Oral probiotic treatment of Lactobacillus rhamnosus Lcr35® prevents visceral hypersensitivity to a colonic inflammation and an acute psychological stress.

AIMS: This study evaluated the efficacy of a repeated oral treatment with two active pharmaceutical ingredients (Lcr Lenio® and Lcr Restituo® ) derivated from the probiotic bacterial strain Lactobacillus rhamnosus Lcr35® in two animal models mimicking different features of irritable bowel syndrome (IBS). IBS is characterized by visceral pain associated with alteration of bowel transit. IBS patients present visceral hypersensitivity with peripheral and central origins. METHODS AND RESULTS: The injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS) into the proximal colon as well as an acute partial restraint stress (PRS) produces colonic hypersensitivity measured in conscious rats by a decrease in pain threshold in response to distal colonic distension. Visceral hypersensitivity was produced by injection of TNBS 7 days before colonic distension or by acute PRS on testing day. Treatments were performed once a day during eight consecutive days. CONCLUSIONS: This study indicates that an 8-day probiotic treatment (Lcr Lenio and Lcr Restituo) produces an antihypersensitivity activity in both TNBS and PRS visceral pain models. As this probiotic strain attenuates peripherally and centrally induced visceral hypersensitivity in rats, it may be active in treatment of IBS symptoms. An immunomodulatory effect of the probiotics was highlighted in the TNBS model on the IL-23 secretion, suggesting a mechanism of action involving a regulation of the local IL-23/Th17 immune activation. SIGNIFICANCE AND IMPACT OF THE STUDY: Two formulas of Lcr35® probiotic strain show very encouraging results for the treatment of IBS patients. Further studies are needed to better understand the role and mechanisms of probiotics on the pathogenesis of IBS.

[Rhegmatogenous retinal detachment: Topography of breaks and agreement with lincoff's rules]. / Décollement de rétine rhegmatogène : topographie des déhiscences et conformité aux lois de Lincoff.

PURPOSE: To study the topography of retinal breaks and their agreement with Lincoff's rules. MATERIALS AND METHODS: We performed a retrospective descriptive study of patients with recent rhegmatogenous retinal detachments followed on the ophthalmology service of Abass Ndao Hospital from January 2006 through December 2016. Patients with no prior retinal treatment were included. RESULTS: Over 11 years, we reviewed 97 patients with 107 eyes with retinal detachments. The mean age of our patients was 51.7 years, range 23-79 years. There were 69 male patients, for a male:female ratio of 2.46. Refraction revealed that 38.1% of patients were myopes. Fourteen percent (14%) of patients had experienced trauma to the eye with the detachment. The right eye was involved in 54.6% of patients. The onset was insidious in 54.6% of cases and sudden in 23.7% of cases. All patients had decreased visual acuity, associated with a scotoma in 26.8% of cases. Visual acuity was decreased to light perception through 7/10. In 64.9% of cases, Lincoff's rules were observed. DISCUSSION: Lincoff's rules are still relevant for localization of the breaks in retinal detachments. CONCLUSION: Diagnosis of a retinal detachment is an essential step, since it determines the treatment. Lincoff's rules still have a role in finding the retinal break in retinal detachments.

[Surgical and Orthodontic Treatment of Impacted Canines: A Clinical Report]. / Prise en charge chirurgicale et orthodontique de canines incluses : rapport d'une observation clinique.

Impaction of tooth can be defined as a failure of a tooth to emerge usually due to insufficient space or the presence of a supernumerary tooth blocking its path of eruption. Impaction of the canines deserves particular attention due to their importance regarding occlusal stability and aesthetic. A case of a young girl who presented with an impaction of both upper canines and the lower left canine is reported here. Good therapeutic results have been obtained after 18 month of treatment with a multidisciplinary team involving oral surgeons, periodontists and orthodontists.

Spin reorientation and magnetic structure of HoCo12B6 ferrimagnetic compound.

