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1.
Gastroenterol Res Pract ; 2021: 6616334, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33824659

RESUMO

BACKGROUND: EndoFaster® analyzes gastric juice in real time during gastroscopy allowing the detection of hypo-achlorhydric conditions, like corpus atrophic gastritis. Narrow-band imaging (NBI) endoscopy allows to accurately detect and perform target biopsies in areas of intestinal metaplasia, a histological change often associated to corpus atrophic gastritis. AIMS: To compare the diagnostic accuracy of EndoFaster® with histological evaluation for corpus atrophic gastritis through high-resolution (HR) NBI targeted biopsies. METHODS: Prospective study on consecutive adult patients undergoing gastroscopy between April and November 2018. Patients in therapy with proton pump inhibitors, previous gastric surgery, and/or known gastric neoplasia were excluded. At the beginning of gastroscopy, gastric juice was aspirated and analyzed by EndoFaster® in 15 seconds. Endoscopists were blinded to the report of EndoFaster®. Evaluation of gastric mucosa in HR-white light was firstly performed, then with HR-NBI allowing to perform targeted biopsies on areas suspected for intestinal metaplasia; otherwise, biopsies were performed according to the updated Sydney System protocol and sent for histopathological evaluation. RESULTS: Overall, 124 patients were included [64% F; 56 (18-85) years]. Corpus atrophic gastritis was present in 41.9% of patients. EndoFaster® showed an accuracy for corpus atrophic gastritis diagnosis, compared to histopathological evaluation as gold standard, of 87.1% and a sensitivity, specificity, PPV, and NPV of 78.8%, 93.1%, 89.1%, and 85.9%, respectively. pH showed a positive correlation with the severity score of atrophy (r = 0.67, 95% CI: 0.73-0.81, and p < 0.0001). EndoFaster® allowed to diagnose corpus atrophic gastritis in 3.7% of patients negative to NBI (corpus atrophic gastritis without intestinal metaplasia). CONCLUSION: EndoFaster® seems a promising tool to diagnose corpus atrophic gastritis. The evaluation of hypo-achlorhydria during gastroscopy can address bioptic sampling in corpus atrophic gastritis patients without intestinal metaplasia.

2.
Eur Rev Med Pharmacol Sci ; 19(19): 3674-81, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26502857

RESUMO

OBJECTIVE: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. Several clinical indexes have been proposed for UC disease activity evaluation, but none have been properly validated. Moreover, the reference parameter for the scores and their prognostic value is not clear. Mucosal healing has been recently proposed as an important end-point. Aim of the present study was to evaluate the correlation of four clinical indexes with objective diagnostic tools for UC evaluation, the discriminative ability in identifying patients with endoscopic mucosal healing, and to analyze the possible prognostic indication for disease course in 1 year of follow-up. PATIENTS AND METHODS: We analyzed data of 75 patients recorded in regular follow-up visit in IBD clinic at S. Andrea Hospital, Rome, between 2007-2011. We recorded clinical data and lab tests at the time of the visit, and endoscopic/histological reports performed within 1 month. Clinical indexes (Seo' activity index, Simple Clinical Colitis Activity Index, partial Mayo score and Endoscopic-Clinical Correlation Index) were calculated and correlation to endoscopic and histologic activity, and to C-reactive protein increment, was assessed by mean of Spearman's rank correlation. Discriminative ability of the indexes for patients with and without endoscopic mucosal healing was tested by calculation of area under ROC curve (AUC). Patients with low and high clinical scores were compared for number of flares and increment of therapy during 1 year of follow-up. RESULTS: Clinical indexes had a good correlation with endoscopic activity (mean r = 0.73 ± 0.06), a fair correlation with CRP-increment (mean r = 0.55 ± 0.01) and a poor one with histologic activity (mean r = 0.35 ± 0.01). The discriminatory ability of the indexes for endoscopic mucosal healing was good for all the indexes (mean AUC = 0.87 ± 0.05). Patients with high clinical score had more flares and required more frequently increase of therapy at 1 year of follow up compared with patients with low score. CONCLUSIONS: Clinical indexes have a good correlation with endoscopic activity and can discriminate patients with and without mucosal healing. Patients with low and high score have different risk of disease flare and of need to increase therapy at 1 year. Clinical indexes may represent a useful tool for disease assessment in clinical practice in UC outpatients with mild-moderate disease.


