RESUMO
BACKGROUND: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H. pylori-infected asymptomatic humans, and to investigate the effect of eradication of H. pylori. MATERIALS AND METHODS: Biopsies of corpus and antrum of asymptomatic H. pylori positive and negative humans served for determination of the gastritis score and H. pylori status; iNOS was measured by reverse transcriptase polymerase chain reaction and immunohistochemistry and superoxide dismutase and catalase by immunohistochemistry. IL-8 in biopsies was assessed by enzyme-linked immunosorbent assay. RESULTS: Immunostaining of iNOS, catalase and superoxide dismutase was significantly associated with H. pylori infection and was localized to inflammatory cells. IL-8 concentrations were greater in the H. pylori positive than H. pylori negative group and decreased after bacterial eradication. A decrease in staining for iNOS and catalase was observed after H. pylori eradication. CONCLUSIONS: INOS and antioxidant enzymes are present in gastric biopsies of asymptomatic H. pylori positive humans. Eradication caused a significant decrease in staining for iNOS and catalase. These results indicate that oxidative stress occurs in asymptomatic patients and can be modulated by H. pylori eradication.
Assuntos
Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Estresse Oxidativo/efeitos dos fármacos , Adulto , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Biomarcadores , Biópsia , Catalase/metabolismo , Claritromicina/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por Helicobacter/microbiologia , Humanos , Interleucina-8/metabolismo , Masculino , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Omeprazol/uso terapêutico , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: The supernatant of Lactobacillus johnsonii La1 culture was shown to be bactericidal and to have a partial, acid-independent suppressive effect on Helicobacter pylori in humans. The aim of the present study was to investigate the effect of L. johnsonii La1-acidified milk (LC-1) on H. pylori infection. DESIGN AND METHODS: Fifty-three volunteers infected with H. pylori as determined by positive 13C-urea breath test and positive serology were randomized to receive either LC-1 or a placebo 180 ml twice a day for 3 weeks. All subjects also received clarithromycin 500 mg bid during the last two weeks of acidified milk therapy. Oesophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4-8 weeks after the end of the treatment. H. pylori infection was confirmed by urease test and histology. H. pylori density and inflammation were scored using a modified Sydney classification. RESULTS: LC-1 ingestion induced a decrease in H. pylori density in the antrum (P= 0.02) and the corpus (P= 0.04). LC-1 also reduced inflammation and gastritis activity in the antrum (P= 0.02 and P= 0.01, respectively) and of activity in the corpus (P= 0.02). Clarithromycin eradicated H. pylori in 26% of the subjects; LC-1 did not improve the antibiotic effect. CONCLUSION: These results suggest that H. pylori infection and gastritis can be down-regulated by LC-1.
Assuntos
Gastrite/microbiologia , Gastrite/terapia , Infecções por Helicobacter/terapia , Helicobacter pylori , Lactobacillus acidophilus , Leite/microbiologia , Animais , Antibacterianos/uso terapêutico , Testes Respiratórios , Claritromicina/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Antro Pilórico/microbiologiaRESUMO
BACKGROUND AND STUDY AIMS: Several published studies have examined various self-expanding metal esophageal stents for use in the palliative treatment of esophageal or cardiac neoplasia, but few have compared different self-expanding metal stents. The aim of this study was to evaluate non-covered Wallstent and Ultraflex prostheses in the treatment of malignancies in the esophagus and the cardiac region. MATERIALS AND METHODS: In a retrospective study, the effectiveness of non-covered Wallstents (46 patients) and Ultraflex stents (36 patients) was compared in the treatment of malignancies in the esophageal and cardiac regions. RESULTS: Reintervention procedures were necessary in 16 of the 46 Wallstent patients (six patients during an early phase) and in 22 of the 36 Ultraflex patients (13 during an early phase) (overall P = 0.022; early P = 0.018). The major complication in the Wallstent group was tumor ingrowth (12 of 35 complications), while in the Ultraflex group, it was incomplete deployment (18 of 49 complications). Incomplete stent deployment occurred more often in patients treated with Ultraflex (P = 0.01), and food impaction was more often observed in the Wallstent group (P = 0.001). In addition, in patients with Ultraflex stents, more complex reinterventions were necessary than those required with Wallstents (four vs. 13 complex reinterventions, P = 0.0046). Wallstents tended to improve dysphagia better than Ultraflex stents. CONCLUSION: Compared to Ultraflex stents, Wallstents have several significant short-term and long-term advantages in the palliative treatment of malignancy of the esophagus and cardia.