The magnetic phase diagram is determined by combining magnetization measurements, ac susceptibility and neutron diffraction. The crystal and magnetic structures are also investigated. The HoCo12B6 compound exhibits ferrimagnetic behavior below TC = 147 K. Two antiferromagnetically coupled sublattices cancel out at the compensation temperature TComp = 46 K. HoCo12B6 undergoes a spin reorientation transition at TSR = 76 K; the easy magnetization axis changes from axial to basal plane upon heating. The magnitude of the magnetic moments and their orientation are described and discussed. It is revealed that HoCo12B6 compound exhibits a commensurate magnetic structure below TSR and an incommensurate one slightly above TSR. Significantly different magnetic moments have been observed on the two Co crystal sites, a very low magnetic moment of 0.14 µB being refined on the Co 18 g position. In addition, the second order crystal electric-field parameter A2(0) at the rare-earth site is determined. This result is discussed and used to explain the observed spin reorientation transition by a competition between the Co and Ho sublattice anisotropy.

Selective modification of renal alpha 2-adrenergic receptors in Milan hypertensive rat strain.

Cerebral and renal alpha-adrenergic receptors play an important role in the control of blood pressure. We studied alpha-adrenergic receptors in the cerebral and renal cortex of Milan hypertensive strain (MHS) and normotensive strain (MNS) rats, a genetic model of spontaneous hypertension linked to a kidney abnormality. Binding of the selective alpha 1-adrenergic antagonist [3H]prazosin and the alpha 2-adrenergic antagonist [3H]rauwolscine was used for receptor studies in tissues of prehypertensive (24-day-old) and hypertensive (60-day-old) rats. In the cerebral cortex, no between-strain differences in alpha 1-adrenergic and alpha 2-adrenergic receptor density and affinity were observed in prehypertensive and hypertensive periods. The density of these receptors increased similarly with age in MHS and MNS rats. In the renal cortex, the differences between MHS and MNS rats concerned alpha 2-adrenergic receptors only. Compared with their age-matched normotensive controls, MHS rats showed 1) a lower affinity for the antagonist (p less than 0.05) in the prehypertensive period, 2) absence of the normal age-related increase in receptor density, and 3) a lower density of [3H]rauwolscine binding sites (p less than 0.001) in the hypertensive period. In this period, studies of competitive inhibition of [3H]rauwolscine binding showed that l-epinephrine bound to one class of sites in MHS rats (pseudo-Hill plot, 0.90) and to two classes in MNS rats (pseudo-Hill plot, 0.68). In addition, the lack of any guanylylimidodiphosphate effect on the l-epinephrine competition curve observed in MHS rats suggests the uncoupling of these receptors from the guanosine 5'-triphosphate binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Noradrenaline content and adrenergic receptors in kidney and heart of the prehypertensive and hypertensive Lyon rat strain.

Sympathetic activity modulates the blood pressure in part by activation of cardiac and renal adrenergic receptors. Thus an alteration of tissue noradrenaline content and/or adrenergic receptors in heart and kidney might be involved in the pathogenesis of hypertension. In order to verify this possibility, we studied tissue noradrenaline content and alpha and beta adrenergic receptors in the heart and kidney of Lyon hypertensive (LH), normotensive (LN), and low-pressure (LL) rats. Density and affinity of receptors were determined using the specific radioligands [3H]-prazosin (alpha 1), [3H]-rauwolscine (alpha 2), and [3H]-dihydroalprenolol (beta) in prehypertensive (5-week-old) and hypertensive (21-week-old) rats. In the prehypertensive period, no differences concerning renal and cardiac noradrenaline content and adrenergic receptor densities and affinities were observed. In the hypertensive period, an age-related decrease of renal alpha 1 and beta receptors was observed in LN and LL (P less than 0.01) but not in LH rats. Consequently, at this time, density of renal alpha 1 and beta receptors was higher in LH than in LN and LL (P less than 0.01). In contrast, the density and affinity of renal alpha 2 and cardiac alpha 1 and beta receptors and tissue noradrenaline content were similar in the three rat strains. Because renal alpha 1 and beta receptors mediate various functions involved in the control of blood pressure such as tubular sodium reabsorption, renin secretion, and glomerular filtration, the different density of these receptors in LH rats might be involved in the development or maintenance of hypertension.

