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  • 1
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 25, No. 14 ( 2021-07), p. 6988-7000
    Abstract: Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by periods of remission and exacerbation. Among the risk factors to develop IBS, psychosocial stress is widely acknowledged. The water avoidance stress repeatedly applied (rWAS) is considered effective to study IBS etio‐pathogenesis. Otilonium bromide (OB), a drug with multiple mechanisms of action, is largely used to treat IBS patients. Orally administered, it concentrates in the large bowel and significantly ameliorates the IBS symptomatology. Presently, we tested whether rWAS rats developed neuro‐muscular abnormalities in the distal colon and whether OB treatment prevented them. The investigation was focussed on the nitrergic neurotransmission by combining functional and morphological methodologies. The results confirm rWAS as reliable animal model to investigate the cellular mechanisms responsible for IBS: exposure to one‐hour psychosocial stress for 10 days depressed muscle contractility and increased iNOS expression in myenteric neurons. OB treatment counteracted these effects. We hypothesize that these effects are due to the corticotropin‐releasing factor (CRF) release, the main mediator of the psychosocial stress, followed by a CRF1receptor activation. OB, that was shown to prevent CRF1r activation, reasonably interrupted the cascade events that bring to the mechanical and immunohistochemical changes affecting rWAS rat colon.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2076114-4
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2001
    In:  Neuroscience Letters Vol. 300, No. 2 ( 2001-3), p. 120-124
    In: Neuroscience Letters, Elsevier BV, Vol. 300, No. 2 ( 2001-3), p. 120-124
    Type of Medium: Online Resource
    ISSN: 0304-3940
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
    detail.hit.zdb_id: 1498535-4
    SSG: 12
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  • 3
    In: Journal of Cellular Physiology, Wiley, Vol. 199, No. 2 ( 2004-05), p. 293-309
    Abstract: At least two populations of c‐kit positive interstitial cells of Cajal (ICC) lie in the gastric wall, one located at the myenteric plexus level has a pace‐making function and the other located intramuscularly is intermediary in the neurotransmission and regenerates the slow waves. Both of these ICC sub‐types express full‐length dystrophin . Mdx mice, an animal model lacking in full‐length dystrophin and used to study Duchenne muscular dystrophy (DMD), show gastric dismotilities. The aim of the present study was to verify in mdx mice whether: (i) gastric ICC undergo morphological changes, through immunohistochemical and ultrastructural analyses; and (ii) there are alterations in the electrical activity, using intracellular recording technique. In control mice, ICC sub‐types showed heterogeneous ultrastructural features, either intramuscularly or at the myenteric plexus level. In mdx mice, all of the ICC sub‐types underwent important changes: coated vesicles were significantly more numerous and caveolae significantly fewer than in control; moreover, cytoskeleton and smooth endoplasmic reticulum were reduced and mitochondria enlarged. c‐Kit ‐positivity and integrity of the ICC networks were maintained. In the circular muscle of normal mice slow waves, which consisted of initial and secondary components, occurred with a regular frequency. In mdx mice, slow waves occurred in a highly dysrhythmic fashion and they lacked a secondary component. We conclude that the lack of the full‐length dystrophin is associated with ultrastructural modifications of gastric ICC, most of which can be interpreted as signs of new membrane formation and altered Ca 2+ handling, and with defective generation and regeneration of slow wave activity. J. Cell. Physiol. 199: 293–309, 2004© 2003 Wiley‐Liss, Inc.
    Type of Medium: Online Resource
    ISSN: 0021-9541 , 1097-4652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 1478143-8
    SSG: 12
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  • 4
    In: British Journal of Pharmacology, Wiley, Vol. 147, No. 4 ( 2006-02), p. 430-436
    Type of Medium: Online Resource
    ISSN: 0007-1188
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2029728-2
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    Georg Thieme Verlag KG ; 2023
    In:  Planta Medica Vol. 89, No. 08 ( 2023-07), p. 848-855
    In: Planta Medica, Georg Thieme Verlag KG, Vol. 89, No. 08 ( 2023-07), p. 848-855
    Abstract: Microemulsions are optically nanosized emulsions, isotropic and thermodynamically stable. They represent versatile drug delivery systems with high potential because they can be administered regardless of route. In the present study, we report on the formulation of a microemulsion made with glycerol (2.25%), Labrasol (20.25%) vitamin E acetate (2.50%), and water (75.00%), which was developed using the pseudo-ternary phase diagram. Globules of the microemulsion had PdI less than 0.25 and size of about 17 nm, evaluated by DLS analysis. These values did not change after loading khellin, a natural lipophilic molecule with interesting biological activities, used as a model of lipophilic drug. Carboxymethyl cellulose was selected as gelling polymer to obtain a microemulgel. Viscosity was 22 100.0 ± 1555.6 mPas·s at 21 ± 2 °C, while it was 8916.5 ± 118.1 mPas·s at 35 ± 2 °C, remaining stable over time. Khellin recovery was 93.16 ± 4.39% and was unchanged after 4 weeks of storage (93.23 ± 2.14%). The pH was 6.59 ± 0.19 and it was found to be 6.42 ± 0.34 at the end of the storage lifetime. The diffusion of khellin from the developed formulation was prolonged over an extended period. Based on overall results and due to the dermatological properties of the ingredients of the formulation, the developed microemulgel loaded with khellin is very promising and suitable for skin care applications.
