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Biomedical subjects

M Corsi

Publications and source records attributed to M Corsi.

At least 55 records · Page 3Linked to original sources
PubMed1998

[European trial of PGE1 alpha cyclodextrin. Short-term vs. long-term therapy in intermittent claudication].

BACKGROUND: The efficacy, safety and cost of prostaglandin E1 (PGE1 alpha-ciclodestrina) in the treatment of severe intermittent claudication was studied comparing a long term treatment protocol (LTP) with a short term treatment protocol (STP) in a randomised, 20-week study. METHODS: The study has selected 120 patients (109 were included and 99 completed the study). The average total walking distance at inclusion was 65.5 +/- 8 m (range 20-109). Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP phase 2 was the main treatment phase. The treatment was performed with 2-hour infusions (60 micrograms PGE1 alpha-ciclodestrina, 5 days each week for 4 weeks. In phase 3 (4-week interval period) PGE1 alpha-ciclodestrina was administered twice a week (same dosage). In phase 4 (monitoring lasting 3 months, from week 9 to 20) no drugs were used. In STP phase 2 treatment was performed in two days with a 2-hour infusion (1st day: morning 20 micrograms, afternoon 40 micrograms; 2nd day 60 micrograms, morning and afternoon). The reduced dosage was used only at the first cycle to evaluate reduced tolerability or side effects. Full dosage (60 micrograms b.i.d.) was used for all other cycles. The same cycle was repeated at the beginning of weeks 4, 8, 12 (phase 3). The observation period was between weeks 12 and 20 (phase 4). For both protocols a treadmill test was performed at inclusion, at the beginning of each phase and at the end of 20th week. A similar progressive physical training plan (based on walking) and a reduction in risk factors plan was used in both groups. RESULTS: Intention-to-treat analysis indicated an increase in walking distance which improved at 4 weeks (101.5% in STP vs 78.3% in LTP), at 8 weeks (260.9% in STP vs 107.3% in LTP) and at 20 weeks (351% in STP vs 242% in LTP). Comparable increases in pain-free walking distance were observed in the two groups. No serious drug-related side effects were observed. Local, mild, adverse reactions were seen in 7% of the treated subjects in the LTP and 5% in the STP. The average cost of LTP was approximately 6.588 ECU; for STP the average costs was approximately 1881 ECU. The cost to achieve an improvement in walking distance of 1 m was 35.6 ECU with the LTP and 9.45 ECU with the STP (26% of the LTP cost; P < 0.02). For an average 100% increase in walking distance LTP cost was 1937 ECU vs 550 ECU with STP (P < 0.02). The cost of PGE1 alpha-ciclodestrina (including infusion and operative costs) was 25% of the total cost for LTP (24.9% for STP). CONCLUSION: In summary between-group-analysis favours STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE1 alpha-ciclodestrina treatment. With STP less time is spent in infusion and more can be spent in the exercise program. STP reduces costs, speeds up rehabilitation and may be used in a larger number of non-specialised units available to follow the protocol.

Alprostadil↗
PubMed1998

[Intramuscular injections of PGE1 in patients with severe claudication].

BACKGROUND: In this pilot study we selected 12 patients with short range claudication and treated, after informed consent, 6 patients (mean age 63 +/- 5; range 55-65) with severe claudication (walking distance < 100 m). Selection criteria were patent common and deep femoral artery, occluded superficial femoral artery with patent popliteal artery, with posterior tibial Doppler pressure > 50 mmHg and anterior tibial > 40 mmHg. METHODS: Patients were evaluated with a treadmill test performed to their walking limit. PGE1 was used by intramuscular injections (for a total of 80 micrograms, divided in 4 injections). The injections were about 2 cm deep in the posterior calf muscles. An exercise program was associated. Patients were required to walk 20 minutes just after the injections and to follow an exercise program (walking slowly at least 30 minutes, 3 times daily, in the following 4 weeks). RESULTS: Both the PGE1 group and a comparable control group (12 patients mean age 62 +/- 4; range 56-65) were treated with ASA and pentoxyfillin (400 mg t.i.d.). In the PGE1 group the average total walking distance at inclusion was 25 +/- 16 (range 0-52); it increased to 113 +/- 55 (range 50-289) (after 1 week) and to 117 +/- 27 (range 30-1020) at 4 weeks. No important changes were observed in the control group (54 +/- 6 m at inclusion, 58 +/- 8 after one week and 63 +/- 7 after 4 weeks). There were no important side effects. One patient experienced important injection pain which disappeared in a few hours. No significant changes in tibial pressures were observed. CONCLUSIONS: Intramuscular injection of PGE1 may be an interesting treatment option in patients with severe intermittent claudication but these preliminary findings should be verified in larger randomised studies.

