Biomedical subjects
Publications and source records attributed to G Clementi.
The anti-ulcer activity of calcitonin gene-related peptide (CGRP) was inhibited, in a dose-dependent manner, by pretreatment with NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase. Our results suggest that endogenous nitric oxide is involved in the anti-ulcer activity of CGRP.
The anti-inflammatory activity of calcitonin gene-related peptide (CGRP) has been studied in cutaneous inflammation induced by croton oil (CO), arachidonic acid (AA), tetradecanoylphorbol acetate (TPA) or cantharidin (CA). Our results show that mouse ear inflammation induced by CO, AA or TPA is decreased by topical administration of CGRP, whereas that induced by CA is not affected. The dose-response and temporal analysis of CGRP effect show that the maximal activity is present at the dose of 30 pmol/ear and when administered 30 min after the irritating agent. Moreover, pretreatment with capsaicin is able to mimic the anti-inflammatory effect of exogenous CGRP, while simultaneous administration of CGRP and capsaicin produces a reduced response. Our results suggest that CGRP released from sensory.
Intravenous administration of calcitonin gene-related peptide (CGRP) prevented in a dose-dependent manner reserpine-induced gastric mucosal damage, but failed to affect the lesions produced by ethanol administration. In pylorus-ligated rats, CGRP significantly reduced gastric volume, total acid and peptic activity output as well as ulcer formation. These protective effects of CGRP were not present when rats were pretreated with cysteamine. Our data suggest that CGRP exerts its antisecretory and antiulcer activity, at least in part, by interfering with somatostatin transmission.
The authors examined the effects of clonidine, a preferential alpha-adrenergic agonist, upon myocardial oxygen balance and pulmonary function during the perioperative period in patients undergoing CABG surgery. Anesthesia was provided by fentanyl infusion reaching the final dose of 100 micrograms.kg.min-1 in 10 minutes before skin incision. Ten patients received clonidine 0.125 mg intravenously after induction of anesthesia; a group of 10 patients was managed identically except for nitroglycerin infusion during the pre-CPB period, in order to keep the aortic pressure in the normal range. Intergroup differences in hemodynamics, respiratory data, rewarming time, post-operative ST-tract pattern and enzyme values were evaluated. Results are suggestive (in the clonidine group) for ameliorating myocardial oxygen balance by reducing oxygen consumption indexes (systolic aortic pressure, cardiac index, rate pressure product) and increasing coronary blood flow [coronary perfusion pressure (p < 0.01)] at the end of the surgery and intensive care. Global oxygen consumption reduction, recorded in the clonidine group patients, the oxygen available being unchanged, ameliorated the total oxygen balance mainly after sternotomy (p < 0.05) and at the end of bypass (p < 0.05). Cardiac index was greater during the awakening and rewarming period in intensive care and the ventilatory/perfusion ratio was improved, allowing a minor minute ventilation required in clonidine group patients, specially during admission to intensive care.
The effects of central administration of calcitonin gene-related peptide (CGRP, 1 or 100 ng/rat) on behavioral and biochemical parameters related to the extrapyramidal motor system were investigated in male rats. The peptide-induced catalepsy occurred only at the dose of 100 ng/rat and hypomotility at both doses used. Calcitonin gene-related peptide increased haloperidol-induced catalepsy and decreased apomorphine-induced hypermotility at the doses of 1 and 100 ng/rat. Although these behaviors are related to dopamine, no significant change of striatal DA or DOPAC concentration were observed after central administration of the peptide. Other neurotransmitters may be directly or indirectly involved in these behavioral effects of CGRP.
We have studied the effect of intravenous injection of eel calcitonin (ECT) on creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats. CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel calcitonin increased CKBB immunoreactivity in the renal medulla in a dose-dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The distribution of activated CKBB in the kidney occurs in the same areas where highly specific CT-binding sites have been previously demonstrated, and is in agreement with the current concepts on renal actions of this hormone.
The pulmonary artery catheterization has been reviewed in 1207 patients submitted to cardiovascular surgery. The feasibility of the technique in skilled hands has been outlined and a routine and prophylactic use of pulmonary artery monitoring as a safe way to manage critically ill patients has been advocated.
[Asu1,7]Eel-calcitonin, a semisynthetic analog of eel-calcitonin displaying high stability and full biological activity, was used to study the effect of calcitonin on phosphoinositide turnover in cultured anterior pituitary cells. Incubation of cells with [Asu1,7]eel-calcitonin produced a slight, concentration-dependent increase in [3H]inositol monophosphate accumulation, without modifying thyrotropin-releasing hormone (TRH)-stimulated phosphoinositide hydrolysis. This effect was correlated with a stimulatory action on prolactin secretion. Conversely, a long-term preincubation with [Asu1,7]eel-calcitonin reduced basal as well as TRH-induced [3H]inositol monophosphate formation. This effect was concentration-dependent, was not due to an increase of cyclic AMP intracellular levels, and was attenuated in the presence of maximally effective concentrations of TRH. Such a long incubation in the presence of [Asu1,7]eel-calcitonin resulted in a marked inhibition of prolactin secretion. The present data confirm and extend previous findings showing an interference of calcitonin with the intracellular cascade consequent to membrane phospholipase C activation and further support a role for calcitonin in the modulation of hormone secretion at the pituitary.
We investigated the effect of the administration of rat parathyroid hormone-(1-34) on acute or chronic inflammatory processes in different experimental animal models. Fragment 1-34 of parathyroid hormone had an inhibitory effect in all inflammatory acute tests. The dose-response experiments showed that the maximal anti-inflammatory and anti-exudative effects appeared at the dose of 3.30 and 0.33 micrograms/kg, respectively. The anti-inflammatory effect was observed in the first phase of the inflammatory process. In the carrageenin-induced edema test the anti-inflammatory activity began to decline after 180 min. In contrast, this peptide was inactive in the inflammatory chronic test we used.
