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1.
Urol Oncol ; 42(1): 24.e1-24.e8, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38052712

RESUMO

BACKGROUND: Testicular cancer (TC) survivors cured with chemotherapy (CT) are prone to develop cardiovascular diseases, as part of an accelerated aging phenotype. A mechanism contributing to these events can be telomere shortening. PATIENTS AND METHODS: In a prospective cohort of patients with disseminated TC who received cisplatin-based CT, mean absolute leukocyte telomere length (TL) was measured before and 1 year after start of treatment. Cardiovascular risk factors, including development of the metabolic syndrome and hypogonadism, were assessed before and up to 5 years after CT. RESULTS: For the whole group (n = 55), TL did not change 1 year after CT (5.7 (2.2-13.4) vs. 5.8 kb (1.6-19.2), P = 0.335). At baseline, patients with a BMI >30 kg/m2 (n = 12) had shorter TL (4.9 (2.2-13.4) vs. 6.3 kb (3.1-12.9), P = 0.045), while no age-dependent differences were measured. Patients with TL shortening after 1 year (n = 7) showed a significant increase in diastolic blood pressure (P = 0.007) and triglycerides (P = 0.003), compared to those with unchanged TL. There was no association between telomere shortening after 1 year or short TL at baseline (n = 7+11) and development of metabolic syndrome (25% vs. 21%; P = 0.777), or hypogonadism (38% vs. 17%; P = 0.120) after 5 years. CONCLUSIONS: A small subset of TC patients treated with cisplatin-based CT showed telomere shortening 1 year after treatment. This shortening was associated to a rise in diastolic blood pressure and triglycerides, but not to newly developed metabolic syndrome and hypogonadism after 5 years.


Assuntos
Doenças Cardiovasculares , Hipogonadismo , Síndrome Metabólica , Neoplasias Testiculares , Masculino , Humanos , Doenças Cardiovasculares/genética , Síndrome Metabólica/complicações , Síndrome Metabólica/genética , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/genética , Estudos Prospectivos , Cisplatino/efeitos adversos , Fatores de Risco , Encurtamento do Telômero , Fatores de Risco de Doenças Cardíacas , Triglicerídeos , Sobreviventes , Telômero/genética , Hipogonadismo/complicações , Hipogonadismo/genética
2.
Ageing Res Rev ; 93: 102141, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38030088

RESUMO

Cellular senescence is a state of terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory phenotype. In the brain, senescent cells naturally accumulate during aging and at sites of age-related pathologies. Here, we discuss the recent advances in understanding the accumulation of senescent cells in brain aging and disorders. Here we highlight the phenotypical heterogeneity of different senescent brain cell types, highlighting the potential importance of subtype-specific features for physiology and pathology. We provide a comprehensive overview of various senescent cell types in naturally occurring aging and the most common neurodegenerative disorders. Finally, we critically discuss the potential of adapting senotherapeutics to improve brain health and reduce pathological progression, addressing limitations and future directions for application and development.


Assuntos
Envelhecimento , Doenças Neurodegenerativas , Humanos , Envelhecimento/fisiologia , Senescência Celular/fisiologia , Encéfalo/fisiologia , Pontos de Checagem do Ciclo Celular
3.
Radiother Oncol ; 190: 109984, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37926332

