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1.
Gastrointest Endosc ; 96(5): 829-839.e1, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35697127

RESUMEN

BACKGROUND AND AIMS: Piecemeal EMR of colorectal laterally spreading tumors (LSTs) >20 mm is effective. Experience is limited in the use of cap-assisted EMR (EMR-C) for resection of colonic lesions. We compared the efficacy and the safety of EMR-C for the removal of colonic LSTs ≥30 mm with "inject-and-cut" standard EMR (EMR-S). METHODS: In this randomized trial from 4 Italian centers, 138 patients were treated with EMR-C and 102 with EMR-S. The rates of residual lesions, percentage of recurrence after 12 months, and adverse events were evaluated. RESULTS: One hundred forty-three lesions were resected with EMR-C and 102 with EMR-S. Argon plasma coagulation (APC) was used as adjunctive treatment in 2.9% of EMR-Cs and in 22.5% of EMR-Ss (P < .001). The median time required was 20 minutes for EMR-C and 30 minutes for EMR-S (P < .001). Adverse events (AEs) occurred in 14 EMR-Cs (10.1%; 2 perforations, 11 bleeding events, and 1 stenosis) and in 22 EMR-Ss (21.6%; 1 perforation and 21 bleeding events) (P = .017). Intraprocedural AEs occurred in 3.6% of EMR-Cs and 16.7% of EMR-Ss (P = .001). Overall, residual lesions within 12 months were found to be significantly higher with EMR-S (32 patients, 31.4%) than with EMR-C (8 patients, 5.8%) (P < .001). Recurrence at follow-up colonoscopy in 12 months occurred in 7 EMR-Cs (5.1%) and 17 EMR-Ss (16.7%; P < .001). CONCLUSIONS: The study demonstrated the feasibility and safety of EMR-C for removing large colorectal LSTs, with higher eradication rates, shorter resection time, and less use of APC when compared with EMR-S. (Clinical trial registration number: NCT03498664.).


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Colonoscopía , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Neoplasias del Colon/cirugía , Neoplasias del Colon/patología , Coagulación con Plasma de Argón
2.
Sensors (Basel) ; 21(17)2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34502787

RESUMEN

The possibility to shape stimulus-responsive optical polymers, especially hydrogels, by means of laser 3D printing and ablation is fostering a new concept of "smart" micro-devices that can be used for imaging, thermal stimulation, energy transducing and sensing. The composition of these polymeric blends is an essential parameter to tune their properties as actuators and/or sensing platforms and to determine the elasto-mechanical characteristics of the printed hydrogel. In light of the increasing demand for micro-devices for nanomedicine and personalized medicine, interest is growing in the combination of composite and hybrid photo-responsive materials and digital micro-/nano-manufacturing. Existing works have exploited multiphoton laser photo-polymerization to obtain fine 3D microstructures in hydrogels in an additive manufacturing approach or exploited laser ablation of preformed hydrogels to carve 3D cavities. Less often, the two approaches have been combined and active nanomaterials have been embedded in the microstructures. The aim of this review is to give a short overview of the most recent and prominent results in the field of multiphoton laser direct writing of biocompatible hydrogels that embed active nanomaterials not interfering with the writing process and endowing the biocompatible microstructures with physically or chemically activable features such as photothermal activity, chemical swelling and chemical sensing.


Asunto(s)
Materiales Biocompatibles , Hidrogeles , Rayos Láser , Polímeros , Impresión Tridimensional
3.
Int J Mol Sci ; 22(8)2021 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-33920464

RESUMEN

Salmon calcitonin is a good model for studying amyloid behavior and neurotoxicity. Its slow aggregation rate allows the purification of low molecular weight prefibrillar oligomers, which are the most toxic species. It has been proposed that these species may cause amyloid pore formation in neuronal membranes through contact with negatively charged sialic acid residues of the ganglioside GM1. In particular, it has been proposed that an electrostatic interaction may be responsible for the initial contact between prefibrillar oligomers and GM1 contained in lipid rafts. Based on this evidence, the aim of our work was to investigate whether the neurotoxic action induced by calcitonin prefibrillar oligomers could be counteracted by treatment with neuraminidase, an enzyme that removes sialic acid residues from gangliosides. Therefore, we studied cell viability in HT22 cell lines and evaluated the effects on synaptic transmission and long-term potentiation by in vitro extracellular recordings in mouse hippocampal slices. Our results showed that treatment with neuraminidase alters the surface charges of lipid rafts, preventing interaction between the calcitonin prefibrillar oligomers and GM1, and suggesting that the enzyme, depending on the concentration used, may have a partial or total protective action in terms of cell survival and modulation of synaptic transmission.


