Search PubMed⌕ Search

Biomedical subjects

N Lattuada

Publications and source records attributed to N Lattuada.

15 recordsLinked to original sources

Different skeletal regional response to continuous brain infusion of leptin in the rat.

This study was designed to evaluate whether or not continuous intracerebroventricular infusion of leptin (1.5 microg/rat/24 h, for 28 days) produced different regional response on the skeleton of growing rats. Leptin reduce the accretion of total femoral bone mineral content (BMC) and density (BMD). This effect was related to a reduction of metaphyseal femur as no changes were detected in the diaphysis. Despite the reduced accretion in the volumetric of both femur and tibia compared to controls, leptin had no significant effects on the lumbar vertebrae. Urine deoxypyrydinoline and serum osteocalcin remained more elevated in the leptin-treated group as compared to controls. The results demonstrate that long-term central infusion of leptin activates bone remodeling with a negative balance. Leptin induces distinct responses in the different structure of bone and in the axial and appendicular skeleton.

Animals↗

Effects of hexarelin against acid-independent and acid-dependent ulcerogens in the rat.

The effects of intracerebroventricular (icv) or subcutaneous (sc) hexarelin (Hexa) administration, against gastric ulcers induced by ethanol (50%, 1 ml/rat/os) or Indomethacin (20 mg/kg/os) were examined in conscious rats. Hexa at 1 nmol/rat, icv or 10 nmol/kg, sc reduced ethanol-induced ulcers by 47% and 32% respectively. Hexa, but not ghrelin significantly worsened (+40%) Indomethacin-induced ulcers when injected sc. Hexa-gastroprotection against ethanol-induced ulcers was removed by the GHS-R antagonist (D-Lys3)-GRPR-6 and by the inhibitor of NO-synthase (NOS) Nomega-nitro-L-arginine methyl ester. Semiquantitative RT-PCR assay of gastric NOS mRNA isoforms revealed that the reduction in iNOS-derived NO and the increase of constitutive-derived NO are relevant for the gastroprotection of Hexa against ethanol-induced gastric damage.

Animals↗

Long-term effects on bone of postnatal immunization against GHRH in female and male rats.

The effects of neonatal passive immunization against GHRH on bone was examined in male and female rats. Pups were treated subcutaneously with GHRH-antiserum (GHRH-Ab) from day 1 to day 10 of age. Bone mineral content (BMC) and bone mineral density (BMD) were evaluated at monthly intervals until 7 months. Markers of bone resorption (urinary lysylpyridinoline, LP), bone formation (serum osteocalcin, OC) and serum IGF-I were measured at 2, 3 and 7 months. In male rats, GHRH-Ab did not modify BMC and BMD when compared with controls. In contrast, female rats demonstrated lower whole body and femoral BMC and BMD from 2 to 7 months of age. Reduced bone growth in the females was associated with lower IGF-I levels than controls at 2 and 3 months of age, whereas in males IGF-I titers did not change during the period of the study. LP excretion was higher in GHRH-Ab-treated rats at 2 and 3 months in both sexes. In females, no difference in OC values was recorded, whereas in GHRH-Ab-treated males, there was an increase in OC levels at 2 and 3 months. These data indicate that transient GHRH deprivation induces an osteopenic effect in female rats which is not evident in male rats.

Amino Acids↗

Bone effects of hexarelin, a GH-releasing peptide, in female rats: influence of estrogen milieu.