RESUMO

BACKGROUND & AIM: Irradiation of the salivary glands during head and neck cancer treatment induces cellular senescence in response to DNA damage and contributes to radiation-induced hyposalivation by affecting the salivary gland stem/progenitor cell (SGSC) niche. Cellular senescence, such as that induced by radiation, is a state of cell-cycle arrest, accompanied by an altered pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP) with potential detrimental effects on the surrounding microenvironment. We hypothesized that the pro-regenerative properties of mesenchymal stem cells (MSCs) may attenuate cellular senescence post-irradiation. Therefore, here we evaluated the effects of adipose-derived MSCs (ADSCs) on the radiation-induced response of salivary gland organoids (SGOs). METHODS: Proteomic analyses to identify soluble mediators released by ADSCs co-cultured with SGOS revealed secretion of hepatocyte growth factor (HGF) in ADSCs, suggesting a possible role in the stem cell crosstalk. Next, the effect of recombinant HGF in the culture media of ex vivo grown salivary gland cells was tested in 2D monolayers and 3D organoid models. RESULTS: Treatment with HGF robustly increased salivary gland cell proliferation. Importantly, HGF supplementation post-irradiation enhanced proliferation at lower doses of radiation (0, 3, 7 Gy), but not at higher doses (10, 14 Gy) where most cells stained positive for senescence-associated beta-galactosidase. Furthermore, HGF had no effect on the senescence-associated secretory phenotype (SASP) of irradiated SGOs, suggesting there may be compensatory proliferation by cell-division competent cells instead of a reversal of cellular senescence after irradiation. CONCLUSION: ADSCs may positively influence radiation recovery through HGF secretion and can promote the ex vivo expansion of salivary gland stem/progenitor cells to enhance the effects of co-transplanted SGSC.


Assuntos
Fator de Crescimento de Hepatócito , Células-Tronco Mesenquimais , Humanos , Fator de Crescimento de Hepatócito/farmacologia , Proteômica , Glândulas Salivares , Senescência Celular/efeitos da radiação , Proliferação de Células
4.
Aging Cell ; 22(12): e14011, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37969056

RESUMO

Accurate biomarkers for predicting COVID-19 severity have remained an unmet need due to an incomplete understanding of virus pathogenesis and heterogeneity among patients. Cellular senescence and its pro-inflammatory phenotype are suggested to be a consequence of SARS-CoV-2 infection and potentially drive infection-dependent pathological sequelae. Senescence-associated markers in infected individuals have been identified primarily in the lower respiratory tract, while little is known about their presence in more easily accessible bio-specimens. Here, we measured the abundance of senescence-associated signatures in whole blood, plasma and peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and patients without an infection. Bulk transcriptomic and targeted proteomic assays revealed that the level of senescence-associated markers, including the senescence-associated secretory phenotype (SASP), is predictive of SARS-CoV-2 infection. Single-cell RNA-sequencing data demonstrated that a senescence signature is particularly enriched in monocytes of COVID-19 patients, partially correlating with disease severity. Our findings suggest that monocytes are prematurely induced to senescence by SARS-CoV-2 infection, might contribute to exacerbating a SASP-like inflammatory response and can serve as markers and predictors for COVID-19 and its sequelae.


Assuntos
COVID-19 , Monócitos , Humanos , Leucócitos Mononucleares , Proteômica , SARS-CoV-2 , Progressão da Doença
5.
Int J Environ Health Res ; 32(5): 1164-1174, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33249915

RESUMO

This study is part of the health surveillance system set up with the construction of a waste-to-energy (WTE) plant in Turin (Italy). Circulatory and respiratory diseases in emergency room (ER) accesses and first hospital admissions were considered. Main concerns of population living in the area near WTE were to know whether single and repeated peaks in emissions would correspond to adverse health effects. We tackle this issue using spatio-temporal analyses, comparing an exposed group (EXP) living near the WTE with a reference group (NOEXP). Age-standardized rates of ER accesses between EXP and NOEXP were temporally compared, testing whether there have been significantly different changes over time. We also examined the relationship between emission peaks and ER accesses in the following days. Finally, with time-series analysis, we investigated variations in ER accesses and pollutants before and after WTE start-up. No significant relationship has been found for the outcome considered.


Assuntos
Poluentes Ambientais , Incineração , Serviço Hospitalar de Emergência , Hospitais , Itália
6.
Nat Protoc ; 16(5): 2471-2498, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33911261

RESUMO

The development of genetic tools allowed for the validation of the pro-aging and pro-disease functions of senescent cells in vivo. These discoveries prompted the development of senotherapies-pharmaceutical interventions aimed at interfering with the detrimental effect of senescent cells-that are now entering the clinical stage. However, unequivocal identification and examination of cellular senescence remains highly difficult because of the lack of universal and specific markers. Here, to overcome the limitation of measuring individual markers, we describe a detailed two-phase algorithmic assessment to quantify various senescence-associated parameters in the same specimen. In the first phase, we combine the measurement of lysosomal and proliferative features with the expression of general senescence-associated genes to validate the presence of senescent cells. In the second phase we measure the levels of pro-inflammatory markers for specification of the type of senescence. The protocol can help graduate-level basic scientists to improve the characterization of senescence-associated phenotypes and the identification of specific senescent subtypes. Moreover, it can serve as an important tool for the clinical validation of the role of senescent cells and the effectiveness of anti-senescence therapies.