Asunto(s)
Neuropatías Amiloides , Calcitonina/toxicidad , Proteínas de Peces/toxicidad , Neuraminidasa/farmacología , Salmón , Neuropatías Amiloides/inducido químicamente , Neuropatías Amiloides/metabolismo , Neuropatías Amiloides/patología , Neuropatías Amiloides/prevención & control , Animales , Gangliósido G(M1)/metabolismo , Masculino , Microdominios de Membrana/metabolismo , Microdominios de Membrana/patología , Ratones , Ratones Endogámicos BALB C , Electricidad Estática
4.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-34575979

RESUMEN

MicroRNAs (miRNAs) play an essential role in the regulation of a number of physiological functions. miR-133a and other muscular miRs (myomiRs) play a key role in muscle cell growth and in some type of cancers. Here, we show that miR133a is upregulated in individuals that undertake physical exercise. We used a skeletal muscle differentiation model to dissect miR-133a's role and to identify new targets, identifying Tropomyosin-4 (TPM4). This protein is expressed during muscle differentiation, but importantly it is an essential component of microfilament cytoskeleton and stress fibres formation. The microfilament scaffold remodelling is an essential step in cell transformation and tumour progression. Using the muscle system, we obtained valuable information about the microfilament proteins, and the knowledge on these molecular players can be transferred to the cytoskeleton rearrangement observed in cancer cells. Further investigations showed a role of TPM4 in cancer physiology, specifically, we found that miR-133a downregulation leads to TPM4 upregulation in colon carcinoma (CRC), and this correlates with a lower patient survival. At molecular level, we demonstrated in myocyte differentiation that TPM4 is positively regulated by the TA isoform of the p63 transcription factor. In muscles, miR-133a generates a myogenic stimulus, reducing the differentiation by downregulating TPM4. In this system, miR-133a counteracts the differentiative TAp63 activity. Interestingly, in CRC cell lines and in patient biopsies, miR-133a is able to regulate TPM4 activity, while TAp63 is not active. The downregulation of the miR leads to TPM4 overexpression, this modifies the architecture of the cell cytoskeleton contributing to increase the invasiveness of the tumour and associating with a poor prognosis. These results add data to the interesting question about the link between physical activity, muscle physiology and protection against colorectal cancer. The two phenomena have in common the cytoskeleton remodelling, due to the TPM4 activity, that is involved in stress fibres formation.


Asunto(s)
Diferenciación Celular/genética , Neoplasias del Colon/genética , MicroARNs/genética , Factores de Transcripción/genética , Tropomiosina/genética , Proteínas Supresoras de Tumor/genética , Citoesqueleto de Actina/genética , Carcinogénesis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Neoplasias del Colon/patología , Citoesqueleto/genética , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Células Musculares/citología , Desarrollo de Músculos/genética , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , Fibras de Estrés/genética
5.
Cell Physiol Biochem ; 54(4): 736-747, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32749090