Alprostadil↗
PubMed1997

Potentiation of NMDA and AMPA responses by group I mGluR in spinal cord motoneurons.

Application of the metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and the Group I selective mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) potentiated NMDA- and AMPA-induced potential changes recorded from ventral roots of the isolated hemisected baby rat spinal cord. Potentiation produced by 1S,3R-ACPD was completely abolished by the Group I selective mGluR antagonists (S)-4-carboxyphenylglycine (4CPG) or (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). In addition, the protein kinase C (PKC) blockers staurosporine or chelerythrine chloride were able to antagonize the 1S,3R-ACPD-induced potentiation of both NMDA and AMPA response, suggesting that the enhancing effect induced by Group I mGluRs is modulated by a PKC-mediated mechanism. The mGluRs-induced potentiation of NMDA and AMPA responses may be important in modulating various forms of synaptic plasticity and nociceptive processes.

Animals↗
PubMed1996

Co-agonism in drug-receptor interaction: illustrated by the NMDA receptors.

The co-agonism between glutamate and glycine at the NMDA receptor raises uncertainty about the estimation of the values of dissociation constants for agonists and antagonists and of efficacy for agonists. In this article, Mauro Corsi, Paolo Fina and David Trist discuss how to analyse the interaction of the two agonists with the NMDA receptor by applying an operational receptor model. Data simulation indicates that co-agonism can affect the potency as well as the efficacy of agonists. Moreover, the interaction of antagonists with the NMDA receptor can also be affected, leading to altered estimation of the antagonist dissociation constants.

Animals↗
PubMed1996

Upregulation of spinal glutamate receptors in chronic pain.

Recent studies indicate that glutamate binding to N-methyl-D-aspartate receptors in the spinal cord is involved in triggering the development of chronic pain However, the processes which directly underlie the increased pain remain unclear. Here we report that, following peripheral nerve injury (ligation of the sciatic nerve) in the rat, there is an increase in immunoreactive labelling of non-N-methyl-D-asparatate, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate), glutamate receptors in the superficial laminae of the lumbar spinal cord ipsilateral to the ligation. The increase in AMPA receptor expression peaks 14 days after nerve ligation and decreases 35 days post-ligation, corresponding to the time-course of heightened sensitivity to mechanical and thermal noxious stimuli (hyperalgesia) induced by the ligation. Given evidence that AMPA receptors in the superficial laminae mediate fast nociceptive transmission in the spinal cord, our findings suggest that an upregulation of spinal AMPA receptors contributes to hyperalgesia following peripheral nerve injury.

Animals↗
PubMed1996

Pharmacological characterization of tachykinin NK2 receptors on isolated human urinary bladder, prostatic urethra and prostate.

The contractile effect of two highly potent, selective and peptidase-resistant neurokinin (NK) 1 and NK2 receptor agonists, namely delta-Aminovaleryl-[L-Pro9, N-MeLeu10]substance P-(7-11) (GR 73632) and [Lys3, Gly8-R-gamma-lactam-Leu9]NKA-(3-10) (GR 64349), respectively, was investigated on smooth muscle strips dissected from specimens of human detrusor, prostatic urethra and prostate. Furthermore, the potencies of two peptidic NK2 receptor antagonists, GR 87389 L 659,837, in antagonizing GR 64349-induced contractions were compared in these three tissues. In human detrusor muscle the rank order of agonist potency was: [beta Ala8 (NKA-(4-10)] > GR 64349 >> NKA-(4-10) >> SP = GR 73632 >> SP-methylester. The NK2 receptor antagonist, GR 87389, antagonized GR 64349-induced contractions in a competitive manner, whereas L 659,837 was a noncompetitive antagonist. In the prostatic urethra the rank order of agonist potency was GR 64349 > NKA-(4-10) > SP > GR 73632, whereas in the prostate it was: GR 64349 >> [beta Ala8 (NKA-(4-10)] > NKA-(4-10) > SP; GR 73632 was ineffective up to 30 microM. In the prostatic urethra and in the prostate GR 87389 was a noncompetitive antagonist with a potency similar to that exhibited in the detrusor. On the contrary, L 659,837 appeared to be a competitive antagonist in the prostate and in the prostatic urethra, having approximately the similar potency in these two tissues. The selective NK3 agonist senktide was ineffective up to 30 microM in all three tissues. These results are discussed in the view of the proposed NK2 receptor subtypes and considering possible therapeutic implications in the treatment of urinary bladder disorders.

