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Biomedical subjects

G Giordano

Publications and source records attributed to G Giordano.

At least 145 records · Page 8Linked to original sources

Opioid tonus and luteinizing hormone secretion in anorexia nervosa: priming effect with serotonin precursor L-5-hydroxytryptophan during pulsatile gonadotropin-releasing hormone administration.

In anorexia nervosa (AN) luteinizing hormone (LH) release is often impaired during opioid blockade. We investigated whether a restoration of the endogenous sex steroid milieu, together with a rise in central serotonergic tone, could increase LH responsiveness to Naloxone (NAL) in seven young women affected by AN. The spontaneous pulsatility of gonadotropins and their response to gonadotropin-releasing hormone (GnRH) and NAL challenges were tested before and after 13 days of pulsatile GnRH treatment and oral administration of L-5-hydroxytryptophan. Low and unpulsatile gonadotropin levels, responsive to GnRH, but not to NAL, were found before treatment. Pulsatile GnRH brought about a quasi-normal secretory pattern and 17 beta-estradiol increased to preovulatory levels in six of seven patients. On day 13 the lack of response to NAL administration was still present, however. A neuroendocrine disorder seems to be present in AN, which appears more complex than in other forms of hypothalamic amenorrhea.

5-Hydroxytryptophan↗

Excimer laser photoablative filtration surgery: histology and ultrastructure in 4 human cadaver eyes.

The purpose of this study was to verify the feasibility of ab externo layer-by-layer excimer laser photoablative removal of limbal tissue down to the trabecular meshwork and to assess the damage caused by this procedure to the neighbouring structures. Excimer laser photoablation (193 nm) can remove layers of corneal tissue effectively with little or no damage to the adjacent areas. Previous experimental studies have demonstrated a decrease in outflow resistance after ab-externo photoablative removal of juxtacanalicular tissue. We have performed ab-externo photoablative removal of limbal tissue overlying the trabecular meshwork in four freshly enucleated eyes from our Eye Bank. The beam of an excimer laser (wavelength 193 nm; fluence 180 mJ/Sq.cm) was shaped using a metal mask with a rectangular opening of 1.2 x 2.5 mm. After removing the conjunctiva, photoablation was carried out at maximum surgical microscope magnification (40 x) until trabecular meshwork appeared at the bottom of the crater. Light microscopy showed that craters had smooth walls and their base reached the Schlemm's canal area; all structures appeared of normal morphology. Transmission electron microscopy showed a thin layer of amorphous material or pseudomembrane on the side walls of the crater; corneoscleral collagen fibers were abruptly interrupted and undistorted. At the bottom of the crater the trabecular meshwork and Schlemm's canal tissues appeared normal.

Aged↗

A cross-over study with the two novel dopaminergic drugs cabergoline and quinagolide in hyperprolactinemic patients.

Cabergoline and quinagolide, two new dopamine agonist drugs with long-lasting activity, are currently under investigation for the treatment of hyperprolactinemia. At present, studies comparing these drugs for tolerability and efficacy in the same patients are lacking. It was our aim to make such a comparison in an open randomized cross-over trial. Cabergoline (0.5 mg twice weekly) and quinagolide (75 micrograms once daily) were given orally. Each drug was administered for 12 weeks. Treatment with the second drug was started after the recurrence of hyperprolactinemia. Twelve women with hyperprolactinemia due to idiopathic disease (n = 6), microprolactinoma (n = 5) or postsurgical empty sella (n = 1) were evaluated. Six women were amenorrheic and 6 were oligomenorrheic. Ten had spontaneous or provoked galactorrhea. Baseline characteristics (age, clinical signs and PRL levels) of patients initially allocated to the two treatment groups were similar. Nine patients completed both treatment cycles and PRL levels were lower under cabergoline (10.7 +/- 3.7 micrograms/L) than under quinagolide (25.0 +/- 7.7 micrograms/L; p < 0.05). One patient discontinued cabergoline because of dryness of the eyes after having completed the quinagolide cycle and 2 patients initially treated with cabergoline discontinued quinagolide because of gastrointestinal symptoms. After completion of the first treatment cycle, the time of recurrence of hyperprolactinemia was significantly longer after cabergoline (14 +/- 7 weeks) than after quinagolide (5 +/- 1 weeks; p < 0.05). At week 12, normal PRL levels (< 20 micrograms/L) were observed in 10 and 6 women during cabergoline and quinagolide, respectively. Only one case was resistant to both drugs. The clinical effects of the two treatments were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Assessment of growth hormone insulin like growth factor-I axis in Down's syndrome.

