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M Corsi

Publications and source records attributed to M Corsi.

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

A further analysis of the contraction induced by activation of cholecystokinin A receptors in guinea pig isolated ileum longitudinal muscle-myenteric plexus.

The activity of a selective cholecystokinin (CCK)-A receptor agonist, N-acetyl derivative of A71623 (Ac-Trp-Lys(epsilon-N-[2-methylphenylamino-carbonyl]) -Asp-(NMe)Phe-NH2) was investigated in the guinea pig isolated ileum longitudinal muscle myenteric plexus. NAA caused both a phasic and tonic contraction at all concentrations tested (1-1000 nM). The selective CCK-A antagonist L-364,718 (Devazepide) antagonized both types of contraction with a pKB of 10.10 and 9.95, respectively. The CCK-B selective antagonist L-365,260 ((3R(+)-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3yl)-N-(3-methylphenyl)-urea) was inactive up to a concentration of 30 nM. Atropine at 300 nM and 1000 nM reduced the maximal response of NAA by only 17% and 50%, respectively. The selective neurokinin (NK)-1 antagonists GR 82334 ([D-pro9[Spiro-gamma-Lactam] Leu10, Trp11]-Phys (1-11)9) at 300 and 1000 nM and (+-) CP-96,345 [(2S, 3S)-cis- 2-(diphenylmethyl)-N- [(2-methoxyphenyl)-methyl] -1-azabici-clo [2.2.2]octan-3-amine] at 10 nM were inactive or partially active. When atropine and GR 82334 or (+/-) CP-96,345 were combined, they produced a dose-dependent synergistic inhibition of both phasic and tonic contractions induced by NAA. The selective NK-3 receptor agonist senktide induced both phasic and tonic contractions that were blocked by tetrodotoxin. In the presence of atropine and GR 82334, both 300 nM, a synergistic depression of the response to senktide similar to that observed for the agonist NAA was disclosed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Increased cAMP levels in human hair follicles due to local treatment with trichoriboside.

Local therapy with trichoriboside and trichosaccharide, which have been found to be beneficial for scalp hair maintenance in adult males affected by androgenic alopecia, was found to increase cAMP levels in human scalp hair follicles. The increase was significant in men affected by androgenic alopecia, whereas it was not significant in unaffected control men. Trichoriboside showed a greater activity than trichosaccharide, and such activity was accompanied by a significant concomitant reduction of ATP in the hair.

Adenosine Triphosphate↗
PubMed1994

ADP beta S induces contraction of the human isolated urinary bladder through a purinoceptor subtype different from P2X and P2Y.

The classification of purinergic receptors is seriously hampered by the lack of specific antagonists. Furthermore, there is increasing evidence that other purinoceptor subtypes may exist that are different than the relatively well characterized P2X, P2Y, P2Z and P2T. Human isolated urinary bladder was reported to contract in response to challenge with alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP) and adenosine 5'-triphosphate (ATP), probably through activation of P2X purinoceptors. In this work, we tried to classify the purinoceptors subtypes present in human detrusor muscle by using adenosine 5'-[beta-thio]diphosphate (ADP beta S), alpha,beta-MeATP, 2-methylthio adenosine 5'-triphosphate (2-MeSATP), ATP and uridine 5'-triphosphate (UTP). We also examined the activity of two putative P2 antagonists (p-chloromercuribenzensulfonic acid [PCMBS] and Reactive Blue 2 [RB-2]). The agonist rank order of potency was alpha,beta-MeATP = ADP beta S > 2-MeSATP > ATP >> UTP. Cumulative responses to alpha,beta-MeATP induced a very rapid desensitization, but responses to alpha,beta-MeATP and ADP beta S, both at 100 microM, were additive. PCMBS antagonized ADP beta S-induced contractions with a pKB of 6.49, but it was inactive against alpha,beta-MeATP. The putative P2Y antagonist RB-2 had no effect against ADP beta S-induced contraction. We conclude that human detrusor muscle contains two contractile purinoceptor subtypes. One is activated by alpha,beta-MeATP and is probably the P2X subtype; the other is activated by ADP beta S and appears to be different from those accepted by the current classification. The similarity between our results and those obtained by other investigators is discussed.