Assuntos
Neoplasias Esofágicas/complicações , Estenose Esofágica/terapia , Cuidados Paliativos , Stents , Neoplasias Gástricas/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Cárdia , Estenose Esofágica/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents/efeitos adversosRESUMO
Bombesin (BN)-related peptides, such as gastrin-releasing peptide (GRP), have been shown in vivo to stimulate release of pepsinogen. However, whether this is due to a direct interaction with chief cells is not clear. To clarify this we prepared isolated chief cells (> 90% pure) from guinea pig stomach. BN, GRP, or neuromedin B (NMB), at concentrations up to 1 microM, did not stimulate pepsinogen release or affect the stimulation caused by vasoactive intestinal peptide (VIP) (100 nM) or CCK-8 (10 nM), respectively. In addition, BN, GRP, or NMB at a concentration of 1 microM did not increase cAMP nor did they alter the increase in cAMP caused by VIP or secretin. BN (1 microM) did not alter basal cytosolic calcium [Ca2+]i or affect the increase in [Ca2+]i caused by CCK-8 (1 microM). Furthermore, BN, GRP, or NMB at a concentration of 1 microM did not increase the generation of inositol phosphates (IP) or alter the increase in [3H]IP1, [3H]IP2, or [3H]IP3, caused by CCK-8 (1 microM) or carbachol (1 mM). Binding studies demonstrated no saturable binding of either [125I][Tyr4]BN or [125I][D-Tyr0]NMB using experimental conditions where binding with other peptide ligands to other receptors on chief cells is seen. We conclude that BN-related peptides do not interact directly with specific receptors on chief cells to stimulate or alter stimulated pepsinogen secretion, increase the breakdown of inositol phosphates, or alter [Ca2+]i or cAMP.
Assuntos
Bombesina/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Pepsinogênios/metabolismo , Receptores da Bombesina/metabolismo , Análise de Variância , Animais , Bombesina/análogos & derivados , Bombesina/metabolismo , Mucosa Gástrica/metabolismo , Cobaias , Técnicas In Vitro , Masculino , Ensaio Radioligante , Estimulação QuímicaRESUMO
Inhibition both in vivo and in vitro of pepsinogen secretion by somatostatin (SS) and the histological demonstration that fundic D-cells contain long cytoplasmic processes extending to chief cells suggest a possible direct effect of SS on chief cell function. The aim of the present study was to determine whether SS interacts directly with receptors on isolated gastric chief cells and, if so, how SS alters cell function. Binding of 125I-[Tyr11]SS14 to chief cells was saturable, time and temperature dependent, and was inhibited by both SS14 (Ki 1.6 nM) and SS28 (Ki 5.2 nM). SMS-201-995 was 1,300-fold less potent than SS14. Calcium-mobilizing secretagogues reduced binding of 125I-[Tyr11]SS14 with efficacies of cholecystokinin octapeptide (CCK-8) > carbachol > gastrin. Adenosine 3',5'-cyclic monophosphate (cAMP)-activating secretagogues also inhibited binding with efficacies of secretin > vasoactive intestinal polypeptide (VIP). 12-O-tetradecanoylphorbol 13-acetate (TPA) or A-23187 also decreased binding. Analyses demonstrated that CCK-8 and TPA were decreasing the affinity of SS receptors for 125I-[Tyr11]SS14 without affecting their binding capacity. Both SS14 and SS28 at a maximally effective concentration inhibited cAMP production caused by VIP or secretin (20-30%) but did not alter cytosolic calcium ([Ca2+]i), inositol phosphates, or pepsinogen release. We conclude that chief cells possess SS receptors with a high affinity for both SS14 and SS28 but low affinity for SMS-201-995 and thus resemble the SSB receptors described in the rat cerebral cortex. Although occupation of these receptors by SS has no effect on pepsinogen release induced by secretagogues acting through either the calcium or the cAMP pathway, SS receptor occupation is regulated by agents activating phospholipase C, adenylate cyclase, protein kinase C, and [Ca2]i.
