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101.
102.
Markus F. Neurath Ivan Fuss Manolis Pasparakis Lena Alexopoulou Sylva Haralambous Karl-Hermann Meyer zum Büschenfelde Warren Strober George Kollias 《European journal of immunology》1997,27(7):1743-1750
Antibodies to tumor necrosis factor (TNF)-α have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-α in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10–30-fold higher levels of TNF-α mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-α, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-α-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-α in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-α-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-α gene had been inactivated by homologous recombination. Complementation of TNF-α function in TNF?/? mice by the expression of a mouse TNF-α transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-α in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-α for the treatment of patients with Crohn's disease. 相似文献
103.
104.
Vesna Čapkun Davor Eterović 《European journal of nuclear medicine and molecular imaging》1985,11(4):120-122
Radionuclide-angiography (RNA_ left-to-right intracardiac-shunt quantification algorithms, based on the part-by-part fit technique and the use of a so-called gamma variate model function (GVF), were tested via simulation analysis using data obtained from normal subjects. A good bolus of radioindicator was obtained by administering it directly into the vena subclavia. Normal subjects were defined as those having pulmonary histograms (PH) with no visible distortion caused by a shunt. Pure, non-superimposed data on the downslope of the PH curves, which are lost in presence of a shunt, proved to be appropriate reference values for testing the accuracy of results of standard shunt quantification algorithms. A generalized four-parameter GVF was introduced in order to extend the flexibility of the model function. The use of the three-parametric GVF to reconstruct the downslope of the PH curve out of the upslope data proved to be inadequate. This reveals an evident source of error in algorithms that calculate the shunt contribution by fitting GVF parameters to so-called difference-curve data. It is concluded that the inherent restricted statistical weight of RNA data prevents accurate results being obtained from standard RNA-shunt-assessment algorithms. 相似文献
105.
106.
Milica Zrnic Ciric Miodrag Ostojic Ivana Baralic Jelena Kotur-Stevuljevic Brizita I. Djordjevic Stana Markovic Stefan Zivkovic Ivan Stankovic 《Nutrients》2021,13(3)
Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS (n = 42) or placebo (n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS (r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events. 相似文献
107.
Flavio Roberto Takeda Marcus Fernando Kodama Pertille Ramos Marina Alessandra Pereira Renan Rosetti Muniz Francisco Tustumi Tiago Biachi de Castria Rubens Antonio Aissar Sallum Bruno Zilberstein Ulysses Ribeiro Junior Ivan Cecconello 《American journal of surgery》2021,221(3):631-636
IntroductionAdenocarcinoma of the esophagogastric junction (AEGJ) represents a poor prognostic tumor. We evaluated the recurrence pattern and risk factors associated with recurrence in patients undergoing surgical resection by AEJG.MethodsRecurrences were categorized as locoregional, peritoneal, or distant. These three recurrence groups and a non-recurrence group were compared, and overall survival (OS) and disease-free survival (DFS) for each one was obtained.ResultsWe analyzed 188 patients with curative surgical treatment. Recurrence was observed in 72 (38.3%) patients. Locoregional recurrence was observed in 17 (23.6%); 20 (27.8%) peritoneal recurrence and 35 (48.6%) distant metastasis. DFS was 9, 5, and 8 months, and OS was 21.8, 13.2, and 20.8, respectively. Tumors larger than 5 cm are risk factors for peritoneal recurrence (OR:2.88, p = 0.012). Positive lymph nodes were related to distant metastasis (OR:9.15, p = 0.040), and lymphatic invasion for locoregional recurrence (OR:3.81, p = 0.028).ConclusionAEGJ is associated with high rates of early recurrence. 相似文献
108.
Shamsah Kazani David J. Rowlands Ivan Bottoli Julie Milojevic Jose Alcantara Ieuan Jones Kenneth Kulmatycki Surendra Machineni Lidia Mostovy Ian Nicholls Jerry A. Nick Steven M. Rowe Nicholas J. Simmonds Raju Vegesna Jeroen Verheijen Henry Danahay Martin Gosling Phaninatha Sarma Ayalavajjala Robert Strieter 《Journal of cystic fibrosis》2021,20(2):250-256
BackgroundThis is the first-in-human study of icenticaftor, an oral potentiator of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) channel. Restoration of CFTR activity has shown significant clinical benefits, but more studies are needed to address all CFTR mutations.MethodsSafety, pharmacodynamics/pharmacokinetics of icenticaftor were evaluated in a randomized, double-blind, placebo-controlled study in healthy volunteers. Efficacy was assessed in adult CF patients with ≥1 pre-specified CFTR Class III or IV mutation (150 and 450 mg bid), or homozygous for F508del mutation (450 mg bid). Primary efficacy endpoint was change from baseline in lung clearance index (LCI2.5). Secondary endpoints included %predicted FEV1 and sweat chloride level.ResultsClass IV mutations were present in 22 patients, Class III in 2 (both S549N), and 25 were homozygous for F508del. Icenticaftor was well-tolerated in healthy and CF subjects with no unexpected events or discontinuations in the CF groups. The most frequent study-drug related adverse events in CF patients were nausea (12.2%), headache (10.2%), and fatigue (6.1%). Icenticaftor 450 mg bid for 14 days showed significant improvements in all endpoints versus placebo in patients with Class III and IV mutations; mean %predicted FEV1 increased by 6.46%, LCI2.5 decreased by 1.13 points and sweat chloride decreased by 8.36 mmol/L. No significant efficacy was observed in patients homozygous for a single F508del.ConclusionsIcenticaftor was safe and well-tolerated in healthy volunteers and CF patients, and demonstrated clinically meaningful changes in lung function and sweat chloride level in CF patients with Class III and IV CFTR mutations.ClinicalTrials.gov: NCT02190604 相似文献
109.
110.
Kutner Bryan A. Simoni Jane M. Aunon Frances M. Creegan Emma Balán Ivan C. 《Archives of sexual behavior》2021,50(4):1651-1663
Archives of Sexual Behavior - Gay, bisexual, and other men who have sex with men (MSM) experience alarming HIV disparities alongside sub-optimal engagement in HIV interventions. Among MSM, stigma... 相似文献