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Biomedical subjects

M Landi

Publications and source records attributed to M Landi.

At least 19 recordsLinked to original sources
PubMed2004

Microsatellite DNA variation reveals high gene flow and panmictic populations in the Adriatic shared stocks of the European squid and cuttlefish (Cephalopoda).

In the semienclosed Adriatic Sea, the shared stocks of the cephalopods Loligo vulgaris and Sepia officinalis represent important marine fisheries resources exploited by all coastal countries. The improving of knowledge on the demographic features of these shared stocks is internationally relevant for adopting responsible management and conservation of these marine resources. Analyses of microsatellite variation in geographical samples collected from all parts of the Adriatic Sea were performed using arrays of species-specific di-nucleotide and tri-nucleotide loci. In L. vulgaris the level of genetic variability was consistent with that observed in other loliginid species, whereas the S. officinalis stock showed a microsatellite variation markedly lower than that estimated for the Atlantic and Mediterranean populations collected around the Iberian peninsula. The weak spatial genetic differentiation, the discordant results of the genetic divergence estimators and the lack of any geographical cline in the spatial genetic differences suggest the occurrence of single genetically homogeneous populations within the Adriatic stocks of both species, recommending a coordinated management of the squid and cuttlefish by the Adriatic fishing countries. On the contrary, significant differences detected in temporal replicates of S. officinalis might suggest that allelic frequency can change relating to reproductive behaviour.

Animals↗
PubMed2004

Separation of trophoblastic and vascular cell lineages and vascular maturation in early human placental development.

The trophoblast and vascular cell lineages have been studied by immunohistochemistry at 6 and 12-14 weeks of pregnancy. Perivillous and extravillous cytotrophoblasts were specifically stained by anti-cytokeratin 7 whereas endothelial cells were labelled by anti-CD34 at these two stages of pregnancy. Perivillous and extravillous cytotrophoblasts together with erythroblasts showed mitotic figures and anti-Ki67 positive nuclei at the 6th week. In the perivillous cytotrophoblast, the number of Ki67 positive nuclei decreased by 12-14 weeks and the staining was limited to the proximal extravillous trophoblast of cell islands. Some endothelial and perivascular cells were labelled with anti-Ki67 at 12-14 weeks. Erythroblasts did not stain at all at this stage. Endothelial cells bound lectin UEA1 and vessels exhibited a fluorescent signal after anti-myosin staining at 12-14 weeks. These data showed that the cytotrophoblast and endothelial cell lineages are not related from 6 to 12-14 weeks of pregnancy. Because mitotic figures or anti-Ki67 staining were not observed in endothelium or perivascular cells at the 6th week, it seems likely that the endothelial cells committed to vasculogenesis derived from stromal cells. By 12-14 weeks, endothelial cells had nearly achieved their maturation by acquiring 1-fucosyl-binding sites revealed by UEA1-lectin binding and insuring their own renewal by mitosis. The maturation of perivascular cells at 12-14 weeks was shown by the anti-sm-myosin staining. We conclude that placental vasculogenesis involves mesenchymal cells rather than trophoblast. The differenciation of vessels organizing from random plexi to a vascular arborescence may involve paracrine regulatory loops with the trophoblast.

Blood Vessels↗
PubMed2003

[Identification of risk factors for allogenic transfusion in cardiac surgery from an observational study].

OBJECTIVE: To determine perioperative variables for predicting allogenic transfusion in adult cardiac surgery. STUDY DESIGN: Prospective study. PATIENTS: We included 335 consecutive patients undergoing cardiac surgery between February and April 2001. METHODS: Perioperative variables were prospectively collected in a database. For each patient who received transfusion, hemoglobin threshold for transfusion and total number of units of red cell concentrates were collected. Univariate and multivariate analysis were performed. RESULTS: The two strategies for blood conservation which were predominantly used were aprotinin therapy (78%) and blood salvage from the extracorporeal circuit (68%). During perioperative period, 42% of patients [95% CI: 37-47%] received allogenic transfusion. The haemoglobin threshold for transfusion was 7.4 +/- 1.1 and 8.0 +/- 0.7 g x dl(-1) in operating room and in intensive care unit, respectively. On average, 3.4 +/- 2.7 units of red cell concentrates were transfused perioperatively per patient. Using multivariate analysis, perioperative allogenic transfusion was significantly associated with the following variables: preoperative haemoglobin level < 12 g x dl(-1) (odds ratio 8.9; p = 0.001), emergency procedure (odds = 3.7, p = 0.01), reoperation (odds ratio = 3.3; p = 0.002), chronic obstructive pulmonary disease (odds ratio = 2.5; p = 0.03) and complex surgery (odds ratio = 2.4; p = 0.01). The age, the gender, and body mass index were only independent risk factors by univariate analysis. CONCLUSION: In despite of techniques to limit requirement of allogenic transfusion, a large proportion of cardiac surgical patients remains transfused. Independent risk factors of perioperative transfusion are haemoglobin level < 12 g x dl(-1), emergency procedure, reoperation, chronic obstructive pulmonary disease and complex surgery.