RESUMEN

BACKGROUND/AIMS: The study of the effects of simulated microgravity on primary cultures of human satellite cells represents a reliable model for identifying the biomolecular processes involved in mechanic load-related muscle mass loss. Therefore, this study aims to investigate the role of myostatin and Bone Morphogenetic Protein-2 in human satellite cells response to simulated microgravity condition. METHODS: In order to identify the main molecules involved in the phenomena of degeneration/regeneration of muscle tissue related to the alteration of mechanic load, we performed a morphological and immunohistochemical study on 27 muscle biopsies taken from control, osteoporotic and osteoarthritic patients, underwent hip arthroplasty. For each patient, we set up primary satellite cell cultures subjected to normogravity and simulated microgravity (110h) regimens. Cellular functionality has been studied through a morphological evaluation performed by optical microscopy, and an ultrastructural evaluation carried out by transmission electron microscopy. Furthermore, we evaluated the expression of Bone Morphogenetic Protein-2 and myostatin through immunocytochemical reactions. RESULTS: Our results showed that in the very early phases of simulated microgravity condition the satellite cells are more active than those subjected to the normogravity regime, as demonstrated by both the increase in the number of myotubes and the significant increase in the expression of Bone Morphogenetic Protein-2 in all experimental groups. However, with prolongated exposure to simulated microgravity regime (>72h), satellite cells and new formed myotubes underwent to cell death. It is important to note that, in early phases, simulated microgravity can stimulate the formation of new myotubes from satellite cells derived by osteoporotic patients. Furthermore, we observed that simulated microgravity can induce changes in myostatin expression levels by group-dependent variations. CONCLUSION: The results obtained allowed us to hypothesize a possible molecular mechanism of response to simulated microgravity, confirming the importance of Bone Morphogenetic Protein-2 and myostatin in the physio-pathogenesis of muscle tissue. In addition, these data can lay the foundation for new therapeutic approached in the prevention/cure of osteoporosis and sarcopenia.


Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/metabolismo , Miostatina/metabolismo , Osteoartritis/metabolismo , Osteoporosis/metabolismo , Adulto , Anciano , Proteína Morfogenética Ósea 2/genética , Muerte Celular , Células Cultivadas , Humanos , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Miostatina/genética , Células Satélite del Músculo Esquelético/citología , Células Satélite del Músculo Esquelético/ultraestructura , Simulación de Ingravidez
6.
Gastrointest Endosc ; 88(2): 283-291.e3, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29653120

RESUMEN

BACKGROUND AND AIMS: Self-expandable metal stents (SEMSs) are used to relieve malignant biliary obstructions. We aimed to compare stent patency, the adverse events rate, and overall survival of covered versus uncovered self-conformable metal stents in patients with primary malignant extrahepatic biliary strictures, not eligible for surgery. METHODS: This is a multicenter randomized trial analyzing 158 patients with inoperable distal malignant biliary obstruction conducted in 5 Italian referral centers between December 2014 and October 2016. Seventy-eight patients were randomized to receive a fully covered SEMS (FCSEMS), and 80 patients received uncovered SEMSs (USEMSs). Data from 148 (72 FCSEMSs and 76 USEMSs) of 158 patients were analyzed. RESULTS: Median time of stent patency was lower for FCSEMSs (240 days vs 541 days for USEMSs; P = .031). Adverse events occurred with 19 FCSEMSs (26.4%) and 10 USEMSs (13.2%); P = .061. The main causes of FCSEMS dysfunction were migration (7% vs 0% in the USEMS group) and early occlusion mainly because of sludge or overgrowth; late stent occlusion because of tumor ingrowth occurred in 13.2% of patients in the USEMS group. There were no significant differences either in levels of conjugated bilirubin improvement or in overall survival between the FCSEMS and USEMS groups. Median survival was 134 days in the FCSEMS group and 112 days in the USEMS group (P = .23). CONCLUSION: The number of stent-related adverse events was higher, although not significantly, among patients in the FCSEMS group. FCSEMSs had a significantly higher rate of migration than USEMSs, and stent occlusion occurred earlier. A significant difference in the patency rate was observed in favor of the USEMS group. (Clinical trial registration number: NCT02102984.).


Asunto(s)
Neoplasias del Sistema Biliar/complicaciones , Colestasis Extrahepática/cirugía , Drenaje/instrumentación , Neoplasias Pancreáticas/complicaciones , Falla de Prótesis , Stents Metálicos Autoexpandibles , Anciano , Anciano de 80 o más Años , Colangiopancreatografia Retrógrada Endoscópica , Colestasis Extrahepática/etiología , Drenaje/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Politetrafluoroetileno , Falla de Prótesis/efectos adversos , Stents Metálicos Autoexpandibles/efectos adversos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
7.
Phytother Res ; 32(9): 1803-1811, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29785769