Involvement of prostaglandins and CGRP-dependent sensory afferents in peritoneal irritation-induced visceral pain.

This study investigates the contribution of prostaglandins (PG) and calcitonin gene-related peptide (CGRP) pathways in visceral pain induced by peritoneal irritation in rats. Peritoneal irritation was produced by i.p. administration of acetic acid (AA: 0.06-1.0%, 10 ml/kg). Visceral pain was scored by counting abdominal contractions. The effect of CGRP (3-100 microg/kg, i.p.) was also evaluated. Like AA, CGRP induced abdominal pain. Neonatal pretreatment with capsaicin reduced abdominal contractions produced by AA (0.6%) and CGRP (20 microg/kg) with 64.6% and 45.6%, respectively. Abdominal contractions induced by AA and CGRP were blocked by two antinociceptive drugs, mu-and kappa-opioid agonists, morphine and (+/-)-U-50,488H, respectively. Indomethacin (3 mg/kg, s.c.) reduced the number of abdominal contractions produced by AA by 78.1%+/-6.4% but did not inhibit abdominal contractions produced by CGRP. The CGRP, receptor antagonist, hCGRP(8-37) (300 microg/kg, i.v.) inhibited AA- and CGRP-induced abdominal contractions with 57.5%+/-12.4% and 51.6%+/-11.3%, respectively. Concomitant i.p. administration of PGE1 and PGE2 (0.3 mg/kg of each) produced abdominal contractions which were inhibited 45.6%+/-9.3% by hCGRP(8-37) (300 microg/kg i.v.). Taken together, these results suggest that peritoneal irritation is likely to trigger the release of prostaglandins, which in turn produces a release of CGRP from primary sensory afferents.

Adrenergic receptor and catecholamine distribution in rat cerebral cortex: binding studies with [3H]prazosin, [3H]idazoxan and [3H]dihydroalprenolol.

The tritiated adrenergic antagonists [3H]dihydroalprenolol ([3H]DHA; beta-receptors), [3H]prazosin ([3H]PRZ; alpha 1-receptors), and [3H]idazoxan ([3H]IDA; alpha 2-receptors) were used to determine the distribution of these sites in 5 defined areas of the adult rat cerebral cortex. The highest density of [3H]PRZ binding was found in the prefrontal cortex, with a lower and homogeneous distribution for the frontal, parietal, occipital and temporal areas. The [3H]IDA binding sites were fairly uniform for all areas, except for the temporal cortex where it was very dense. In contrast, beta-adrenoceptors labelled by [3H]DHA were very homogeneous for all the regions examined. The functional significance of the distribution of alpha 1, alpha 2 and beta-adrenoceptors is discussed in relation to the catecholamine innervation and monoamine contents measured by high performance liquid chromatography.

Monoclonal antibodies to rat brain alpha-adrenoceptors.

We have developed three hybridomas that produce monoclonal antibodies to rat cerebral alpha-adrenoceptors. Splenic lymphocytes from BALB/c mice immunized with unpurified digitonin-solubilized alpha-adrenoceptors were fused with the mouse myeloma line P3-x 63-Ag 8.653 to yield hybridoma cultures producing alpha-adrenoceptor monoclonal antibodies of the IgG class. However, these antibodies inhibited both alpha 1 and alpha 2 ligand binding suggesting that some molecular homology exists between alpha 1- and alpha 2-adrenoceptors in the rat brain.

Peripheral kappa-opioid receptors mediate the antinociceptive effect of fedotozine (correction of fetodozine) on the duodenal pain reflex inrat.