    Type of Medium: Online Resource
    ISSN: 0032-0943 , 1439-0221
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2023
    detail.hit.zdb_id: 2037089-1
    SSG: 15,3
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2006
    In:  Cell and Tissue Research Vol. 325, No. 2 ( 2006-8), p. 211-217
    In: Cell and Tissue Research, Springer Science and Business Media LLC, Vol. 325, No. 2 ( 2006-8), p. 211-217
    Type of Medium: Online Resource
    ISSN: 0302-766X , 1432-0878
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2006
    detail.hit.zdb_id: 1458496-7
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 18 ( 2021-09-16), p. 9990-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 18 ( 2021-09-16), p. 9990-
    Abstract: It is known that nitric oxide (NO) plays a key physiological role in the control of gastrointestinal (GI) motor phenomena. In this respect, NO is considered as the main non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter responsible for smooth muscle relaxation. Moreover, many substances (including hormones) have been reported to modulate NO production leading to changes in motor responses, further underlying the importance of this molecule in the control of GI motility. An impaired NO production/release has indeed been reported to be implicated in some GI dysmotility. In this article we wanted to focus on the influence of NO on gastric motility by summarizing knowledge regarding its role in both physiological and pathological conditions. The main role of NO on regulating gastric smooth muscle motor responses, with particular reference to NO synthases expression and signaling pathways, is discussed. A deeper knowledge of nitrergic mechanisms is important for a better understanding of their involvement in gastric pathophysiological conditions of hypo- or hyper-motility states and for future therapeutic approaches. A possible role of substances which, by interfering with NO production, could prove useful in managing such motor disorders has been advanced.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Bentham Science Publishers Ltd. ; 2016
    In:  Current Stem Cell Research & Therapy Vol. 11, No. 5 ( 2016-05-09), p. 383-389
    In: Current Stem Cell Research & Therapy, Bentham Science Publishers Ltd., Vol. 11, No. 5 ( 2016-05-09), p. 383-389
    Type of Medium: Online Resource
    ISSN: 1574-888X
    Language: English
    Publisher: Bentham Science Publishers Ltd.
    Publication Date: 2016
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  • 9
    Online Resource
    Online Resource
    Wiley ; 2014
    In:  Journal of Cellular and Molecular Medicine Vol. 18, No. 10 ( 2014-10), p. 2000-2008
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 18, No. 10 ( 2014-10), p. 2000-2008
    Abstract: Urinary bladder voiding is a complex mechanism depending upon interplay among detrusor, urothelium, sensory and motor neurons and connective tissue cells. The identity of some of the latter cells is still controversial. We presently attempted to clarify their phenotype(s) in the human urinary bladder by transmission electron microscopy ( TEM ) and immunohistochemistry. At this latter aim, we used CD 34, PDGFR α, α SMA , c‐Kit and calreticulin antibodies. Both, TEM and immunohistochemistry, showed cells that, sharing several telocyte ( TC ) characteristics, we identified as TC ; these cells, however, differed from each other in some ultrastructural features and immunolabelling according to their location. PDGFR α/calret‐positive, CD 34/c‐Kit‐negative TC were located in the sub‐urothelium and distinct in two subtypes whether, similarly to myofibroblasts, they were α SMA ‐positive and had attachment plaques. The sub‐urothelial TC formed a mixed network with myofibroblasts and were close to numerous nerve endings, many of which n NOS ‐positive. A third TC subtype, PDGFR α/α SMA /c‐Kit‐negative, CD 34/calret‐positive, ultrastructurally typical, was located in the submucosa and detrusor. Briefly, in the human bladder, we found three TC subtypes. Each subtype likely forms a network building a 3‐D scaffold able to follow the bladder wall distension and relaxation and avoiding anomalous wall deformation. The TC located in the sub‐urothelium, a region considered a sort of sensory system for the micturition reflex, as forming a network with myofibroblasts, possessing specialized junctions with extracellular matrix and being close to nerve endings, might have a role in bladder reflexes. In conclusions, the urinary bladder contains peculiar TC able to adapt their morphology to the organ activity.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2076114-4
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  • 10
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 21, No. 4 ( 2017-04), p. 735-745
    Abstract: Otilonium bromide ( OB ) is a spasmolytic drug successfully used for the treatment of irritable bowel syndrome ( IBS ). Its efficacy has been attributed to the block of L‐ and T‐type Ca 2+ channels and muscarinic and tachykinin receptors in the smooth muscle. Furthermore, in healthy rats, repeated OB administration modified neurotransmitter expression and function suggesting other mechanisms of action. On this basis, we investigated whether repeated OB treatment prevented the functional and neurochemical changes observed in the colon of rats underwent to wrap restrain stress ( WRS ) a psychosocial stressor considered suitable to reproduce the main IBS signs and symptoms. In control, WRS and OB / WRS rats functional parameters were measured in vivo and morphological investigations were done ex vivo in the colon. The results showed that OB counteracts most of the neurotransmitters changes caused by WRS . In particular, the drug prevents the decrease in SP ‐, NK 1r‐, nNOS ‐, VIP ‐, and S100β‐immunoreactivity ( IR ) and the increase in CGRP ‐, and CRF 1r‐ IR . On the contrary, OB does not affect the increase in CRF 2r‐ IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS . Finally, OB per se increases the Mr2 expression in the muscle wall and decreases the number of the myenteric Ch AT ‐ IR neurons. Functional findings show a significantly reduction in the number of spontaneous abdominal contraction in OB treated rats. The ability of OB to block L‐type Ca 2+ channels, also expressed by enteric neurons, might represent a possible mechanism through which OB exerts its actions.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2076114-4
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