4-Chloromercuribenzenesulfonate↗
PubMed1994

[Chondrocalcinosis and diabetes mellitus. The clinico-statistical data].

Chondrocalcinosis is an important, common, age-related joint disease. Its characteristic is the deposit of calcium pyrophosphate dihydrate crystals in hyaline and fibrous cartilages. Occasionally, it is a familial disorder; more often, it is a sporadic disease of adults sometimes in association with hormonal and metabolic disorders. The relationship between CC and diabetes mellitus (DM) is disputed. In this study the prevalence of radiographic CC (knee and/or wrist) in 184 DM patients was evaluated. For comparison two matched groups without DM were studied: i) 184 consecutive unselected out-patients seem in Rheumatology Department of Ancona University with X-rays of knee and/or wrist; ii) 184 consecutive unselected outpatients observed in a Radiology Department with X-rays of knee and/or wrist. No statistical difference was found between the prevalence of CC in DM patients vs controls. Moreover 113 CC patients were studied. No statistical difference was observed between the prevalence of DM and impaired glucose tolerance in CC patients vs controls. These results may suggest that there is no relationship between CC and diabetes mellitus, as other studies have recently shown.

Adult↗
PubMed1993

Analysis of the CCKB receptor antagonism of virginiamycin in guinea-pig ileum longitudinal myenteric plexus.

1. Virginiamycin, a macrolide reported to bind selectively to CCKB/gastrin receptors has been studied in a functional test, namely cholecystokinin-induced contraction of guinea-pig ileum myenteric plexus (LMMP). 2. Virginiamycin (1-10 microM) antagonized the selective CCKB agonist cholecystokinin tetrapeptide (CCK-4). The antagonism appeared not to be competitive as the highest concentration (10 microM) caused a reduction of its maximal effect. An apparent pA2 of 6.64 +/- 0.06 (s.e.) could be estimated if this depression was ignored. The selective CCKB antagonist, L-365,260 (0.01-0.3 microM) antagonized competitively the CCK-4 induced contraction and a pKB of 8.60 +/- 0.16 (s.e.) was estimated. 3. The combined dose-ratio analysis for virginiamycin, tested at 3 and 10 microM in association with 0.03 and 0.1 microM L-365,260, respectively, resulted in observed log dose-ratios of 1.39 and 1.53. That was consistent with both antagonists acting on the same receptor in LMMP. 4. These data, represent the first evidence of the antagonism of virginiamycin in a functional assay and they support the hypothesis of homogeneity between CCKB receptors in the CNS and in peripheral tissues.

Animals↗
PubMed1993

Antiischaemic effect of defibrotide treatment in rat kidney.

The authors previously demonstrated the protective activity of defibrotide (a profibrinolytic and antithrombotic drug) on endothelial cells. In the present work they examine the efficacy of defibrotide in protecting rat kidney from ischaemic/reperfusion injury by studying the modifications of intrarenal adenine nucleotide levels. Right renal ischaemia of 60 min and reperfusion of 30 min were induced in adult male Wistar rats. Defibrotide was administered as a bolus through a catheter inserted into the left femoral vein 5 min before the beginning of ischaemia at the dose of 32 mg/kg and continuously infused during ischaemia/reperfusion through the same vein at the final dose of 32 mg/kg in 5 ml of saline at the rate of 3 ml/h. Rats treated with vehicle of the drug were used as controls. At the end of postischaemic reperfusion, the ischaemic and left kidneys were rapidly removed and frozen in liquid nitrogen. Tissue extracts were prepared, and their ATP, ADP, AMP, cAMP, NAD+, and NADH contents were determined by using luminescence methods. In controls, ATP intrarenal levels were significantly higher in the left kidney than in the ischaemic organ of the same rat (3405 +/- 320 vs. 378 +/- 36 nmol/g fresh tissue and mean +/- s.e.m. of 10 experiments). Defibrotide treatment significantly protected ischaemic kidneys from the drop in ATP intrarenal content (1465 +/- 147 vs. 3124 +/- 303 nmol/g fresh tissue measured in the left kidney).

