RESUMEN
Chronic intestinal pseudo-obstruction is a rare disease stemming from numerous causes characterized by disturbances in gastrointestinal motility. Symptomatology is often misleading and topography is variable, thus putting the clinician in serious difficulty. Diagnosis is based on a body of arguments, ranging from the clinical examination to surgical biopsies in expert centers. Treatment is non-consensual and mostly symptomatic. It is based on the use of prokinetics and optimal nutritional support. In the most serious cases, surgery can be required. The etiological treatment should be that of the causal disease when it exists and when the etiology is identified. Results of such treatment are variable. Chronic intestinal pseudo-obstruction is a disease which remains poorly understood. Progress had been made in terms of diagnosis and treatment but it seems obvious that a better comprehension of physiopathological mechanisms is necessary in order to improve our practice.
Asunto(s)
Seudoobstrucción Intestinal , Adulto , Edad de Inicio , Enfermedad Crónica , Motilidad Gastrointestinal/fisiología , Humanos , Seudoobstrucción Intestinal/diagnóstico , Seudoobstrucción Intestinal/epidemiología , Seudoobstrucción Intestinal/etiología , Seudoobstrucción Intestinal/terapiaRESUMEN
BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common obesity-related co-morbidity that is assessed objectively by 24-h pH monitoring. Some concerns have been raised regarding the risk of de novo GORD or exacerbation of pre-existing GORD after laparoscopic sleeve gastrectomy. Here, 24-h pH monitoring was used to assess the influence of laparoscopic sleeve gastrectomy on postoperative GORD in obese patients with or without preoperative GORD. METHODS: From July 2012 to September 2014, all patients scheduled for laparoscopic sleeve gastrectomy were invited to participate in a prospective follow-up. Patients who underwent preoperative 24-h pH monitoring were asked to repeat the examination 6 months after operation. GORD was defined as an oesophageal pH < 4 for at least 4·2 per cent of the total time recorded. RESULTS: Of 89 patients, 76 had preoperative pH monitoring for GORD evaluation and 50 had postoperative reassessment. Patients without (group 1, 29 patients) or with (group 2, 21 patients) preoperative GORD were similar regarding age, sex ratio and body mass index. In group 1, the median (i.q.r.) total time at pH < 4 was significantly higher after surgery than before: 5·6 (2·5-9·5) versus 1·6 (0·7-2·9) per cent (P < 0·001). Twenty of the 29 patients experienced de novo GORD as determined by 24-h pH monitoring (P < 0·001). In group 2, total time at pH < 4 after surgery was no different from the preoperative value: 5·9 (3·9-10·7) versus 7·7 (5·2-10·3) per cent (P = 0·296). CONCLUSION: Laparoscopic sleeve gastrectomy was associated with de novo GORD in over two-thirds of patients, but did not seem to exacerbate existing GORD.
Asunto(s)
Monitorización del pH Esofágico/métodos , Gastrectomía/métodos , Reflujo Gastroesofágico/metabolismo , Laparoscopía/métodos , Obesidad/cirugía , Adulto , Femenino , Estudios de Seguimiento , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Prospectivos , Factores de TiempoAsunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Gastritis/tratamiento farmacológico , Gastritis/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/microbiología , Adulto , Factores de Edad , Niño , Estudios Transversales , Quimioterapia Combinada , Francia , Humanos , Pruebas de Sensibilidad Microbiana , Inhibidores de la Bomba de Protones/uso terapéutico , Estudios Retrospectivos , Factores SexualesRESUMEN
BACKGROUND: The pathogenesis of Crohn's disease (CD) involved microbial factors. Some Helicobacter species, the so-called entero-hepatic Helicobacters (EHH), can naturally colonize the intestinal surface and have been detected in humans. Aim To look for an association between CD and the presence of EHH DNA in intestinal biopsies. METHODS: Two groups of patients were included prospectively in a multicentre cross-sectional study: CD patients with an endoscopic post-operative recurrence within 2 years following a surgical resection and controls screened for colorectal polyps or cancer. Intestinal biopsies were taken for Helicobacter culture and Helicobacter 16S DNA detection. If positive, the EHH species were identified with specific PCRs, sequencing and denaturing gradient gel electrophoresis. RESULTS: In the 165 included patients (73 CD and 92 controls), Helicobacter cultures were negative. PCR was positive in 44% of CD and 47% of controls. After age-adjustment, CD was significantly associated with EHH in intestinal biopsies (OR = 2.58; 95%CI: 1.04-6.67). All EHH species detected were identified as Helicobacter pullorum and the closely related species Helicobacter canadensis. CONCLUSION: Crohn's disease is associated with the presence of EHH species DNA in intestinal biopsies after adjustment for age. Whether these species play a role in the pathophysiology of CD remains to be determined.
