ITMI20091125A1 - USE OF CROMOGRANIN A AND ITS PEPTIDIC DERIVATIVES IN THE TREATMENT OF CHANNEL INFLAMMATIONS - Google Patents
USE OF CROMOGRANIN A AND ITS PEPTIDIC DERIVATIVES IN THE TREATMENT OF CHANNEL INFLAMMATIONS Download PDFInfo
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- ITMI20091125A1 ITMI20091125A1 IT001125A ITMI20091125A ITMI20091125A1 IT MI20091125 A1 ITMI20091125 A1 IT MI20091125A1 IT 001125 A IT001125 A IT 001125A IT MI20091125 A ITMI20091125 A IT MI20091125A IT MI20091125 A1 ITMI20091125 A1 IT MI20091125A1
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- 238000011282 treatment Methods 0.000 title claims description 19
- 206010061218 Inflammation Diseases 0.000 title description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 24
- 102100031186 Chromogranin-A Human genes 0.000 claims description 23
- 108010060757 vasostatin Proteins 0.000 claims description 23
- 108010038447 Chromogranin A Proteins 0.000 claims description 19
- 102000010792 Chromogranin A Human genes 0.000 claims description 19
- 108010033276 Peptide Fragments Proteins 0.000 claims description 16
- 102000007079 Peptide Fragments Human genes 0.000 claims description 16
- 210000002249 digestive system Anatomy 0.000 claims description 12
- 208000027866 inflammatory disease Diseases 0.000 claims description 12
- 102400000194 Vasostatin-1 Human genes 0.000 claims description 11
- 239000012634 fragment Substances 0.000 claims description 11
- 108010059391 vasostatin I Proteins 0.000 claims description 11
- 230000001684 chronic effect Effects 0.000 claims description 10
- 230000002265 prevention Effects 0.000 claims description 10
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 7
- 208000011231 Crohn disease Diseases 0.000 claims description 7
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000000816 peptidomimetic Substances 0.000 claims description 5
- 208000037976 chronic inflammation Diseases 0.000 claims description 4
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- 125000000539 amino acid group Chemical group 0.000 claims description 2
- 102400000195 Vasostatin-2 Human genes 0.000 claims 1
- 239000008203 oral pharmaceutical composition Substances 0.000 claims 1
- 230000001175 peptic effect Effects 0.000 claims 1
- 108010077020 vasostatin II Proteins 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Proteomics, Peptides & Aminoacids (AREA)
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Description
DESCRIZIONE DESCRIPTION
La presente invenzione ha per oggetto l’uso della cromogranina A, dei suoi frammenti peptidici e dei loro derivati peptidomimetici non-peptidici nei trattamento e nella prevenzione delle patologie infiammatorie dell’apparato digerente. In particolare, l'invenzione concerne l’uso di frammenti attivi della cromogranina A, ad esempio della vasostatina, ne! trattamento e/o nella prevenzione di malattie quali il morbo dt C<’>rohn, la colite ulcerosa e, più in generale, delle malattie croniche intestinali. The present invention relates to the use of chromogranin A, its peptide fragments and their non-peptide peptidomimetic derivatives in the treatment and prevention of inflammatory diseases of the digestive system. In particular, the invention concerns the use of active fragments of chromogranin A, for example of vasostatin, ne! treatment and / or prevention of diseases such as C <'> rohn's disease, ulcerative colitis and, more generally, chronic intestinal diseases.
Il morbo di Crohn (qui di seguito anche solo "CD” dall’inglese “Crohn's disease”Ee la colite ulcerosa (qui di seguito anche solo “UC” dall<’>inglese “ulcerative coiitis”), sono conosciuti collettivamente come malattie infiammatorie croniche intestinali (qui “IBD” dall’inglese “Inflammatory Bowel Disease”), Tali patologie sono disordini caratterizzati dall'inframmazionc cronica e idiopatica del tessuto della mucosa intestinale, infiammazione che causa una serie di sintomi tra cui dolore addominale, grave diarrea, sanguìnamento del retto e deperimento. Crohn's disease (hereinafter also only "CD" from the English "Crohn's disease" E and ulcerative colitis (hereinafter also only "UC" from the English "ulcerative coiitis"), are collectively known as inflammatory diseases bowel disease (here "IBD" from the English "Inflammatory Bowel Disease"), These diseases are disorders characterized by chronic and idiopathic inflammation of the intestinal mucosa, inflammation that causes a series of symptoms including abdominal pain, severe diarrhea, bleeding of the rectum and wasting.
