Biomedical subjects

F Facchinetti

Publications and source records attributed to F Facchinetti.

At least 19 recordsLinked to original sources

PubMed1992

Evidence of alpha-N-acetyl beta-endorphin in human cerebrospinal fluid.

Alpha-N-acetyl-beta-endorphin (Ac-beta-EP) is a post-translational product of beta-endorphin (beta-EP) with no analgesic properties. Ac beta-EP is present in human fetal and adult pituitary gland and cross-reacts in all available beta-EP assays. This study evaluates levels of Ac-beta-EP in the cerebrospinal fluid (CSF) of 22 normal subjects and 15 chronic headache sufferers. Since dopamine may play a role in the acetylation process, homovanillic acid levels were also determined. After extraction and high performance liquid chromatographic (HPLC) fractionation of CSF, an immunoreactive Ac-beta-EP peak was detected coeluting with reference peptide. Ac-beta-EP was detectable in all but 5 normal subjects. In headache sufferers, Ac-beta-EP levels were always detectable and their mean value was significantly higher than that of healthy subjects (11.6 +/- 11.8 vs 3.9 +/- 3.6 fmol/ml; P less than 0.01). Conversely, CSF beta-endorphin (beta-EP) concentrations were decreased in headache patients (9.8 +/- 9.4 vs 15.7 +/- 9.7 fmol/ml; P less than 0.05), and as a consequence the beta-EP/Ac-beta-EP ratio was also markedly reduced (P less than 0.005). No difference was observed for CSF homovanillic acid concentrations. These data demonstrate that HPLC coupled to radioimmunoassay allows the identification of low but significant amounts of Ac beta-EP in human CSF. This compound represents a confounding factor when beta-EP immunoreactivity is assessed by conventional methods. In headache sufferers, Ac-beta-EP levels were higher than normal, whereas beta-EP concentrations were lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Antagonists of the NMDA receptor and allopurinol protect the olfactory cortex but not the striatum after intra-cerebral injection of kainic acid.

Overstimulation of the NMDA receptor, as well as generation of excessive amounts of free radicals, has been implicated in excitotoxic brain injuries. We report here that two antagonists of the NMDA receptor and an inhibitor of the free radical-generating enzyme, xanthine oxidase, protect the olfactory cortex but not the striatum after intrastriatal injection of kainic acid. Our results suggest the existence of a precise link between excitotoxic activation of the NMDA receptor and neuropathology related to excessive amounts of free radicals. The focal point of this link may be the entry of Ca2+ through the NMDA receptor and the consequent activation of proteases and free radical-generating systems.

Allopurinol↗

PubMed1992

Induction of brain ornithine decarboxylase after systemic or intrastriatal administration of kainic acid.

The activity of ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, dramatically increases after different types of brain injuries. The role of this induction is still unclear. We report here data on the temporal pattern of ODC induction caused by the excitotoxin kainic acid. After systemic administration, ODC activity increases severalfold peaking at 8 h in the prefrontal cortex and at 16 h in the olfactory cortex and hippocampus. After intrastriatal injection, the peak of induction is reached at 32 h, while a smaller and more transient increase is also observed in the contralateral, saline-injected striatum. We suggest that ODC induction is initially linked to overactivation of neural circuits and, later on, to the development of widespread neural damage.

Animals↗

PubMed1992

Occurrence of immunoreactive Met- and Leu-enkephalin-like peptides in the ovary of the green frog, Rana esculenta.

In the present study, we have localized for the first time Met- and Leu-enkephalin-like material in the ovary of the anuran, Rana esculenta, using the indirect immunofluorescence method. The ovaries were sampled during the main representative phases of the annual reproductive cycle of the frog, living in a mountain pond (Colfiorito, Umbria at 820 m a.s.l.). Strong immunoreactivity to Met- and Leu-enkephalin antisera was observed in the follicle cells of the granulosa layer of vitellogenic oocytes; moreover, during this phase, immunofluorescent materials were also radially localized in the cytoplasm and in the perinuclear zone. The mature oocytes showed Met- and Leu-enkephalin-like immunostaining in the thecal layer and in several granules scattered in the peripheral zone of the yolk. The different pattern of Leu- and Met-enkephalin-like immunoreactivity in the frog ovary parallels and complements the changes occurring in the reproductive (May) and in the vitellogenetic (September) phases during the ovarian cycle. Consequently, these findings strongly support the hypothesis for a local synthesis of these peptides in the ovary and suggest their possible involvement in the control of ovarian function.