As GH therapy has been reported to increase growth velocity in children with Down's syndrome (DS), we studied the GH-IGF-I axis in some DS patients affected by growth retardation without serious congenital malformation, malnutrition or pathological thyroid or adrenal function. IGF-I and IGF-II were evaluated in 39 patients in basal conditions. The patients were subsequently divided into two groups with respect to the IGF-I basal value: Group 1 (GR 1) consisting of patients with abnormally low basal IGF-I concentration as compared to age matched control subjects, group 2 (GR 2) consisting of patients with IGF-I in the normal range. In 6 GR 1 patients and 12 GR 2 patients we evaluated GH and IGF-I concentrations after stimulation with arginine (0.5 g/kg bw), and recombinant GH (4 IU im). In the same patients, GH radioreceptor assay and serum GH-binding protein were evaluated. In all patients IGF-II proved normal (534 +/- 23 ng/ml; mean +/- SE), while IGF-I was pathological in 36% of subjects. The cause of the defective IGF-I secretion in these patients does not seem to depend on an impaired GH axis, as no significant difference in arginine-stimulated GH peak values was seen between GR 1 (29.6 +/- 5.3 ng/ml) and GR 2 (15.1 +/- 2.24 ng/ml). IGF-I concentration evaluated 12, 24, and 48 h after arginine stimulation was significantly increased only in GR 2 patients (peak value: 0.95 +/- 0.1, p = 0.0003 vs baseline; GR 1: 0.34 +/- 0.05 U/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗

Hodgkin's disease: diagnostic accuracy of fine needle aspiration; a report based on 62 consecutive cases.

We report on our series of 62 cases occurring between January 1977 and December 1990, which were diagnosed as Hodgkin's disease by fine needle aspiration (FNA) samples. The overall accuracy of the cytological diagnosis was high, with only four incorrect diagnoses and a positive predictive value of 93.5%. The value of FNA as a first level diagnostic technique in the screening of lymphadenopathies is discussed, as well as the limitations and pitfalls of the cytological diagnosis.

Adolescent↗

Differing responses of cortisol to oCRF during endonasal and oral treatment with DDAVP.

Arginine vasopressin (AVP) exerts a potentiating effect on the responses of cortisol and ACTH to ovine CRF (oCRF). A stimulation test using AVP plus oCRF to assess ACTH reserve has been proposed. In central diabetes insipidus, long-term substitution therapy is commonly undertaken with desmopressin (DDAVP), an analogue of the natural hormone which has a greater antidiuretic action but whose effects on the ACTH-cortisol axis are still controversial. The aim of our study was to evaluate the variations in the responses of ACTH and cortisol to oCRF in various phases of the treatment of central diabetes insipidus: no treatment, endonasal treatment with DDAVP solution and oral treatment with DDAVP in tablet form. Seven patients suffering from central diabetes insipidus underwent testing with oCRF during the various phases of treatment. In the absence of DDAVP treatment, normal responses were registered for cortisol (basal 164.1 +/- 29.4 ng ml-1, peak 396.1 +/- 37.9 ng ml-1; P < 0.05) and ACTH (basal 20.4 +/- 3.9 pg ml-1, peak 86.3 +/- 20.9 pg ml-1; P < 0.05) in all patients. During oral treatment with DDAVP, no variation in cortisol response to oCRF was seen. By contrast, when DDAVP was administered endonasally, a significant reduction in cortisol responsiveness to oCRF (secretory area: 2429 +/- 548 ng ml-1 120 min) was noted in comparison with that found during the other two tests (no treatment: 3070 +/- 704 ng ml-1 120 min; oral DDAVP: 3419 +/- 650 ng ml-1 120 min; P < 0.05) performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

TMAO anaerobic respiration in Escherichia coli: involvement of the tor operon.

