51 research outputs found
Second Trimester Amniocentesis Is Not a Risk Factor for Very Low Birth Weight and Extremely Low Birth Weight
Objectives. To assess the risk of very low birth weight (VLBW) and extremely low birth weight (ELBW) attributable to second trimester amniocentesis. Methods. Records of 4,877 consecutive amniocentesis, performed between 1997 and 2003, were analyzed. Only VLBW and ELBW in the study population (exposed) and in the control group (unexposed) were evaluated. Comparisons were made between the amniocentesis group versus nonexposed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated for VLBW and ELBW classes. Results. In the study population, the VLBW were 35 (0.71%) and the ELBW were 20 (0.41%). In the control group, the VLBW were 220 (0.67%) and the ELBW were 112 (0.34%). The Odds ratios of the VLBW between the study and the control group did not show any statistical significant risk (OR = 1.07, 95% CI = 0.72–1.54). Also in ELBW odds ratios between study and control group were not statistically significant (OR = 1.20, 95% CI = 0.7–1.95). Conclusions. No effect of the second trimester amniocentesis was noted on VLBW and ELBW
DDS-induced colorectal fibrosis in mice: anti-fibrotic effects of GED 0507-34 levo, a novel PPARγ ligand
Intestinal fibrosis is a progressive process characterized by de novo synthesis and uncontrolled deposition of extracellular matrix components (ECM) following a tissue chronic inflammation mainly regulated by Transforming Growth Factor (TGF)β/ Smads pathway. Frequently associated to Inflammatory Bowel Disease (IBD), intestinal fibrosis may lead to stenosis and obstructions that require surgery up to 75% of patients as drugs currently used in IBD are unable to improve fibrostenosis lesions (1). Peroxisome proliferator-activated receptor (PPAR)-γ is able to antagonize (TGF) β/Smads and could be an crucial target to develop novel antifibrotic therapeutic strategies (2). Aim of this study is to evaluate the antifibrotic action of a novel PPARγ agonist, GED 0507-34 levo, in colonic fibrosis in mice. Immunohistochemistry and immunoblotting evaluations, TGFβ1, CTGF, Collagen types I-III, Smad3, α-SMA, were performed in in three groups of C57BL/6 mice: Dextran Sulphate Sodium (DSS) colitis group, DSS+GED group and controls. Evident macroscopic and microscopic lesions in the most of colons of DSS treated mice were observed compared to DSS+GED mice and controls. The tissue levels of the main markers of fibrosis resulted significantly increased in DSS mice and restored by administration of GED. GED seems to prevents ECM colonic deposition and to improve the intestinal fibrotic lesions by its ability in controlling TGFβ/Smads pathway signalling activation
Anti-fibrotic effect of a novel PPAR-γ ligand, GED-0507-34 LEVO, in DSS induced colonic fibrosis in mice
Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) in which chronic inflammation leads to abnormal deposition of extracellular matrix components (ECM) causing obstruction and loss of function of the intestinal tract involved (1). Fibrogenesis is mainly regulates by trasforming growth factor (TGF) β/Smad pathway and a key antagonist of this signaling is represented by peroxisome proliferator-activated receptor (PPAR)-γ. As the anti-inflammatory drugs currently used in IBD are unable to improve intestinal fibrosis the exploration of new therapeutical approaches has now became crucial (2). Aim of this study is to evaluate the antifibrotic action of a novel PPARγ agonist, GED-0507-34-LEVO (GED), in colon fibrosis in mice. Chronic colitis and fibrosis were induced in C57BL/6 mice by administration of 2,5% (w/v) dextrane sulphate sodium (DSS) in drinking water for 5 days followed by 7 days of water for 3 cycles. Mice were divided into 3 groups: DSS, DSS+GED and control. 30mg/Kg/mice of GED was daily administrated by oral gavage starting from the second DSS cycle. Samples from colon were excised and processed to assess macroscopic lesions, histological and morphometrical aspects and immunohistochemical and immunoblotting analysis for TGFβ1, CTGF, collagen types I-III, Smad3,α-SMA. Evident shortening and dilation in the most of colons of DSS treated mice were observed. Macroscopic and microscopic findings were significantly improved in DSS mice+GED compared with control mice. The tissue levels of collagen and α-SMA, specific markers of fibrosis, resulted significantly increased in mice receving DSS compared to control mice, as well as the expression of TGFβ1, CTGF, Smad3. DSS+GED group showed reduced expression of all markers involved. GED significantly improves the intestinal fibrotic lesions in DSS chronic colitis murine model and controls the pivotal molecular events leading to fibrosis
Interaction between sphingosine kinase/sphingosine 1 phosphate and transforming growth factor-β/Smads pathways in experimental intestinal fibrosis. An in vivo immunohistochemical study
A concomitant action of multiple profibrotic mediators appears crucial in the development and progression of fibrosis. Sphingosine kinase/sphingosine 1 phosphate and transforming growth factor-β/Smads pathways are both involved in pathogenesis of fibrosis in several organs by controlling differentiation of fibroblasts to myofibroblasts and the epithelial to-mesenchymal transition. However, their direct involvement in chronic colitis-associated fibrosis it is not yet known. In this study we evaluated the immunohistochemical expression of some proteins implicated in sphingosine kinase/sphingosine 1 phosphate and transforming growth factor-β/Smads pathways in Dextrane Sodium Sulphate (DSS)-induced colorectal fibrosis in mice. Compared to control mice, DSS-induced chronic colitis mice developed a marked intestinal fibrosis associated with a concomitant overexpression of TGF-β, p-Smad3, α-SMA, collagen I-III, SPHK1, RhoA, PI3K, Akt, p-Akt, p-mTOR. This study highlights the relationship between the two pathways and the possible role of SPHK1 in the intestinal fibrosis. These results, if confirmed by in vitro studies, may have important clinical implications in the development of new therapeutical approaches in inflammatory bowel disease