Fedotozine has been shown to act on gastrointestinal sensitivity through peripheral kappa-opioid receptors. The present study investigated the action of fedotozine and reference compounds, morphine and (+/-)-U-50,488H, on duodenal pain in anesthetized rats. The noxious stimulus was produced by duodenal distension (100 mm Hg; 30 s). Fedotozine (1-5 mg/kg i.v.) produced a dose-dependent inhibition of the cardiovascular reflex induced by duodenal distension (ED50 = 1.87 mg/kg) but had no effect at doses up to 300 micrograms/rat by either intracerebroventricular (i.c.v.) or intrathecal routes (i.t.). The mu-opioid receptor agonist, morphine, was active by both i.v. (ED50 = 0.62 mg/kg) and i.c.v. routes (ED50 = 2.17 micrograms/rat) as was the kappa-opioid receptor agonist, (+/-)-U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1- pyrrolidinyl]cyclohexyl)benzeneacetamide) (ED50 = 0.25 mg/kg and 149 micrograms/rat for i.v. and i.c.v. routes, respectively). The selective kappa-opioid receptor antagonist, nor-binaltorphimine (10 mg/kg s.c.), abolished the response to fedotozine (5 mg/kg i.v.) and (+/-)-U-50,488H (2 mg/kg i.v.) but not that to morphine (1 mg/kg i.v.). In contrast, naloxone (30 micrograms/kg i.v.) blocked the response to morphine (1 mg/kg i.v.) but not that to fedotozine (5 mg/kg i.v.) or (+/-)-U-50,488H (2 mg/kg i.v.). It is concluded that the antinociceptive effects of fedotozine on duodenal pain are mediated by peripheral kappa-opioid receptors.

Sabra rats as a model to differentiate between Na+ and GTP regulation of alpha 2-adrenoceptor densities.

Sodium ions and guanyl nucleotides play an important role in increasing alpha 2-adrenoceptor densities in cerebral and renal cortex of normotensive rats. The in vitro effect of Na+ and GTP was investigated on cerebral and renal alpha-adrenoceptors in hypertensive (SBH, salt-sensitive) and normotensive (SBN, salt-resistant) Sabra rats. In SBH and SBN rats, guanyl nucleotides increased cerebral and renal high-affinity alpha 2-adrenoceptor densities. Sodium ions, in contrast, markedly increased cerebral and renal high affinity alpha 2-adrenoceptor densities only in SBH rats. Under these conditions, alpha 1-adrenoceptor densities were unchanged. Thus, although Na+ and GTP both increase alpha 2-adrenoceptor densities, these agents appear to mediate their regulatory effects via different membrane components. Moreover, the absence of sodium regulation of alpha 2-adrenoceptors in SBN rats may be responsible for the resistance to salt-induced hypertension.

Effect of fedotozine on the cardiovascular pain reflex induced by distension of the irritated colon in the anesthetized rat.

The effect of fedotozine was evaluated in a model of colonic hypersensibility to balloon distension in anesthetized rats. Acetic acid (0.6%, intracolonically) significantly enhanced the hypotension reflex response to colonic distension (P < 0.05). At a noxious pain pressure (75 mm Hg), fedotozine ((+)-(-1R)-1-phenyl-1-[(3,4,5- trimethoxy)benzyloxymethyl]-N,N-dimethyl-n-propylamine) had no effect at 0.6 and 1 mg/kg i.v. in saline-treated rats and higher doses were required to produce antinociception (ED50 = 2.57 mg/kg i.v.). By contrast, fedotozine at 0.6 and 1 mg/kg i.v. displayed 38 and 54% antinociception (P < 0.05) respectively, in acetic acid-treated animals, leading to a decrease in its ED50 (1.15 mg/kg i.v.). Similar results were obtained with (+/-)-trans-N-methyl-N-[2-(pyrrolidinyl)-cyclohexyl]benzo[b]-thiophene- 4-acetamide (PD-117,302), a kappa-opioid receptor agonist, while the antinociceptive action of morphine and a kappa-opioid receptor agonist, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1- pyrrolidinyl]cyclohexyl)benzenacetamide ((+/-)-U-50,488H), was identical in control and acetic acid-treated animals. Nor-binaltorphimine, a selective kappa-opioid receptor antagonist, reversed the enhanced antinociceptive activity of fedotozine and PD-117,302. It is concluded that acetic acid induces colonic hypersensibility to painful mechanical stimuli and that some but not all kappa-opioid receptor ligands can have enhanced efficacy in this pathological situation.

Role of vagal afferents in the antinociception produced by morphine and U-50,488H in the colonic pain reflex in rats.