The trimethylamine N-oxide (TMAO) respiratory system is subject to a strict positive control by the substrate. This property was exploited in the performance of miniMu replicon-mediated in vivo cloning of the promoter region of gene(s) positively regulated by TMAO. This region, located at 22 min on the chromosome, was shown to control the expression of a transcription unit composed of three open reading frames, designated torC, torA and torD, respectively. The presence of five putative c-type haem-binding sites within the TorC sequence, as well as the specific biochemical characterization, indicated that torC encodes a 43,300 Da c-type cytochrome. The second open reading frame, torA, was identified as the structural gene for TMAO reductase. A comparison of the predicted amino-terminal sequence of the torA gene product to that of the purified TMAO reductase indicated cleavage of a 39 amino acid signal peptide, which is in agreement with the periplasmic location of the enzyme. The predicted TorA protein contains the five molybdenum cofactor-binding motifs found in other molybdoproteins and displays extensive sequence homology with BisC and DmsA proteins. As expected, insertions in torA led to the loss of TMAO reductase. The 22,500 Da polypeptides encoded by the third open reading frame does not share any similarity with proteins listed in data banks.

Amino Acid Sequence↗

[Portal thrombosis: the diagnostic and therapeutic aspects and clinical cases].

The authors report their experience, from 1983 to 1992, in the treatment of portal vein thrombosis and discuss various aetiological factor of obstruction also underlining the frequent and important association with portal hypertension. The authors emphasize the crucial role of the modern diagnostic techniques such as endoscopy and imaging radiology (U.S., C.T., angiography). Although these techniques not always allow a conclusive evidence in relation to aetiology, however, it is possible to have a rationale for the treatment, i.e. medical, sclerotherapeutic or surgical. As related to the surgical procedures, the authors--based on their personal experience--believe the best are the non-derivative ones.

Anti-Bacterial Agents↗

Effects of hypertension on intimal-medial thickness, left ventricular mass and aortic distensibility.

The aim of the study was to evaluate arterial distensibility, intimal-medial thickening of the common carotid artery, left ventricular mass and the eventual correlations among these parameters in the hypertensive state. Our study population consisted of 89 hypertensive patients aged 35 to 80 years (mean age 60.8 +/- 10.6 years), and 76 normotensive subjects aged 45 to 85 years (mean age 61.2 +/- 11.1 years). Those patients constantly presenting systolic blood pressure values > or = 160 mmHg or diastolic blood pressure > 90 mmHg were diagnosed as hypertensive. Each patient underwent a B-mode echotomographic examination of the extracranial carotid tract performed with a Vingmed CFM 750 echotomographer with a 7.5 MHz probe and M-mode echocardiography with a Vingmed CFM 750 device equipped with a 3.0 MHz transducer. The results show the intimal-media thickness value in hypertensive patients (0.90 +/- 0.22 mm on the right and 0.92 +/- 0.22 mm on the left), was significantly greater than that in normotensive subjects (0.64 +/- 0.13 mm on the right and 0.64 +/- 0.13 mm on the left, p < 0.001); in hypertensive subjects, interventricular septum thickness (12.1 +/- 1.25 mm) was significantly greater than that in normotensive patients (9.1 +/- 0.77 mm, p < 0.001). In conclusion, we can say that hypertensive subjects have higher values of common carotid artery intimal-medial thickness than normotensives and that this finding is associated with the presence of left ventricular hypertrophy and with a reduction in arterial compliance. Vascular ultrasonography, as well as echocardiography and arterial mechanography can show, in hypertensive subjects, cardiac and vascular abnormalities in a non invasive way.

Aorta↗

[Behavior of the pituitary-thyroid axis in acromegalic subjects during prolonged intermittent and pulsatile treatment with octreotide].

Octreotide, as well as endogenous somatostatin, inhibits GH and TSH secretion. The drug is employed in the medical therapy of acromegaly. We studied the effects of a long-term (1-120 months; median 12 months) therapy with octreotide (300 micrograms/day) given in 3-times intermittent s.c. administration or in pulsatile s.c. (25 micrograms/120 min) way, upon the pituitary-thyroid axis. Thirteen patients (11 with normal thyroid function, 1 with secondary hypothyroidism, 1 with toxic goiter) with active acromegaly were studied. In the euthyroid patients no significative variations in both TSH levels and thyroid hormones were found during octreotide therapy. In the non-euthyroid patients octreotide did not induce changes in the dosages of drugs acting to thyroid function. The 24-hour IC-TSH levels did not show any variation during octreotide. TSH response to TRH was reduced (P < 0.05) during octreotide therapy. No correlation among TSH, IGF-I and GH levels was observed. Long-term treatment of acromegaly with octreotide reduces TSH response to TRH but do not interfere with both 24-hour IC-TSH levels and thyroid function.