The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle
Satellite cells represent myogenic stem cells that allow the homeostasis and repair of adult skeletal muscle. Here the authors report that the transcription factor NF-Y is expressed in satellite cells and is important for their maintenance and proper myogenic differentiation
Reversal of Defective Mitochondrial Biogenesis in Limb-Girdle Muscular Dystrophy 2D by Independent Modulation of Histone and PGC-1α Acetylation
Mitochondrial dysfunction occurs in many muscle degenerative disorders. Here, we demonstrate that mitochondrial biogenesis was impaired in limb-girdle muscular dystrophy (LGMD) 2D patients and mice and was associated with impaired OxPhos capacity. Two distinct approaches that modulated histones or peroxisome proliferator-activated receptor-gamma coactivator 1 \u3b1 (PGC-1\u3b1) acetylation exerted equivalent functional effects by targeting different mitochondrial pathways (mitochondrial biogenesis or fatty acid oxidation[FAO]). The histone deacetylase inhibitor Trichostatin A (TSA) changed chromatin assembly at the PGC-1\u3b1 promoter, restored mitochondrial biogenesis, and enhanced muscle oxidative capacity. Conversely, nitric oxide (NO) triggered post translation modifications of PGC-1\u3b1 and induced FAO, recovering the bioenergetics impairment of muscles but shunting the defective mitochondrial biogenesis. In conclusion, a transcriptional blockade of mitochondrial biogenesis occurred in LGMD-2D and could be recovered by TSA changing chromatin conformation, or it could be overcome by NO activating a mitochondrial salvage pathway
The association of indwelling urinary catheter with delirium in hospitalized patients and nursing home residents: an explorative analysis from the "Delirium Day 2015"
Backround: Use of indwelling urinary catheter (IUC) in older adults has negative consequences, including delirium.
Aim: This analysis, from the "Delirium Day 2015", a nationwide multicenter prevalence study, aim to evaluate the association of IUC with delirium in hospitalized and Nursing Homes (NHs) patients.
Methods: Patients underwent a comprehensive geriatric assessment, including the presence of IUC; inclusion criteria were age > 65 years, being Italian speaker and providing informed consent; exclusion criteria were coma, aphasia, end-of-life status. Delirium was assessed using the 4AT test (score ≥ 4: possible delirium; scores 1-3: possible cognitive impairment).
Results: Among 1867 hospitalized patients (mean age 82.0 ± 7.5 years, 58% female), 539 (28.9%) had IUC, 429 (22.9%) delirium and 675 (36.1%) cognitive impairment. IUC was significantly associated with cognitive impairment (OR 1.60, 95% CI 1.19-2.16) and delirium (2.45, 95% CI 1.73-3.47), this latter being significant also in the subset of patients without dementia (OR 2.28, 95% CI 1.52-3.43). Inattention and impaired alertness were also independently associated with IUC. Among 1454 NHs residents (mean age 84.4 ± 7.4 years, 70.% female), 63 (4.3%) had IUC, 535 (36.8%) a 4AT score ≥ 4, and 653 (44.9%) a 4AT score 1-3. The multivariate logistic regression analysis did not show a significant association between 4AT test or its specific items with IUC, neither in the subset of patients without dementia.
Discussion: We confirmed a significant association between IUC and delirium in hospitalized patients but not in NHs residents.
Conclusion: Environmental and clinical factors of acute setting might contribute to IUC-associated delirium occurrence
"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool
Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys
Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia
Prenatal diagnosis and postnatal follow-up of a child with mosaic trisomy 22 with several levels of mosaicism in different tissues
We report on the case of a patient with mosaic trisomy 22, who was diagnosed prenatally by amniocentesis during the 16(th) week of pregnancy. In the foetus, three trisomic clones were found out of the nine that were analyzed (the other six clones had a 46,XY karyotype). Cytogenetic analysis of cord blood during the 20(th) week of pregnancy showed a normal male karyotype; however, a placental biopsy that was performed at the same time showed 100% and 95% trisomic cells in the chromosomal analysis of direct and long-term cultures, respectively. A follow-up ultrasonographic examination excluded major congenital malformations and the abdominal and cranial circumferences were normal until the 24(th) week of pregnancy. At this point, a deflection of the growth curve occurred and the values were persistently below the 3(rd) centile until birth. After birth, karyotypic and fluorescent in situ hybridisation analyses performed on the fibroblasts of the neonate showed that 3-4% of the cell lines were trisomic, and studies using microsatellite markers showed normal allelic segregation, which excluded uniparental disomy. The period of postnatal follow-up was characterised by a significant growth deficit (height and head circumference were less than the 3(rd) centile) and by mental retardation. The present case is compatible with other earlier reports that showed that the levels of trisomy 22 are tissue-specific and are of little help in establishing the prognosis of the chromosomal abnormality
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