RESUMEN

Total flower extracts of Hypericum perforatum L. obtained with 3 different solvent systems were tested on tumour cell line cultures by comparing two groups of plants harvested in different times and places. The extracts, characterized according to the spectroscopic profile and the hypericin content, were tested on the growth and apoptotic death of K562 cells, a human erythroleukemic cell line. Growth and apoptosis were analysed by viable cell count, flow cytometry, and fluorescence microscopy at 6, 24, and 48 hr of culture following 1 hr exposure to the extracts under investigation. Here, we show that Hypericum extracts are able to reduce the growth of K562 cells and induce different degrees and kinetics of apoptosis according to the group of plants of origin. Also, we highlighted interesting differences in terms of efficacy among the extracts, with some samples losing their effectiveness along the culture time and others able to maintain or even increase their efficacy. Furthermore, the data herein obtained confirm the role of non hypericin compounds that are present in different proportions in the two plant groups and in the extracts analysed.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Hypericum/química , Extractos Vegetales/farmacología , Antracenos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Flores/química , Humanos , Células K562 , Perileno/análogos & derivados , Perileno/farmacología , Solventes
8.
J Surg Oncol ; 115(3): 344-350, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27859280

RESUMEN

BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) in gastric cancer (GC) is associated with older age. We present the clinicopathological results of younger and older patients with MSI GC. METHODS: We analyzed 472 patients with GC. MSI analysis was done on fresh frozen tissue using five quasimonomorphic mononucleotide repeats: NR-21, NR-24, NR-27, BAT-25, and BAR-26. Clinical and pathological analysis was performed for different age groups. RESULTS: We observed better survival in elderly MSI GC patients compared to younger patients. The percentage of MSI GC increases gradually with increasing age, accounting for 48% of patients over the age of 85 years. A difference in survival was seen between MSI and MSS groups of patients older than 65 years, while no statistical difference was seen for younger groups. Multivariate analysis revealed that MSI status has a significant prognostic factor in patients aged over 70 years (MSS vs. MSI; HR 1.82, P = 0.013). CONCLUSION: MSI is an important prognostic factor above all in elderly GC patients. It is associated with favorable prognosis and may help in planning different approaches to treatment in this subgroup. J. Surg. Oncol. 2017;115:344-350. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Inestabilidad de Microsatélites , Neoplasias Gástricas/genética , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/patología
10.
Dev Growth Differ ; 58(4): 400-8, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27189526

RESUMEN

In the last years adenosine triphosphate (ATP) and subsequent purinergic system activation through P2 receptors were investigated highlighting their pivotal role in bone tissue biology. In osteoblasts ATP can regulate several activities like cell proliferation, cell death, cell differentiation and matrix mineralization. Since controversial results exist, in this study we analyzed the ATP effects on differentiation and mineralization in human osteoblast-like Saos-2 cells. We showed for the first time the altered functional activity of ATP receptors. Despite that, we found that ATP can reduce cell proliferation and stimulate osteogenic differentiation mainly in the early stages of in vitro maturation as evidenced by the enhanced expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2) and Osteocalcin (OC) genes and by the increased ALP activity. Moreover, we found that ATP can affect mineralization in a biphasic manner, at low concentrations ATP always increases mineral deposition while at high concentrations it always reduces mineral deposition. In conclusion, we show the osteogenic effect of ATP on both early and late stage activities like differentiation and mineralization, for the first time in human osteoblastic cells.


Asunto(s)
Adenosina Trifosfato/farmacología , Calcificación Fisiológica/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Osteoblastos/metabolismo , Fosfatasa Alcalina/biosíntesis , Línea Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/biosíntesis , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Osteoblastos/citología , Osteocalcina/biosíntesis
11.
Tumour Biol ; 37(2): 1959-66, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26334620

RESUMEN

CA 19-9 is a marker correlated to the clinical evolution of pancreatic adenocarcinoma. To analyze the clinical value of pre- and postoperative CA 19-9 serum levels in stage I and II pancreatic cancer. We analyzed 61 patients resected for pancreatic cancer. Patients were evaluated about the pre-operative CA 19-9 values and then divided into 3 groups: high, high-low and low, on the basis of pre- and postoperative CA 19-9 levels. The correlations between these groups and age, sex, pT, pN, tumor stage, jaundice, surgical radicality, tumor size, number of harvested and positive lymph nodes, grading, overall and major morbidities and post-operative mortality together with survival rates were analyzed. Higher values of pre-operative CA 19-9 were significantly correlated to the presence of jaundice, high pT, pN, stage and higher number of metastatic lymph nodes. In 49 patients (80.3 %) an R0 resection was performed. Five-year overall survival (OS) and disease free survival (DFS) were significantly better in patients with high levels of pre-operative CA 19-9, even in R0 cases. After stratification, 30 patients were included in the high group, 13 in the high-low group and 18 in the low group. A statistically significant correlation was found between the CA 19-9 groups and the lymph nodal positivity, not between CA 19-9 and pT. OS and DFS were significantly better in low group patients. We confirm the prognostic value of preoperative CA 19-9 serum levels. We do not support early postoperative modifications of CA19-9 as an adjunctive prognostic variable.