Le IBD tendono ad emergere nella tarda infanzia e sono diffuse prevalentemente nelle regioni occidentalizzate del mondo. Il CD e la UC si possono distinguere dagli organi interessati: il CD può essere localizzato in ogni regione del tubo digerente in modo discontinuo e transmurale, mentre nella UC la patologia è limitata alla superficie mueosale del colon. IBDs tend to emerge in late childhood and are prevalent in the westernized regions of the world. CD and UC can be distinguished from the organs involved: CD can be localized in every region of the digestive tract in a discontinuous and transmural way, while in UC the pathology is limited to the mueosal surface of the colon.
In Europa e negli Stati Uniti, l’incidenza de! morbo di Crohn è di 6-7, 1 : 100,000 persone/anno mentre per la colite ulcerosa si contano circa 10-12 casi ogni 100.000 persone/anno. Sì è osservato che i pazienti affetti da queste patologie mostrano una maggiore incidenza dì tumore al colon. In Europe and the United States, the incidence of! Crohn's disease is 6-7.1: 100,000 people / year while for ulcerative colitis there are about 10-12 cases per 100,000 people / year. It has been observed that patients affected by these pathologies show a higher incidence of colon cancer.
I trattamenti farmacologici attualmente in uso comprendono farmaci ami- Pharmacological treatments currently in use include ami-
7 infiammatori steroidei, farmaci immunosoppressori, e anticorpi anti-TNF. Tali trattamenti non hanno tuttavia mostrato alcun effetto curativo ma sono indicati solamente per il contenimento dei disturbi conseguenti all'infiammazione. 7 steroidal inflammatory drugs, immunosuppressive drugs, and anti-TNF antibodies. However, these treatments have not shown any curative effect but are indicated only for the containment of the ailments resulting from inflammation.
Non è infatti attualmente disponibile alcun farmaco in grado di curare tali patologie. Inoltre le terapie a base dì corticosteroidi e immunosoppressori provocano, come è noto, seri effetti collaterali che portano spesso aH'interruzione della terapia, in questi casi, Punico trattamento perseguìbile risulta essere l’asportazione chirurgica del tratto intestinale danneggiato. In fact, no drug is currently available that can cure these pathologies. Furthermore, corticosteroid and immunosuppressant-based therapies cause, as is known, serious side effects that often lead to the interruption of therapy. In these cases, the only possible treatment is the surgical removal of the damaged intestinal tract.
La cromogranina A è una proteina endogena il cui ruolo biologico è ancora poco conosciuto. Chromogranin A is an endogenous protein whose biological role is still poorly understood.
Sono stati altresi descritti in letteratura dei frammenti amminoacidici della cromogranina A, in particolare la vasostatina I e la vasoslatina 11. Amino acid fragments of chromogranin A have also been described in the literature, in particular vasostatin I and vasoslatin 11.
Scopo della presente invenzione è di fornire un trattamento curativo e preventivo delle malattie croniche dell’apparato digerente, che ovvi agli inconvenienti dei trattamenti dell’arte nota sopra descritti. The purpose of the present invention is to provide a curative and preventive treatment of chronic diseases of the digestive system, which obviates the drawbacks of the prior art treatments described above.
È stato infatti ora sorprendentemente trovato che è possibile trattare con successo le malattie infiammatorie del l’apparato digerente, in particolare, ma non solo, le malattìe infiammatorie croniche intestinali de! tratto gastrointestinale, somministrando cromogranina A è/o i suoi frammenti peptidici attivi, quali la vasostatina e/o altri frammenti peptidici della Cromogranina A di peso molecolare più limitato. In fact, it has now been surprisingly found that it is possible to successfully treat inflammatory diseases of the digestive system, in particular, but not limited to, chronic inflammatory bowel diseases! gastrointestinal tract, by administering chromogranin A and / or its active peptide fragments, such as vasostatin and / or other peptide fragments of chromogranin A of more limited molecular weight.
