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991.
The administration of cisapride as an adjuvant to PEG-electrolyte solution for colonic cleansing: a double-blind randomized study 总被引:3,自引:0,他引:3
Katsinelos P Pilpilidis I Paroutoglou G Xiarchos P Tsolkas P Papagiannis A Giouleme O Kapelidis P Papageorgiou A Dimiropoulos S Eugenidis N 《Hepato-gastroenterology》2005,52(62):441-443
BACKGROUND/AIMS: Traditional bowel preparation before colonoscopy involves lavage with approximately 4L of polyethylene glycol (PEG)-electrolyte solution. Only a few studies have been published evaluating the use of cisapride in routine bowel preparation. METHODOLOGY: We conducted a blinded, placebo-controlled trial with the prokinetic agent, cisapride, in addition to standard PEG-electrolyte lavage. Of 115 patients undergoing colonoscopy, 58 were randomized (double-blind) to PEG plus cisapride (10 mg per os thrice per day three days before the procedure and one 10-mg dose on the morning of the procedure) and 57 to PEG plus a placebo of identical appearance. The adequacy of the preparation was scored on a four-point grading scale for each anatomic-segment and for the overall impression. A questionnaire was also used to assess each patient's symptoms during lavage. RESULTS: The difference in the overall score between the two groups was not significant (p=0.21). The quality of bowel preparation was significantly better in transverse (p=0.001), ascending (p=0.0053), and cecum (p=0.0001) in the cisapride group than in the placebo group. The differences in symptoms scores between the two groups were not significant in nausea, abdominal cramps and bloating but there was improvement in symptom score of vomiting in cisapride group (p=0.0422). CONCLUSIONS: The administration of cisapride to patients undergoing colonic lavage may be an effective adjuvant to PEG-electrolyte solution particularly with respect to increase patient acceptability. 相似文献
992.
Daniel J. Raines Olga V. Moroz Elena V. Blagova Johan P. Turkenburg Keith S. Wilson Anne-K. Duhme-Klair 《Proceedings of the National Academy of Sciences of the United States of America》2016,113(21):5850-5855
To acquire essential Fe(III), bacteria produce and secrete siderophores with high affinity and selectivity for Fe(III) to mediate its uptake into the cell. Here, we show that the periplasmic binding protein CeuE of Campylobacter jejuni, which was previously thought to bind the Fe(III) complex of the hexadentate siderophore enterobactin (Kd ∼ 0.4 ± 0.1 µM), preferentially binds the Fe(III) complex of the tetradentate enterobactin hydrolysis product bis(2,3-dihydroxybenzoyl-l-Ser) (H5-bisDHBS) (Kd = 10.1 ± 3.8 nM). The protein selects Λ-configured [Fe(bisDHBS)]2− from a pool of diastereomeric Fe(III)-bisDHBS species that includes complexes with metal-to-ligand ratios of 1:1 and 2:3. Cocrystal structures show that, in addition to electrostatic interactions and hydrogen bonding, [Fe(bisDHBS)]2− binds through coordination of His227 and Tyr288 to the iron center. Similar binding is observed for the Fe(III) complex of the bidentate hydrolysis product 2,3-dihydroxybenzoyl-l-Ser, [Fe(monoDHBS)2]3−. The mutation of His227 and Tyr288 to noncoordinating residues (H227L/Y288F) resulted in a substantial loss of affinity for [Fe(bisDHBS)]2− (Kd ∼ 0.5 ± 0.2 µM). These results suggest a previously unidentified role for CeuE within the Fe(III) uptake system of C. jejuni, provide a molecular-level understanding of the underlying binding pocket adaptations, and rationalize reports on the use of enterobactin hydrolysis products by C. jejuni, Vibrio cholerae, and other bacteria with homologous periplasmic binding proteins.With the rapid rise in bacterial resistance to antibiotics, a better understanding of cooperative behavior in microbial communities is urgently needed for the development of novel approaches to controlling infections caused by resistant bacteria (1, 2). As an essential nutrient, iron is often a growth-limiting factor for beneficial, commensal, and pathogenic bacteria alike, not only due to its low solubility in water under aerobic conditions at and around neutral pH, but also because the host organism and competing