Asunto(s)
Biomarcadores de Tumor/sangre , Antígeno CA-19-9/sangre , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Adulto , Anciano , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/mortalidad , Pronóstico , Estudios Retrospectivos
12.
Endoscopy ; 48(6): 530-5, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26990509

RESUMEN

BACKGROUND AND STUDY AIM: Precut sphincterotomy is a technique usually employed for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of bile duct disease. It is a validated risk factor for post-ERCP pancreatitis (PEP), but it is not clear whether the risk is related to the technique itself or to the repeated biliary cannulation attempts preceding it. The primary aim of the study was to assess the incidence of PEP in early precut compared with the standard technique in patients with difficult biliary cannulation. Secondary aims were to compare complications and cannulation success. PATIENTS AND METHODS: In this prospective, multicenter, randomized, clinical trial, patients who were referred for therapeutic biliary ERCP and difficult biliary cannulation were randomized to early precut (Group A) or repeated papillary cannulation attempts followed, in cases of failure, by late precut (Group B). PEP was defined as the onset of upper abdominal pain associated with an elevation in serum pancreatic enzymes of at least three times the normal level at more than 24 hours after the procedure. No rectal indomethacin or diclofenac was used for prevention of PEP. RESULTS: A total of 375 patients were enrolled. PEP developed in 10 of the 185 patients (5.4 %) in Group A and 23 of the 190 (12.1 %) in Group B (odds ratio [OR] 0.35; 95 % confidence interval [CI] 0.16 - 0.78). The incidence of PEP was significantly lower in the early precut group (10/185, 5.4 %) than in the delayed precut subgroup (19/135 [14.1 %]; OR 0.42, 95 %CI 0.17 - 1.07). There were no differences in biliary cannulation success rates, bleeding, perforation, and cholangitis. CONCLUSIONS: In patients with difficult biliary cannulation, early precut is an effective technique and can significantly reduce the incidence of PEP. Repeated biliary cannulation attempts are a real risk factor for this complication.


Asunto(s)
Cateterismo/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Pancreatitis/prevención & control , Complicaciones Posoperatorias/prevención & control , Esfinterotomía Endoscópica/métodos , Anciano , Anciano de 80 o más Años , Conducto Colédoco , Terminación Anticipada de los Ensayos Clínicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/etiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Factores Protectores
13.
Clin Sci (Lond) ; 129(7): 515-27, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25948052

RESUMEN

The physical and immunological properties of the human intestinal epithelial barrier in aging are largely unknown. Ileal biopsies from young (7-12 years), adult (20-40 years) and aging (67-77 years) individuals not showing symptoms of gastrointestinal (GI) pathologies were used to assess levels of inflammatory cytokines, barrier integrity and cytokine production in response to microbial challenges. Increased expression of interleukin (IL)-6, but not interferon (IFN)γ, tumour necrosis factor (TNF)-α and IL-1ß was observed during aging; further analysis showed that cluster of differentiation (CD)11c(+) dendritic cells (DCs) are one of the major sources of IL-6 in the aging gut and expressed higher levels of CD40. Up-regulated production of IL-6 was accompanied by increased expression of claudin-2 leading to reduced transepithelial electric resistance (TEER); TEER could be restored in in vitro and ex vivo cultures by neutralizing anti-IL-6 antibody. In contrast, expression of zonula occludens-1 (ZO-1), occludin and junctional-adhesion molecule-A1 did not vary with age and overall permeability to macromolecules was not affected. Finally, cytokine production in response to different microbial stimuli was assessed in a polarized in vitro organ culture (IVOC). IL-8 production in response to flagellin declined progressively with age although the expression and distribution of toll-like receptor (TLR)-5 on intestinal epithelial cells (IECs) remained unchanged. Also, flagellin-induced production of IL-6 was less pronounced in aging individuals. In contrast, TNF-α production in response to probiotics (VSL#3) did not decline with age; however, in our experimental model probiotics did not down-regulate the production of IL-6 and expression of claudin-2. These data suggested that aging affects properties of the intestinal barrier likely to impact on age-associated disturbances, both locally and systemically.