Asunto(s)
Enfermedad de Crohn/microbiología , ADN Bacteriano/análisis , Infecciones por Helicobacter/patología , Helicobacter/genética , Mucosa Intestinal/patología , Adolescente , Adulto , Anciano , Biopsia/métodos , Enfermedad de Crohn/patología , Estudios Transversales , Femenino , Infecciones por Helicobacter/genética , Humanos , Mucosa Intestinal/microbiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , ARN Ribosómico 16S/análisis , Adulto JovenRESUMEN
OBJECTIVES: To produce valid information, an evaluation of professional practices has to assess the quality of all practices before, during and after the procedure under study. Several auditing techniques have been proposed for colonoscopy. The purpose of this work is to describe a straightforward original validated method for the prospective evaluation of professional practices in the field of colonoscopy applicable in all endoscopy units without increasing the staff work load. METHODS: Pertinent quality-control criteria (14 items) were identified by the endoscopists at the Cochin Hospital and were compatible with: findings in the available literature; guidelines proposed by the Superior Health Authority; and application in any endoscopy unit. Prospective routine data were collected and the methodology validated by evaluating 50 colonoscopies every quarter for one year. RESULTS: The relevance of the criteria was assessed using data collected during four separate periods. The standard checklist was complete for 57% of the colonoscopy procedures. The colonoscopy procedure was appropriate according to national guidelines in 94% of cases. These observations were particularly noteworthy: the quality of the colonic preparation was insufficient for 9% of the procedures; complete colonoscopy was achieved for 93% of patients; and 0.38 adenomas and 0.045 carcinomas were identified per colonoscopy. CONCLUSION: This simple and reproducible method can be used for valid quality-control audits in all endoscopy units. In France, unit-wide application of this method enables endoscopists to validate 100 of the 250 points required for continuous medical training. This is a quality-control tool that can be applied annually, using a random month to evaluate any changes in routine practices.
Asunto(s)
Colonoscopía , Garantía de la Calidad de Atención de Salud/métodos , Neoplasias del Colon/diagnóstico , Colonoscopía/métodos , Colonoscopía/normas , Francia , Humanos , Auditoría Médica/métodos , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Garantía de la Calidad de Atención de Salud/normasRESUMEN
The daily practice of medicine in the remote Leeward Islands of French Polynesia is a particularly gratifying experience. The population of 1200 inhabitants is eager to receive continuous medical services after many years of waiting for better care. Relatively good access to various specialists working in the hospitals of Raiatea or Papeete and to emergency and scheduled medical evacuation services make medical practice far more attractive on the Leeward Islands than in remote communities in underdeveloped countries of Third World. The first cause of morbidity is overweight associated with a high incidence of type II diabetes and attendant complications.
Asunto(s)
Medicina Clínica , Atención a la Salud/estadística & datos numéricos , Humanos , PolinesiaRESUMEN
We studied the actions of purified Helicobacter pylori endotoxin (3 mg kg(-1), i.v.) on rat intestinal vascular permeability (assessed by the radiolabelled human serum albumin leakage technique) and on nitric oxide synthase induction (assessed by the citrulline assay) 4 h later. We found increased albumin leakage and expression of the inducible nitric oxide synthase in jejunum and colon, effects reversed by a selective inducible nitric oxide synthase inhibitor N-(8-(aminomethyl)benzyl)-acetamidine (1400W; 0.2-1 mg kg(-1), s.c., concurrently with endotoxin). Thus, H. pylori endotoxin seems to be capable of provoking an inflammatory response in the rat intestinal tissue. Systemic liberation of H. pylori endotoxin might possibly attenuate jejunal and colonic mucosal barrier function, a process mediated by the expression of the inducible nitric oxide synthase.