Assuntos
Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Gerenciamento Clínico , Endoscopia Gastrointestinal/métodos , Mucosa Intestinal/patologia , Índice de Gravidade de Doença , Cicatrização/fisiologia , Adulto , Idoso , Proteína C-Reativa/análise , Colite Ulcerativa/metabolismo , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
3.
Clin Ter ; 166(4): e269-72, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26378761

RESUMO

Gastrointestinal (GI) diseases, such as inflammatory bowel diseases (IBD), can manifest themselves with intestinal and extra-intestinal symptoms. Among the latter, cutaneous manifestations, such as pyoderma gangraenosum (PG) and metastatic Crohn's disease (MCD), represent a possible onset of IBD, with or without simultaneous bowel alterations. In such cases, intestinal and skin lesions are supported by the same immune-mediated mechanism. We hereby report two cases of patients with skin manifestations together with signs and symptoms suggestive of IBD. IBD and some skin lesions arise from the same immune-mediated mechanism. A multidisciplinary approach to these immune-mediated diseases is needed for an early and correct diagnosis, which in turn may lead to the use of the right drug avoiding useless treatment.


Assuntos
Doenças Inflamatórias Intestinais/diagnóstico , Dermatopatias/etiologia , Adulto , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Pessoa de Meia-Idade , Pioderma Gangrenoso/etiologia
4.
Aliment Pharmacol Ther ; 40(6): 639-47, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25066096

RESUMO

BACKGROUND: Adequate gluten-free diet (GFD) is the only treatment for coeliac disease (CD). However, no agreement has been reached on either how and when to assess patient adherence to GFD or its effectiveness on villous atrophy. AIM: To assess, in a prospective study, patient adherence to and efficacy of GFD on histological recovery after 1-year of GFD. METHODS: Between 2009 and 2012, we enrolled 65 consecutive newly-diagnosed adult patients (median age 38 years, 18-70) with biopsy-proven atrophic CD. Patients were re-evaluated after 1 year of GFD with duodenal histology, serological assays, symptoms and a dietary interview based on a validated questionnaire. Complete histological recovery was defined as the absence of villous atrophy and ≤30/100 intraepithelial lymphocytes. RESULTS: Overall, 81.5% of patients had adequate adherence (ADA) to GFD, whereas 18.5% had an inadequate adherence (IADA); 66% of ADA patients and no IADA patients achieved complete histological recovery (P < 0.00001). Among ADA patients, antibody seroconversion and symptoms were not significantly different between patients who achieved complete histological recovery and those who achieved partial histological recovery with P = 0.309 and P = 0.197, respectively. Multivariate analysis showed that Marsh 3C was a risk factor for incomplete histological recovery in ADA patients (OR 8.74, 95% CI: 1.87-40.83). CONCLUSIONS: This study shows that complete histological recovery after 1-year of GFD in adult patients, who are assessed as adherent to the GFD, can be obtained in 66% of patients. Patients with severe histological damage at diagnosis are at risk for incomplete histological recovery 1 year later.


Assuntos
Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Duodeno/patologia , Adulto , Atrofia/dietoterapia , Atrofia/patologia , Biópsia , Doença Celíaca/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , Inquéritos e Questionários
5.
Int J Immunopathol Pharmacol ; 25(3): 765-70, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23058028

RESUMO

Chronic urticaria (CU) is defined as the occurrence of spontaneous wheals for a duration of more than 6 weeks and is the most frequent skin disease, with prevalence ranging between 15 and 25%, and is a seriously disabling condition, with social isolation and mood changes causing a significant degree of dysfunction and quality of life impairment to many patients. The main clinical features of CU are the repeated occurrence of transient eruptions of pruritic wheals or patchy erythema on the skin that last less than 24 hours and disappear without sequelae. CU is often defined as chronic idiopathic urticaria (CIU) because the causes of CU remain unknown in the great majority (70-95%) of patients. Drugs, food, viruses, alimentary conservative substances or inhalant substances often seem to be involved in determining CIU skin flare. Despite a general agreement that bacteria infections and parasitic infestations can be involved in the pathogenesis of CIU, proven evidence of these relationships is lacking. The aim of the present study is to evaluate the prevalence of Helicobacter pylori (Hp) infection, and the extension and severity of gastritis in a group of CIU patients compared to controls and to evaluate the effectiveness of eradication of Hp on the CIU symptomatology, and the role of Hp infection in pathogenesis of CIU.