Animals↗

PubMed1992

Immunoreactive Met-enkephalin-like material in the testis of Rana esculenta: identification and localization.

Methionine-enkephalin (Met-Enk) has been detected in the testis of the frog, Rana esculenta, using a reverse-phase high-performance liquid chromatography system coupled with a specific radioimmunoassay. By means of immunocytochemical techniques Met-Enk positive cells have been localized in interstitial and germinal compartments. Particularly, spermatogonia, spermatocytes, and spermatozoa were stained in seminiferous tubules, and numerous interstitial cells showed strong cytoplasmic immunoreactivity in summer animals. Variations in the concentration of Met-Enk immunoreactive material occurred during the annual cycle. Our data show that Met-Enk is present in testes of nonmammalian vertebrate species. These results suggest that autocrine and/or paracrine mechanisms may regulate testicular activity in amphibians.

Amino Acid Sequence↗

PubMed1992

Ovarian opioids and the reproductive cycle of the frog Rana esculenta.

In mammals, proopiomelanocortin-related peptides are involved in reproductive processes both at the hypothalamo-pituitary and ovarian levels. Using immunocytochemical, biochemical and physiological "in vitro" studies, we provide here evidence for a diffuse POMC-related opioid system in the frog Rana esculenta. Ovarian beta-endorphin (beta-EP) is expressed in thecal cells and changes during the reproductive cycle in an inverse relationship with follicular development. Seasonal changes in the ovary are different to those in the brain or in the pituitary. The ratio of acetylated vs native beta-EP in the ovary also changes over the reproductive period, affecting the biological activity of the peptide. During both the reproductive spring period and the summer post-reproductive phase pMol amounts of beta-EP stimulate follicular androgen secretion in vitro, in a naloxone-reversible way. In either period, an inhibition of estradiol, possibly mediated via other factors, is the result of opioid action. In conclusion, these data demonstrate for the first time the widespread presence of beta-EP-related peptides in the frog Rana esculenta. Both immunocytochemical and biochemical evidence, as well as in vitro responses, support a physiological role for beta-EP in ovarian seasonality during the reproductive cycle of this amphibian.

Amino Acid Sequence↗

PubMed1992

Central changes of beta-endorphin-like immunoreactivity during rat tonic pain differ from those of purified beta-endorphin.

Several studies have described changes in beta-endorphin-like immunoreactivity (beta-ELI) in the rat brain in response to pain and stress stimuli. In order to ascertain the components of beta-ELI, brain samples of rats experiencing acute prolonged (tonic) pain were evaluated for their beta-ELI and later submitted to a chromatographic purification allowing the measurement of beta-endorphin (beta-EP) and acetyl beta-EP. The chromatographic analysis of both ventromedial hypothalamus (VMH) and periaqueductal grey (PAG) homogenates indicates that beta-ELI is distributed in several fractions including shortened forms of beta-EP and their respective acetylated compounds. Quantitatively, while beta-ELI in formalin-injected animals was increased by 48% in VMH and 45% in PAG in respect to controls, the net increase of purified beta-EP was 1100% and 470%, respectively, for VMH and PAG. Moreover, the maximal increase of beta-ELI was evident at 120 min, in both tissues. In contrast, the beta-EP peak was reached at 30 min in VMH and at 60 min in PAG. Acetyl beta-EP was unchanged by treatment in both central areas. No correlation of beta-ELI and beta-EP was found in VMH. These data demonstrate that the evaluation of beta-ELI gives a poor estimate of beta-EP changes, due to several components of the endorphin family.

Animals↗

PubMed1992

Psychosomatic disorders related to gynecology.