Si è anche trovato che la somministrazione di cromogranina A e/o dei suoi frammenti peptidici attivi, quali la vasostatma e/o di altri frammenti peptidici inferiori produce un effetto preventivo nei soggetti predisposti a sviluppare malattie infiammatorie croniche dell’apparato digerente. It has also been found that the administration of chromogranin A and / or its active peptide fragments, such as vasostatma and / or other lower peptide fragments, produces a preventive effect in subjects predisposed to developing chronic inflammatory diseases of the digestive system.
Così secondo uno dei suoi aspetti, l’invenzione ha per oggetto l’uso della cromogranina A, dei suoi frammenti pcptidici -attivi o dei loro derivati peptidomimetici non-peptidici, per la preparazione di un medicamento per il trattamento e/o la prevenzione delle malattie infiammatorie dell’apparato digerente. Come detto sopra, la cromogranina A è un peptide endogeno di 439 amminoacidi, descritto in letteratura (Koneckì et al J Gioì Chem, 1987 262 17026). La numerazione delle sequenze secondo la presente invenzione si riferisce alla sequenza riportata da Koneeki et al. di cui sopra. Thus, according to one of its aspects, the invention relates to the use of chromogranin A, of its peptide-active fragments or of their non-peptide peptidomimetic derivatives, for the preparation of a medicament for the treatment and / or prevention of inflammatory diseases of the digestive system. As mentioned above, chromogranin A is an endogenous peptide of 439 amino acids, described in the literature (Koneckì et al J Gioì Chem, 1987 262 17026). The numbering of the sequences according to the present invention refers to the sequence reported by Koneeki et al. above.
Secondo la presente invenzione, per “frammenti peptidici attivi” si intendono indicare i frammenti della cromogranina A che sono in grado di esercitare il suo stesso effetto nel trattamento delle patologie sopra indicate. Esempi di tali frammenti sono la vasostatina f, che è il frammento 1-76 e la vasostatina il, che è il frammento 1-) 13, entrambi descritti in letteratura. According to the present invention, by "active peptide fragments" we mean the fragments of chromogranin A which are capable of exerting its same effect in the treatment of the aforementioned pathologies. Examples of such fragments are vasostatin f, which is fragment 1-76 and vasostatin il, which is fragment 1-) 13, both described in the literature.
Altri esempi di frammenti peptidici attivi secondo l’invenzione sono frammenti della vasostatina di lunghezza variabile, ad esempio i frammenti costituiti da 5-10, 10-20, 20-40, 40-60 o 40-75 residui amminoacidici. Other examples of active peptide fragments according to the invention are vasostatin fragments of variable length, for example fragments consisting of 5-10, 10-20, 20-40, 40-60 or 40-75 amino acid residues.
L’espressione “frammenti peptidici attivi” comprende inoltre i pepi idi aventi le sequenze amminoacidiche scelte tra le sequenze della cromogranina A 1 -76. 1-78, 7-57, 47-76, 47-91, 39-68 e 46-63, The expression "active peptide fragments" also includes pepiids having the amino acid sequences chosen from the chromogranin A 1 -76 sequences. 1-78, 7-57, 47-76, 47-91, 39-68 and 46-63,
La sequenza 46-63 è nuova e costituisce un ulteriore oggetto della presente invenzione. The sequence 46-63 is new and constitutes a further object of the present invention.
Dei derivati peptidomimetici non-peptidici preferiti sono i derivati delle sequenze della vasostatina 1, della vasostatina 11 e delle sequenze peptidiche sopra indicate. Secondo la presente invenzione, per “malattie infiammatorie dell’apparato digerente’’ si intendono indicare tutte le patologie infiammatorie a carico dell<’>apparato digerente, in particolare le malattie infiammatorie croniche e più specificatamente, le patologie a carico del sistema gastrointestinale. Of the preferred non-peptide peptidomimetic derivatives are the derivatives of the vasostatin 1 sequences, of the vasostatin 11 and of the peptide sequences indicated above. According to the present invention, "inflammatory diseases of the digestive system '' means all inflammatory diseases affecting the digestive system, in particular chronic inflammatory diseases and more specifically, diseases affecting the gastrointestinal system.
Secondo una forma di realizzazione preferita detrinvenzione, tali malattie sono scelte tra le malattie infiammatorie croniche intestinali, la colite ulcerosa e il morbo di Crohn. According to a preferred embodiment of the invention, these diseases are selected from chronic inflammatory bowel diseases, ulcerative colitis and Crohn's disease.