The mechanisms underlying the antinociception induced by morphine or U-50,488H (trans-(+-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]- cyclohexyl)benzeneacetamide) against painful colonic distension were examined in anaesthetized rats. The respective ED50 values for morphine and U-50,488H were 0.34 and 0.35 mg/kg for the i.v. route, and 1.68 and 167 micrograms/rat for the i.c.v. route. Morphine was active by the intrathecal route (ED50 = 7.8 micrograms) whereas U-50,488H had no effect at doses up to 100 micrograms/rat. The morphine response was selectively antagonized by naloxone (30 micrograms/kg i.v.) whereas that of U-50,488H was blocked by nor-binaltorphimine (10 mg/kg s.c.). Bilateral vagotomy abolished the response to morphine at 0.35 mg/kg i.v. and reduced by 41.3% that to 1 mg/kg morphine, but had no effect on that to U-50,488H or i.c.v. morphine (10 micrograms/rat). It is concluded that peripheral mu- and kappa-opioid receptors may produce antinociception for colonic pain and that vagal integrity is required for mu-opioid but not kappa-opioid peripheral antinociception.

Fedotozine blocks hypersensitive visceral pain in conscious rats: action at peripheral kappa-opioid receptors.

The effect of fedotozine on visceral hypersensitivity was evaluated in conscious rats. One hour after colonic irritation (0.6% acetic acid intracolonically), a 30 mmHg colonic distension was applied for 10 min. Irritation increased the number of abdominal contractions induced by colonic distension (23.4 +/- 4.1 versus 4.8 +/- 1.4 in saline-treated rats, P < 0.001). Facilitation of colonic pain was reversed in a dose-dependent manner by fedotozine ((+)-(-1R1)-1-phenyl-1-[(3,4,5-trimethoxy)benzyloxymethyl]-N ,N-dimethyl-n-propylamine), (+/-)-U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-1-pyrrolidinyl]cyclohexyl)benzen eacetamide) and morphine (respective ED50 values 0.67, 0.51 and 0.23 mg/kg s.c.). The kappa-opioid receptor antagonist, nor-binaltorphimine, abolished the effects of fedotozine and (+/-)-U-50,488H but not those of morphine. Low doses of naloxone (30 microg/kg s.c.) blocked the effect of morphine but not of fedotozine or (+/-)-U-50,488H. After intracerebroventricular administration, morphine was very potent (ED50 1.7 microg/rat), (+/-)-U-50,488H poorly active (58% of antinociception at 300 microg/rat) and fedotozine inactive up to 300 microg/rat. These results show that fedotozine blocks hypersensitive visceral pain by acting on peripheral kappa-opioid receptors in animals.

Changes in central alpha-adrenoceptors and noradrenaline content after high sodium intake in Sabra salt-sensitive and salt-resistant rats.

Several studies have suggested a correlation between sodium accumulation and the development of hypertension. However, the mechanisms whereby sodium is able to increase blood pressure remain unclear. In the present study, alpha-adrenoceptors and noradrenaline contents have been studied in the cerebral cortex, hypothalamus and medulla oblongata in the Sabra rat strain in order to define their role in the resistance or sensitivity to sodium-induced hypertension. Alpha-Adrenoceptors were defined using the selective ligands 3H-prazosin and 3H-rauwolscine for alpha 1- and alpha 2-adrenoceptors, respectively. Under normal sodium diet, alpha 2-adrenoceptor density was higher in cerebral cortex and lower in hypothalamus and medulla oblongata of SBN (salt-resistant) compared to SBH (salt-sensitive) rats. Five weeks of high sodium intake induced a decrease in alpha 2-adrenoceptor density in cerebral cortex and an increase in hypothalamus only in SBN rats. These changes abolished the differences between SBH and SBN rats observed with a normal sodium diet. No changes in density and affinity of alpha 2-adrenoceptors were observed in medulla oblongata of SBN and SBH rats. Density and affinity of alpha 1-adrenoceptors were similar in SBN and SBH rats in all the tissues studied and they were unaffected by the high sodium diet. Noradrenaline contents in cerebral cortex, hypothalamus and medulla oblongata were also similar in the two rat substrains under normal sodium diet, but high sodium intake induced a decrease cerebrocortical noradrenaline content only in SBN rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Noradrenergic effects on rat visual cortex: single-cell microiontophoretic studies of alpha-2 adrenergic receptors.