Assuntos
Antibacterianos/uso terapêutico , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Urticária/tratamento farmacológico , Adolescente , Adulto , Idoso , Biópsia , Testes Respiratórios , Estudos de Casos e Controles , Feminino , Gastrite/diagnóstico , Gastrite/epidemiologia , Gastrite/microbiologia , Gastroscopia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Indução de Remissão , Cidade de Roma , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Urticária/diagnóstico , Urticária/epidemiologia , Urticária/microbiologia , Adulto Jovem
6.
Aliment Pharmacol Ther ; 33(12): 1361-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21492197

RESUMO

BACKGROUND: Long-term observational studies assessing the incidence of type I gastric carcinoid (typeIGC) in patients with chronic atrophic gastritis are few. AIM: To evaluate the occurrence of typeIGC at diagnosis and during follow-up and to identify patient features associated with the presence of typeIGC in a cohort of chronic atrophic gastritis patients. METHODS: Three hundred and sixty-seven chronic atrophic gastritis patients [245 women, age 54 (18-79) years] underwent regular follow-up by gastroscopy. The incidence of typeIGC was determined in chronic atrophic gastritis patients with at least 2 years of follow-up (n = 214). Baseline clinical and histological features were analysed as factors associated with the presence of typeIGC by univariate analysis. RESULTS: Type I gastric carcinoid was diagnosed in nine (2.4%) patients at the moment when chronic atrophic gastritis was diagnosed. After 1463 person-years, six patients developed typeIGC with an annual incidence rate (person-year) of 0.4%. Patients with typeIGC had significantly higher levels of gastrin, chromogranin A and more frequently the presence of body polyps and ECL-dysplasia compared with chronic atrophic gastritis patients without typeIGC. CONCLUSIONS: This cohort study shows that typeIGC is a rare complication in patients with chronic atrophic gastritis, and the presence of body polyps and ECL-dysplasia at gastroscopic/histologic evaluation is strongly associated with the presence of typeIGC.


Assuntos
Tumor Carcinoide/patologia , Gastrite Atrófica/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Adolescente , Adulto , Idoso , Tumor Carcinoide/classificação , Estudos de Coortes , Feminino , Mucosa Gástrica/patologia , Gastroscopia/métodos , Humanos , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/classificação , Adulto Jovem
7.
Minerva Gastroenterol Dietol ; 56(4): 397-404, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21139539

RESUMO

AIM: In the elderly, prevalence of bleeding- and/or iron malabsorption-related gastrointestinal (GI) causes of iron deficiency anemia (IDA) has not been addressed yet. The aim of this study was to assess the occurrence of malabsorptive diseases and bleeding lesions of the upper and lower GI tract in early (65-74 year-old) and late (over 75 year-old) elderly group compared with adult (50-64 year-old) outpatients. METHODS: The study enrolled 136 consecutive adult (N.=31), early (N.=48) and late elderly (N.=57) IDA outpatients who were referred to the Gastroenterology Department for IDA evaluation and underwent gastroscopy/histology and colonoscopy. RESULTS: Bleeding lesions were significantly less frequent in adult patients than in elderly patients (29% vs. 49.5%, P=0.0252). The most common bleeding lesions were large hiatal hernia (14.7%) and colon cancer (12.5%). Iron malabsorption diseases (Hp-related pangastritis, atrophic body gastritis and celiac disease) were more frequent in the adult group than in the early elderly group (80.6% vs. 56.2%, P=0.0367). In elderly patients, the observed prevalence of bleeding and iron malabsorption IDA causes was similar, whereas in adult patients iron malabsoptive diseases were more frequently detected (P<0.0001). The occurrence of concomitant IDA causes was not different among the three age-groups. CONCLUSION: In the early and late elderly, almost half of GI IDA causes are related to bleeding lesions which are more frequently observed respect to the adult patients. Iron malabsorption diseases affect almost 60% of early and late elderly groups. As for adult patients, an accurate upper and lower endoscopical/histological evaluation diagnoses IDA causes in the vast majority of the elderly outpatients.