Secondo un’altra forma di realizzazione preferita, l'invenzione ha per oggetto l’uso della vasostatina [ do della vasostatina fi e/o di uno dei loro frammenti attivi e/o dei loro derivati peptidomi melici non-peptidici, per il trattamento e/o la prevenzione delle malattie infiammatorie croniche intestinali, della colite ulcerosa e/o del morbo di Crohn, According to another preferred embodiment, the invention relates to the use of vasostatin and / or of one of their active fragments and / or of their non-peptide melic peptidome derivatives, for the treatment and / or the prevention of chronic inflammatory bowel disease, ulcerative colitis and / or Crohn's disease,
Per l<’>uso secondo l’invenzione, la cromogran ina A e i suoi frammenti peptidici attivi possono essere somministrati per via orale, Ciò rappresenta un ulteriore aspetto sorprendente dell’invenzione, considerando che si tratta di peptidi, normalmente non attivi per via orale. For the use according to the invention, cromogranine A and its active peptide fragments can be administered orally. This represents a further surprising aspect of the invention, considering that they are peptides, normally not active orally. .
Secondo altro dei suoi aspetti, la presente invenzione ha per oggetto l’uso dì un peptide che presenta una omologia di almeno il 60%, preferibilmente di almeno il 80%, con la cromogranina A o con la vasostatjna I o con la vasostatina (f, per la preparazione di un medicamento per il trattamento e/o la prevenzione delle patologìe sopra indicate. According to another of its aspects, the present invention relates to the use of a peptide which has a homology of at least 60%, preferably at least 80%, with chromogranin A or with vasostatin I or with vasostatin (f , for the preparation of a medicament for the treatment and / or prevention of the aforementioned pathologies.
Per ‘"peptide che presenta ima omologia di almeno il 60%, preferibilmente di almeno il 80%”»si intende qui indicare una variante del peptide, cioè una sequenza peptidiea che differisce in una o più posizioni aminoacidi clic rispetto a quella dei peptidi sopra descritti, ma che conserva almeno il 60, preferibilmente almeno P80% di identità anuninoacidica con i detti peptidi. By "peptide which has a homology of at least 60%, preferably at least 80%" is meant herein a variant of the peptide, that is, a peptide sequence that differs in one or more amino acid positions from that of the above peptides described, but which retains at least 60, preferably at least 80% anuninoacid identity with said peptides.
Per l’uso secondo l’invenzione, è possibile somministrare il o ì peptidi o i loro derivati pepiidomimetiei di cui sopra, in formulazioni orali, preparate come noto alla tecnica. Possono così essere preparate delle compresse, delle capsule, dei granulali e delle composizioni liquide comprendenti il o i peptidi prescelti, in combinazione con gli eccipienti comunemente impiegati nella formulazione dj composizioni orali e ben note all’esperto del ramo. Secondo una forma di realizzazione preferita, le composi/ioni orali dell’invenzione come sopra definite sono composizioni gastrorcsistenli La preparazione di tali composizioni può essere realizzata come noto all'esperto de! ramo. For use according to the invention, it is possible to administer the peptide or peptides or their pepiidomimetic derivatives referred to above, in oral formulations, prepared as known in the art. It is thus possible to prepare tablets, capsules, granules and liquid compositions comprising the selected peptide or peptides, in combination with the excipients commonly used in the formulation of oral compositions and well known to those skilled in the art. According to a preferred embodiment, the oral compositions / ions of the invention as defined above are gastroresistant compositions. The preparation of such compositions can be carried out as known to the skilled in the art branch.
In saggi di valutazione in vitro delle capacità di ripristinare l'epitelio intestinale danneggialo meccanicamente, i peptidi sopra descritti, e in particolare la vasostalina. si sono dimostrati molto efficaci. In in vitro assays for the ability to restore the intestinal epithelium by mechanically damaging it, the peptides described above, and in particular vasostaline. they have proven to be very effective.