Adenosine Diphosphate↗
PubMed1993

Possible role of defibrotide in endothelial cell protection.

Defibrotide is a single-stranded DNA fraction obtained from mammalian lung and is able to increase prostacyclin production by endothelial cells. It has profibrinolytic and antithrombotic properties, and we have successfully used it as an anti-ischaemic drug in many in-vivo experimental models. In fact, we showed that defibrotide treatment significantly protected rat heart, kidney and liver from ischaemia and postischaemic reperfusion injury. In rats treated with defibrotide, the functionality and metabolic activity of ischaemic organs were significantly protected from impairment as compared to controls treated only with the vehicle of the drug. In the present work we evaluated all our results, together with those of others, in order to hypothesize the mechanism of action of the drug. We postulated that the prominent function of defibrotide is to inhibit platelet and leukocyte adhesion to endothelial cells: this may depend on reduced cell activation possibly following drug interaction with adenosine receptors. Defibrotide could also favour endothelial-cell function through binding with haemoglobin: such binding permits oxygen release and preservation of endothelium-derived relaxing factor. Moreover, prostacyclin production by endothelial cells is responsible for many drug activities and also limits superoxide radical generation.

Adenine Nucleotides↗
PubMed1992

Respiratory chain enzymes in muscle of endurance athletes: effect of L-carnitine.

The effects of L-carnitine on respiratory chain enzymes in muscle of long distance runners were studied in 14 athletes. These subjects received placebo or L-carnitine (2 g orally b.i.d.) during a 4-week period of training. Athletes receiving L-carnitine showed a significant increase (p < 0.01) in the activities of rotenone-sensitive NADH cytochrome c reductase, succinate cytochrome c reductase and cytochrome oxidase. In contrast, succinate dehydrogenase and citrate synthase were unchanged. No significant changes were observed after placebo administration. The levels of both total and free carnitine from athletes receiving placebo were significantly decreased (p < 0.01) after treatment. By contrast, total and free carnitine levels were markedly increased (p < 0.01) after supplementation with L-carnitine. Our results suggest that L-carnitine induces an increase of the respiratory chain enzyme activities in muscle, probably by mechanisms involving mitochondrial DNA.

Analysis of Variance↗
PubMed1992

Cyclosporine-induced insulin release in rats is related to an increase in plasma lipid levels.

We studied the modifications of plasma lipid levels induced by cyclosporine (CsA), streptozocin (STZ) or both drugs in rats. Male Wistar rats (RT1y) were administered i.p. with CsA or STZ or both at the dosage of 15 mg/kg daily for 8 days and were sacrificed on day 9. Total lipid, triglyceride and total cholesterol plasma levels were measured. The plasma total lipid content was significantly increased in CsA-treated and in CsA + STZ-treated rats with respect to controls (662 +/- 29 and 632 +/- 32, respectively, vs 472 +/- 27 mg/dl). The triglyceride content was significantly higher in CsA-treated and in CsA + STZ-treated animals than in controls (137 +/- 8.7 and 188 +/- 14.1, respectively, vs 79 +/- 7.7 mg/dl). The total cholesterol level was not significantly different in CsA- and STZ-treated rats with respect to controls. CsA-treated and STZ-treated rats concomitantly revealed a significant impairment of glucose tolerance. In fact, 150 min after orogastric administration of 350 mg glucose, glycaemia was significantly more elevated in treated animals than in controls. We conclude that the increase in lipid levels induced by CsA treatment could be related to drug-induced damage to the pancreas islets, as shown by the early insulin release and fatty tissue degeneration.