Asunto(s)
Factores de Edad , Regulación de la Expresión Génica , Íleon/metabolismo , Inmunidad Innata , Adulto , Anciano , Biopsia , Células CACO-2 , Niño , Medios de Cultivo Condicionados/química , Citocinas/metabolismo , Células Dendríticas/metabolismo , Impedancia Eléctrica , Endoscopía , Epitelio/metabolismo , Perfilación de la Expresión Génica , Humanos , Técnicas de Cultivo de Órganos , Adulto Joven
14.
J Magn Reson Imaging ; 39(5): 1198-205, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-25006631

RESUMEN

PURPOSE: To evaluate bone age determination using MRI of the hand and wrist. MATERIALS AND METHODS: A total of 179 (78 female and 101 males, 11 to 16 years old) subjects of 252 normal volunteers met entrance criteria. A low field open magnet (0.2 Tesla) was used for this study; coronal T1-weighted images with a slice thickness of 1.3mm were acquired. Two blinded radiologists evaluated the studies and the following elements were considered: the appearance of cartilage, vacuolization of cartilage, provisional calcification, progression of ossification, and complete ossification. Correlation between chronologic age and MR bone age was determined by means of simple linear regression analysis. RESULTS: Strong correlation between MR skeletal age and chronological age was observed for both investigators, Pearson correlation R2 = 0.9 for each. CONCLUSION: Determination of bone age with MRI is feasible and shows good interobserver reproducibility. Data from this study may be useful to develop an atlas of skeletal development and bone age.


Asunto(s)
Determinación de la Edad por el Esqueleto/métodos , Envejecimiento/fisiología , Desarrollo Óseo , Huesos del Carpo/anatomía & histología , Huesos de la Mano/anatomía & histología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Adolescente , Envejecimiento/patología , Huesos del Carpo/crecimiento & desarrollo , Niño , Preescolar , Estudios de Factibilidad , Femenino , Huesos de la Mano/crecimiento & desarrollo , Humanos , Masculino , Proyectos Piloto , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Método Simple Ciego
15.
PLoS One ; 19(3): e0300888, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38512830

RESUMEN

Neuronal death could be responsible for the cognitive impairments found in astronauts exposed to spaceflight, highlighting the need to identify potential countermeasures to ensure neuronal health in microgravity conditions. Therefore, differentiated HT22 cells were exposed to simulated microgravity by random positioning machine (RPM) for 48 h, treating them with a single administration of Trolox, recombinant irisin (r-Irisin) or both. Particularly, we investigated cell viability by MTS assay, Trypan Blue staining and western blotting analysis for Akt and B-cell lymphoma 2 (Bcl-2), the intracellular increase of reactive oxygen species (ROS) by fluorescent probe and NADPH oxidase 4 (NOX4) expression, as well as the expression of brain-derived neurotrophic factor (BDNF), a major neurotrophin responsible for neurogenesis and synaptic plasticity. Although both Trolox and r-Irisin manifested a protective effect on neuronal health, the combined treatment produced the best results, with significant improvement in all parameters examined. In conclusion, further studies are needed to evaluate the potential of such combination treatment in counteracting weightlessness-induced neuronal death, as well as to identify other potential strategies to safeguard the health of astronauts exposed to spaceflight.