In this paper current issues on four psychosomatic disorders related to gynecology will be reviewed. The history, nosological problems and psychoneuroendocrine correlates of psychogenic amenorrhea have been summarized taking into account the important role of psychological factors in inducing loss of menses. Definition and diagnostic problems in assessing menstrually related disorders (formerly premenstrual syndrome) have been reviewed, looking at this syndrome as a disorder of adaptation to the cyclical changes of neuroendocrine functions. The impact of stress on fertility and, on the other hand, the effects of infertility on psychological well-being have been pointed out trying to ascertain the pathways involved in these mutual relationships. Finally, the issue of mood changes at menopause and the effects of steroid replacement on affective state have been discussed. As a whole, these evidences indicate the importance of a close cooperation between gynecologist and psychiatrist in the management of gynecological disorders.

Adolescent↗

PubMed1992

Oral magnesium supplementation improves fetal circulation.

It is well known that pregnancy is a condition in which plasma magnesium falls because of accumulation of the ion in the placenta and fetus. Magnesium (Mg) is therefore widely given as a supplement during pregnancy, particularly in cases of preterm labour. In our experience, the combination of oral Mg (magnesium pyrrolidone carboxylic acid) at a dose of 360 mg/day with conventional ritodrine treatment allows a reduction in ritodrine dosage, accompanied by a significant reduction in side effects. We therefore evaluated changes in fetal blood flow, using pulsed Doppler, in women submitted to combined magnesium and ritodrine treatment compared to those treated with ritodrine plus placebo. The Mg-treated group showed a decrease in vessel resistance both in the umbilical artery and in the fetal middle cerebral artery, indicating that fetal vasculature is sensitive to exogenous Mg. Measurement of plasma and mononuclear cell Mg showed an intracellular increase in the cation of about 10 per cent. We conclude that oral magnesium supplementation in pregnancy is safe and that it has a positive effect on the fetal circulation.

Cerebral Arteries↗

PubMed1991

Central beta-endorphin system involvement in the reaction to acute tonic pain.

The involvement of the beta-endorphin (B-EP) system during acute prolonged (tonic) pain was investigated by biochemical and behavioral approaches in freely-moving rats after subcutaneous injection of a small amount of a dilute formaldehyde solution (0.08 ml, 5%) in a forepaw. Beta-endorphin-like immunoreactivity levels were increased over the respective control groups in rats killed 30, 60 and 120 min after injection in discrete regions of the rat brain, namely ventro-medial hypothalamus, ventro-basal thalamus and periaqueductal gray matter, and at 30 and 60 min in postero-medial thalamus. In a separate group of experiments a small amount of anti-B-EP or normal rabbit serum was injected in the lateral ventricle; 6 h later rats received formalin injection as in previous groups and their behavior was scored over the following 2 h. A significant hyperalgesia (as expressed by an increase in the amount of time rats spent licking or chewing the injected paw) was observed 10-50 min and 70-80 min after formalin in the anti-B-EP icv-injected group. Other behavioral parameters such as general motor activity, grooming and limb flexion were not different in the two groups, nor was animal behavior prior to formalin injection. Altogether these data suggest that the central beta-endorphin system is triggered by prolonged noxious stimulation in freely-moving animals, and in turn plays a physiological role in the modulation of the reaction to, or perception of, tonic pain.

Acute Disease↗

PubMed1991

Pituitary and brain beta-endorphin in male and female rats: effects of shock and cues associated with shock.

The present experiment was designed to study whether or not prior exposure to inescapable shock is accompanied by sex-dependent changes in pituitary and central levels of immunoreactive beta-endorphin, which is proposed to play an important role in opioid analgesia induced by aversive stimulation. Further, the effects of brief reexposure (5 min) to the chamber where inescapable shock was experienced earlier, were established in both sexes. Elevated levels of beta-endorphin were found 24 hours after inescapable shock, in the anterior pituitary of males and in the midbrain periaqueductal gray of both males and females. Reexposure to the experimental chamber only affected beta-endorphin levels if shock had been experienced in this chamber. Reexposure after inescapable shock reduced beta-endorphin content of the arcuate nucleus of males and beta-endorphin content of the periaqueductal gray of males and females. The present results are related to previous findings of sensitization and conditioning of analgesic reactions. The sex differences found in the present experiment are discussed with respect to sex-dependent behavioral consequences of inescapable shock.