OBJECTIVE: The present study was performed to evaluate the potential influence of the estrogen milieu in modulating the effects of GH/IGF stimulation by a GH-releasing peptide, hexarelin (HEXA), on bone metabolism and mineral density in middle-aged female rats. METHODS: HEXA was administered for 60 days (50 microg/kg s.c. twice a day) to intact and ovariectomized (OVX) 11-month-old female rats and changes in bone parameters were evaluated with respect to those of the same rats under baseline conditions and with those of control rats (intact and OVX) administered isovolumetric amounts of physiological saline. Serum total alkaline phosphatase (ALP) and urinary deoxypyridinoline (Dpd) were measured before and at various times during HEXA treatment. Bone mineral content (BMC) and density of lumbar vertebrae and femoral mid-diaphyses were measured by dual energy X-ray absorptiometry before and after treatment. In all groups, serum IGF-I levels were determined before and during treatment and the GH secretory response to HEXA was assessed at the end of the experiment. RESULTS: In intact rats, HEXA did not modify Dpd urinary excretion, induced a trend toward an increase of serum ALP activity and significantly increased BMC (+6.5%) and bone area (+4.1%) only at lumbar vertebrae. In OVX rats, HEXA did not modify the OVX-induced increase in bone turnover markers (Dpd and ALP) and did not affect the OVX-induced vertebral bone loss, but significantly increased BMC (+7.2%) and bone area (+5.3%) at femoral mid-diaphyses. HEXA significantly increased serum IGF-I levels at day 14, but not at day 60, in both intact and OVX rats, whereas the GH secretory response to HEXA was higher in the former than in the latter. CONCLUSIONS: Overall, the present data demonstrate that chronic HEXA treatment increases BMC and bone area at lumbar vertebrae in intact rats and at femoral diaphyses in OVX rats. The different sensitivity to HEXA of the skeletal districts examined is related to the estrogen milieu and may reflect a complex interplay between estrogens and GH/IGF function.

Animals↗

Amylin compared with calcitonin: competitive binding studies in rat brain and antinociceptive activity.

Binding studies for rat amylin (AMY) and salmon calcitonin (sCT) were performed on rat membranes prepared from pons and medulla oblongata of rats. The aim was to see whether specific binding sites for AMY and/or for sCT present in these areas could be relevant to some of the biological activities of the two peptides. Binding sites specific for [125I]AMY are present in the pons-medulla of rat brain as AMY, but not sCT, was able to displace radiolabeled AMY binding with an IC50 = 3.7+/-0.5x10(-10) M. In contrast, binding of [125I]sCT was displaced by both sCT and AMY, although with different potencies, the IC50 for sCT being 1+/-0.1x10(-11) M, and for AMY, 1.8+/-0.08x10(-7) M. The functional significance of the presence of these binding sites was evaluated in two different nociceptive tests, hot-plate and tail-flick. In the tail-flick test neither AMY (5-10 microg/rat, i.c.v.) nor sCT (10 microg/rat i.c.v.) showed antinociceptive activity, whereas in the hot-plate test AMY (10 microg/rat, i.c.v.) significantly increased the response latencies as did sCT (250 ng/rat, i.c.v.). These results demonstrated that a 40-fold greater dose of AMY is necessary to produce a comparable antinociceptive effect to that exerted by sCT. These findings are in accordance with the low affinity of AMY for sCT binding sites in rat pons-medulla. It is therefore suggested that the central inhibitory activity of AMY on pain perception involves interaction with sCT receptors whereas the selective AMY binding sites subserve other (as yet unknown) functions.

Amyloid↗

Hexarelin, a growth hormone - releasing peptide, counteracts bone loss in gonadectomized male rats.

The age-related decline in growth hormone (GH) secretion has been implicated in the pathogenesis of involutional bone loss. Whether restoration of GH secretion might be helpful in maintaining and/or improving bone mass during aging is still unsettled. The aim of the present study was to examine the effects of 30-day treatment with hexarelin (HEXA, 50 microg/kg subcutaneously b.i.d.), a highly effective GH-releasing compound, on bone metabolism and bone mineral density (BMD) in intact and osteopenic gonadectomized (GDX) mature male rats. Serum total alkaline phosphatase (ALP, bone formation marker) and bone resorption markers (lysylpyridinoline, LP and hydroxylysylpyridinoline, HP) were measured before and 7, 14 and 30 days after treatment. BMD was measured by dual-energy X-ray absorptiometry at lumbar vertebrae, femoral metaphysis and diaphysis before and at the end of the experiment. In intact rats, HEXA significantly (P<0.05) decreased LP (-36.3%) and HP (-22.8%) excretion at day 7, whereas it did not change serum ALP activity and BMDs. In GDX rats, HEXA completely prevented the significant (P<0. 01) increase in urinary excretion of both LP (+143.8%) and HP (+119. 4%), the early decrease in ALP activity (-26.5%) and the significant (P<0.05) decrease in BMDs in the femoral metaphysis (-7.9%) and lumbar vertebrae (-6.8%) caused by androgen deficiency. The bone-protective effects of HEXA could be attributed, at least in part, to its GH-releasing activity since chronic-treated rats maintained the GH response to an acute challenge with HEXA. The evidence that HEXA, unlike GH, inhibits bone resorption indicates that other mechanisms contribute to the bone sparing effect of HEXA.

