggest that this peptide may exert regulatory function at the testicular and ovarian levels.

Female↗
PubMed1990

Plasma prolactin response to domperidone in acute schizophrenia and schizophreniform illness.

The prolactin (PRL) response to 20 mg of domperidone, a peripheral dopamine (DA) blocking agent, was evaluated in a group of 16 drug-free, acute, young schizophreniform and schizophrenic males and in a group of age-matched normal males. Although basal plasma PRL levels were normal, the PRL responses following domperidone were blunted in both patient groups. The PRL response was more blunted in the schizophreniform patients than in the schizophrenic patients. Possible explanations for these results include pharmacokinetic factors or abnormalities of the pituitary D2 DA receptors.

Acute Disease↗
PubMed1990

Complement, complement activation and anaphylatoxins in human ovarian follicular fluid.

Functionally active complement was sought and detected in human follicular fluids obtained during the pre-ovulatory period. All the functional complement activities tested, including total haemolytic complement, classical pathway activity and alternative pathway activity were present in nine fluids from four different donors with values within the normal serum range. The immunochemical analysis demonstrated the presence of complement factors from C1 to C9, of B and of C1 INH, H, I. Complement anaphylatoxins were found employing RIA techniques in amounts significantly higher than in human plasma, thus demonstrating that follicular fluid complement, at least during the pre-ovulatory period, is partially activated. A possible role for urokinase-like substances in such an activation was indicated by further in vitro experiments. The presence of active complement in follicular fluid can be relevant for the function of the enzymatic multi-factorial mechanism of ovulation.

Anaphylatoxins↗
PubMed1990

Prolactin and growth hormone responses to growth hormone-releasing hormone in acute schizophrenia.

Growth hormone (GH), and prolactin (PRL) responses to the administration of growth hormone-releasing hormone (GHRH) (1 microgram/kg) were evaluated in a group of 18 drug-free, acute, young male schizophrenics and in a group of age-matched normal controls. Cortisol responses were also evaluated. No difference in mean plasma GH, PRL and cortisol plasma basal values or in GH and PRL responses to GHRH between schizophrenics and controls was observed. Our failure to demonstrate a difference in GH response to GHRH between schizophrenics and controls would seem to indicate that GH secretory pituitary reserve is intact in young acute male schizophrenics. Cortisol values did discriminate between schizophrenics and controls (p less than 0.05). In our sample, both schizophrenics and normal controls showed a slight but significant (p less than 0.03) and transitory increase in plasma PRL response to GHRH.

Acute Disease↗
PubMed1990

Receptor-mediated actions of growth hormone releasing factor on granulosa cell differentiation.

GRF promotes follicular maturation and ovulation when administered with FSH in the treatment of infertility. Such actions could be mediated by stimulation of GH secretion and insulin-like growth factor I production, but the known actions of the structurally related hormone, vasoactive intestinal peptide (VIP), on granulosa cell function suggested that GRF may also act directly on the ovary to stimulate follicular development. Radioligand binding and activation studies, performed in granulosa cells from immature estrogen-treated rats, revealed a common receptor for VIP and rat (r) GRF in the ovary. Specific binding of [125I]VIP to granulosa cells was saturable and dependent on time and temperature. The relative potencies of VIP-related peptides for inhibition of radioligand binding were: VIP greater than rGRF greater than peptide histidine isoleucinamide greater than [His1,Nle27] human GRF(1-32)NH2 greater than secretin. In binding studies with the potent GRF agonist, [125I] [His1,Nle27]GRF(1-32)NH2, relative potencies were: rGRF(1-43)OH greater than [His1,Nle27]human GRF(1-32)NH2 greater than VIP greater than peptide histidine isoleucinamide greater than secretin. Glucagon and gastric inhibitory peptide, other peptides of the glucagon superfamily, and unrelated peptides including CRF and beta-endorphin, did not inhibit binding of either radioligand to ovarian receptors. In cultured granulosa cells, rGRF and VIP stimulated cAMP formation, consistent with coupling of their receptors to the adenylate cyclase system, and potentiated FSH-induced cAMP production. Both peptides also amplified FSH-induced progesterone biosynthesis, aromatase activity, and LH receptor formation. These observations demonstrate that rGRF is a potent cAMP-mediated agonist in the rat ovary and acts on a common VIP/GRF receptor in maturing granulosa cells. It is likely that the potentiating effect of administered GRF on gonadotropin-stimulated follicular development in vivo is in part mediated by direct actions of the peptide on the VIP/GRF receptor. Also, since GRF is present in the gonads, it is possible that the locally-produced peptide promotes follicular maturation by paracrine modulation of the stimulatory action of FSH on granulosa cell function.

Animals↗
PubMed1989

Neuroendocrine control of male reproductive function. The opioid system as a model of control at multiple sites.