Assuntos
Algoritmos , Senescência Celular , Técnicas Citológicas/métodos , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo
7.
Ageing Res Rev ; 67: 101267, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33556549

RESUMO

Aging is characterized by a progressive loss of tissue integrity and functionality due to disrupted homeostasis. Molecular oxygen is pivotal to maintain tissue functions, and aerobic species have evolved a sophisticated sensing system to ensure proper oxygen supply and demand. It is not surprising that aberrations in oxygen and oxygen-associated pathways subvert health and promote different aspects of aging. In this review, we discuss emerging findings on how oxygen-sensing mechanisms regulate different cellular and molecular processes during normal physiology, and how dysregulation of oxygen availability lead to disease and aging. We describe various clinical manifestations associated with deregulation of oxygen balance, and how oxygen-modulating therapies and natural oxygen oscillations influence longevity. We conclude by discussing how a better understanding of oxygen-related mechanisms that orchestrate aging processes may lead to the development of new therapeutic strategies to extend healthy aging.


Assuntos
Longevidade , Oxigênio , Senescência Celular , Fenótipo , Espécies Reativas de Oxigênio
8.
Trends Cell Biol ; 30(10): 777-791, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32800659

RESUMO

Cellular senescence is a state of stable cell cycle arrest associated with macromolecular alterations and secretion of proinflammatory cytokines and molecules. From their initial discovery in the 1960s, senescent cells have been hypothesized as potential contributors to the age-associated loss of regenerative potential. Here, we discuss recent evidence that implicates cellular senescence as a central regulatory mechanism of the aging process. We provide a comprehensive overview of age-associated pathologies in which cellular senescence has been implicated. We describe mechanisms by which senescent cells drive aging and diseases, and we discuss updates on exploiting these mechanisms as therapeutic targets. Finally, we critically analyze the use of senotherapeutics and their translation to the clinic, highlighting limitations and suggesting ideas for future applications and developments.


Assuntos
Senescência Celular , Doença , Longevidade , Animais , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Modelos Biológicos
9.
Rev Esp Anestesiol Reanim (Engl Ed) ; 66(8): 425-433, 2019 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31477336

RESUMO

Target controlled infusion (TCI) of Propofol has been the subject of discussion during its 20 years of use, including the validity of the models that represent the course of the effect, such as: Are the different EEG indexes representative of the effect? Is the reactivity of the EEG index used to build models comparable to each other? What is the real reacting time of each monitor? Is the ke0 influenced by the infusion speed? Is the ke0 or the time to peak effect affected by age? How valid are the current Emax models? Are the induction and wakening simple mirror phenomenon as they are represented in the E max models? This review discusses issues related to the complexity and difficulty in obtaining a representation of the effect, and the lack of agreed definitions to be able to construct representative models of the temporary installation of the effect of Propofol for its use in TCI.


Assuntos
Anestésicos Intravenosos/farmacologia , Encéfalo/efeitos dos fármacos , Propofol/farmacologia , Fatores Etários , Algoritmos , Período de Recuperação da Anestesia , Anestésicos Intravenosos/administração & dosagem , Anestésicos Intravenosos/sangue , Anestésicos Intravenosos/farmacocinética , Animais , Artérias , Coleta de Amostras Sanguíneas , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/fisiologia , Ondas Encefálicas/efeitos dos fármacos , Estado de Consciência/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletroencefalografia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiologia , Infusões Intravenosas , Injeções Intravenosas , Modelos Neurológicos , Propofol/administração & dosagem , Propofol/farmacocinética , Ratos , Veias
10.
Environ Int ; 121(Pt 2): 1087-1097, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30366659