Alkaline Phosphatase↗

Effects of amylin and salmon calcitonin on beta-endorphin-induced growth hormone and prolactin secretion in the rat.

In this study we examined the possible interplay of amylin (AMY) and salmon calcitonin (sCT) in the central control of growth hormone (GH) and prolactin (PRL) secretion in male rats. For this purpose we first compared effects of central intracerebroventricular (i.c.v.) admininstration of various doses of AMY (2.5-2,500 ng/rat) and sCT (2.2-220 ng/rat) on beta-endorphin (beta-END, 0.5 microg/rat)-induced GH and PRL secretion. AMY and sCT dose-dependently inhibited beta-END-induced GH secretion, whereas only sCT was able to inhibit beta-END-induced PRL secretion. To examine whether the GH inhibitory effect of AMY was due to the possible cross-reactivity of AMY and sCT on the same receptors in the CNS, we pretreated some rats with the AMY antagonist (AMY8-37, 2. 5 microg/rat, i.c.v.). AMY8-37 significantly enhanced the GH-stimulatory action of beta-END. AMY8-37, administered prior to AMY and sCT, significantly removed the inhibitory effect of both AMY and sCT on beta-END-induced GH release, suggesting that both peptides mediate their response on GH through a common receptor. In vitro competition binding studies on rat hypothalamic membranes have shown that both AMY and sCT compete with [125I]rAMY binding with half inhibition (IC50) values of 3.6 x 10(-11) and 1.6 x 10(-10) M, respectively. Binding of [125I]sCT was inhibited by sCT with an IC50 of 1.09 x 10(-10) M and to a lesser extent by AMY with an IC50 of 1. 3 x 10(-6) M. Thus it is possible that the two peptides recognize a common hypothalamic receptor but with different affinities (sCT > AMY). Overall these data indicate that AMY behaves as a mimic of sCT in the central control of GH secretion. The failure of AMY, at variance with sCT, to modify the PRL-releasing activity of beta-END indicates that different receptor subtypes for sCT are involved in the endocrine effects of sCT and only those mediating the modulatory action of GH respond to AMY.

Amyloid↗

Inhibitory effect of amylin on growth hormone responsiveness to growth-hormone-releasing hormone in the rat.

The effects of intracerebroventricular (i.c.v.) or intracarotid (i.a.) administration of amylin (AMY) on growth hormone (GH) release induced by GH-releasing hormone (GHRH) were examined in conscious male rats. Amylin (25 ng-5 micrograms/rat, i.c.v. or 10 micrograms/rat, i.a.) was administered 10 min before GHRH (2 micrograms/kg, i.a.). I.c.v. administration of AMY dose-dependently inhibited GH secretion induced by GHRH but when given peripherally, AMY did not modify the GH response to GHRH. Amylin (10(-8)-10(-6) M) had no direct effect on the rat anterior pituitary in vitro either alone or when incubated with GHRH. To characterize the mechanism(s) involved in vivo in the inhibition of GH by AMY, we examined, at first, the effects of AMY on GHRH-induced GH release in rats depleted of somatostatin by pretreatment (4 h before) with cysteamine (300 mg/kg s.c.). The inhibitory activity of AMY on GH secretion elicited by GHRH seems to be independent of hypothalamic somatostatin; in fact, AMY was still active in rats treated with cysteamine. In addition, we examined the effects of i.c.v. AMY administration on clonidine (CLO)-induced GH secretion and on dopamine and noradrenaline content in the brain, since it is known that GHRH is a stimulus sensitive to changes in central catecholaminergic activity. The failure of AMY to affect GH secretion induced by activation of postsynaptic alpha 2-receptors by CLO and the finding that the peptide decreased noradrenaline content in the hypothalamus and striatum, indicates that AMY may inhibit GH release by interfering with the facilitatory influence of the catecholaminergic system on GH secretion.

Amyloid↗

Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects.