Adult↗
PubMed2003

Target-controlled infusion of propofol and remifentanil in cardiac anaesthesia: influence of age on predicted effect-site concentrations.

BACKGROUND: Propofol-anaesthesia administrated via target-controlled infusion (TCI) has been proposed for cardiac surgery. Age-related changes in pharmacology explain why propofol dose requirement is reduced in elderly patients. However, the Marsh pharmacokinetic model incorporated in the Diprifusor propofol device does not take age into account as a covariable. In the absence of depth of anaesthesia monitoring, this limitation could cause adverse cardiovascular effects resulting from propofol overdose in older patients. We assessed the influence of age on effect-site propofol concentrations predicted by the Diprifusor and titrated to the bispectral index score (BIS) during cardiac anaesthesia. METHODS: Forty-five patients received propofol by Diprifusor and remifentanil by software including Minto model. Propofol and remifentanil effect-site concentrations were adapted to BIS (40-60) and haemodynamic profile, respectively. The influence of age on effect-site concentrations was assessed by dividing patients into two groups: young (<65 yr) and elderly (> or =65 yr). RESULTS: For a similar depth of anaesthesia, effect-site propofol concentrations were significantly lower in elderly patients at the different stages of cardiac surgery. The mean dose of propofol required to perform tracheal intubation was significantly lower in elderly patients. However, the overall doses of propofol were comparable in both groups. Neither effect-site remifentanil concentrations nor overall doses of remifentanil were significantly different between the two groups. CONCLUSIONS: In cardiac anaesthesia, target concentrations of propofol must be reduced in elderly patients. Although this probably contributes to improving intraoperative haemodynamic stability, the absence of decrease in overall dose requirement of propofol suggests that this adjustment is relatively moderate.

Adolescent↗
PubMed2001

The role of patient training in the management of seasonal rhinitis and asthma: clinical implications.

BACKGROUND: Allergic rhinitis is an inflammatory disease often associated with bronchial asthma. Intranasal corticosteroids and oral antihistamines are the first-choice drugs. Patient training is relevant to asthma management, but little is known about its impact on rhinitis. We evaluated the role of patient training in the treatment of allergic rhinitis and its effects on nasal and bronchial symptoms. METHODS: One hundred and one patients (M/F = 62/39, age range 12-62 years) with pollen-induced rhinitis (32 with concomitant mild asthma) were enrolled. They were randomized into three groups: A (n = 30) with drug therapy alone, B (n = 35) with drug therapy plus training on the use of nasal spray, and C (n = 36) the same as B plus a lesson on rhinitis and asthma. All patients received mometasone furoate nasal spray for 8 weeks as regular therapy, plus rescue medications on demand. Symptoms and drug consumption were evaluated during the pollen season. RESULTS: The rate of noncompliance/dropout was highest in the untrained patients (P = 0.001). No difference in nasal symptoms was seen among the three groups. On the other hand, group C had significantly fewer asthma symptoms (P = 0.02) and less albuterol use (P = 0.005) than group A. Moreover, the trained group globally used less rescue medication than the other groups (P = 0.02). CONCLUSIONS: Detailed training of patients seems to improve compliance with treatment, reduce concomitant asthma symptoms, and reduce the use of symptomatic drugs.

Administration, Intranasal↗
PubMed2000

Influence of coronary artery and contralateral carotid artery status on long-term results of carotid artery surgery.

The main cause of death and long-term disability of patients undergoing carotid artery surgery is coronary artery disease. To identify the prognostic value of the status of the contralateral artery, we studied the course of 224 consecutive patients in whom one or both carotid arteries were operated on at our institution between 1985 and 1995. The 224 patients were divided into three groups: group I (n = 56) had an occluded contralateral carotid artery, in group II (n = 56) both carotids were operated on, and group III (n = 112) had a normal contralateral carotid artery. The clinical status of all patients except one was ascertained by one of us. We found that the status of the contralateral artery does not influence the long-term prognosis of patients undergoing carotid artery surgery. A periodic cardiological and vascular follow-up of these patients seems warranted to improve their survival.