RESUMO

BACKGROUND: The LIFE MED HISS project aims at setting up a surveillance system on the long term effects of air pollution on health, using data from National Health Interview Surveys and other currently available sources of information in most European countries. Few studies assessed the long term effect of air pollution on hospital admissions in European cohorts. OBJECTIVE: The objective of this paper is to estimate the long term effect of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) on first-ever (incident) cause-specific hospitalizations in Italy. METHODS: We used data from the Italian Longitudinal Study (ILS), a cohort study based on the 1999-2000 National Health Interview Survey (NHIS), followed up for hospitalization (2001-2008) at individual level. The survey contains information on crucial potential confounders: occupational/educational/marital status, body mass index (BMI), smoking habit and physical activity. Annual mean exposure to PM2.5 and NO2 was assigned starting from simulated gridded data at spatial resolution of 4 × 4 km2 firstly integrated with data from monitoring stations and then up-scaled at municipality level. Statistical analyses were conducted using Cox proportional hazard models with robust variance estimator. RESULTS: For each cause of hospitalization we estimated the hazard ratios (HRs) adjusted for confounders with 95% Confidence Interval (CI) related to a 10 µg/m3 increase in pollutants. For PM2.5 and NO2, respectively, we found positive associations for circulatory system diseases [1.05(1.03-1.06); 1.05(1.03-1.07)], myocardial infarction [1.15(1.12-1.18); 1.15(1.12-1.18)], lung cancer [1.18(1.10-1.26); 1.20(1.12-1.28)], kidney cancer [1.24(1.11-1.29); 1.20(1.07-1.33)], all cancers (but lung) [1.06(1.04-1.08); 1.06(1.04-1.08)] and Low Respiratory Tract Infections (LRTI) [1.07 (1.04-1.11); 1.05 (1.02-1.08)]. DISCUSSION: Our results add new evidence on the effects of air pollution on first-ever (incident) hospitalizations, both in urban and rural areas. We demonstrated the feasibility of a low-cost monitoring system based on available data.


Assuntos
Poluição do Ar/análise , Hospitalização/estatística & dados numéricos , Exposição por Inalação/estatística & dados numéricos , Humanos , Itália/epidemiologia , Estudos Longitudinais
11.
Q J R Meteorol Soc ; 144(Suppl Suppl 1): 16-26, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30774158

RESUMO

The Time-Resolved Observations of Precipitation structure and storm Intensity with a Constellation of Smallsats (TROPICS) mission was selected by NASA as part of the Earth Venture-Instrument (EVI-3) program. The overarching goal for TROPICS is to provide nearly all-weather observations of 3D temperature and humidity, as well as cloud ice and precipitation horizontal structure, at high temporal resolution to conduct high-value science investigations of tropical cyclones. TROPICS will provide rapid-refresh microwave measurements (median refresh rate better than 60 min for the baseline mission) which can be used to observe the thermodynamics of the troposphere and precipitation structure for storm systems at the mesoscale and synoptic scale over the entire storm life cycle. TROPICS comprises six CubeSats in three low-Earth orbital planes. Each CubeSat will host a high-performance radiometer to provide temperature profiles using seven channels near the 118.75 GHz oxygen absorption line, water vapour profiles using three channels near the 183 GHz water vapour absorption line, imagery in a single channel near 90 GHz for precipitation measurements (when combined with higher-resolution water vapour channels), and a single channel near 205 GHz which is more sensitive to precipitation-sized ice particles. This observing system offers an unprecedented combination of horizontal and temporal resolution to measure environmental and inner-core conditions for tropical cyclones on a nearly global scale and is a major leap forward in the temporal resolution of several key parameters needed for assimilation into advanced data assimilation systems capable of utilizing rapid-update radiance or retrieval data. Launch readiness is currently projected for late 2019.