Eptastigmine is a new cholinesterase inhibitor, which may be potentially useful for the symptomatic treatment of Alzheimer's disease. A preliminary evaluation of its pharmacodynamic and pharmacokinetic profiles in the elderly has now been made in 6 healthy subjects (63-84 years of age) given 30 mg eptastigmine as a single oral dose. Blood was collected prior to and 1, 2, 3, 4, 6, 8, and 12 h after eptastigmine administration for measurement of cholinesterase inhibition in plasma and red blood cells and the plasma drug concentrations. The maximum plasma cholinesterase inhibition was 17%, which was reached 2.7 h after treatment. In red cells the maximum inhibition of the enzyme was 29% after 3.8 h. The estimated half-time of cholinesterase recovery was 12.4 h in plasma and 13.6 h in red blood cells. The peak plasma concentration of eptastigmine of 0.86 ng.ml-1 was reached after 1.4 h. Following absorption the drug was rapidly distributed into tissues (t1/2 alpha = 0.44 h) and then eliminated with a half-life of 12.1 h. The drug was well tolerated in all but one subject, who showed bradycardia with hypertension and nausea for about 2 h after the dose. The results indicate that oral administration of eptastigmine to elderly subjects produces long lasting inhibition of cholinesterase activity in plasma and in red blood cells.

Administration, Oral↗

Rapid potentiometric determination of cholinesterases in plasma and red cells: application to eptastigmine monitoring.

Eptastigmine (MF 201) is a new physostigmine derivative with potent inhibitory activity on cholinesterases. Here we present a new potentiometric cholinesterase activity assay suitable for MF 201 monitoring. The analysis is performed on a differential pH system and has the following characteristics: (a) within-run precision: C.V. 2.0% (plasma cholinesterase), 1.8% (red cell cholinesterase); (b) between-run precision: C.V. 4.0% (plasma cholinesterase); (c) linearity: 1-10 kU/l (plasma cholinesterase), 6-70 U/g Hb (red cell cholinesterase); (d) comparison with a reference method (x, HITACHI 737 Boerhinger Mannheim, Italy): y = 0.785x - 0.07; n = 37; r = 0.998. The assay has been applied to the determination of plasma and red cell cholinesterase activity in volunteers over 60 years of age treated with a single oral dose of 30 mg eptastigmine. We found that red cell cholinesterase is selectively inhibited after MF 201 administration with the following kinetics (time, % of inhibition, mean +/- S.E., n = 6): 0 h, 0; 1 h, 17 +/- 4.6; 2 h, 24 +/- 4; 4 h, 23 +/- 4.4; 12 h, 14 +/- 3. Eptastigmine plasma levels were also determined by a HPLC method: maximum concentration was found one hour after drug administration.

Administration, Oral↗

[Hypoplasia of the gallbladder (report of a case)].

The authors, starting from the recent observation of a case of gall-bladder hypoplasia, point out the extreme rareness of the disease, the aspecificity of the symptomatology and the frequent impossibility to reach a preoperative diagnosis.

Aged↗

[Initial therapeutic evaluations of 141 patients with carcinoma of the breast under 40 years of age].

The Authors, considering 141 cases of patient women under 40, suffering from breast cancer, analyse the prognostic factors in relation to the different therapeutical approach, histologic type, dimensions of T, and presence or absence of metastases at the axillary lymph nodes. They, moreover, appraise the actuarial global survival with no disease (NED) of this group of patients as compared with the survival of women in more advanced age.

Adult↗

[Experiences with cytodiagnosis of laryngeal pathology].

The advantages and limitations of exfoliative cytology in laryngeal pathology is evaluated and a comparison is made between cytological and histological diagnosis in 110 patients. By adding the absolute agreement to that of relative discordance one obtains a 90% confirmation of the validity of cytology although this in no way diminishes the 10% absolute discordance. Cytology is not, therefore, an absolute tool in diagnosis although it does offer a support, rounding out the patient's overall clinical picture. Finally, the authors attest to the usefulness of cytology, particularly in cases of chronic inflammatory processes (where cytological and histological findings are in good agreement). Laryngeal cytology is a non invasive clinical instrument which gives more data than obtained with case history or laryngoscopy. Furthermore, it can direct diagnosis and, above all, limit the use of more invasive tests (such as biopsy).

Adult↗