Asunto(s)
Endotoxinas , Enteritis/inducido químicamente , Helicobacter pylori , Óxido Nítrico Sintasa/antagonistas & inhibidores , Amidinas/farmacología , Animales , Bencilaminas/farmacología , Permeabilidad Capilar/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Endotoxinas/farmacología , Inhibidores Enzimáticos/farmacología , Humanos , Intestinos/irrigación sanguínea , Intestinos/enzimología , Masculino , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Ratas , Ratas Wistar , Albúmina Sérica/farmacocinéticaRESUMEN
Clarithromycin resistance of Helicobacter pylori is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (PPI-AC) therapy, which is the first-line regimen in our country. We determined the respective effects of clarithromycin primary and secondary resistances on efficacy of the PPI-AC regimen and examined whether failures were associated with persistence of the same strain or with emergence of a new one. Hundred and twenty three H. pylori-infected patients were treated for seven days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. MICs of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. The pre-treatment and post-treatment prevalences of clarithromycin resistance were 18.7% (23/123) and 69.2% (9/13), respectively. The rates of eradication were 67.6% (69/102), 78.8% (67/85), and 11.8% (2/17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection; resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. In conclusion, in our hospital, failures of the PPI-AC therapy are related to both clarithromycin primary and secondary resistances but emergence of secondary resistance does not explain all failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.
Asunto(s)
Amoxicilina/uso terapéutico , Antiulcerosos/uso terapéutico , Claritromicina/farmacología , Resistencia a Múltiples Medicamentos , Resistencia a Medicamentos , Quimioterapia Combinada/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Gastritis/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Metronidazol/farmacología , Omeprazol/uso terapéutico , Adolescente , Adulto , Anciano , Amoxicilina/administración & dosificación , Antiulcerosos/administración & dosificación , Biopsia , Claritromicina/administración & dosificación , Claritromicina/uso terapéutico , ADN Bacteriano/genética , Quimioterapia Combinada/administración & dosificación , Dispepsia/microbiología , Dispepsia/patología , Inhibidores Enzimáticos/administración & dosificación , Femenino , Fundus Gástrico/microbiología , Fundus Gástrico/patología , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/microbiología , Gastritis/patología , Genotipo , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Helicobacter pylori/genética , Humanos , Linfoma de Células B de la Zona Marginal/microbiología , Linfoma de Células B de la Zona Marginal/patología , Linfoma no Hodgkin/microbiología , Linfoma no Hodgkin/patología , Masculino , Metronidazol/administración & dosificación , Metronidazol/uso terapéutico , Persona de Mediana Edad , Omeprazol/administración & dosificación , Úlcera Péptica/tratamiento farmacológico , Úlcera Péptica/microbiología , Úlcera Péptica/patología , Antro Pilórico/microbiología , Antro Pilórico/patología , Estudios Retrospectivos , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type is closely related to Helicobacter pylori (H. pylori) infection. In vitro studies have demonstrated H. pylori-induced B cell proliferation to be strain dependent. High prevalences of CagA protein and FldA protein have been reported in strains obtained from patients with gastric lymphoma of MALT type. The aims of the present study were to evaluate the prevalence of H. pylori infection and to search for antigenic particularities in 53 patients with primary gastric lymphoma in comparison with a group of infected patients with benign disease. METHODS: Of the 53 patients, 37 presented with low-grade lymphoma of MALT type (LGLM) and 16 with diffuse large B-cell lymphoma (DLBCL). They were compared to a group of 162 H. pylori-infected subjects comprising the control group: 111 had gastric or duodenal ulcer (GDU) and 51 nonulcer dyspepsia (NUD). Diagnosis of gastric lymphoma was established on histological examination of endoscopic specimens. Anti-H. pylori antibodies were assayed by third-generation ELISA. Western blot assay was used to detect antibodies against nine antigens (including CagA protein), which were recognized on the basis of their molecular weight. RESULTS: Of the 53 patients with gastric lymphoma, 45 were H. pylori-positive (85%): of these, 25 (56.5%) had anti-CagA antibodies. The prevalence of H. pylori seropositivity was 78% (29/37) in LGLM and 100% (16/16) in DLBCL. The prevalence of CagA seropositivity in H. pylori-positive patients was 44.8% (13/29) and 75% (12/16), respectively (p < 0.05). In comparison, the seroprevalence of CagA was 77.4% (86/111) in GDU patients and 43.1% (22/53) in NUD patients. The prevalence of antibodies to other antigenic proteins detected with Helicoblot 2.0 (19.5kd, 30kd, 35kd, VacA, HSPb, Urease A, and Urease B) did not differ among the groups except for 35kd protein, which was significantly higher (p < 0.01) in GDU than in NUD and in LGLM (76.6% vs 49% and 46.7%). CONCLUSION: These findings suggest that in patients who develop gastric lymphomas in response to H. pylori, virulent strains expressing CagA protein are preferentially associated with DLBCL.