Animals↗

PubMed1991

Peripheral opioid secretory pattern in anorexia nervosa.

The peripheral secretion of endogenous opioids was studied in 10 women with restrictive anorexia nervosa and 10 age- and sex-matched healthy controls. The circadian rhythm of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH), and their responses to the administration of corticotropin releasing hormone (CRH, 1 micrograms/kg body weight, i.v.), clonidine (150 microgram, i.v.), domperidone (10 mg, i.v.), and 5-hydroxytryptophan (5-HTP, 200 mg, p.o.) were examined in patients and controls. The results revealed increased nocturnal secretion of beta-EP and diurnal-nocturnal secretion of beta-LPH with loss of circadian rhythmicity of both peptides, normal response to CRH stimulation, blunted response to clonidine and domperidine, and normal beta-EP and blunted beta-LPH response to 5-HTP stimulation. The data suggest a complex alteration of peripheral opioids and of central aminergic mechanisms that regulate proopiomelanocortin-derived peptide secretion and eating behavior.

5-Hydroxytryptophan↗

PubMed1991

Unresponsiveness of the endorphinergic system to its physiological feedback in obesity.

Beta-endorphin (beta-Ep) plasma levels are higher in obese patients than in normal subjects. To establish that this finding constitutes hyperendorphinemia, 28 obese patients aged 12-55 years, six males and 22 females, (weighing 61-117 kg) were investigated twice by an overnight 1-mg p.o. dose dexamethasone suppression test (DST) before and after weight loss. beta-Ep was measured by radioimmunoassay (RIA). Before body weight loss, beta-Ep was higher than normal and unresponsive to DST, whereas ACTH and cortisol were suppressible. After weight loss, beta-Ep was slightly reduced but still insensitive to DST. ACTH and cortisol were responsive as usual. Findings suggest a resistance to DST in obesity as far as beta-Ep is concerned. The disorder persists even after weight loss, indicating that hyperendorphinemia is not secondary to body weight excess. Accordingly, one can argue that the unresponsiveness of the endorphinergic system to its physiological feedback is a pathophysiological characteristic of obesity.

Adolescent↗

PubMed1991

Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium.

The effects of oral Magnesium (Mg) pyrrolidone carboxylic acid were evaluated in 20 patients affected by menstrual migraine, in a double-blind, placebo controlled study. After a two cycles run-in period, the treatment (360 mg/day of Mg or placebo) started on the 15th day of the cycle and continued till the next menses, for two months. Oral Mg was then supplemented in an open design for the next two months. At the 2nd month, the Pain Total Index was decreased by both Placebo and Mg, with patients receiving active drug showing the lowest values (P less than 0.03). The number of days with headache was reduced only in the patients on active drug. Mg treatment also improved premenstrual complaints, as demonstrated by the significant reduction of Menstrual Distress Questionnaire (MDQ) scores. The reduction of PTI and MDQ scores was observed also at the 4th month of treatment, when Mg was supplemented in all the patients. Intracellular Mg++ levels in patients with menstrual migraine were reduced compared to controls. During oral Mg treatment, the Mg++ content of Lymphocytes (LC) and Polymorphonucleated cells (PMN) significantly increased, while no changes in plasma or Red Blood Cells were found. An inverse correlation between PTI and Mg++ content in PMN was demonstrated. These data point to magnesium supplementation as a further means for menstrual migraine prophylaxis, and support the possibility that a lower migraine threshold could be related to magnesium deficiency.

Administration, Oral↗

PubMed1991

Use of meclofenamic acid in gynecology and obstetrics: effects on postsurgical stress.