12.
Rev. salud pública (Córdoba) ; 19(3): 21-31, 2015. tab, graf
Artigo em Espanhol | LILACS | ID: lil-788703

RESUMO

Objetivo: Determinar el estado de vacunación de losprofesionales y técnicos del equipo de salud de hospitalesestatales de la provincia de Córdoba respecto de lasvacunas contra la hepatitis B, la triple o doble viral, ladoble bacteriana y antiinfluenza. Métodos: Se realizóun estudio de corte transversal, sobre una muestra de844 trabajadores de hospitales públicos pertenecientesal ministerio de salud de la provincia de Córdoba,durante los años 2013 y 2014. Se aplicó un cuestionarioauto-administrado y se realizaron análisis univariadosy bivariados. Para la evaluación de factores asociadoscon la vacunación se aplicó el estadístico chi cuadrado,definiéndose un margen de error del 5% (p < 0,05)y un intervalo de confianza del 95%. Resultados: Laproporción de profesionales y técnicos con coberturasfueron: doble bacteriana 87,2%, anti hepatitis B 77,6% triple o doble viral 69,0% y antiinfluenza el 55,2%. En todas se encontró un mejor estadode vacunación entre quienes poseen mayor educación, menor antigüedad, los más jóvenes,con diferencias significativas según sexo a hepatitis B, y con menos antigüedad en la dobleviral. Conclusión: Los trabajadores estudiados poseen un estado de vacunación inferior alrecomendado internacionalmente, sin embargo resultó similar o superior al reportado endiversos países, poniendo de manifiesto que la sub-cobertura de vacunación en el personalsanitario es una problemática extendida, que debe ser priorizada por las autoridades, dadaslas implicancias para el propio trabajador y la población que atienden.


Objective: To determine the immunization status of health professionals and techniciansbelonging to the health team from state hospitals of the province of Cordoba regardingHepatitis B vaccine; Measles and Rubella vaccine; Measles, Mumps and Rubella Vaccine(MMR); Diphtheria and Tetanus vaccine (DT); and influenza (flu) vaccine. Methods:A cross sectional study was carried out on a sample of 844 workers from public hospitalsbelonging to the Ministry of Health of the province of Cordoba during the years 2013 and2014. A self administered questionnaire was used and univariate analysis and bivariateanalysis were done. For the assessment of factors associated with vaccination, chi squarestatistics was applied; a 5% margin of error was defined (p < 0.05) and a confidence intervalof 95 %. Results: The proportion of professionals and technicians with coverage was:Diphtheria and Tetanus Vaccine (DT) 87.2%, Hepatitis B vaccine 77.6%, MMR vaccineor Measles and Rubella vaccine 69.0% and influenza vaccine 55.2%. Better immunizationstatus was found among those with higher education, less seniority, and younger agewith significant differences regarding sex in hepatitis B and less seniority in Measles andRubella vaccine. Conclusion: The workers studied present an immunization status belowthe one internationally recommended. However, it is similar or higher to the level reportedin different countries, showing that the under-coverage of health professionals is an outspreadproblem that must be prioritized by the authorities, given the implications for theworkers themselves and the population they assist.


Escopo: Determinar o estado de vacinação de profissionais e técnicos da equipe de saú-de de hospitais públicos na província de Córdoba respeito de vacinas contra a hepatite B, adupla ou tríplice viral, a dupla bacteriana e a anti-gripal. Métodos: Um estudo transversalem uma amostra de 844 trabalhadores de hospitais públicos pertencentes ao Ministério daSaúde da província de Córdoba foi realizado durante os anos de 2013 e 2014.Empregou-se um questionário auto-administrado e foram realizadas análises univariadase bivariadas. Para avaliar os fatores associados à vacinação aplicou-se o chi-quadradoestatístico, definindo-se uma margem de erro de 5% (p < 0,05) e um intervalo de confiançade 95%. Resultados: A proporção de profissionais e técnicos com coberturas foia seguinte: duplo bacteriana 87,2%, anti hepatite B 77,6%, tríplice ou dupla 69,0% eanti-gripal 55,2%. Em todas foi encontrado um melhor estado de vacinação entre aquelescom maiores estudos, menor antiguidade, os mais jovens, com diferenças significativas deacordo com o sexo para a hepatite B, e com menos antiguidade na dupla viral. Conclusão:Os trabalhadores estudados têm um estado de vacinação inferior ao recomendado internacionalmente, porém, foi semelhante ou superior ao registrado em vários países, mostrandoque a insuficiente cobertura de-vacinação em profissionais de saúde é um problema generalizadoque deve ser priorizado pelas autoridades dadas as implicações para o trabalhadore para a população que ele serve.