Animals↗
PubMed1992

Extraocular muscles in congenital strabismus: muscle fiber and nerve ending ultrastructure according to different regions.

The ultrastructure of the extraocular muscles of patients affected by congenital strabismus is not completely known, and the structures responsible of the pathogenesis of this condition are still to be determined. Specimens obtained from patients suffering from congenital strabismus were studied and compared with specimens obtained from patients enucleated for various pathologies and not affected by any disorder in the oculomotor system. The scleral myotendinous junction, where the occurrence of an altered proprioceptive innervation was already reported, was examined, and findings obtained were compared with those observed in the muscle body (venter), where motor innervation is prominent and usually described as normal. Only a small number of damaged muscle fibers was found everywhere. The damage consisted in alterations of both contractile structures and mitochondria and resulted in severer lesions in the scleral myotendinous junction rather than in the muscle body. The normal muscle fibers were innervated by motor nerve endings with normal features and by few altered proprioceptors. The less damaged muscle fibers were innervated by normal motor nerve endings and severely damaged proprioceptors. The most severely damaged muscle fibers did not receive any type of innervation. These data seem to imply that the most important functional alteration in strabismus regards the scleral myotendinous junction. It is the authors' opinion that these findings might have a clinical importance in choosing the treatment to be pursued in patients with a squint.

Adolescent↗
PubMed1991

[Injury of the popliteal artery].

Injuries to the lower limbs are now commonplace, in particular due to the increased number of car accidents, work accidents, injuries from knives or fire arms, or sporting injuries. The popliteal artery is involved in 6% of all these injuries. A clinical case is described of a subject who was injured, causing laceration to the popliteal artery, and brought to our attention six months after the event.

Adult↗
PubMed1991

Carnitine in muscle, serum, and urine of nonprofessional athletes: effects of physical exercise, training, and L-carnitine administration.

Efficient utilization of fatty acids to sustain prolonged physical efforts is thought to be dependent on the carnitine shuttle of muscle. A study has been carried out in 24 athletes (13 long-distance runners and 11 sprinters). These subjects received placebo or L-carnitine (1 g/orally b.i.d.) during a 6-month period of training. In endurance athletes, training induced lowering of total and free muscle carnitine. Increase of esterified muscle carnitine was also observed. Post-exertional overflow of acetylcarnitine and long-chain acylcarnitine, as well as reduction of the free fraction was also noticed in the blood. Fasting plasma carnitine levels, however, were not affected in carnitine-treated athletes at rest. These changes were likely related with the significantly increased urinary excretion of esterified and total carnitine which occurred after physical exercise. In the sprinters only, a decrease in free and total carnitine of muscle was detected after training. Both these potentially unfavorable effects were prevented by oral administration of L-carnitine. Our data suggest that training in endurance athletes, and to a lesser extent, in sprinters, is associated with a decrease in free and total carnitine of muscle, due to an increased overflow of short-chain carnitine esters in urine.

Adult↗
PubMed1991

Pharmacological analysis of 5-hydroxytryptamine effects on electrically stimulated human isolated urinary bladder.