Humans↗
PubMed1996

[Macro- and microcirculation study in diabetic patients].

In diabetics, vascular examination may consider great and medium arteries and microcirculation. The aim of this study is correlation between stenosis in carotid and femoral bifurcation, ultrasound biopsy, and laser-Doppler measurements of distal microcirculation in diabetics. During a six month period, we have examined 90 diabetics in the diabetological service of the Civita Castellana Hospital (Viterbo, Italy), asymptomatic for any vascular distal, cerebral or coronary disease. Subjects were 49 +/- 20 years old with 15 +/- 5 years of diabetes; glycosilate haemoglobin was 7% (mean). 70% of diabetics (62% type I, 38% type II) had an altered veno-arteriolar reflex and 30% of these an ultrasound biopsy value of more than 25. These data demonstrate that most diabetic subjects develop an early, preclinical neuropathy that is directly proportional to the arterial wall condition.

Adult↗
PubMed1996

[Bilateral aneurysm of the popliteal vein. A case report and review of the literature].

We report a case of a 86-year-old woman, with a 1-year history of pain during walking and standing; a duplex scanning of the popliteal fossa was performed bilaterally. We pointed out the presence of a bilateral popliteal vein aneurysm, partially thrombosed. She was treated only with oral anticoaugulant therapy, because of her age. Venous aneurysms are quite rare and are considered to be true when all three cell layers are present in the vessel wall; bilateral popliteal venous aneurysm is very rare and only one case was previously described. This report describes, moreover, with a large review of the world literature, histologic features and diagnostics and therapeutic choices.

Aged↗
PubMed1996

Evaluation of recombinant allergens Bet v 1 and Bet v 2 (profilin) by Pharmacia CAP system in patients with pollen-related allergy to birch and apple.

Sixty-five patients presenting either rhinoconjunctivitis or asthma and sensitized to pollens of trees of the order Fagales were studied by the Pharmacia CAP system in order to assess specific IgE for the important birch pollen allergens Bet v 1 and Bet v 2. All 65 subjects reacted to at least one of the recombinant birch allergens: 43% to Bet v 1, 30.7% to Bet v 2, and 26% to both. Patients monosensitized to birch did not react to Bet v 2. Of patients with a history of oral allergy syndrome after eating apples, 16/28 (57%) reacted to Bet v 1; among 20 polysensitized subjects presenting oral allergy syndrome after consumption of apple, four reacted to Bet v 2 (20%). Among patients with IgE against both recombinant allergens, six (35.30%) presented symptoms of allergy after eating apples. Our results indicate that sensitization to Bet v 1 is specific for birch and apple allergies, whereas sensitization to Bet v 2 is common in polysensitized patients.

Adolescent↗
PubMed1995

Use of resampling techniques to estimate the variance of parameters in pharmacological assays when experimental protocols preclude independent replication: an example using Schild regressions.

Estimates of variance in pharmacological assays are usually made by repeating the experiment with different tissues. Biological factors, such as the inability to wash a drug from tissue, may preclude the type of replication that is appropriate for the statistics of interest. For example, in Schild regressions, replication is usually done at each concentration of antagonist. In some test systems, replication of dose-response curves is not possible. For example, some persistent agonists cannot be removed from tissues after exposure, while in other systems, rapid desensitization severely alters tissue sensitivity to repeated challenge with agonist. In this paper, we demonstrate how a statistical resampling method, bootstrapping, can be used to derive estimates of the confidence intervals for pA2, pKB, and slope from Schild plots. This method utilizes the speed of the computer to estimate variance by repeatedly resampling the data. The advantage to this method is that it can be used for many different experimental designs. For a data set obtained from a Schild regression of atenolol antagonism of isoproterenol in the guinea pig left atrium, bootstrap estimates of confidence limits were calculated for cases where dose ratios were derived from the same tissue and randomly paired tissues. These estimates showed good agreement with estimates obtained using conventional analytical methods, thus suggesting that this method may be useful in practice.

Adrenergic beta-Agonists↗
PubMed1995

Evidence for the presence of both pre- and postjunctional P2-purinoceptor subtypes in human isolated urinary bladder.