Acromegaly↗

The isolation and characterization of estradiol-fatty acid esters in human ovarian follicular fluid. Identification of an endogenous long-lived and potent family of estrogens.

The estradiol-fatty acid esters are highly potent and long-lived estrogens that were first isolated and identified from in vitro biosynthetic experiments (Mellon-Nussbaum S., Ponticorvo, L., Schatz, F., and Hochberg, R. B. (1982) J. Biol. Chem. 257, 5678-5684). Other studies have indicated that these esters exist endogenously, but the evidence is indirect, resting solely on the presence of a nonpolar saponifiable metabolite. Although there are similar reports of other naturally occurring fatty acid esters of biologically active steroid hormones, likewise, none has been isolated and characterized. In this study we have found that follicular fluid from the ovaries of women stimulated with gonadotrophins contains relatively large amounts of a nonpolar saponifiable derivative of estradiol (approximately 10(-7)M), which we presumed to be fatty acid esters. Using a combination of chromatographic techniques we isolated these estradiol metabolites and identified them by mass spectral analysis. They are a mixture of five different estradiol-17 fatty acid esters. The amount of each present was determined by separating the esters by reversed phase high performance liquid chromatography and then quantifying each peak by radioimmunoassay and UV absorption. The esters of estradiol are predominantly unsaturated, with linoleate the most abundant comprising 43% of the total. The other esters are: palmitate (20%), arachidonate (19%), oleate (14%), and stearate (4%). Thus these studies conclusively demonstrate the existence of these unusually powerful estrogens.

Arachidonic Acid↗

Removal of the high-potential [4Fe-4S] center of the beta-subunit from Escherichia coli nitrate reductase. Physiological, biochemical, and EPR characterization of site-directed mutated enzymes.

The beta-subunit of the nitrate reductase of Escherichia coli contains four groups of Cys residues (I-IV) which are thought to bind the single [3Fe-4S] center and the three [4Fe-4S] centers. The first or second Cys residue of group I was substituted by site-directed mutagenesis with Ala or Ser. Physiological, biochemical, and EPR studies were performed on the mutated enzymes. With small variations, the properties of these mutant enzymes do not differ from one another. They were found to be as abundant and as stably bound to the membrane as the native enzyme, provided the gamma-subunit was present. Although physiological activity was reduced, it was sufficient to allow growth on nitrate. The study of variations in EPR intensity as a function of the redox potential indicated that these enzymes only contained three iron-sulfur centers instead of the usual four in the native enzyme. Spectral EPR analysis showed that the [4Fe-4S] center of high redox potential (center 1, +80 mV) was missing. The loss of this center did not affect the stable integration of the other three centers. The data presented here are in total contrast to those we have reported for each of the other three centers (centers 2-4), the loss of which was detrimental to the integration of all centers and to the integration of the molybdenum cofactor (Augier et al., in press). Taken together, our results demonstrated that the first and second Cys residues of group I are the ligands of the [4Fe-4S] center (center 1, +80 mV) and that this center participates in electron transfer, but is dispensable. On the basis of these results, it is proposed that the [3Fe-4S] center (center 2, +60 mV) also plays a biological role and that in the native enzyme both high-potential centers, centers 1 and 2, contribute independently and in parallel to the electron transfer to the molybdenum cofactor.

Cell Membrane↗

Site-directed mutagenesis of conserved cysteine residues within the beta subunit of Escherichia coli nitrate reductase. Physiological, biochemical, and EPR characterization of the mutated enzymes.