Actuarial Analysis↗
PubMed2000

Minimal persistent inflammation is also present in patients with seasonal allergic rhinitis.

BACKGROUND: The allergic reaction is characterized by an inflammatory response, which is correlated to the allergen exposure, and is detectable in mite allergic patients, even when symptoms are absent. OBJECTIVE: The study was aimed at assessing the presence of inflammation in patients with pollen allergy during a long observation period. METHODS: Six patients, sensitized only to Betula alba, were enrolled. Evaluated parameters were (1) nasal symptoms, (2) inflammatory markers (ie, neutrophil and eosinophil number and intercellular adhesion molecule-1 expression on nasal epithelial cells), and (3) pollen count. Patients were examined during the pollen season every 4 days for 40 days and were observed 3 times after the pollen season. RESULTS: A significant inflammatory reaction was evident throughout the pollen season, even during the days with a low pollen count and low or absent symptoms. CONCLUSIONS: The results of this study indicate that the global therapeutic strategy for allergic rhinitis should be revised and targeted to inflammatory phenomena rather than to symptoms alone.

Adolescent↗
PubMed2000

HLA-G expression in trophoblast cells is independent of embryonic development.

HLA-G is a nonclassical major histocompatibility complex class I molecule that is selectively expressed on cytotrophoblasts at the feto-maternal interface where it may play a major role in maternal-fetal tolerance. In this study, we compared HLA-G expression in trophoblasts from normal and pathologic pregnancies by immunohistochemical analysis. First, we found a defective HLA-G expression in miscarriages associated with hypotrophic but normal eggs. Conversely, by studying molar pregnancies, we observed a high HLA-G expression in complete and partial hydatidiform moles. Finally, HLA-G expression could be visualized in extravillous trophoblasts that develop outside of their normal environment, as reported here in ectopic pregnancies. Taken together, these results suggest that HLA-G expression in extravillous trophoblasts is induced in an autonomous manner, independently of embryonic development, and may be an integral part of placental development allowing its tolerance from maternal immune system.

Abortion, Spontaneous↗
PubMed1999

Continuous antihistamine treatment controls allergic inflammation and reduces respiratory morbidity in children with mite allergy.

BACKGROUND: Allergic reaction is characterized by a complex inflammatory process. Some of the new antihistamines have antiallergic effects and can affect the inflammatory cell recruitment via adhesion molecule downregulation. We aimed to assess in a 12-month study whether continuous treatment with an antihistamine (terfenadine) can reduce respiratory symptoms and local inflammation in children with mite allergy. METHODS: The study was double-blind and placebo-controlled: it involved two parallel groups of children suffering from rhinoconjunctivitis and/or mild intermittent asthma due to mite allergy. They received either terfenadine (1 mg/kg per body weight per day) or placebo for 1 year. Nasal, conjunctival, and bronchial symptoms were recorded by diary cards; at each of the programmed control visits, a nasal scraping for inflammatory cells and ICAM-1 was performed. Some additional clinical parameters were also recorded: days of school absence, extra visits for acute respiratory symptoms, and days of hospital admission. RESULTS: Only children treated with terfenadine achieved significant control of symptoms (P<0.05 in 8 out of 12 months) and allergic inflammation, as shown by inflammatory cell infiltrate and ICAM-1 expression at nasal level (P<0.001), and had significantly fewer extra visits and school absences than the placebo group (P<0.03). No side-effects were reported in either group. CONCLUSIONS: The present study demonstrates that continuous terfenadine treatment (1 mg/kg body weight per day) could decrease respiratory symptoms and allergic inflammation, and it had an additional antiallergic effect in reducing ICAM-1 expression on nasal epithelial cells. Therefore, the present results confirm the efficacy of a long-term therapeutic strategy in controlling allergic inflammation.

Adolescent↗
PubMed1999

SR146131: a new potent, orally active, and selective nonpeptide cholecystokinin subtype 1 receptor agonist. II. In vivo pharmacological characterization.