Asunto(s)
Antígenos Bacterianos , Proteínas Bacterianas/sangre , Infecciones por Helicobacter/sangre , Helicobacter pylori , Linfoma de Células B de la Zona Marginal/microbiología , Linfoma de Células B/microbiología , Linfoma de Células B Grandes Difuso/microbiología , Neoplasias Gástricas/microbiología , Análisis de Varianza , Antineoplásicos/uso terapéutico , Western Blotting , Distribución de Chi-Cuadrado , Femenino , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Humanos , Linfoma de Células B/sangre , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Neoplasias Gástricas/sangre , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patologíaRESUMEN
The actions of a purified Helicobacter pylori lipopolysaccharide (3 mg x kg(-1), i.v.) on rat gastric antral and duodenal microvascular integrity (determined as radiolabelled albumin leakage) and the expression of the inducible nitric oxide (NO) synthase (iNOS; assessed by the citrulline assay) were investigated 4 h after challenge. Significant increases of albumin leakage and expression of iNOS in both antral and duodenal tissues were observed following challenge. Concurrent administration of the selective iNOS inhibitor, 1400W (N-(8-(aminomethyl)benzyl)-acetamidine; 0.2-1 mg x kg(-1), s.c.), with lipopolysaccharide, caused a dose-dependent attenuation of the gastric and duodenal albumin leakage. Thus, H. pylori lipopolysaccharide can initiate the expression of iNOS in the stomach and duodenum following systemic challenge, which can provoke gastroduodenal microvascular dysfunction.
Asunto(s)
Permeabilidad Capilar/efectos de los fármacos , Sistema Digestivo/efectos de los fármacos , Lipopolisacáridos/toxicidad , Óxido Nítrico Sintasa/metabolismo , Amidinas/farmacología , Animales , Bencilaminas/farmacología , Sistema Digestivo/irrigación sanguínea , Sistema Digestivo/patología , Relación Dosis-Respuesta a Droga , Duodeno/efectos de los fármacos , Duodeno/enzimología , Duodeno/patología , Inhibidores Enzimáticos/farmacología , Helicobacter pylori/química , Humanos , Masculino , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II , Antro Pilórico/efectos de los fármacos , Antro Pilórico/enzimología , Antro Pilórico/patología , Ratas , Ratas Wistar , Albúmina Sérica/metabolismoRESUMEN
BACKGROUND: Helicobacter pylori resistance to clarithromycin is relatively frequent in France and is assumed to be the main cause of failure of the proton pump inhibitor-amoxicillin-clarithromycin (proton pump inhibitor-AC) therapy, which is the first-line regimen in France. AIM: To determine the respective effects of clarithromycin primary and secondary resistances on efficacy of the proton pump inhibitor-AC regimen and to determine whether failures are associated with persistence of the same strain or with emergence of a new one. METHODS: A total of 123 H. pylori-infected patients were treated for 7 days with omeprazole 20 mg b.d., amoxicillin 1 g b.d., and clarithromycin 500 mg b.d. Eradication was assessed by breath test in 102 patients. Minimal inhibitory concentrations of clarithromycin were determined by E-test. Strain genotyping was performed by random amplified polymorphic DNA. RESULTS: The pre-treatment and post-treatment prevalences of clarithromycin resistance were 19% (23 out of 123) and 69% (nine out of 13), respectively. The rates of eradication were 68% (69 out of 102), 79% (67 out of 85), and 12% (two out of 17) for all, susceptible and resistant strains, respectively. The post-treatment isolate was available for six patients with a susceptible pre-treatment isolate and a persistent infection. Resistance emerged in two patients and was associated with persistence of the pre-treatment strain in one and with selection of a new strain in the other. CONCLUSIONS: In our hospital, failures of the proton pump inhibitor-AC therapy are related to both clarithromycin primary and secondary resistances, but the emergence of secondary resistance does not explain all of the failures in the initial clarithromycin-susceptible group. In that group a new strain can emerge after failure.