The catecholamine noradrenaline has been proposed to modulate the excitability of cortical neurons, and such a regulation may be mediated by specific adrenergic receptors. We characterized, using electrophysiological recordings, the types of responses of single cells in the rat visual cortex (areas 17 and 18) to the iontophoretic application of adrenergic agents. For the majority of spontaneous and visually-driven cells sampled, noradrenaline decreased the firing frequency, and in some cases of visually-driven cells could increase the signal/noise ratio. These effects were also documented after the application of the alpha-2 adrenergic agonists clonidine and oxymetazoline, and could be reduced or blocked by a previous ejection of the specific alpha-2 antagonist idazoxan. The present study supports a role for alpha-2 adrenoceptors in the modulation of sensory inputs to the visual cortex.

Travel stress alters the intestinal migrating myoelectric complex in rats: antagonist effect of trimebutine.

A novel stress model was developed that may closely resemble a real-life situation. Intestinal motility was monitored in rats before and after a 12 hour train voyage (travel stress). Travel stress reduced the duration of phase III of the intestinal MMC by 30% (3.2 +/- 0.3 vs 4.7 +/- 0.6 min; p less than 0.001) while the durations of phase I and II were unaffected. This effect persisted for two days. Phase III duration returned to basal values after 3 days indicating a reversible alteration on intestinal migrating myoelectric complex (MMC). The infusion of trimebutine at a flow rate of 166 micrograms/kg/h during the stress exposure abolished the changes observed in the duration of phase III of the MMC; the infusion of diazepam (16.6 micrograms/kg/h) had no effect. These results indicate that the travel stress model may be similar to common life events that induce alterations of intestinal motility. Furthermore, trimebutine prevented the reduction of phase III duration induced by travel stress suggesting its possible action on mechanisms involved in the mediation of the stress-induced intestinal motility changes.

Antinociceptive effects of morphine and U-50,488H on vaginal distension in the anesthetized rat.

The antinociceptive activity of the kappa- and mu-opioid receptor agonists, (+/-)-U-50,488H and morphine, was examined in a vaginal distension model in anaesthetized female rats. Vaginal distension induced a reproducible cardiovascular response (CVR) which was inhibited in a dose related manner by morphine (0.03-1.0 mg/kg i.v., ED50 = 0.16 mg/kg) and (+/-)-U-50,488H (0.08-1.6 mg/kg i.v., ED50 = 0.49 mg/kg). Morphine (0.3 microg/rat) administered i.c.v. inhibited the CVR by 81.6 +/- 7.9% whereas (+/-)-U-50,488H (30-300 microg/rat) was inactive by this route. A low dose of naloxone (30 microg/kg i.v.) blocked the effect of morphine but not that of (+/-)-U-50,488H. The kappa-opioid antagonist, nor-binaltorphimine (10 mg/kg s.c.) abolished the response to (+/-)-U-50,488H but not that of morphine. This demonstrates that both central and peripheral mu-opioid receptors may be involved in morphine-induced antinociception whereas the kappa-opioid agonist, (+/-)-U-50,488H, blocks vaginal nociception by acting on peripheral kappa-opioid receptors.

[Lipoma of the larynx]. / Lipome du larynx.

Cancer is the most frequently observed tumor of the larynx, benign laryngeal tumors being as rare as they are varied. A case is reported of lipoma of larynx revealed by a respiratory distress syndrome.

[Cystic lymphangioma: a practical problem of cervical oncology. Apropos of 4 cases]. / Le lymphangiome kystique: un problème pratique de l'oncologie cervicale. A propos de 4 observations.

Cystic hygroma is a benign dysembryoplasia of the lymphatic system of mainly cervical expression. Clinical findings of a stereotyped nature were found in 4 cases of this particular aspect of infantile surgical affections. On operation there was an obvious relation with the internal jugular vein, and an entire segment had to be removed in 2 cases. These data confirm conventional pathogenic theories.