Assuntos
Humanos , Masculino , Feminino , Médicos , Programas de Imunização/estatística & dados numéricos , Programas de Imunização/organização & administração , Saúde Ocupacional , Vacinas
13.
Cell Death Dis ; 4: e727, 2013 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-23868060

RESUMO

Senescence is a cellular response to damage and stress. The senescence response prevents cancer by suppressing the proliferation of cells with a compromised genome and contributes to optimal wound healing in normal tissues. Persistent senescent cells are also thought to drive aging and age-associated pathologies through their secretion of inflammatory factors that modify the tissue microenvironment and alter the function of nearby normal or transformed cells. Understanding how senescent cells alter the microenvironment would be aided by the ability to induce or eliminate senescent cells at will in vivo. Here, we combine the use of the synthetic nucleoside analog ganciclovir (GCV) with herpes simplex virus thymidine kinase (HSVtk) activity to create or eliminate senescent human cells. We show that low concentrations of GCV induce senescence through the accumulation of nuclear DNA damage while higher concentrations of GCV, similar to those used in vivo, kill non-dividing senescent cells via mitochondrial DNA (mtDNA) damage and caspase-dependent apoptosis. Using this system, we effectively eliminated xenografted normal human senescent fibroblasts or induced senescence in human breast cancer cells in vivo. Thus, cellular senescence and mtDNA damage are outcomes of synthetic nucleoside analog treatment, indicating that the GCV-HSVtk combination can be used effectively to promote the targeted formation or eradication of senescent cells.


Assuntos
Apoptose , Senescência Celular , Dano ao DNA , DNA Mitocondrial/genética , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Fibroblastos/transplante , Ganciclovir/administração & dosagem , Ganciclovir/farmacologia , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Nus , Simplexvirus/enzimologia , Timidina Quinase/biossíntese , Timidina Quinase/genética , Proteínas Virais/biossíntese , Proteínas Virais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Intern Med ; 273(5): 429-36, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23600398

RESUMO

Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder.


Assuntos
Envelhecimento , Senescência Celular , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Neuroglia , Doença de Parkinson/etiologia , Doença de Parkinson/patologia , Humanos , Mediadores da Inflamação/metabolismo , Neuroglia/patologia , Doença de Parkinson/metabolismo , Fenótipo , Transdução de Sinais , Fatores de Tempo
15.
Cell Death Differ ; 19(8): 1390-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22402588

RESUMO

The transcription factor signal transducer and activator of transcription 3 (STAT3) acts downstream of many pro-oncogenic signals, including cytokines, growth factors and oncogenes, and is accordingly constitutively active in a wide variety of tumors that often become addicted to it. Moreover, STAT3 is a key player in mediating inflammation-driven tumorigenesis, where its aberrant continuous activation is typically triggered by local or systemic production of the pro-inflammatory cytokine IL-6. We recently showed that mouse embryonic fibroblasts (MEFs) derived from STAT3C k/in mice, which express physiological levels of the constitutively active mutant STAT3C, display features of transformed cells such as increased proliferation, resistance to apoptosis and senescence, and aerobic glycolysis. Here, we show that pre-existing constitutively active STAT3 is sufficient to prime primary MEFs for malignant transformation upon spontaneous immortalization. Transformation is strictly STAT3-dependent and correlates with high resistance to apoptosis and enhanced expression of anti-apoptotic/pro-survival genes. Additionally, hypoxia inducible factor (HIF)-1α level is elevated by twofold and contributes to STAT3 oncogenic activity by supporting high rates of aerobic glycolysis. Thus, constitutively active STAT3, an accepted essential factor for tumor growth/progression, can also act as a first hit in multistep carcinogenesis; this ability to predispose cells to malignant transformation may be particularly relevant in the pro-oncogenic niche represented by chronically inflamed tissues.