Asunto(s)
Amoxicilina/farmacología , Antibacterianos/farmacología , Claritromicina/farmacología , ADN Bacteriano/análisis , Inhibidores Enzimáticos/farmacología , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Omeprazol/farmacología , Penicilinas/farmacología , Administración Oral , Adolescente , Adulto , Anciano , Amoxicilina/uso terapéutico , Pruebas Respiratorias , Resistencia a Medicamentos , Quimioterapia Combinada , Inhibidores Enzimáticos/uso terapéutico , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/uso terapéutico , Penicilinas/uso terapéutico , Reacción en Cadena de la Polimerasa , Inhibidores de la Bomba de ProtonesRESUMEN
Rats transgenic for HLA-B27/human beta2-microglobulin develop a spontaneous multisystem inflammatory disorder that closely mimics human spondyloarthropathies. Prominent features of this disorder are gut inflammation that predominates in the colon, and arthritis. Several mediators such as IFN-gamma, IL-1beta, TNF-alpha, and inducible nitric oxide synthase (iNOS) have been found increased in the inflamed colonic mucosa. In the colon of HLA-B27 transgenic rats, iNOS is predominantly expressed by epithelial cells, and iNOS transcripts are detected in the hip cartilage of those rats, but not in nontransgenic littermates. The role of iNOS in this disorder was evaluated by administering the corticosteroid dexamethasone, or the NOS inhibitor L-N6-(1-iminoethyl)lysine (L-NIL) to HLA-B27 transgenic rats with established disease. Treatment with dexamethasone attenuated some aspects of gut inflammation, although it had no effect on iNOS expression. In contrast, treatment with L-NIL effectively inhibited iNOS activity, and resulted in an increase in colitis. Cytokine transcripts in the colon were modified by these treatments: IFN-gamma and IL-1beta were decreased after dexamethasone treatment, whereas administration of L-NIL resulted in decreased IFN-gamma, and TNF-alpha. A trend towards increased IL-1b expression was observed which could have contributed to the L-NIL pro-inflammatory effect. These results suggest that iNOS exerts a protective effect on colitis, in the inflammatory disorder of HLA-B27 transgenic rats.
Asunto(s)
Colitis/enzimología , Antígeno HLA-B27/fisiología , Óxido Nítrico Sintasa/metabolismo , Microglobulina beta-2/genética , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Enfermedad Crónica , Cartilla de ADN , Dexametasona/farmacología , Inhibidores Enzimáticos/farmacología , Antígeno HLA-B27/genética , Humanos , Inmunohistoquímica , Lisina/análogos & derivados , Lisina/farmacología , Óxido Nítrico Sintasa de Tipo II , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
1. Cardiovascular events and outcome in septic shock may be predicted by monitoring the fall in intramural pH (pHi), as an index of splanchnic perfusion and mucosal ischaemia. In the present study, a small animal model for monitoring the changes of gastric pHi or intramucosal [H+] following challenge with the endotoxin lipopolysaccharide (LPS) was developed in the rat. The role of nitric oxide (NO) in these events in this model was evaluated using the non-selective NO synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-monomethyl-L-arginine (L-NMMA). 2. The pHi and intramucosal [H+] were evaluated in omeprazole-pretreated rats (30 mg/kg, i.p.) using the Henderson equation after estimating the PCO2 and the bicarbonate concentration in gastric wall. To measure gastric wall PCO2, the oesophagus was intubated and the pylorus ligated. The PCO2 was measured by a blood gas analyser in 2 mL saline instilled for 30 min in the gastric lumen to equilibrate with the gastric wall. The pHi was measured under basal conditions and 3 and 5 h after LPS (3 mg/kg) administration. Separate groups received treatment with L-NMMA (25-50 mg/kg) or L-NAME concomitantly or 2.5 h after administration of LPS. 3. Intravenous administration of Escherichia coli LPS provoked a significant fall in gastric pHi from 7.37 to 7.18 (median values; n =10-19) determined after 5 h. In groups treated concurrently with LPS and L-NAME (5 mg/kg; n = 19), there was a similar increase in intramucosal [H+] as that induced by LPS alone (n = 15) in those animals that survived. In contrast, L-NAME (5 mg/kg; n = 12), given 2.5 h after LPS challenge, at a time at which inducible NOS is known to be significantly expressed, prevented the increase in intramucosal [H+] at 3 and 5 h after LPS challenge. Similarly, L-NMMA (25-50 mg/kg; n = 23), given 2.5 h after LPS challenge, dose-dependently inhibited the increase in intramucosal [H+] at 3 and 5 h. 4. In conclusion, these findings indicate that this rat model could be useful in exploring the pathophysiology of acute endotoxin shock. Delayed administration of L-NAME and L-NMMA abolished the increase in gastric intramucosal [H+], supporting the involvement of excess NO in the tissue dysfunction associated with endotoxin shock. This suggests the potential value of this small animal model in evaluating the therapeutic activity of novel agents for use in septic shock.