Assuntos
Cálcio/metabolismo , AMP Cíclico/metabolismo , Mucosa Gástrica/metabolismo , Receptores de Somatostatina/metabolismo , Somatostatina/metabolismo , Animais , Ligação Competitiva , Células Cultivadas , Toxina da Cólera/farmacologia , Colforsina/farmacologia , Células Epiteliais , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Cobaias , Cinética , Masculino , Octreotida/farmacologia , Receptores de Somatostatina/análise , Receptores de Somatostatina/efeitos dos fármacos , Sistemas do Segundo Mensageiro , Secretina/farmacologia , Somatostatina/análogos & derivados , Somatostatina/farmacologia , Acetato de Tetradecanoilforbol/farmacologia , Termodinâmica , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide of the secretin-vasoactive intestinal peptide (VIP) family. To investigate whether PACAP alters chief cell function, we prepared isolated chief cells (> 90% pure) from guinea pig stomach. PACAP-38, PACAP-27, VIP, and secretin all caused a threefold increase in pepsinogen release. The dose-response curves of PACAP-38, PACAP-27, and VIP were biphasic, whereas with secretin it was not. The first phase comprised 40% of maximal release, and each of the three peptides (PACAP-38, PACAP-27, and VIP) were equipotent (EC50 0.1-0.3 nM). For the second phase, comprising 60% of maximal release, the relative potencies were PACAP-38 > PACAP-27 = VIP. 125I-labeled secretin, 125I-VIP, and 125I-PACAP-27 all demonstrated saturable binding to chief cells. Binding of both 125I-PACAP-27 and 125I-VIP was inhibited completely and with similar potencies by PACAP-38, PACAP-27, and VIP. Secretin had a > 500-fold lower affinity than PACAP-38 for displacing both 125I-PACAP-27 and 125I-VIP. With 125I-secretin, secretin was the most potent, and was 197 times more potent than PACAP-38, which was 6-8 times more potent than both PACAP-27 and VIP. We conclude that both PACAP-38 and PACAP-27 stimulate pepsinogen secretion from dispersed chief cells. In contrast to a number of other tissues, no evidence for a high-affinity receptor that interacted only with PACAP was found. PACAP and VIP interact with equal high affinity with a common receptor and with low affinity with the secretin receptor.
Assuntos
Mucosa Gástrica/metabolismo , Neuropeptídeos/metabolismo , Pepsinogênios/metabolismo , Receptores de Superfície Celular/fisiologia , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Ligação Competitiva , Relação Dose-Resposta a Droga , Cobaias , Masculino , Neuropeptídeos/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores de Superfície Celular/metabolismo , Secretina/metabolismo , Secretina/farmacologia , Estômago/citologia , Peptídeo Intestinal Vasoativo/farmacologiaRESUMO
The present study was designed to assess the respective effect of altered lipid metabolism and hyperglycemia on glucose metabolism in vivo in obese subjects. Six young obese non-diabetic volunteers were studied on four occasions during hyperinsulinemic clamp, twice during euglycemia and twice during hyperglycemia, with or without the infusion of beta-pyridylcarbinol, an inhibitor of lipid metabolism. Glucose oxidation was calculated from continuous respiratory exchange measurements, and glucose storage was obtained as the difference between total glucose disposal and glucose oxidation. Two-way analysis of variance (with interaction term) demonstrated (i) a significant increase for total glucose disposal with beta-pyridylcarbinol but no significant effect of hyperglycemia and no interaction between the two treatments, and (ii) an important increase of beta-pyridylcarbinol to enhance glucose storage but no significant effect of hyperglycemia and no interaction between the two treatments. These results show that obese people, at physiological insulinemia, enhance their glucose disposal and glucose storage when lipid oxidation is artificially lowered. This suggests that enhanced lipid oxidation is related to insulin resistance in these patients. However, hyperglycemia in these patients failed to compensate for defective glucose disposal or storage.