microbes actively limit its availability (3, 4). Microorganisms evolved efficient Fe(III) uptake mechanisms to overcome this challenge, a common strategy being the production of siderophores, small Fe(III)-chelating molecules with high affinity and selectivity for Fe(III), with over 500 examples known to date (5). The sharing of siderophores is a recognized example for positive cooperativity that has been linked to bacterial virulence (6). The best-characterized siderophores are hexadentate ligands that form coordinatively saturated, octahedral 1:1 complexes with Fe(III) (3, 5, 7), the most studied being the triscatecholate enterobactin (H6-ENT) produced by many enteric bacteria (8).In Escherichia coli, enterobactin is synthesized within the cell and secreted through the cell membranes to capture Fe(III) from the environment. The resulting Fe(III)-enterobactin complex [Fe(ENT)]3− is recognized by the outer membrane receptor FepA and actively transported into the periplasm. In the periplasm, [Fe(ENT)]3− is sequestered by the periplasmic binding protein (PBP) FepB, which transfers it to an inner membrane transporter for further transport into the cytoplasm (9). Once there, [Fe(ENT)]3− is hydrolyzed by an intracellular esterase to release Fe(III) for use in the cell (8).Along with the development of structurally diverse siderophores, microorganisms adapted their associated receptor and transport proteins for the uptake of the appropriate Fe(III) complexes (9). To gain a competitive advantage, many bacteria have evolved to poach siderophores produced by other bacteria. Campylobacter jejuni, for example, does not itself produce siderophores yet possesses an uptake system that is able to use siderophores from competing species (10). Initially, it was proposed that in C. jejuni [Fe(ENT)]3− is transported across the outer membrane by the receptors CfrA and CfrB (11). Once in the periplasm, [Fe(ENT)]3− was proposed to bind to the PBP CeuE, the resulting complex enabling the transport of the ferric siderophore into the cytoplasm (12, 13).In addition, increasing numbers of lower-denticity siderophores are being isolated from bacterial cultures and found to coordinate Fe(III) and mediate its uptake (14–18). For example, the trilactone backbone of enterobactin makes it prone to hydrolysis, and although this lability is necessary to allow the intracellular release of Fe(III) from the siderophore, it in addition leads to its slow degradation in aqueous media (7, 19–21). Three hydrolysis products are formed: tris(2,3-dihydroxybenzoyl-l-Ser) (H7-trisDHBS), bis(2,3-dihydroxybenzoyl-l-Ser) (H5-bisDHBS), and 2,3-dihydroxybenzoyl-l-Ser (H3-monoDHBS), with all three found in the growth medium of E. coli (Fig. 1). Although enterobactin, once secreted, is also available to other cells (producers or nonproducers), it can only be used once because Fe(III) release requires its hydrolysis. The enterobactin hydrolysis products, however, could be used again as secondary, lower-denticity siderophores.Open in a separate windowFig. 1.Molecular structure of enterobactin, its hydrolysis products, the siderophore mimic H6-MECAM, and a selection of tetradentate siderophores.It has been demonstrated that the human pathogens C. jejuni (10, 22, 23) and Vibrio cholerae (24), the causes of food poisoning and cholera, respectively, can use enterobactin hydrolysis products for the uptake of Fe(III) from their environment. Both are known not to produce enterobactin.An alternative Campylobacter Fe(III) acquisition model that relies on these linear hydrolysis products was recently proposed based on the finding that Cee, the sole trilactone esterase of C. jejuni and Campylobacter coli, is located in the periplasm, i.e., these bacteria are unable to degrade enterobactin within the cytoplasm (25). The model suggests that, once the Fe(III) complex of enterobactin enters the periplasm, its ester backbone is cleaved by Cee, which is highly efficient in hydrolyzing both the Fe(III) complex and apo-enterobactin. The resulting hydrolysis products, mainly the tetradentate ligand bisDHBS5− and the bidentate ligand monoDHBS3−, are then used to mediate the subsequent transport of Fe(III) into the