Meclofenamic acid has been successfully used in several obstetrical and gynecological disorders sustained by a prostaglandin overproduction. A brief review of meclofenamic acid use for primary dysmenorrhea, menorrhagia, and episiotomy pain is followed by an original study of this compound in postsurgical pain and stress. Thirty gynecological patients undergoing abdominal hysterectomy and 10 pregnant women submitted to cesarean section at term were considered. In gynecological patients, meclofenamic acid suppositories (200 mg) or placebo were given every 12 h during the immediate postsurgical period; pregnant women were given the active drug only. Subjective pain was evaluated [through visual analogue scale (VAS)] in basal conditions (2 h from the end of surgery) and 2, 4, 6, 24, and 28 h from the first drug dose. At the same time, blood was drawn for the evaluation of plasma cortical levels (through coated-tube radioimmunoassay). A significant pain relief was obtained after only 4 h posttreatment both in gynecological patients and pregnant women. Meclofenamic acid was superior to placebo from 6 h after treatment and it almost suppressed subjective pain at the end of the observation period (28th h). Cortisol levels were already high at the basal evaluation and showed a further increase during the first postsurgery hours. Patients treated with meclofenamic acid had cortisol values lower than those who were treated with placebo. The former recovered normal levels after 24 h, whereas the latter already had increased values. These data demonstrate that meclofenamic acid is a safe, powerful and specific analgesic for the postsurgical period. The reduction of pain stimulation is also accompanied by a reduced activation of the neuroendocrine axis with a prompt recovery from postsurgical stress.

Adult↗

PubMed1991

Oral magnesium successfully relieves premenstrual mood changes.

Reduced magnesium (Mg) levels have been reported in women affected by premenstrual syndrome (PMS). To evaluate the effects of an oral Mg preparation on premenstrual symptoms, we studied, by a double-blind, randomized design, 32 women (24-39 years old) with PMS confirmed by the Moos Menstrual Distress Questionnaire. After 2 months of baseline recording, the subjects were randomly assigned to placebo or Mg for two cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were drawn premenstrually, during the baseline period, and in the second and fourth months of treatment. The Menstrual Distress Questionnaire score of the cluster "pain" was significantly reduced during the second month in both groups, whereas Mg treatment significantly affected both the total Menstrual Distress Questionnaire score and the cluster "negative affect." In the second month, the women assigned to treatment showed a significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes were observed in plasma and erythrocytes. These data indicate that Mg supplementation could represent an effective treatment of premenstrual symptoms related to mood changes.

Administration, Oral↗

PubMed1990

Maternal plasma concentrations of magnesium, calcium, zinc and copper in normal and pathological pregnancies.

In this study, plasma levels of magnesium, calcium, zinc and copper were simultaneously determined in pregnancies complicated by either abortion, intrauterine growth retardation (IUGR), diabetes or EPH (edema, proteinuria, hypertension) gestosis. The levels of the four cations in non-pregnant women and in healthy, pregnant women were also determined. Compared with controls, a significant decrease in magnesium, with increase of the Ca/Mg ratio, was found in spontaneous abortions, but not when patients had a successful continuation of pregnancy. In EPH gestosis, total calcium was reduced, with a significant decrease of the plasma Ca/Mg ratio. A slight, but significant, increase in plasma zinc was observed in women affected by either diabetes or IUGR, probably as a result of reduced zinc uptake by the fetus. In addition, higher copper levels were found in the pathologies studied, with the exception of missed abortions. The possible role of an altered Ca/Mg ratio homeostasis in relation to gestational pathologies is discussed.

Abortion, Spontaneous↗

PubMed1990

Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in goldfish brain.

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively damages dopaminergic neurons in mammals, caused a marked depletion of tyrosine hydroxylase (TH) immunoreactivity in the goldfish brain. The concomitant ultrastructural observations showed the neurotoxic effect of MPTP on telencephalic, diencephalic and medullar neurons. The affected neurons revealed darkening of the cytoplasm and swelling of the mitochondria and the endoplasmic reticulum. Concomitant significant decreases in dopamine (DA) and noradrenaline (NA) levels were determined in the brain areas where morphological observations were performed. The loss of catecholamine levels was completely prevented by the treatment with the monoamine oxidase (MAO) inhibitor pargyline to prevent MPTP oxidation. The results indicate that in goldfish brain, acute MPTP administration causes selective catecholamine depletion, without altering the serotoninergic system.

Animals↗