Assuntos
Glucose/metabolismo , Hiperglicemia/metabolismo , Insulina/fisiologia , Metabolismo dos Lipídeos , Obesidade/metabolismo , Adulto , Glicemia/análise , Ácidos Graxos não Esterificados/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/complicações , Hiperinsulinismo/complicações , Hiperinsulinismo/metabolismo , Insulina/sangue , Resistência à Insulina , Masculino , Álcool Nicotinílico , Obesidade/sangue , OxirreduçãoRESUMO
1. To investigate the acute effects of insulin and triacylglycerol ('triglyceride') on circulating plasminogen activator inhibitor-1 concentrations, seven healthy volunteers were studied during hyperinsulinaemic clamps in the presence of euglycemia (mean glucose concentration 5 mmol/l) and hyperglycaemia (mean glucose concentration 9 mmol/l) with and without triacylglycerol infusions. 2. During euglycemia, plasma insulin levels rose from baseline values [median (range)] of 13 (6.6-20.6) m-units/l to 89 (74-105) m-units/l and 99 (74-109) m-units/l after 1 and 2 h of insulin infusion, respectively. Concentrations of plasminogen activator inhibitor-1 fell from 27.5 (10-47) ng/ml to 25.0 (14.5-55) ng/ml and 15.5 (11.5-28.5) ng/ml (P less than 0.02) over the same time. 3. During hyperglycaemia, plasma insulin concentrations were 12.1 (9.3-17.1) m-units/l at the run-in period and rose to 87 (73-112) m-units/l and 91 (84-97) m-units/l after 1 and 2 h of insulin infusion, respectively. Concentrations of plasminogen activator inhibitor-1 again showed a gradual fall from 24.7 (22-50) ng/ml to 14 (8.3-25.5) ng/ml and 13 (6.0-35.0) ng/ml (P less than 0.02) over the same period. 4. Infusion of Intralipid in the presence of hyperinsulinaemia with either euglycemia or hyperglycaemia was associated with a similar fall in concentrations of plasminogen activator inhibitor-1 over the study period. 5. The results from this study indicate that short-term increases in insulin, glucose or triacylglycerol do not cause acute increases in plasma concentrations of plasminogen activator inhibitor-1.
Assuntos
Glucose/administração & dosagem , Insulina/administração & dosagem , Inativadores de Plasminogênio/sangue , Triglicerídeos/administração & dosagem , Adulto , Feminino , Glucose/farmacologia , Técnica Clamp de Glucose , Humanos , Infusões Intravenosas , Insulina/farmacologia , Masculino , Triglicerídeos/farmacologiaRESUMO
The present study was designed to assess the role of hyperglycemia (150 mg/dl) vs. euglycemia (90 mg/dl) on glucose metabolism in vivo during the infusion of a triglyceride emulsion (Intralipid). Seven young healthy volunteers were studied on four occasions using the hyperinsulinemic clamp technique, twice during euglycemia and twice during hyperglycemia, without or with Intralipid. Glucose oxidation (O) was calculated from continuous respiratory exchange measurements, and glucose storage (S) was obtained as the difference between total glucose disposal (M) and O. Two-way analysis of variance with interaction term demonstrated 1) a significant increase for M with hyperglycemia and a decrease with Intralipid; no interaction, and 2) in euglycemia, O/M and S/M occurred in one-to-one ratios; on the other hand, during 150-mg/dl hyperglycemia, the ratio dropped roughly to 1:2. Intralipid had no effect on the ratio, and no interaction could be observed. These results suggest the existence of physiological regulatory mechanisms by which 1) the rise in plasma free fatty acid inhibits both oxidative and nonoxidative glucose disposal, and 2) the rise in glycemia stimulates predominantly nonoxidative glucose disposal.