SR146131 is a potent and selective agonist at cholecystokinin subtype 1 (CCK1) receptors in vitro. The present study evaluates the activity of the compound in vivo. SR146131 completely inhibited gastric and gallbladder emptying in mice (ED50 of 66 and 2.7 micrograms/kg p.o., respectively). SR146131 dose dependently reduced food intake in fasted rats (from 0.1 mg/kg p.o.), in nonfasted rats in which food intake had been highly stimulated by the administration of neuropeptide Y (1-36) (from 0.3 mg/kg p.o.), in fasted gerbils (from 0.1 mg/kg p.o.), and in marmosets maintained on a restricted diet (from 3 mg/kg p.o.). SR146131 (10 mg/kg p.o.) also increased the number of Fos-positive cells in the hypothalamic paraventricular nucleus of rats. Locomotor activity of mice was reduced by orally administered SR146131 (from 0.3 mg/kg p.o.). When administered intrastriatally, SR146131 elicited contralateral turning behavior in mice. Furthermore, orally administered SR146131 (0.3-10 mg/kg), also reduced the levels of cerebellar cyclic GMP. Finally, SR146131 (0.1 microgram/kg to 1 mg/kg, p.o.) significantly and dose dependently antagonized fluphenazine-induced mouth movements in rats. The CCK1 antagonist SR27897B prevented all the effects of SR146131. Conversely, SR146131 was unable to elicit any agonist or antagonist effects in a model of CCK2 receptor stimulation in vivo. SR146131 is a very potent and selective nonpeptide CCK1 agonist in vivo. SR146131 is more potent than any other CCK1 agonists reported to date. Because pharmacodynamic studies suggest that SR146131 should have a high absolute bioavailability, it may be a promising drug for the treatment of eating and motor disorders in humans.

Animals↗
PubMed1999

[Cytological screening of uterine cervical cancer by samples in liquid medium (CytoRich). Preliminary study of a series of 111 292 patients].

We report on the preliminary results of a series of 111,292 patients who benefited from a liquid medium sample (CytoRich) for cervical cancer screening. The number of dubious or limited smears was reduced by 0.03% and 0.53% respectively. The junction zone was better explored, and metaplastic changes were observed in 35.71% of the cases. This method improved the identification of low-grade lesions by +56% (2751/111,292; 2.47%) and of high-grade lesions by +75% (860/111,292; 0.77%), with a reduction in the number of ASCUS/AGUS by -44% (2065/111,292; 1.85%). This preliminary study confirms the results already published. The results demonstrating cytohistological correlation should prove to be a decisive factor, enabling the testing of the sensitivity and specificity of this technique. It will then be possible to envisage a future 'new paradigm' for screening cervical cancer as the result of a liquid medium sample, computer-assisted screening and HPV viral identification by Hybrid capture II.

Cervix Uteri↗
PubMed1998

Allergen-specific nasal challenge: response kinetics of clinical and inflammatory events to rechallenge.

Allergen-specific nasal challenge is a valid and reliable tool for studying the pathophysiological mechanisms involved in allergic inflammation. Nasal challenge induces an immediate clinical response in allergic subjects and a concomitant appearance of an inflammatory infiltrate. The mucosal inflammation may persist up to 48-72 h after allergen exposure. If the subjects are rechallenged within this period the response is more pronounced: the so-defined priming effect. The aim of the study was to evaluate the effects of the nasal rechallenge, performed at different time intervals: 3 days, 1, 2 and 4 weeks after the first challenge. Forty allergic subjects underwent two nasal challenges: at baseline and after the periods mentioned above (10/group). Symptoms and inflammatory cells (eosinophils and neutrophils recovered by nasal brushing) were assessed. The 3-day-interval group showed a hyperreactive response (priming effect), the 1- and 4-week-interval groups showed a response similar to baseline, and the 2-week-interval group showed a hyporeactive response ('tolerogenic effect'). The last phenomenon may be due to a possible immunologic response similar to that achievable during local specific immunotherapy. The present results further elucidate the kinetics of allergen-driven inflammatory events and highlight the importance of the time period chosen for rechallenge. The latter fact may be of primary importance in clinical trials involving specific challenge.

Adolescent↗
PubMed1998

The embryogenesis of congenital vertebral dislocation: early embryonic buckling?