1. In order to characterize P2-purinoceptor(s) in human urinary bladder the contractile effects of ATP and its slowly-hydrolyzable analogues alpha, beta-methylene ATP (alpha, beta-MeATP) and beta, gamma-methylene ATP (beta, gamma-MeATP) were investigated on human detrusor strips taken from patients undergoing cystectomy for bladder carcinoma. 2. Serial concentration-response curves (SCRC) for ATP, alpha, beta-MeATP and beta, gamma-MeATP were constructed with an interval of 25 min between two successive doses to avoid tachyphylaxis. ATP (10 microM-10 mM) induced a phasic contraction, which was very rapid in onset. The dose-response curve to ATP appeared not to be monophasic: at the lower concentrations (10-300 microM) the curve was shallow, whilst at high concentrations (1-10 mM) the curve was steeper. The magnitude of the response obtained at the highest concentration tested (10 mM) was only 21.1 +/- 2.8% (mean +/- s.e. mean; n = 4) of the KCl (100 mM)-induced contraction. 3. alpha, beta-MeATP (0.3 microM-1 mM) and beta, gamma-MeATP (10 microM-1 mM) elicited a phasic contraction with a time course similar to that exhibited by ATP. The magnitude of the response obtained at the highest concentration tested (1 mM) was 70.3 +/- 6.3% for alpha, beta-MeATP (n = 10) and 27.9 +/- 4.5% for beta, gamma-MeATP (n = 8) of KCl (100 mM)-induced contraction. The rank order of potency was alpha, beta-MeATP > beta, gamma-MeATP > ATP. A plateau of response could not be achieved by any of these agonists. 4. The P2-purinoceptor antagonist, suramin (10-300 microM), dose-dependently antagonized only the lower part of alpha,beta-MeATP dose-response curve. Data were analysed in terms of dose-ratio estimated at two levels of response (10% and 35% of KC1 100 mM-induced contraction). At 10% of KCl response the Schild plot slope was 0.98 and the estimated pKB was 5.85, whereas using the dose-ratio at the 35% level of the KCl response, the Schild plot was not linear suggesting an interaction of alpha,beta-MeATP with a heterogeneous receptor population.5. The putative P2-purinoceptor antagonist, Coomassie Brilliant Blue G (CB-G) at 0.3 and 1 l micro M(n = 5), shifted to the left the alpha,beta-MeATP SCRC. The response at the highest concentration of agonist was potentiated, being equal to 78.8 +/- 11.7% of the KCl (100 mM) response (n = 5). CB-G at 0.3 microM also shifted to the left the beta,upsilon-MeATP SCRC and significantly potentiated the response at 1 mM up to 46.3 +/- 5.6% of KCl 100 mM response (n = 4).6. Pretreatment with terodotoxin (TTX) at 1 microM shifted to the left the alpha,beta-MeATP SCRC but the response to the highest concentration of the agonist was not potentiated, being 73.6 +/- 9.9% of the KCl(100 mM) response (n = 5). TTX (1 micro M) shifted to the left the beta,upsilon-MeATP SCRC and significantly potentiated the response at 1 mM (61.6 +/- 3.1% of KCl response; n = 4).7. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at 100 micro M did not modify the SCRC to either alpha, beta or beta,upsilon-MeATP.8. We conclude that in human detrusor muscle there is a heterogeneity of purinoceptors. The complex antagonism exhibited by suramin suggests the presence not only of Ph-purinoceptors but also of another contractile P2-purinoceptor subtype insensitive to suramin. Moreover, the activity of CB-G and TTX seems to support the existence of a prejunctional P2-purinoceptor subtype inducing the release of one or more inhibitor neurotransmitters.

Adenosine Triphosphate↗
PubMed1995

Failure of the putative neuropeptide Y antagonists, benextramine and PYX-2, to inhibit Y2 receptors in rat isolated prostatic vas deferens.

1. The pharmacological activity of neuropeptide Y (NPY) and some analogues in inhibiting the twitch contractions induced by electrical stimulation (single pulses at 25 V, 0.15 Hz, 1 ms) in the prostatic portion of the rat isolated vas deferens was investigated. The rank order of agonist potency was: PYY > NPY2-36 > NPY >> NPY13-36 >> NPY18-36 >> [Leu31,Pro34]NPY = hPP, which is consistent with the activation of a Y2 receptor. 2. The putative Y1 and Y2 antagonist, benextramine (BXT), incubated at 100 microM for 10 or 60 min, was ineffective against PYY-induced inhibition of the twitch response, suggesting that the prejunctional Y2 receptor in this tissue is different from the postjunctional one reported in the literature to be sensitive to BXT blockade. 3. The putative NPY antagonist, PYX-2, incubated at 1 microM for 20 min, was completely ineffective in antagonizing PYY-induced inhibition of twitches. 4. The twitch response was totally inhibited by suramin (100 microM) but was little affected by prazosin (1 microM). Furthermore, NPY was without effect on the dose-response curve to ATP in resting conditions. Taken together, these results suggest that in our paradigm, NPY inhibits the release of a purinergic neurotransmitter which mediates contraction of the prostatic portion of the rat vas deferens.