cytoplasm.The identification of the esterase Cee and in particular the observation that bisDHBS5− can be used independently of enterobactin (25) raise important questions about the siderophore preference of the PBP CeuE and its role in the iron uptake in C. jejuni. By using siderophore mimics, we previously demonstrated that CeuE can bind the Fe(III) complexes of both hexadentate and tetradentate catecholate ligands (26, 27). Our cocrystal structures revealed that CeuE interacts with the coordinatively saturated Fe(III) complex of the hexadentate mimic MECAM6− through electrostatic interactions and hydrogen bonding, whereas it binds the coordinatively unsaturated complex of the tetradentate mimic 4-LICAM4− by recruiting the side chains of two amino acid residues (His227 and Tyr288) to complete the coordination sphere of the Fe(III) center. We established that His227 and Tyr288 are conserved among a subset of related PBPs, including VctP from V. cholerae, and suggested that this subset of PBPs undergo similar structural changes to adapt to the binding of lower-denticity sidero-phores (27). The recent report that V. cholerae most efficiently uses trisDHBS7− and bisDHBS5− for the acquisition of Fe(III) provided a partial confirmation of this prediction (24).Here, we report that CeuE binds [Fe(bisDHBS)]2− with much higher affinity than the Fe(III) complex of enterobactin, reveal the structural basis for this difference in binding strength, and examine key aspects of the relevant Fe(III) coordination chemistry in solution. 相似文献
993.
Olga Vera-Lastra Christian Alexis Sauceda-Casas María del Pilar Cruz Domínguez Sergio Alberto Mendoza Alvarez Jesús Sepulceda-Delgado 《Reumatología clinica》2018,14(4):230-232
Systemic sclerosis sine scleroderma (ssSSc) is a form of systemic sclerosis that is characterized by Raynaud's phenomenon (RP), visceral involvement without thickening of skin and anticentromere antibodies (ACA). We studied 10 ssSsc patients with a prevalence of 2%. The clinical signs were: RP 9/10, esophageal manifestations 8/10, pulmonary arterial hypertension 4/10, interstitial lung disease 4/10, cardiac signs 3/10 and ACA 8/10.
Conclusion
In patients with RP, esophageal dysmotility, interstitial lung disease and pulmonary arterial hypertension should be tested for ACA in order to establish a prompt diagnosis and treatment of ssSSc. 相似文献994.
Mattana C Vega A Gómez P Puig de Centorbi O 《Enfermedades infecciosas y microbiología clínica》2004,22(4):227-229
We performed a seroepidemiological study of anti-Helicobacter pylori IgG by a commercial enzyme immunoassay kit (Meridian Diagnostics, USA) in 509 serum samples from 314 randomly selected asymptomatic subjects from among the population, and grouped into children (n = 124), adolescents (n = 74) and adults (n = 116), and in 195 serum samples from subjects presenting clinical gastric symptoms, grouped into children (n = 38) and adults (n = 157). The cut-off value was redefined and set at OD450 = 0.050. The percentage of seropositive individuals was not significantly different between the two groups of adults studied (75.9% and 80.2%, respectively) (p < 0.05), suggesting a high degree of contact with the microorganism in this region. 相似文献
995.
Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis 总被引:10,自引:0,他引:10
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Leung SY Chen X Chu KM Yuen ST Mathy J Ji J Chan AS Li R Law S Troyanskaya OG Tu IP Wong J So S Botstein D Brown PO 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(25):16203-16208
We analyzed gene expression patterns in human gastric cancers by using cDNA microarrays representing approximately equal 30,300 genes. Expression of PLA2G2A, a gene previously implicated as a modifier of the Apc(Min/+) (multiple intestinal neoplasia 1) mutant phenotype in the mouse, was significantly correlated with patient survival. We confirmed this observation in an independent set of patient samples by using quantitative RT-PCR. Beyond its potential diagnostic and prognostic significance, this result suggests the intriguing possibility that the activity of PLA2G2A may suppress progression or metastasis of human gastric cancer. 相似文献
996.
997.