We have used site-directed mutagenesis to alter the ligands to the iron-sulfur centers of Escherichia coli nitrate reductase A. The beta subunit of this enzyme contains four Cys groups which are thought to accommodate the single [3Fe-4S] center and the three [4Fe-4S] centers involved in the electron-transfer process from quinol to nitrate. The third Cys group (group III) contains a Trp at a site occupied by a Cys residue in typical ferredoxin arrangements or in the DmsB subunit of dimethyl sulfoxide (DMSO) reductase. In an attempt to determine the coordination site of the different iron-sulfur centers in the amino acid sequence, we have changed the Trp of group III to Cys, Ala, Phe, and Tyr and the first Cys residue of groups II-IV to Ala and Ser. Physiological, biochemical, and EPR studies were performed on the mutated enzymes. Substitution of Ala for either Cys184, Cys217, or Cys244 results in the full loss of all four iron-sulfur centers present in the wild-type enzyme. These inactive enzymes still possess the alpha,beta, and gamma polypeptides associated in a membrane-bound complex. These Cys have important structural roles and are very likely involved in the coordination of the iron-sulfur centers. Substitution of Cys184 with a Ser residue produces an enzyme containing the four iron-sulfur centers, but displaying reduced activity. EPR studies suggest that Cys184 is a ligand of the [4Fe-4S] center whose midpoint potential is -200 mV in the native enzyme. All substitutions performed in this study on Trp220 lead to mutant enzymes harboring the four iron-sulfur centers and a nitrate reductase activity close to that of the wild-type. In spite of the high similarity between the NarH and DmsB subunits, the Trp220-->Cys substitution does not allow the conversion of the [3Fe-4S] center of the nitrate reductase into a [4Fe-4S] center. Therefore, Trp220 does not seem to play any major role in the beta subunit.

Amino Acid Sequence↗

Cerebrospinal fluid proteins in patients with leucoaraiosis: possible abnormalities in blood-brain barrier function.

Some CSF protein abnormalities have been proposed as a possible marker for vascular dementia. We studied the CSF protein levels and albumin ratio in 21 patients (mean age 64.04 +/- 7.5) with progressive bilateral motor impairment, and a CT picture of leucoaraiosis. Seven of these patients also presented with dementia. Twenty-seven Alzheimer's disease patients (mean age 59.59 +/- 5.30) without leucoaraiosis were taken as controls. We also evaluated the correlations of the albumin ratio values with the diagnosis of dementia, the severity of cognitive impairment, the degree of cerebral atrophy and presence of infarcts on CT, and the abnormalities in CSF circulation, found on isotopic cisternography, in the leucoaraiosis group. After controlling for age and sex, the patients with leucoaraiosis showed greater CSF albumin levels (0.27 g/l +/- 0.11 vs. 0.21 g/l +/- 0.06; covariance analysis P = 0.066), CSF IgG values (4.68 mg/100 ml +/- 1.45 vs. 2.85 mg/100 ml +/- 1.03; covariance analysis P < 0.001), and a higher albumin ratio (0.0078 +/- 0.0027 vs. 0.0058 +/- 0.0019; covariance analysis P = 0.013) than those with Alzheimer's disease. The variations of these parameters were not apparently related to the presence of dementia in the leucoaraiosis group. A significantly higher albumin ratio was observed in patients with a slowed CSF circulation compared to those with normal CSF circulation (0.0086 +/- 0.0028 vs. 0.0059 +/- 0.0019; covariance analysis P = 0.05). We conclude that, independently from the presence of dementia, patients with leucoaraiosis have CSF abnormalities consistent with functional blood-brain barrier alterations.

Aged↗

Delta sleep-inducing peptide administration does not influence growth hormone and prolactin secretion in normal women.

The aim of this study was to analyze the effects of delta sleep-inducing peptide (DSIP) on growth hormone (GH) and prolactin (PRL) secretion in eight healthy women with normal cycles (aged 17-36 years). GH and PRL secretion was studied in five women after DSIP (25 micrograms/kg bw IV over 30 min), arginine chlorhydrate (0.5 g/kg bw IV over 30 min) and simultaneous DSIP plus arginine chlorhydrate administration. In three other women the circadian rhythm of GH and PRL was studied during DSIP (25 micrograms/kg bw from 2130h to 2230h) and placebo IV infusion. Serum GH and PRL levels were normal under basal conditions and no effects were noted after the infusion of DSIP. The GH and PRL circadian rhythm was not modified by DSIP administration. DSIP did not influence GH and PRL responsiveness to arginine chlorhydrate. We found that at dosages which are known to modify ECG patterns, DSIP is unable to modify spontaneous or arginine chlorhydrate-induced GH and PRL secretion.

Adolescent↗