Assuntos
Anemia Ferropriva/diagnóstico , Anemia Ferropriva/etiologia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Trato Gastrointestinal Inferior/patologia , Pacientes Ambulatoriais , Trato Gastrointestinal Superior/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/etiologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
8.
Int J Immunopathol Pharmacol ; 23(2): 671-5, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20646366

RESUMO

Recent studies have indicated that Toll-like receptor polymorphisms or their impaired signalling, specifically TLR-2 and TLR-4, were correlated with a higher risk for allergy. The purpose of this study is to evaluate the associations of TRL-2 and TRL-4 single nucleotide polymorphisms (SNP) and atopic traits in a cohort of 159 Italian allergic children (102 affected by eczema and 57 by IgE-mediated food allergy) and 147 healthy controls recruited in Rome, Italy. DNA was isolated from the peripheral blood and TLR-2 R753Q/TLR-4 D299G polymorphisms were determined by TaqMan MGB probes using Real-Time PCR technique. In the control group, the TLR-2 polymorphism R753Q had a prevalence of 2.5% while the frequency of the TLR-4 D299G was 12%. None of the 159 allergic patients showed the R753Q SNP. By contrast, 7/57 patients with food allergy (12%) and 6/102 subjects with eczema (6%) carried the TLR-4 mutation. In our cohort, no evidence of correlation between TLR-2 or TLR-4 polymorphism and eczema and food allergy incidence and/or severity was found. Further studies are needed to clarify the possible role of TLR-2 and TLR-4 polymorphism in allergic disease, in Italian children.


Assuntos
Eczema/genética , Hipersensibilidade Alimentar/genética , Polimorfismo de Nucleotídeo Único , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino
9.
Aliment Pharmacol Ther ; 27(4): 355-65, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18047563

RESUMO

BACKGROUND: Atrophic body gastritis patients are at increased risk for gastric cancer. IL-1B/IL-1RN polymorphisms have been associated with gastric cancer susceptibility. The relationship between these polymorphisms and the long-term outcome of atrophic body gastritis patients is not known. AIM: To investigate whether the genotyping of IL-1B-511/IL-1RN polymorphisms is useful to characterize atrophic body gastritis patients at increased risk for gastric neoplasms. METHODS: IL-1B-511/IL-1RN polymorphisms were compared between 110 atrophic body gastritis patients and 110 age- and gender-matched controls, and patients were followed up (median 4.1 years) according to a cohort study design. RESULTS: Genotype frequencies of IL-1B-511/IL-1RN were similar between patients and controls. Atrophic body gastritis patients harbouring the wild type of IL-1B-511/IL-1RN polymorphisms were not different from those harbouring the proinflammatory pattern as far as regards gender, age, gastric cancer family history and metaplastic atrophy. Sixteen atrophic body gastritis patients developed a gastric neoplastic lesion at follow-up: eight were IL-1B-511-T carriers and eight were IL-1RN-allele-2 carriers. Harbouring the proinflammatory genotypes was not significantly associated with developing gastric neoplastic lesions. CONCLUSIONS: In atrophic body gastritis patients, IL-1B-511 and IL-1RN polymorphisms do not appear to be associated either with specific clinical, biochemical or histological features or with the development of gastric neoplastic lesions at long-term follow-up.


Assuntos
Gastrite Atrófica/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Polimorfismo Genético , Neoplasias Gástricas/genética , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , DNA/genética , Feminino , Seguimentos , Gastrite Atrófica/complicações , Gastrite Atrófica/patologia , Gastrite Atrófica/terapia , Gastroscopia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia
11.
Neurogastroenterol Motil ; 18(11): 1009-18, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17040412

RESUMO

Vasoactive intestinal peptide (VIP) relaxes smooth muscle by interacting with receptors coupled to cAMP- or cGMP-signalling pathways. Their relative contribution to human gastric relaxation is unknown. This study aimed at investigating, in terms of biological activity, receptor expression and related signalling pathways, the action of VIP separately on the human fundus and the antrum. VIP caused greater relaxation of smooth muscle cells (SMC) and strips of the antrum presenting on the former a higher efficacy and potency (ED(50): 0.53 +/- 0.17 nmol L(-1)) than on the fundus (ED(50): 3.4 +/- 1.4 nmol L(-1)). On both fundus and antrum strips, its effect was tetrodotoxin insentitive. Reverse transcriptase-polymerase chain reaction analysis showed the sole expression of VPAC2 and natriuretic peptide clearance receptors, with VPAC2 being more abundant in the antrum. Functional regional differences in receptor-related signalling pathways were found. Activation of the cAMP-pathway by forskolin or its inhibition by adenylate cyclase (2'5'-dideoxyadenosine) or kinase (Rp-cAMPs) inhibitors had more pronounced effects on antrum SMC. Activation of the cGMP-pathway by sodium nitroprusside or its inhibition by guanylate cyclase (LY83583) or kinase (KT5823) inhibitors had more effects on fundus SMC, on which a higher expression of endothelial nitric oxide synthase was found. In conclusion, regional differences in VIP action on human stomach are related to distinct myogenic properties of SMC of the antrum and the fundus.