Assuntos
Transformação Celular Neoplásica/patologia , Fibroblastos/citologia , Fator de Transcrição STAT3/metabolismo , Células 3T3 , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Progressão da Doença , Feminino , Fibroblastos/metabolismo , Camundongos , Camundongos Transgênicos , Fator de Transcrição STAT3/genética , Transdução de Sinais
16.
Nutr Metab Cardiovasc Dis ; 22(8): 684-90, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21907553

RESUMO

BACKGROUND AND AIMS: We compared direct costs of diabetic and non diabetic people covered by the Italian National Health System, focusing on the influence of age, sex, type of diabetes and treatment. METHODS AND RESULTS: Diabetic people living in Turin were identified through the Regional Diabetes Registry and the files of hospital discharges and prescriptions. Data sources were linked to the administrative databases to assess health care services used by diabetic (n = 33,792) and non diabetic people(n = 863,123). Data were analyzed with the two-part model; the estimated direct costs per person/year were €3660.8 in diabetic people and €895.6 in non diabetic people, giving a cost ratio of 4.1. Diabetes accounted for 11.4% of total health care expenditure. The costs were attributed to hospitalizations (57.2%), drugs (25.6%), to outpatient care (11.9%), consumable goods (4.4%) and emergency care (0.9%). Estimated costs increased from € 2670.8 in diabetic people aged <45 years to € 3724.1 in those aged >74 years, the latter representing two third of the diabetic cohort; corresponding figures in non diabetic people were € 371.6 and € 2155.9. In all expenditure categories cost ratios of diabetic vs non diabetic people were higher in people aged <45 years, in type 1 diabetes and in insulin-treated type 2 diabetes. CONCLUSION: Direct costs are 4-fold higher in diabetic than in non diabetic people, mainly due to care of the elderly and inpatient care. In developed countries, demographic changes will have a profound impact on costs for diabetes in next years.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/economia , Custos de Cuidados de Saúde , Gastos em Saúde , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Adulto , Fatores Etários , Idoso , Assistência Ambulatorial/economia , Diabetes Mellitus/epidemiologia , Custos de Medicamentos , Prescrições de Medicamentos , Serviços Médicos de Emergência/economia , Feminino , Hospitalização/economia , Humanos , Itália/epidemiologia , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Modelos Econômicos , Alta do Paciente , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento
17.
Epidemiol Prev ; 35(5-6 Suppl 4): 181-4, 2011.
Artigo em Italiano | MEDLINE | ID: mdl-22166299

RESUMO

In Italy, complete municipality-level data on specific-cause mortality have been available at central level since 1980; Italy's National Institute of Statistics (Istat) collects data from all municipalities using two sources: i) the Office of Vital Statistics; and ii) the Civil Status Office. The Office of Vital Statistics records data on events such as births, deaths and migration for the population with official residence in the municipality, with the aim of describing the resident population's structure and composition. The Civil Status Office records data on the demographic dynamics (not only marital status but also causes of death); the data refer to the population living in the municipality, independently of official residence. Changes in the status of a municipality (e.g., the creation of a new municipality or the unification of diverse municipalities) are often not recorded simultaneously by these two offices, so that the data do not correspond.


Assuntos
Poluição Ambiental/efeitos adversos , Resíduos Industriais/efeitos adversos , Mortalidade , Vigilância da População/métodos , Saúde da População Urbana/estatística & dados numéricos , Coleta de Dados , Documentação/normas , Exposição Ambiental , Poluição Ambiental/estatística & dados numéricos , Feminino , Controle de Formulários e Registros , Substâncias Perigosas/efeitos adversos , Resíduos Perigosos/efeitos adversos , Resíduos Perigosos/estatística & dados numéricos , Humanos , Resíduos Industriais/estatística & dados numéricos , Itália/epidemiologia , Masculino , Reprodutibilidade dos Testes , População Urbana/estatística & dados numéricos , Estatísticas Vitais
18.
J Epidemiol Community Health ; 62(3): 209-15, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18272735