Asunto(s)
Endotoxinas/farmacología , Inhibidores Enzimáticos/farmacología , Mucosa Gástrica/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Animales , Mucosa Gástrica/efectos de los fármacos , Concentración de Iones de Hidrógeno , Lipopolisacáridos/farmacología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa de Tipo III , Ratas , Choque Séptico/metabolismo , omega-N-Metilarginina/farmacologíaRESUMEN
Nitric oxide (NO) is attracting considerable interest because it mediates many functions. This gas is ubiquitously produced in the body by three enzymes, called NO synthases. Two NO synthases are constitutively expressed, one in the nervous system and the other in the blood vessels, where it regulates tissue perfusion. The third NO synthase can be induced by several stimuli (bacterial endotoxins, cytokines), most notably in inflammatory cells and chondrocytes. The effects of NO produced by the inducible NO synthase range from T-cell response modulation to formation of free radicals responsible fortissue damage and cartilage matrix degradation. Administration of NO synthase inhibitors in animal models of arthritis yields ambiguous effects, often with prevention of arthritis, but sometimes with worsening of established arthritis. The data available to date do not support the use of such inhibitors in the treatment of human arthritis.
Asunto(s)
Artritis Reumatoide/enzimología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico/fisiología , Osteoartritis/enzimología , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/enzimología , Modelos Animales de Enfermedad , Humanos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo IIRESUMEN
Several lines of rats transgenic for human leukocyte antigen (HLA)-B27 spontaneously develop a multisystemic inflammatory disease resembling human spondyloarthropathies. This disease is mediated by cells of the immune system and is dependent on the presence of a normal bacterial flora. Both antigen-presenting cells expressing high levels of HLA-B27 and T cells appear to be of importance in the pathogenesis of this model. HLA-B27 transgenic/b2- microglobulin deficient mice also develop arthritis, under the influence of the bacterial flora. In both types of model, CD8+ T cells appear to be unnecessary, arguing against the "arthritogenic peptide" hypothesis.
Asunto(s)
Modelos Animales de Enfermedad , Espondiloartropatías , Animales , Animales Modificados Genéticamente , Artritis Reactiva/etiología , Artritis Reactiva/inmunología , Bacterias/inmunología , Reacciones Cruzadas , Antígeno HLA-B27/inmunología , Humanos , Ratones , Ratones Transgénicos , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Espondiloartropatías/etiología , Espondiloartropatías/inmunología , Linfocitos T/inmunologíaAsunto(s)
Antibacterianos/uso terapéutico , Resistencia a Múltiples Medicamentos , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Enfermedad de Whipple/tratamiento farmacológico , Actinobacteria/efectos de los fármacos , Actinobacteria/genética , Biopsia , Diagnóstico Diferencial , Femenino , Humanos , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Bacteriano/análisis , Enfermedad de Whipple/diagnósticoRESUMEN
The products released by Helicobacter pylori (H. pylori) in the gastric antral and duodenal mucosa may be involved in mucosal ulceration by stimulating the local formation of cytotoxic factors such as nitric oxide (NO), superoxide or peroxynitrite. The present study investigates the ability of purified H. pylori lipopolysaccharide (LPS) to induce nitric oxide synthase (iNOS) in rat duodenal epithelial cells following in vivo challenge and its interaction with superoxide in promoting cellular damage and apoptosis. H. pylori LPS (0.75-3 mg kg(-1) i.v. or 3-12 mg kg(-1) p.o.) induced a dose - dependent expression of iNOS activity after 5 h in the duodenal epithelial cells, determined by [(14)C] arginine conversion to citrulline. The epithelial cell viability, as assessed by Trypan Blue exclusion and MTT conversion, was reduced 5 h after challenge with H. pylori LPS, while the incidence of apoptosis was increased. The iNOS activity and reduction in cell viability following H. pylori LPS challenge i.v. was inhibited by the selective iNOS inhibitor, 1400 W (0.2-5 mg kg(-1) i.v.). Concurrent administration of superoxide dismutase conjugated with polyethylene glycol (250 - 500 i.u. kg(-1), i.v.), which did not modify the cellular iNOS activity, reduced the epithelial cell damage provoked by i.v. H. pylori LPS, and abolished the increased incidence of apoptosis. These results suggest that expression of iNOS following challenge with H. pylori LPS provokes duodenal epithelial cell injury and apoptosis by a process involving superoxide, implicating peroxynitrite involvement. These events may contribute to the pathogenic mechanisms of H. pylori in promoting peptic ulcer disease.