1. 5-Hydroxytryptamine (5-HT) is able to potentiate the contractions induced by electrical field stimulation of pieces of human isolated urinary bladder. On the basis of available selective 5-HT agonists and antagonists, we have further investigated the receptors involved and their site of action. 2. 5-HT produced a concentration-dependent increase of the contractile response to electrical field stimulation from 0.1 nM to 1 microM. At higher concentrations (up to 100 microM) the effect decreased. These activities were mimicked by a variety of 5-HT agonists, for which the following rank order of potency was found: 5-HT greater than alpha-methyl 5-HT greater than 5-methoxytryptamine greater than 5-carboxamidotryptamine greater than 2-methyl 5-HT much greater than GR 43175. In addition the gastro-prokinetics agents metoclopramide, cisapride and the 5-HT3 antagonist ICS 205-930 behaved as 5-HT agonists, their EC50 values being 2.3, 0.3, and 0.5 (microM) respectively. 3. The 5-HT potentiating effect was resistant to antagonism by ondansetron (1 microM) and cyanopindolol (1 microM), selective 5-HT3 and 5-HT1A/1B antagonists respectively. The 5-HT2 antagonists ketanserin (1 microM), spiperone (1 microM) and methysergide (1 microM) also showed a weak inhibitory activity. Methiothepin (0.1-1 microM) antagonized only the inhibitory effect of 5-HT. Metoclopramide (0.1-1 microM), cisapride (0.01-0.1 microM) and ICS 205-930 (0.3-3 microM) all produced a rightward displacement of the 5-HT response curve with concomitant reduction of the maximum response. The pA2 values calculated were 7.4, 8.5 and 7.0 respectively. The antagonism of metoclopramide was receptor specific and was not apparently related to interactions with dopaminergic activity since domperidone showed no antagonism of 5-HT, and metoclopramide, itself, did not antagonize the potentiating effect of prostaglandin F2a.4. The receptor involved in the potentiating effect of 5-HT may be located prejunctionally because 5-HT did not potentiate responses to acetylcholine (ACh) or electrical field stimulation with the parameters of direct muscle excitation. Also, since the 5-HT potentiating effect was blocked by atropine, it may be attributed to a release of ACh.5. This study suggests that in the human urinary bladder 5-HT causes two opposite effects on the contractile response to electrical field stimulation. A potentiating effect at low concentrations due to an interaction with an atypical receptor, different from the classical 5-HT1, 5-HT2 or 5-HT3 subtypes and an inhibitory effect at greater concentrations probably due to an interaction with 5-HT1-like receptors. The possibility that this atypical receptor possesses some characteristics of those found in other isolated preparations like guinea-pig ileum, rat oesophagus and mouse embryo colliculi neurones is discussed.

Acetylcholine↗
PubMed1991

Muscle carnitine deficiency in patients with severe peripheral vascular disease.

BACKGROUND: This study was designed to evaluate the effect of severe peripheral arterial insufficiency on carnitine concentrations and carnitine acetyltransferase and palmitoyltransferase activities in the ischemic skeletal muscles of patients with severe peripheral vascular disease. METHODS AND RESULTS: Nine biopsy specimens of ischemic muscles were obtained from five patients undergoing reconstructive vascular surgery. Biopsies from 35 normal subjects served as controls. Ischemic muscles showed a significant reduction in total carnitine from the control value of 20.9 +/- 5.2 to 11.6 +/- 6.2 nmol/mg noncollagen protein (p less than 0.01). A significantly lower free carnitine and acylcarnitine content contributed to this reduction. Similarly, carnitine acetyltransferase activity was reduced in the ischemic muscles from the control value of 102.1 +/- 41.2 to 52.9 +/- 22.1 nmol/min/mg noncollagen protein (p less than 0.01). On the contrary, carnitine palmitoyltransferase activity did not show any change (0.29 +/- 0.05 nmol/min/mg noncollagen protein in the ischemic muscles and 0.28 +/- 0.07 nmol/min/mg noncollagen protein in controls). Carnitine, acylcarnitines, and enzyme activities were also measured in the ischemic muscles in four additional patients 2 days after intravenous administration of L-propionylcarnitine (1.5 g as a single bolus followed by an infusion of 1 mg/kg/min for 30 minutes). Treatment restored normal levels of carnitine and its esters in the ischemic muscles but did not affect enzyme activities. CONCLUSIONS: Demonstration of carnitine deficiency in severe peripheral vascular disease substantiates previous findings showing the efficacy of carnitine supplementation to ischemic muscles. Furthermore, the feasibility of restoring carnitine homeostasis with L-propionylcarnitine provides the basis for clinical trials aimed at assessing the efficacy of this carnitine ester in the treatment of peripheral vascular disease.

Aged↗