David H. Overstreet James A. Halikas Sergey B. Seredenin Alexey B. Kampov-Polevoy Kina V. Viglinskaya Olga Kashevskaya Boris A. Badishtov Darin J. Knapp Pierre Mormede Kalervo Kiianmaa Ting-Kai Li Amir H. Rezvani 《Alcoholism, clinical and experimental research》1997,21(5):840-848
Thirteen behavioral variables from six tasks were measured in alcohol-preferring (AA, FH, and P) and -non-preferring (ANA, FRL, and NP) rat lines/strains and subjected to Factor Analysis. Four independent factors accounted for >90% of the variance. Defecation in the open field and ultrasonic vocalizations after an air puff were negatively correlated with alcohol intake and preference, whereas the increase in daily fluid intake in the presence of saccharin was positively correlated. Other factors could be labeled Activity, Emotionality, and Immobility Factors, and each was independent of the Alcohol Factor. When an additional alcohol-preferring rat line (HAD) and two additional non-preferring groups (LAD and ACI) were tested, they were found to differ on most behaviors that were associated with alcohol intake and preference in the Factor Analysis: vocalizations and saccharin-induced increase in fluid intake, but not defecation. A new Factor Analysis was then performed incorporating these three new groups and including five new behavioral measures. The following measures had high loadings on the Alcohol Factor: alcohol intake under choice conditions; alcohol preference; forced alcohol intake; alcohol acceptance (forced alcohol intake/basal water intake × 100); ultrasonic vocalization; saccharin intake; saccharin-induced increase in daily fluid intake; defecation in the open field test; and immobility in a modified forced swim test. These findings indicate that there are indeed certain behavioral characteristics that are common among alcohol-preferring rat lines/strains, but there are also substantial group differences on other behavioral measures. For those behavioral measures reflecting emotionality (defecation and ultrasonic vocalization) that loaded highly on the Alcohol Factor, the alcohol-preferring rats had lower scores. 相似文献
998.
Skowasch D Yeghiazaryan K Schrempf S Golubnitschaja O Welsch U Preusse CJ Likungu JA Welz A Lüderitz B Bauriedel G 《The Journal of heart valve disease》2003,12(1):68-75
BACKGROUND AND AIMS OF THE STUDY: Based on the concept of chronic persistent infections with Chlamydia pneumoniae among variable stressors for aortic valve degeneration, the study aim was to assess the presence of chlamydial heat shock protein (cHSP) 60 and its human homologue (hHSP60) in diseased valvular tissue. METHODS: Surgical specimens of high-grade stenosed, native (n = 33) and bioprosthetic (n = 10) aortic valves were examined immunohistochemically for the localization of cHSP60, hHSP60 and macrophages (CD68), supplemented by polymerase chain reaction (PCR) and electron microscopy to prove microbial presence. RESULTS: Degenerated valves showed specific immunostaining of cHSP60 in 27 cases (65%), of hHSP60 in 26 (63%), and of CD68 in 36 (84%). Both HSP60 homologues were predominantly detected in valvular fibrosa, consistently co-localized with macrophages and, quantitatively, showed a strong correlation (r = 0.81, p < 0.001). Presence of C. pneumoniae was demonstrated by PCR in a subset of 11 of 18 valves (61%). Microbial persistence was confirmed by ultrastructural analysis. Degenerated prosthetic valves revealed markedly higher macrophage infiltration and cHSP60 signaling compared with degenerated native valves (each p < 0.05). CONCLUSION: Beyond detection of C. pneumoniae, the present data on co-localization and valvular predilection sites (fibrosa) of both HSP60 homologues indicate the presence of chronic persistent C. pneumoniae infection as well as regional stressor effects, and suggest their involvement in native and prosthetic valve degeneration. 相似文献
999.