Assuntos
Fundo Gástrico/fisiologia , Relaxamento Muscular/fisiologia , Músculo Liso/fisiologia , Antro Pilórico/fisiologia , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Transdução de Sinais/fisiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Órgãos , Isoformas de Proteínas/fisiologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
Neurogastroenterol Motil ; 18(3): 217-25, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16487413

RESUMO

This study demonstrates the expression of functional somatostatin receptor (sstr) subtypes in human circular and longitudinal colonic smooth muscle cells (SMC). Native somatostatin (SS) and sstr subtype-specific analogues were used to characterize the sstr subtypes present in both cell types by contraction/relaxation studies. Qualitative and quantitative mRNA analysis and immunohistochemistry of sstr subtypes were also carried out. sstr subtype 2 mRNA was expressed in circular SMC, and various levels of subtypes 1, 2 and 3 mRNA were expressed in longitudinal colonic SMC. Native SS and each subtype-specific analogue exerted a modest, but significant, contraction, although inhibition of carbachol-induced contraction (relaxation) was the main effect on SMC from both layers. CH-288, a sstr subtype 1-specific analogue, and octreotide, a sstr subtype 2-specific analogue, were the most effective relaxant analogues on longitudinal and circular SMC, respectively. sstr subtypes display a distinct expression pattern on human colonic SMC; on circular SMC, subtype 2 is the only sstr, whereas sstr subtypes 1, 2 and 3 are expressed on human SMC isolated from the longitudinal layer. The contractile effects of SS are mediated through sstr subtype 2 and sstr subtype 1 on circular and longitudinal human colonic SMC, respectively.


Assuntos
Colo/fisiologia , Contração Muscular/fisiologia , Miócitos de Músculo Liso/metabolismo , Receptores de Somatostatina/biossíntese , Células Cultivadas , Colo/efeitos dos fármacos , Fármacos Gastrointestinais/farmacologia , Humanos , Imuno-Histoquímica , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Octreotida/farmacologia , RNA Mensageiro/análise , Receptores de Somatostatina/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Somatostatina/análogos & derivados , Somatostatina/farmacologia
13.
Dig Liver Dis ; 36(11): 735-43, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15571004

RESUMO

BACKGROUND: Inherent properties of gastrointestinal smooth muscle can be assessed using isolated cell suspensions. Currently available isolation techniques, based on short 2-h enzymatic digestion, however, present the disadvantage of low cellular yield with brief viability. These features are an important limiting factor especially in studies in humans in which tissue may not be available daily and mixing of samples is not recommended. AIMS: To optimise the isolation procedure of cells from human colon to obtain a richly pure primary smooth muscle cell preparation. METHODS: Slices of circular muscle layer, obtained from surgical specimens of human colon, were incubated overnight in Dulbecco's modified eagle's medium supplemented with antibiotics, foetal bovine serum, an ATP-regenerating system and collagenase. On the following day, digested muscle strips were suspended in HEPES buffer, and spontaneously dissociated smooth muscle cells were harvested and used either immediately or maintained in suspension for up to 72 h. Cell yield, purity, viability, contractile responses, associated intracellular calcium signals and RNA and protein extraction were evaluated and compared to cell suspensions obtained with the current short digestion protocol. RESULTS AND CONCLUSION: The overnight isolation protocol offers the advantage of obtaining a pure, homogeneous, long-life viable cell suspension that maintains a fully differentiated smooth muscle phenotype unchanged for at least 72 h and that allows multiple functional/biochemical studies and efficient RNA extraction from a single human specimen.