Adult male rats were used to study the in vivo effects of hypermagnesemia on parathyroid hormone (PTH) and bone Gla protein (BGP) plasma concentrations. Rats were given an Mg-supplemented diet at three different Mg levels (0.40, 0.60 and 0.80%). Results were compared to those obtained in control rats fed a standard diet containing 0.21% of Mg. A significant decrease in PTH plasma levels with no change in total calcium and phosphorus was observed in rats fed the 0.60 and the 0.80% Mg diet. No change of BGP was observed at any level of Mg in the diet. These results suggest that mild hypermagnesemia obtained by dietary Mg supplementation has no apparent effects on both production and binding of BGP to hydroxyapatite.
Parathyroid hormone (PTH) injected peripherally did not interfere with the development of experimental ulcers. Conversely, when PTH was administered i.c.v. the development of ulcers was significantly inhibited. The gastric secretory volume and acid output were also reduced. The possibility is discussed that this antisecretory activity of PTH may be due to a direct effect at the CNS level.
We investigated the effect of acute or chronic peripheral administration of [Asu1.7]eel-calcitonin on the development of tolerance to the analgesic effect of morphine and on the naloxone-precipitated withdrawal syndrome in morphine-dependent rats. Neither the analgesic effect of acute morphine nor the development of tolerance to the antinociceptive effect of this drug was modified by calcitonin. However, the chronic but not the acute administration of calcitonin attenuated some signs and symptoms of morphine withdrawal.
Stimulation of inositol phospholipid hydrolysis by norepinephrine or 5-hydroxytryptamine was reduced in hippocampal or cortical slices from rats repeatedly injected with (Asu1.7)eel-calcitonin (2.5 IU/kg i.p.). This effect was specific, as the basal or carbamylcholine-stimulated inositol phospholipid hydrolysis was unchanged in slices from calcitonin-injected animals. The reduced responsiveness to norepinephrine did not reflect a decreased number or affinity of alpha 1-adrenergic recognition sites, suggesting that calcitonin treatment leads to a reduced coupling between alpha 1-adrenoceptors and phospholipase C.
Giant left atrium (GLA) associated with mitral valve disease (MVD) has been reported as a significant risk factor in mitral valve surgery with mortality ranging from 8%-32%. Plication of the left atrium has been suggested to reduce postoperative left ventricular failure, respiratory failure and mortality. The 203 consecutive patients with MVD operated upon between 1980 and 1986 were reviewed and divided in two groups: group A without GLA (165 patients) and group B with GLA (38 patients = 19%). The pertinent preoperative and intraoperative notes and the early and late postoperative course were reviewed and correlated. The hospital mortality was 2.4% in group A and 2.6% in group B. Late mortality, at a mean follow-up of 54 months was 4.3% in group A and 5.4% in group B. In this series, GLA was not a significant risk factor in MVR and did not affect early and late results as compared with cases without GLA. Plication may not be required in absence of extracardiac signs of compression.
Estrogen deficiency after ovariectomy in the rat is followed by an increase of bone turnover and bone loss. Estrogens are thought to modulate the sensitivity of skeleton to Parathyroid Hormone; according to the recently reported evidence of estrogen receptors on osteoblasts, however, a direct effect on bone cells should not be ruled out. We studied the behaviour of Bone Gla Protein (Osteocalcin), a reliable marker of osteoblast function, in growing rats after ovariectomy and treatment with 17 beta-estradiol. Results indicate that ovariectomy stimulates, as expected, bone turnover, and that estrogen induces a further increase of osteoblast activity revealed by the rise of Bone Gla Protein plasma levels. This data may have clinical implications in humans, where estrogens are currently suggested for prevention and therapy of post menopausal osteoporosis.
Chronic hyperprolactinemia was obtained in the rat by an implantation of two adenohypophyses under the kidney capsule. This experimental model was set to evaluate the influence that high prolactin levels may have on bone mineralization when an intervention of estrogens can reasonably be excluded. Bone density was measured by single photon absorptiometry at the femur level. Our results indicate that the increase in PRL throughout the period of observation was associated with a significant decrease in bone mineral content, while calcium and parathyroid hormone serum levels remained unchanged. This would suggest that PRL plays a role in bone calcium metabolism, that might be included among the effects of this hormone.
Intracerebroventricular (i.c.v.) injection of (Asul,7)eel-calcitonin, a synthetic analogue of eel-calcitonin, at doses of 3 or 6 IU/rat, (but not at 1.5 IU/rat) determined analgesic activity, in male rats, as evaluated by the 'hot-plate' test. Also electrophysiological studies carried out on 13 neurons belonging to the nucleus raphe magnus (NRM) showed that i.c.v. administration of the same doses of (Asul,7)eel-calcitonin increased the spontaneous cellular firing rate. No modification of the discharge frequency was observed when 1.5 IU/rat (Asul,7)eel-calcitonin was used. Authors suggest that the analgesic activity induced by i.c.v. injection of (Asul,7)eel-calcitonin is due, at least in part, to mechanisms affecting NRM neurons.
The effects of different doses of Asu(1,7) eel-calcitonin, peripherally injected, on gastric secretion were studied in conscious Brattleboro rats, which are genetically deficient in vasopressin. Moreover, we evaluated the activity of this analogue on gastric ulcer formation by restraint stress. We found that 5 IU/kg Asu(1,7) eel-calcitonin decreased gastric secretion and inhibited the development of stress-induced ulcers in Brattleboro rats. These data suggest that vasopressin does not play a role in the gastrointestinal activity of Asu(1,7) eel-calcitonin.