Percutaneous Trans‐Coronary Venous Mitral Annuloplasty in Patients With Functional Mitral Regurgitation: Analysis of Poznan Carillon Registry Data
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Piotr Kałmucki M.D. Olga Jerzykowska M.D. Rafał Dankowski M.D. Artur Baszko M.D. Lucyna Kramer Ph.D. Andrzej Szyszka M.D. Tomasz Siminiak M.D. Ph.D. F.E.S.C. F.A.C.C. 《Journal of interventional cardiology》2016,29(6):632-638
Objectives
The purpose of our study is to verify, whether percutaneous mitral annuloplasty results in reverse remodeling in patients with functional mitral regurgitation (FMR) and impaired ejection fraction (EF) and to investigate which echo parameters may help in prediction of the efficacy of the procedure.Background
FMR exacerbates left ventricular (LV) dilatation and contributes to both LV remodeling and heart failure.Methods
We analyzed baseline and 1 month follow‐up data in 22 consecutive patients with FMR, who underwent successful percutaneous trans‐coronary venous mitral annuloplasty with the Carillon device.Results
Significant reduction of FMR echo parameters, including vena contracta (VC), effective regurgitant orifice area (EROA), and regurgitant volume (RV) were observed and maintained throughout 1 month follow up and did not correlate with baseline annular, LV or with the left atrial diameters. Baseline mitral tenting area correlated negatively with the relative improvement (% difference) of EROA (r = ?0.5898) and RV (r = ?0.4363), but not with VC (r = 0.1341). In addition, increased EF as well as a significant reduction in left ventricular diameters were noted. The increase in EF negatively correlated with the change in EROA (r = ?0.50058), PISA (r = ?0.5327), and RV (r = ?0.5457). Baseline mitral tenting area significantly correlated with the 1 month change in EF (r = 0.5946) and stroke volume (r = 0.6913).Conclusions
The improvement of FMR after treatment with the Carillon device is associated with LV reverse remodeling and an increase in systolic performance, that correlates with the reduction in mitral regurgitation, being not dependent on baseline heart diameters. Mitral tenting area seems to be an important parameter in prediction of benefit from percutaneous mitral annuloplasty.1000.
Cotter G Kaluski E Stangl K Pacher R Richter C Milo-Cotter O Perchenet L Kobrin I Kaplan S Rainisio M Frey A Neuhart E Vered Z Dingemanse J Torre-Amione G 《European journal of heart failure》2004,6(5):601-609
BACKGROUND: In previous studies (the RITZ project), tezosentan, an intravenous (i.v.)-balanced dual endothelin (ET-A/B) antagonist, in doses of 50 and 100 mg/h, improved the hemodynamics but not the clinical outcome of patients with acute heart failure (AHF). OBJECTIVE: To evaluate the effect of lower doses of tezosentan in patients with AHF. SUBJECTS AND METHODS: Included were 130 patients hospitalized due to AHF with dyspnea at rest, despite initial treatment, and were in need of hemodynamic monitoring with cardiac index (CI)<2.5 l/min/m(2) and wedge pressure > or = 20 mm Hg. Patients were randomized in a double-blind fashion to receive placebo or tezosentan: 0.2, 1, 5, or 25 mg/h for 24 h. RESULTS: The primary endpoint of the study, CI increase at 6 h of treatment, was significant in the 5 and 25 mg/h groups. Tezosentan induced a dose-dependent increase in CI and a decrease in wedge pressure, peaking after 3 h in the 5 and 25 mg/h groups. In the 1 mg/h group, this effect was smaller during the first 6 h and increased gradually, becoming significant at 24 h and beyond treatment discontinuation. There was no hemodynamic effect in the 0.2 mg/h arm. Type-B natriuretic peptide (BNP) decreased in the 1, 5, and 25 mg/h groups but not on placebo. Endothelin levels were significantly increased by the 5 and 25 mg/h groups but not in the lower (< or = 1 mg/h) tezosentan doses. Urine output decreased on the 25 mg/h dose. There was a trend towards improvement in patients' subjective dyspnea score and worsening heart failure events, mainly in the 1 mg/h group. CONCLUSIONS: In patients admitted with AHF, tezosentan doses of 1-25 mg/h are efficacious in improving the hemodynamics and reducing BNP. Tezosentan doses beyond 1 mg/h increased plasma endothelin levels and reduced urine output, probably limiting their clinical efficacy, as compared to tezosentan 1 mg/h. 相似文献