Assuntos
Separação Celular/métodos , Colo/citologia , Músculo Liso/citologia , Humanos
14.
Dig Liver Dis ; 36 Suppl 1: S8-16, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15077906

RESUMO

The heptahelical receptor superfamily constitutes the largest single family of transmembrane-signalling molecules that regulate a wide range of physiological processes. The five somatostatin receptors represent a distinct subgroup of this seven transmembrane receptor superfamily. They range in size from 356 to 391 amino acids with 39-57% protein identity between the subtypes with 100 residues strictly conserved among the somatostatin receptor sequences. A high grade of mRNA homology exists in somatostatin receptor subtypes cloned from different species. Following somatostatin receptor binding and functional activity studies, two alternative models of ligand-binding interaction have been hypothesised. One relies on the presence of a binding pocket within the receptor structure constituted by specific amino acids residues, the other denies the presence of such binding structures and suggests that it is the interaction of agonists with specific extracellular and/or transmembrane domains that determine stable receptor structure conformation. Somatostatin receptors, as, indeed, all G-protein-coupled receptors are able to regulate their responsiveness to agonist exposure. This agonist-specific regulation includes three main events, namely, desensitisation, receptor internalisation and receptor degradation. The cell expression of somatostatin receptor subtypes, at the mRNA level, has been characterised in rodent and in human organs with multiple subtype expression in brain and peripheral tissues.


Assuntos
Receptores de Somatostatina/metabolismo , Animais , Humanos , Distribuição Tecidual
15.
Dig Liver Dis ; 36 Suppl 1: S42-7, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15077911

RESUMO

Somatostatin analogues are considered first-line therapy in patients with digestive endocrine tumours. Indeed, several studies have investigated their efficacy in the control of specific symptoms and in the decrease of tumour markers. However, randomised controlled trials are needed in order to better define their role in non functioning tumours and their effect on tumour growth, which have seldom been assessed. Several new drugs have been developed over the last few years such as, for example, new long-acting formulations, universal analogues binding to all five somatostatin receptors subtypes, and cytotoxic analogues, all of which offer a promising therapeutic tool in the near future, even if further studies are needed to determine their efficacy and safety in man.


Assuntos
Neoplasias do Sistema Digestório/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Quimioterapia Combinada , Humanos , Interferons/administração & dosagem , Somatostatina/administração & dosagem
16.
J Endocrinol Invest ; 27(1): 6-11, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15053236

RESUMO

BACKGROUND: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors. PATIENTS AND METHODS: Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups. RESULTS: CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non-ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p = 0.04), in NF (95% vs 75%, p = 0.02), and in pancreatic (94% vs 74%, p = 0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p = 0.04). CONCLUSION: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.


Assuntos
Biomarcadores Tumorais/sangue , Cromograninas/sangue , Neoplasias Gastrointestinais/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Polipeptídeo Pancreático/sangue , Adulto , Carcinoma/sangue , Carcinoma/diagnóstico , Cromogranina A , Células Enterocromafins/metabolismo , Células Enterocromafins/patologia , Feminino , Neoplasias Gastrointestinais/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/sangue , Neoplasias Pancreáticas/sangue , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Eur Rev Med Pharmacol Sci ; 8(5): 179-85, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15638227

RESUMO

UNLABELLED: Three CARD15 mutations (SNP8, SNP12, SNP13) were significantly associated with CD, however ethnic variations and genotype-phenotype relationships are still to be defined. AIMS: To evaluate the prevalence of three CARD15 mutations in 91 in-out consecutive CD, 109 Ulcerative Colitis (UC), 101 healthy controls; to examine the genotype-phenotype relationships among italian pts with CD. MATERIAL AND METHODS: The three mutations were determined by direct sequencing analysis. In CD were evaluated several feature of disease phenotype. Data analysis was performed by using c2 or Fisher Test applying Bonferroni's correction. RESULTS: The allelic and genotype frequencies of CARD15 mutations were significantly associated to CD. None of controls or UC were homozygotes (OM) or compound heterozigotes (CET). In CD the carriers of at least one mutation were 26/91 (28.6%). The frequencies of simple heterozygotes (ET), CET and OM were: 19/26, 4/26, 3/26 respectively. A significant positive association was found between small bowel location and an acute intestinal obstruction at diagnosis and the carriers of at least one mutation (p = 0.036, OR:0.33 [0.12-0.9] and p = 0.0025, OR:0.125 [0.03-0.5], respectively), particularly with OM and CET genotype (p = 0.005, OR:0.07 [0.01-0.6]). A positive trend between the number of surgery and the carriers of at least one mutation was found, but it didn't reach statistical significance (p = 0.0469, OR:0.3 [0.1-0.96]). No relationship between CARD15 mutations and the other phenotype characteristics was found. CONCLUSIONS: Our data confirms that CARD15 mutations are significantly associated with CD also in Italian population and with small bowel location (OM and CET genotype). A new positive association was also found between the carriers of at least one mutation and the acute intestinal obstruction at diagnosis.