It is known that the same peptide can be identified in different secretory tissues and in the central nervous system (CNS). We now provide evidence that the same peptides can be found in different organs related to the control of a single function, and speculate on the possibility that this reflects a common neuroendocrine programming. Endogenous opioid peptides (EOP) inhibit the reproductive function acting via the CNS. EOP inhibit gonadotropin secretion in rodents and humans via inhibition of GnRH release and have direct inhibitory actions at the pituitary level via specific binding sites on the gonadotrophs. However, EOP can also be synthesized in the testis and in different compartments of the male genital tract. Several findings indicate that EOP of the reproductive tract have a local, paracrine role. These include: (1) the detection of significant beta-endorphin (beta-EP) production by rat Leydig cells (Lc) in cultures; (2) the hormonal regulation of Lc beta-EP production by positive (gonadotropins) and negative (steroids, glucocorticoids, GnRH) factors; (3) the presence of opioid binding sites (Kd in the nanomolar range) in tubular homogenates and Sertoli cells (Sc) in culture of adult and immature rat testes; (4) the inhibition of basal and FSH-stimulated ABP production by Sc in culture when chronically exposed to beta-EP treatment; (5) the detection of high levels of beta-EP and met-enkephalin in human semen with values 6-12 times higher than in plasma; (6) the evidence for inhibitory functions of seminal opioids on sperm motility, vas deferens muscle contraction and partner immune system. Thus the same peptides, i.e. EOP, may control the reproductive function at multiple sites, operating as a multimessenger system in which the central and peripheral level are unified by the common chemical and inhibitory nature of the message.

Animals↗
PubMed1989

Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.

In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.

Adult↗
PubMed1989

Isolation of a human seminal plasma peptide with bombesin-like activity.

Bombesin (BN) and BN-like peptides such as gastrin-releasing peptide (GRP) belong to the growing group of regulatory peptides. Bombesin and GRP share the same carboxyl-terminal heptapeptide sequence that is essential for receptor recognition and biologic activity. Immunohistochemical findings have indicated the presence of a BN-like peptide in the neuroendocrine cells of the human prostate. These findings, together with the high concentrations of different regulatory peptides recently found in seminal plasma, prompted us to characterize a BN-like peptide in human semen by gel-filtration chromatography, reverse-phase high-pressure liquid chromatography, and in vitro bioassay. Here we demonstrate that human semen contains high levels (mean +/- standard deviation, 288.9 +/- 114.39 pg/ml) of a substance that closely resembles the 14-27 carboxyl-terminal fragment of GRP (GRP 14-27). The partially purified peptide obtained from this source, examined on an in vitro bioassay that is especially useful for testing BN-like activities, elicits a contractile response of the rat uterus that is indistinguishable from that stimulated by standard BN and GRP 14-27. The GRP 14-27 present in human seminal plasma may be involved in some aspect of the process of fertilization.

Adult↗
PubMed1988

Low serum bioactive luteinizing hormone in nonorganic male impotence: possible relationship with altered gonadotropin-releasing hormone pulsatility.

We determined the biological activity of serum LH in 23 men, aged 25-50 yr, complaining of nonorganic impotence of at least 1-yr duration and 20 normal men. All of the impotent men had normal general physical examinations, penile Doppler tests, psychological tests, and peripheral nerve conduction. Serum PRL, FSH, LH, and thyroid hormone concentrations were normal as were the results of provocative tests of TSH, gonadotropin, and PRL secretion. The mean serum immunoreactive LH (I-LH) levels, measured in each impotent and normal man in three samples taken at 15-min intervals, were similar [7.2 +/- 0.5 (+/-SE) vs. 6.4 +/- 0.5 mIU/mL (IU/L)]. In contrast, the mean serum bioactive LH (B-LH) level was significantly lower in the impotent men than in the normal men [15.9 +/- 2.1 (+/-SE) vs. 33.0 +/- 2.8 mIU/mL (IU/L); P less than 0.05], as was the LH bio- to immunoactive (B/I) ratio (2.1 +/- 0.2 vs. 5.6 +/- 0.5; P less than 0.02). The mean serum testosterone level in the impotent men, although all individual values were within the range of normal for our laboratory [200-900 ng/100 mL (693-3120 nmol/L)], was 25% lower than that in the normal men [347 +/- 23 vs. 450 +/- 26 ng/100 mL; P less than 0.05 (1204 +/- 81 vs. 1560 +/- 91 nmol/L)]. In addition, a significant positive correlation was found between serum testosterone levels and LH B/I ratios in the impotent men (r = 0.45; P = 0.029). Pulsatile LH secretion, measured in six impotent and four normal men in blood samples collected every 15 min for 6 h, was similar in the two groups. The mean serum I-LH levels were similar [7.5 +/- 1.1 (+/-SE) vs. 5.1 +/- 1.0 mIU/mL (IU/L)], while the mean serum B-LH level as well as the LH B/I ratio was significantly lower in the impotent men throughout the observation period [11.4 +/- 2.0 (+/-SE) vs. 26.0 +/- 3.2 mIU/mL (IU/L) and 1.4 +/- 0.2 vs. 5.4 +/- 0.6; P less than 0.05 and P less than 0.02, respectively]. The B-LH pulse amplitude in the impotent men was reduced [mean peak LH, 8.6 +/- 0.3 vs. 25.3 +/- 4.0 mIU/mL (IU/L); P less than 0.05], while the LH pulse frequency was similar in the two groups. The median intrapulse LH B/I ratios were significantly higher than the median interpulse ratios in both impotent (P = 0.02) and normal men (P = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