Adenosine Triphosphate↗
PubMed1995

Discrimination by benextramine between the NPY-Y1 receptor subtypes present in rabbit isolated vas deferens and saphenous vein.

1. In order to characterize the neuropeptide Y (NPY) Y1 receptors known to be present in rabbit isolated vas deferens and saphenous vein, the pharmacological activity of the selective NPY Y1 receptor agonists, [Leu31,Pro34] NPY and various other peptide agonists, together with the putative NPY antagonist, benextramine, were compared in the two tissues. 2. In rabbit isolated saphenous vein, cumulative dose-response curves to various NPY agonists were obtained. All the peptides tested caused contractions which developed quite slowly. The rank order of potency obtained was: PYY > NPY > [Leu31,Pro34] NPY = NPY2-36 > hPP >> NPY13-36 = NPY18-36. Incubation with benextramine (BXT) at 100 microM for 30 min irreversibly abolished the contractile response to [Leu31,Pro34] NPY but was ineffective against NPY18-36-induced contractions. 3. Cumulative dose-response curves to [Leu31,Pro34] NPY were performed in the same preparation before and after incubation with 100 microM BXT for 20 min in order to inactivate NPY Y1 receptors. The pKA (-logKA) estimation for [Leu31,Pro34] NPY was 7.60 +/- 0.30 using the operational model and 7.20 +/- 0.33 using the null method; the difference between the two methods was not statistically significant (P = 0.36). 4. Prostatic segments of rabbit vas deferens were electrically stimulated with single pulses. Immediately after stabilization of the contractile response, a cumulative dose-response curve to various NPY agonists was obtained in each tissue. The rank order of potency for twitch inhibition was: PYY> [Leu31,Pro34]NPY > NPY > hPP>NPY2- 36 >>NPY13-36>> NPY 18-36 which indicates the presence of a prejunctional NPY Y1 receptor. BXT at 100 microM incubated for 10 or 60 min did not antagonize the response to[Leu31,Pro34] NPY.5. We conclude that rabbit isolated saphenous vein contains a population of post-junctional NPY Y1 receptors irreversibly blocked by BXT, as well as a population of post-junctional NPY Y2 receptors,which are insensitive to BXT. In contrast, the rabbit isolated vas deferens express a pre-junctional NPYY1 receptor subtype which is not blocked by BXT. Tetramine disulphides such as BXT could be useful tools in classifying NPY receptors.

Animals↗
PubMed1995

Influence of inhalational, neuroleptic and local anaesthesia on lymphocyte subset distribution.

We previously demonstrated that anaesthetics affect leukocyte response by inhibiting lymphocyte capping and metabolism and the phagocytic activity of neutrophils in some experimental models. In the present study, we investigated the effects of the clinical use of three different types of anaesthesia on lymphocyte subset distribution and activity: inhalational anaesthesia (isoflurane), a neuroleptoanalgesia, or local anaesthesia was used in patients submitted to the same operation (hysterectomy). At time 0 (before administering the anaesthesia) and at 10 min and 48 h from the start of the operation, heparinized blood was obtained from each of the 30 patients studied; three lymphocyte subpopulations were isolated (CD4+, CD8+ and CD19+). Cell number was identified for each lymphocyte subset, and (as an indication of cellular function) the intracellular contents of ATP and cAMP were evaluated by luminescence methods. The relevant results for each of the 3 anaesthetic methods were as follows: i) treatment with isoflurane induced a significant reduction in the number and function of CD4+ cells at 10 min, which was reversed at 48 h; a functional but not reversible decrease of CD19+ cells was obtained, ii) treatment with neuroleptic drugs induced a significant progressive functional impairment of CD4+ and CD19+ cells, and iii) local anaesthesia caused a significant functional impairment of CD8+ cells at 48 h and a significant functional impairment of CD19+ cells at 10 min and 48 h.

Adult↗