Congenital vertebral dislocation (CVD) is a rare congenital spinal malformation characterized by a translatory or rotatory vertebral displacement, or both, at a single level, that results in an abrupt angulation of the neural canal. The more caudal vertebra is dysplastic and appears at first glance to be posteriorly dislocated into the vertebral canal as a posterior hemivertebra, but is actually well aligned with the more caudal vertebral column. Unfortunately, the present classification of complex congenital vertebral anomalies is confusing, and CVD has been grouped together with other congenital vertebral malformations under the terms 'segmental spinal dysgenesis', 'medial spinal aplasia', and others. Moreover, a putative embryonic mechanism has never been proposed for CVD. Based upon our experience with 6 children and a critical review of the literature, we identify CVD as a distinct entity having characteristic anatomical features. We propose a novel putative embryonic mechanism - early embryonic 'buckling' - which likely occurs by the 6th embryonic week, prior to the period of axonal outgrowth and the beginning of vertebral chondrification.

Female↗
PubMed1998

[The natural history of asthma].

Asthma is a chronic inflammatory disease of airways with a multifactorial pathogenesis. Both genetic and environmental factors contribute to the development of the disease which can vary in the same patient through time. Due to its complexity, natural history of asthma is poorly well-known. Generally, in the history of asthma three periods of life are taken into consideration: early childhood, adolescence and adult life. It has been demonstrated that less than one third of children who are affected by wheezing in early childhood develop a true asthma afterwards. Usually in these subjects who are male and atopic, viruses and subsequently allergens represent the most important factors responsible for the development of asthma. During adolescence airborne allergens represent the main cause of the disease: mites in infancy and pollens in late childhood. The incidence of asthma during adolescence is growing according to recent studies, and even if the symptomatology of asthma improves through time, about two thirds of patients remain asthmatic in their adult life. As regards adults etiology, it is less known, women are more frequently affected than men and the prognosis is generally poorer. Several factors negatively influence the course of asthma such as age, smoking, the severity of the disease during infancy, the persistence of functional obstructive alterations and the increased aspecific bronchial reactivity. Adequate therapy is crucially important to cope with these factors and can change the course of the disease.

Adolescent↗
PubMed1997

Biochemical and pharmacological activities of SR 144190, a new potent non-peptide tachykinin NK2 receptor antagonist.

(R)-3-(1-[2-(4-benzoyl-2-(3,4-difluorophenyl)-morpholin-2-yl)- ethyl]-4-phenylpiperidin-4-yl)-1-dimethylurea (SR 144190) is a new non-peptide antagonist of tachykinin NK2 receptors. SR 144190 potently and selectively inhibited neurokinin A binding to NK2 receptors from various species, including humans. In in vitro functional assays, it was a potent, selective and competitive antagonist of NK2 receptors with apparent affinities (pA2 values) between 9.08 and 10.10. In vivo, SR 144190 blocked [Nle10]neurokinin A-(4-10)-induced bronchoconstriction in guinea pigs (ID50 = 21 micrograms kg-1 i.v. and 250 micrograms kg-1 i.d.) and [beta Ala8]neurokinin A-(4-10)-induced urinary bladder contraction in rats (ID50 = 11 micrograms kg-1 i.v. and 190 micrograms kg-1 i.d.). It prevented citric acid-induced cough and airway hyperresponsiveness to acetylcholine in guinea pigs (1 mg kg-1 i.p.) as well as castor oil-induced diarrhoea in rats (0.01-10 micrograms kg-1 s.c. or p.o). Finally, it blocked the turning behaviour induced by intrastriatal injections of [Nle10]neurokinin A-(4-10) in mice (ID50 = 3 micrograms kg-1 i.v. and 16 micrograms kg-1 p.o.).

Animals↗
PubMed1997

Negative modulation of nitric oxide production by neurotensin as a putative mechanism of the diuretic action of SR 48692 in rats.