Assuntos
Obstrução Intestinal/epidemiologia , Obstrução Intestinal/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação/fisiologia , Doença Aguda , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/genética , Frequência do Gene , Genótipo , Humanos , Itália/epidemiologia , Proteína Adaptadora de Sinalização NOD2 , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Dig Liver Dis ; 35(8): 585-9, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-14567464

RESUMO

Until recently, the association of primary hyperparathyroidism and gastric carcinoid, with or without hypergastrinaemia, had been considered an incomplete form of multiple endocrine neoplasia type 1. This is because it seemed unlikely that the rare joint appearance of these diseases could occur only by chance. It is now possible to evaluate the pathogenetic involvement of the multiple endocrine neoplasia type 1 gene in many, apparently sporadic, clinical conditions. This is a case report of a female mimicking multiple endocrine neoplasia type 1 due to the presence of hyperparathyroidism, gastric carcinoid, and hypergastrinaemia. However, involvement of the MEN-1 gene (exons 2-10) was not detected, whereas hypergastrinaemia was attributed to a chronic atrophic gastritis.


Assuntos
Gastrite Atrófica/diagnóstico , Expressão Gênica , Neoplasia Endócrina Múltipla Tipo 1/genética , Idoso , Tumor Carcinoide/complicações , Diagnóstico Diferencial , Feminino , Gastrinas/sangue , Humanos , Hiperparatireoidismo/complicações , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Neoplasias Gástricas/complicações
19.
Ann Oncol ; 14(4): 586-91, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12649106

RESUMO

BACKGROUND: In patients with digestive endocrine tumours, complete pre-operative staging is essential in planning proper management and evaluating treatment efficacy. To date, somatostatin receptor scintigraphy (SRS) is considered the 'gold standard' imaging procedure, and very few data are available concerning the use of helical computed tomography (hCT). This study aimed to determine the diagnostic accuracy and the ability to modify the surgical management of hCT, alone or combined with SRS. PATIENTS AND METHODS: Sixty patients were staged before surgery by hCT, SRS and tumour markers, and included in group 1 if suitable for radical surgery, otherwise in group 2. All patients underwent laparotomy followed by subsequent re-staging. RESULTS: SRS sensitivity was 77%, 48% and 67% for primary, lymph-node and liver lesions, respectively. hCT sensitivity was 94%, 69% and 94% for primary, lymph-node and liver lesions, respectively (P = 0.02 versus SRS, for liver lesions). During pre-operative evaluation, hCT correctly staged 92% and SRS 75% of patients (P = 0.02). hCT provided additional information in 17% of patients. CONCLUSIONS: Since hCT has been shown to be extremely accurate, providing essential information for the planning of surgical treatment compared with that of SRS, both techniques should be used in the pre-operative work-up of digestive endocrine tumours.


Assuntos
Neoplasias das Glândulas Endócrinas/diagnóstico por imagem , Neoplasias das Glândulas Endócrinas/patologia , Neoplasias Gastrointestinais/diagnóstico por imagem , Neoplasias Gastrointestinais/patologia , Estadiamento de Neoplasias/métodos , Receptores de Somatostatina/análise , Tomografia Computadorizada Espiral , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias das Glândulas Endócrinas/cirurgia , Feminino , Neoplasias Gastrointestinais/cirurgia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Planejamento de Assistência ao Paciente , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Cintilografia/métodos , Sensibilidade e Especificidade
20.
Dig Liver Dis ; 34(9): 668-80, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12405256

RESUMO

A subset of gastrointestinal neuroendocrine tumours (carcinoids and pancreatic endocrine tumours) show aggressive growth. Early identification of this subset is essential for management; however, clinical, laboratory and histologic features frequently fail to achieve this. Currently, there is an increased understanding of the molecular pathogenesis/changes in neuroendocrine tumours and this may identify important prognostic factors and possibly, new treatments. Recent findings and progress in this area are briefly reviewed in this article.


Assuntos
Neoplasias Gastrointestinais/genética , Genes Supressores de Tumor , Tumores Neuroendócrinos/genética , Oncogenes , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator de Crescimento Transformador alfa/metabolismo , Gastrinoma/genética , Gastrinoma/metabolismo , Gastrinoma/mortalidade , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Humanos , Imuno-Histoquímica , Mutação , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/mortalidade , Taxa de Sobrevida
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