Asunto(s)
Cromanos , Fibronectinas , Ingravidez , Fibronectinas/farmacología , Fibronectinas/metabolismo , Neuronas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Diferenciación Celular
16.
Life (Basel) ; 13(7)2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37511798

RESUMEN

Space colonization represents the most insidious challenge for mankind, as numerous obstacles affect the success of space missions. Specifically, the absence of gravitational forces leads to systemic physiological alterations, with particular emphasis on the musculoskeletal system. Indeed, astronauts exposed to spaceflight are known to report a significant impairment of bone microarchitecture and muscle mass, conditions clinically defined as osteoporosis and sarcopenia. In this context, space medicine assumes a crucial position, as the development of strategies to prevent and/or counteract weightlessness-induced alterations appears to be necessary. Furthermore, the opportunity to study the biological effects induced by weightlessness could provide valuable information regarding adaptations to spaceflight and suggest potential treatments that can preserve musculoskeletal health under microgravity conditions. Noteworthy, improving knowledge about the latest scientific findings in this field of research is crucial, as is thoroughly investigating the mechanisms underlying biological adaptations to microgravity and searching for innovative solutions to counter spaceflight-induced damage. Therefore, this narrative study review, performed using the MEDLINE and Google Scholar databases, aims to summarize the most recent evidence regarding the effects of real and simulated microgravity on the musculoskeletal system and to discuss the effectiveness of the main defence strategies used in both real and experimental settings.

17.
Front Physiol ; 14: 1107933, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37008023

RESUMEN

Spaceflight exposure, like prolonged skeletal unloading, is known to result in significant bone loss, but the molecular mechanisms responsible are still partly unknown. This impairment, characterizing both conditions, suggests the possibility of identifying common signalling pathways and developing innovative treatment strategies to counteract the bone loss typical of astronauts and osteoporotic patients. In this context, primary cell cultures of human osteoblasts derived from healthy subjects and osteoporotic patients were exposed to random positioning machine (RPM) to reproduce the absence of gravity and to exacerbate the pathological condition, respectively. The duration of exposure to RPM was 3 or 6 days, with the aim of determining whether a single administration of recombinant irisin (r-irisin) could prevent cell death and mineralizing capacity loss. In detail, cellular responses were assessed both in terms of death/survival, by MTS assay, analysis of oxidative stress and caspase activity, as well as the expression of survival and cell death proteins, and in terms of mineralizing capacity, by investigating the pentraxin 3 (PTX3) expression. Our results suggest that the effects of a single dose of r-irisin are maintained for a limited time, as demonstrated by complete protection after 3 days of RPM exposure and only partial protection when RPM exposure was for a longer time. Therefore, the use of r-irisin could be a valid strategy to counteract the bone mass loss induced by weightlessness and osteoporosis. Further studies are needed to determine an optimal treatment strategy based on the use of r-irisin that is fully protective even over very long periods of exposure and/or to identify further approaches to be used in a complementary manner.

18.
J Magn Reson Imaging ; 36(1): 183-7, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22359281

RESUMEN

PURPOSE: To correlate the clinical presentation of adult celiac disease with various intestinal fold patterns using MR-enterography. MATERIALS AND METHODS: Fifty-four consecutive adult celiac patients (34 female, 20 male, 18 to 62 years) were studied by MR-enterography. Two radiologists blinded to the patients' clinical history evaluated in consensus MR studies, classifying the intestinal fold pattern into four categories: (a) no fold abnormalities, (b) isolated loss of folds in the duodenum, (c) jejunization of ileum, and (d) jejuno-ileal fold pattern reversal. Patients presented with the varying clinical forms of Celiac disease, classified as: (i) typical disease, (ii) atypical disease, and (iii) silent form. RESULTS: Twenty-three patients showed no intestinal fold abnormalities; 11 patients had isolated loss of duodenal folds; 9 patients showed jejunization of ileum and 11 had jejuno-ileal fold pattern reversal. 18/23 (78%) patients with MRI normal fold pattern had the silent clinical form of Celiac disease (Sensitivity 78%; specificity 100%; PPV = 1, NPV = 0.78); 9/11 (82%) patients with the isolated loss of duodenal folds had the atypical clinical form (sensitivity 82%; and specificity 100%; PPV = 1; NPV = 0.82). All 20 patients with the jejunization of ileum and jejuno-ileal fold pattern reversal had typical celiac disease (sensitivity and specificity of 100%; PPV and NPV = 1). CONCLUSION: MR-enterography findings in patients with celiac disease, demonstrates good correlation between MR findings and clinical severity.