1. We investigated the effect of the non-peptide neurotensin (NT) antagonist SR 48692 on renal function in rats and the involvement of nitric oxide (NO) in the diuretic action of this compound. 2. In fed animals, SR 48692 dose-dependently (0.5 to 12.5 mg kg-1, p.o., 0.03 to 1 mg kg-1, i.p. and 0.1 to 1 microgram/rat, i.c.v.) increased urine output and urinary excretion of Na+, K+ and Cl- and reduced urine osmolality. The diuretic activity was also evident in water-deprived, fasted animals and in fasted, water-loaded rats. 3. NT (0.1 microgram/rat, i.c.v.) had no effect on urine output in fed rats, but reduced the diuretic action of SR 48692 (1 microgram/rat, i.c.v.). The opposite result was obtained in fasted, water-loaded animals: NT dose-dependently (0.01 and 0.1 microgram/rat, i.c.v.) inhibited diuresis and this effect was significantly inhibited by i.c.v. SR 48692. In this experimental condition, SR 48692 did not further increase the on-going diuresis. 4. The NO synthesis inhibitor N(1)-nitro-L-arginine methyl ester (L-NAME; 30 mg kg-1, i.p.) alone had no effect on urine output in fed rats but prevented the diuretic action of i.c.v. or i.p. SR 48692; L-arginine (1 g kg-1, i.p.) but not D-arginine (1 g kg-1, i.p.) restored the SR 48692-dependent increase in diuresis, L-NAME had no effect on furosemide-stimulated diuresis. 5. Systemically administered L-NAME or i.c.v. NT in fasted, water-loaded rats significantly reduced water diuresis but this effect was no longer seen in animals given i.p. L-arginine. Rats receiving i.c.v. NT, whose diuresis was significantly reduced, also excreted less nitrates and nitrites in urine. 6. Increased diuresis after central or systemic administration of SR 48692 to fed rats was paralleled by increased urinary excretion of nitrates and nitrites, this being consistent with peripheral enhancement of NO production after NT-receptor blockade by SR 48692. The increase in diuresis after furosemide also involved an increase of nitrates and nitrites in urine, but this effect was about half that attained with an equipotent diuretic dose of SR 48692. 7. In fed rats, the NO donor isosorbide-dinitrate, reduced systolic blood pressure (unlike SR 48692 which did not affect blood pressure) but also dose-dependently (1 and 5 mg kg-1, i.p.) stimulated urine output. 8. The overall effects of SR 48692 strongly support a link between the actions of endogenous NT, AVP and peripheral NO production in the modulation of renal excretion of water, Na+, K+ and Cl-.

Animals↗
PubMed1997

Role of tachykinins in castor oil diarrhoea in rats.

1. We set out to ascertain the role of tachykinins, neurokinin A and substance P, in castor oil-induced diarrhoea in rats as disclosed by the inhibitory effect of the non-peptide NK1- and NK2-receptor antagonists. SR 140333 and SR 48968, respectively. 2. SR 48968 (0.02 to 20 micrograms kg-1, s.c. or p.o.), and the opioid receptor agonist loperamide (1-10 mg kg-1, p.o.), dose-dependently prevented castor oil effects: % inhibition vs castor oil, diarrhoea 0 to 100, increase in faecal mass 7 to 90 and water content 16 to 90. SR 140333 (0.02 to 20 micrograms kg-1, s.c.) and the platelet activating factor antagonist SR 27417 (5 to 500 micrograms kg-1, p.o.) did not prevent the increase in faecal water content, but reduced faecal mass (35 to 66%) and diarrhoea (0 to 57%). 3. The R-enantiomers of tachykinin NK1 and NK2 receptor antagonists, SR 140603 and SR 48605 (both at 2 or 20 micrograms kg-1, s.c.) had no effect other than reducing faecal mass at the highest dose tested. 4. SR 48968 (20 micrograms kg-1, p.o.) but not loperamide (10 mg kg-1, p.o.) given 24 h before castor oil, still slightly but significantly reduced by 30% the increase of faecal mass output; both treatments significantly reduced (30 to 70%) the effect of castor oil on faecal water content, although the incidence of diarrhoea was only slightly less than in controls. 5. In castor oil-treated rats, naloxone (2 mg kg-1, s.c.) completely blocked the antidiarrhoeal action of loperamide (10 mg kg-1, p.o.) but not of SR 48968 (20 micrograms kg-1, p.o.): a similar result was obtained on faecal mass and water content. 6. Castor oil strongly increased the occurrence of manometrically recorded propulsive giant contractions (500 to 1000% over control values) of transverse and distal colon, this effect being significantly prevented (80 to 100%) by SR 48968 and loperamide and partially by SR 140333 (35% distal colon, 70% transverse colon). 7. In castor oil free rats, loperamide but not SR 48968 or SR 140333 significantly reduced by 50% the gastrointestinal transit of a charcoal test meal, as well as 24 h faecal mass output. Consistently, loperamide, unlike the tachykinin receptor antagonists, had a dramatic effect on manometric recordings of intestinal motility, reducing all kinds of colonic contractions. 8. Our findings suggest that castor oil diarrhoea in rats entails activation of NK1 and NK2 receptors by endogenous tachykinins, whose antagonists may have a potential as antidiarrhoeal agents free from the constipating action of opioids.

Animals↗