Allo stesso modo, studi in vivo su modelli inurini di colite acuta e cronica hanno dimostrato che i peptidi di cui sopra, e in particolare la vasostatina, curano e proteggono dai danni indotti da DSS (sodio destran solfato), dimostrando cosi la loro efficacia nel trattamento come pure nella prevenzione delle patologie infiammatorie del tratto gastroenterico, Similarly, in vivo studies on inurine models of acute and chronic colitis have shown that the aforementioned peptides, and in particular vasostatin, heal and protect against damage induced by DSS (sodium dextran sulfate), thus demonstrating their efficacy in treatment as well as in the prevention of inflammatory diseases of the gastrointestinal tract,
I dettagli della sperimentazione condotta sono fomiti nella sezione sperimentale della presente descrizione. The details of the experimentation conducted are provided in the experimental section of the present description.
Secondo un altro dei suoi aspetti, l'invenzione ha per oggetto un metodo per il trattamento e/o la prevenzione delle malattie infiammatorie dell’apparato digerente, in particolare delle malattie infiammatorie croniche, che comprende somministrare per via orale a un soggetto die lo necessita, una quantità efficace di almeno un peptide scelto tra la cromogranina A, i suoi frammenti peptidici attivi e i peptidi die presentano una omologia di almeno ΓΚ0%. vantaggiosamente il 90%, con la cromogranina A e/o con i suoi frammenti peptidici attivi. According to another of its aspects, the invention relates to a method for the treatment and / or prevention of inflammatory diseases of the digestive system, in particular chronic inflammatory diseases, which comprises administering orally to a subject who needs it. , an effective amount of at least one peptide selected from chromogranin A, its active peptide fragments and the peptides which have a homology of at least ΓΚ0%. advantageously 90%, with chromogranin A and / or with its active peptide fragments.
Sezione sperimentale Experimental section
Esempio 1 Example 1
Valutazione deil’effetto curativo delia vasostatina su cellule epiteliali intestinali Delle cellule Caeo-2 sono state mantenute in un mezzo contenente siero allo 0, 1% per 18 ore prima di essere trattate per il saggio. La coltura di cellule monostrato è stata ferita con la punta di una pipetta e lavate con PBS. Quindi una parte di coltura è stata incubata con un mezzo contenente siero allo 0,1%, una parte con un mezzo contenente siero allo 0,1% e 3 tig/ml di vasostatina (I) e una terza parte con un mezzo contenente siero al 10%, a 37<Q>C. Le colture sono state esaminate ai microscopio ad inversione. Le immagini sono state acquisite con una fotocamera digitale 2, 4, 6 e 24 ore dopo il trattamento e la guarigione delle ièri te è stata calcolata come percentuale dell’area danneggiata coperta da cellule migrate. Evaluation of the curative effect of vasostatin on intestinal epithelial cells Caeo-2 cells were kept in a medium containing 0.1% serum for 18 hours before being treated for the assay. The monolayer cell culture was wound with the tip of a pipette and washed with PBS. Then one part of the culture was incubated with a medium containing 0.1% serum, one part with a medium containing 0.1% serum and 3 tig / ml vasostatin (I) and a third part with a medium containing serum at 10%, at 37 <Q> C. The cultures were examined under an inversion microscope. The images were acquired with a digital camera 2, 4, 6 and 24 hours after treatment and the healing of the lesions was calculated as a percentage of the damaged area covered by migrated cells.
1 risultati sono mostrati nelle figure 1 e 2, Tali risultati mostrano che le cellule esposte a vasostatina I, in un mezzo povero in FBS, ricoprono Parca danneggiata più velocemente rispetto alle cellule non esposte a vasostatina con un andamento paragonabile a quello ottenuto in un mezzo ricco dì FBS, La vasostatina 1 è quindi in grado di promuovere il fisiologico processo di riparazione delle ferite. The results are shown in Figures 1 and 2, These results show that the cells exposed to vasostatin I, in a medium poor in FBS, cover damaged Parca faster than the cells not exposed to vasostatin with a trend comparable to that obtained in a medium. rich in FBS, Vasostatin 1 is therefore able to promote the physiological process of wound repair.