Asunto(s)
Enfermedad Celíaca/patología , Intestinos/patología , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como Asunto , Adulto Joven
19.
Eur Radiol ; 22(11): 2465-77, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22926159

RESUMEN

OBJECTIVES: To prospectively compare paediatric patients (PP) and adult patients (AP) affected by Crohn's disease (CD) in terms of the location and activity of intestinal lesions. METHODS: Forty-three children (mean age 15 years) and 43 adults (mean age 48 years) with proven CD underwent magnetic resonance enterography (MRE) to localise lesions and detect their activity in 9 segments of the small and large bowel. The results were analysed on a per patient and per segment basis. Ileo-colonoscopy was performed in all patients. P values less than 0.05 were considered statistically significant. RESULTS: Involvement of terminal ileum was significantly different in the two groups: observed in 100 % of AP (43/43) versus 58 % (23/43) of PP (P < 0.0001). Conversely, the colon was diseased in 84 % of PP versus 64 % of AP. In particular, left colonic segments were significantly more involved in PP (descending colon 53 % versus 21 %, P < 0.01; rectum 67 % versus 23 %, P < 0.0001; sigmoid colon 56 % versus 37 %, not significant), whereas caecal involvement was equal in both groups. In children the maximal disease activity was found in left colonic segments, whereas in adults it was in the terminal ileum. CONCLUSIONS: MRE detected significant differences between the two populations, showing a more extensive and severe involvement of the left colon in children but the distal ileum in adults. KEY POINTS : • MRI is useful for assessing Crohn's disease in adult and paediatric patients. • Adult and paediatric patients show different intestinal involvement on MRI. • The distal ileum is maximally involved in adults vs. the left colon in children. • The causes of the severe left colonic disease in children are unknown. • The extensive colonic involvement in children has clinical-diagnostic implications.


Asunto(s)
Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/diagnóstico , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Colon/fisiopatología , Femenino , Humanos , Íleon/fisiopatología , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Radiografía , Reproducibilidad de los Resultados
20.
J Perinat Med ; 40(4): 419-26, 2012 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-22752774

RESUMEN

OBJECTIVE: The purpose of this study is to define the role of foetal magnetic resonance imaging (MRI) in evaluating cerebral ischaemic-haemorrhagic lesions and the extension of parenchymal injuries. STUDY DESIGN: From September 2006 to September 2010, 271 foetal MRI have been performed on cases referred to us for ultrasound suspect of brain abnormalities or cytomegalovirus infection and Toxoplasma serum conversion. Foetal MRI was performed with a 1.5-T magnet system without mother sedation. RESULTS: Foetal MRI detected ischaemic-haemorrhagic lesions in 14 of 271 foetuses, consisting of 5% incidence. MRI confirmed the diagnosis in three of 14 cases with ultrasonography (US) suspect of ischaemic-haemorrhagic lesions associated with ventriculomegaly. In one of 14 cases with US findings of cerebellar haemorrhage, MRI confirmed the diagnosis and provided additional information regarding the parenchymal ischaemic injury. In eight of 14 cases with US suspect of ventriculomegaly (3), corpus callosum agenesis (2), hypoplasia of cerebellar vermis (1), holoprosencephaly (1) and spina bifida (1), MRI detected ischaemic and haemorrhagic lesions unidentified at US examination. In two of 14 foetuses with US suspect of intracerebral space-occupying lesion, MRI modified the diagnosis to extra-axial haematoma associated with dural sinus malformation. Results were compared with post-mortem findings or afterbirth imaging follow-up. CONCLUSIONS: Foetal MRI is an additional imaging modality in the diagnosis of cerebral ischemic-haemorrhagic lesions, and it is useful in providing further information on the extension of the parenchymal injury and associated abnormalities, thus improving delivery management.


Asunto(s)
Isquemia Encefálica/embriología , Hemorragia Cerebral/embriología , Enfermedades Fetales/diagnóstico , Imagen por Resonancia Magnética , Diagnóstico Prenatal/métodos , Anomalías Múltiples , Adulto , Agenesia del Cuerpo Calloso/diagnóstico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patología , Enfermedades Cerebelosas/diagnóstico , Cerebelo/anomalías , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/patología , Infecciones por Citomegalovirus/diagnóstico , Anomalías del Ojo/diagnóstico , Femenino , Enfermedades Fetales/patología , Edad Gestacional , Holoprosencefalia/diagnóstico , Humanos , Enfermedades Renales Quísticas/diagnóstico , Embarazo , Retina/anomalías , Disrafia Espinal/diagnóstico
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