Esempio 2 Example 2
Valutazione delPeffetio protettivo della vasostatina su un modello murino di colite acuta Evaluation of the protective effect of vasostatin on a mouse model of acute colitis
Dei topi sono stati alimentati con sodio destran solfato <DSS) al 2% nell’acqua per 7 giorni, provocando così una colite acuta. Al giorno 8, la soluzione di DSS è stata cambiata con acqua da autoclave. Dal giorno 4 gli animali sono siati trattati con vasostatina (I ) (3 o 30 pg/topo al giorno), 1 risultati ottenuti sono riportati nelle figure da 3 a 5 e nella Tabella 1 . Mice were fed 2% sodium dextran sulfate <DSS) in water for 7 days, thus causing acute colitis. On day 8, the DSS solution was changed to autoclave water. From day 4 the animals were treated with vasostatin (I) (3 or 30 pg / mouse per day), the results obtained are reported in Figures 3 to 5 and in Table 1.
Tali risultali mostrano die la vasostatina I somministrata ai topi in cui viene indotta colite acuta ha effetto curativo. La perdita di peso misurabile durante il trattamento con DSS viene evitata somministrando vasostatina, inoltre, i topi trattati con vasostatina 1 hanno una resistenza transepiteliale del colon paragonabile a quella dei topi sani. L’abbassamento della resistenza, misurata negli animali trattati con DSS, è indice de! danno infetto al tessuto che viene invece preservato dalla somministrazione vasostatina L These results show that vasostatin I administered to mice in which acute colitis is induced has a curative effect. Measurable weight loss during DSS treatment is avoided by administering vasostatin, and mice treated with vasostatin 1 have colonic transepithelial resistance comparable to that of healthy mice. The lowering of resistance, measured in animals treated with DSS, is an index of! Infected damage to the tissue which is instead preserved by vasostatin L administration
Valutazione del l'effetto protettivo della vasostatina su un modello murino di colite cronica Evaluation of the protective effect of vasostatin on a mouse model of chronic colitis
7 topi sono stati suddivisi in due gruppi. A un gruppo di tre topi è stata somministrato sodio destran solfato (DSS) a! 2% per 4 cicli secondo lo schema seguente·. 1 ciclo di 7 giorni di DSS seguito da 14 giorni di acqua regolare, A un secondo gruppo di topi è stato somministrato sodio destran solfato (DSS) per 4 cicli secondo lo schema sopra indicato, seguito dalla somministrazione di vasostatina (15 pg/topo) p.o., 5 volte al giorno per 3 settimane. I risultati della resistenza epiteliale sono mostrati nella Tabella 2, Tali risultati mostrano che la vasostatina I ha effetto curativo anche in un modello sperimentale di colite cronica. La sua somministrazione, infatti, permette la riparazione del tessuto danneggiato fino ad ottenere una resistenza transepiteliale paragonabile a quella di un tessuto sano. 7 mice were divided into two groups. A group of three mice were given sodium dextran sulfate (DSS) a! 2% for 4 cycles according to the following scheme ·. 1 7-day course of DSS followed by 14 days of regular water, A second group of mice were given sodium dextran sulfate (DSS) for 4 cycles according to the above schedule, followed by the administration of vasostatin (15µg / mouse) p.o., 5 times a day for 3 weeks. The results of epithelial resistance are shown in Table 2, These results show that vasostatin I has a curative effect even in an experimental model of chronic colitis. Its administration, in fact, allows the repair of damaged tissue to obtain a transepithelial resistance comparable to that of a healthy tissue.
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| WO2000064939A2 (en) * | 1999-04-26 | 2000-11-02 | Institut National De La Sante Et De La Recherche Medicale | Peptides derived from vasostatin i and the use thereof as anti-fungal agents |
| WO2003020301A1 (en) * | 2001-08-31 | 2003-03-13 | Fondazione Centro San Raffaele Del Monte Tabor | Chromogranin a and fragments thereof for the treatment of diseases involving increased vascular permeability |
| WO2009053725A2 (en) * | 2007-10-27 | 2009-04-30 | The Queen's University Of Belfast | Peptides and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2000064939A2 (en) * | 1999-04-26 | 2000-11-02 | Institut National De La Sante Et De La Recherche Medicale | Peptides derived from vasostatin i and the use thereof as anti-fungal agents |
| WO2003020301A1 (en) * | 2001-08-31 | 2003-03-13 | Fondazione Centro San Raffaele Del Monte Tabor | Chromogranin a and fragments thereof for the treatment of diseases involving increased vascular permeability |
| WO2009053725A2 (en) * | 2007-10-27 | 2009-04-30 | The Queen's University Of Belfast | Peptides and uses thereof |
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