RESUMO

BACKGROUND: Several studies have identified strong effects of high temperatures on mortality at population level; however, individual vulnerability factors associated with heat-related in-hospital mortality are largely unknown. The objective of the study was to evaluate heat-related in-hospital mortality using a multi-city case-crossover analysis. METHODS: We studied residents of four Italian cities, aged 65+ years, who died during 1997-2004. For 94,944 individuals who died in hospital and were hospitalised two or more days before death, demographics, chronic conditions, primary diagnoses of last event and hospital wards were considered. A city-specific case-crossover analysis was performed to evaluate the association between apparent temperature and mortality. Pooled odds ratios (OR) of dying on a day with a temperature of 30 degrees C compared to a day with a temperature of 20 degrees C were estimated with a random-effects meta-analysis. RESULTS: We estimated an overall OR of 1.32 (95% confidence interval: 1.25, 1.39). Age, marital status and hospital ward were important risk indicators. Patients in general medicine were at higher risk than those in high and intensive care units. A history of psychiatric disorders and cerebrovascular diseases gave a higher vulnerability. Mortality was greater among patients hospitalised for heart failure, stroke and chronic pulmonary diseases. CONCLUSIONS: In-hospital mortality is strongly associated with high temperatures. A comfortable temperature in hospitals and increased attention to vulnerable patients during heatwaves, especially in general medicine, are necessary preventive measures.


Assuntos
Mortalidade Hospitalar , Temperatura Alta/efeitos adversos , Saúde da População Urbana/estatística & dados numéricos , Idoso , Métodos Epidemiológicos , Feminino , Hospitalização , Humanos , Itália/epidemiologia , Masculino , Temperatura
19.
Int J Biometeorol ; 52(4): 301-10, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18030502

RESUMO

A variety of ambient exposure indicators have been used to evaluate the impact of high temperature on mortality and in the identification of susceptible population sub-groups, but no study has evaluated how airport and city centre temperatures differ in their association with mortality during summer. This study considers the differences in temperatures measured at the airport and in the city centre of three Italian cities (Milan, Rome and Turin) and investigates the impact of these measures on daily mortality. The case-crossover design was applied to evaluate the association between daily mean apparent temperature (MAT) and daily total mortality. The analysis was conducted for the entire population and for subgroups defined by demographic characteristics, socioeconomic status and chronic comorbidity (based on hospitalisation during the preceding 2 years). The percentage risk of dying, with 95% confidence intervals (95% CI), on a day with MAT at the 95th percentile with respect to the 25th percentile of the June-September daily distribution was estimated. Airport and city-centre temperature distributions, which vary among cities and between stations, have a heterogeneous impact on mortality. Milan was the city with the greatest differences in mean MAT between airport and city stations, and the overall risk of dying was greater when airport MAT (+47% increase, 95%CI 38-57) was considered in comparison to city MAT (+37% increase, 95%CI 30-45). In Rome and Turin, the results were very similar for both apparent temperature measures. In all cities, the elderly, women and subjects with previous psychiatric conditions, depression, heart and circulation disorders and cerebrovascular disease were at higher risk of dying during hot days, and the degree of effect modification was similar using airport or city-centre MAT. Studies on the impact of meteorological variables on mortality, or other health indicators, need to account for the possible differences between airport and city centre meteorological variables in order to give more accurate estimates of health effects.


Assuntos
Clima , Mortalidade , Adulto , Idoso , Estudos de Casos e Controles , Estudos Cross-Over , Feminino , Temperatura Alta , Humanos , Itália/epidemiologia , Masculino , Conceitos Meteorológicos , Pessoa de Meia-Idade , Mortalidade/tendências , Saúde da População Urbana
20.
Med Lav ; 98(4): 320-30, 2007.
Artigo em Italiano | MEDLINE | ID: mdl-17679345

RESUMO

BACKGROUND: Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy of the upper extremities. Despite CTS being a priority for public health, only a few studies have investigated the prevalence and incidence in the general population. In Italy, administrative data are available only for CTS cases which were judged work-related by the Workers Compensation Board. These data indicate a steady increase in CTS over the last decade. Hospital admission archives (SDO) also contain information on CTS patients who underwent surgery. OBJECTIVES: To determine: 1) the incidence and prevalence of first CTS, based on hospital records of patients who underwent surgery in the Piedmont Region; 2) to describe the geographical and temporal variation. METHODS: Crude and standardized incidence rates of CTS were computed for the period 2002-2003; geographical variation was assessed using bayesan estimators to detect spatial clusters. Crude and standardized prevalence rates of first hospitalization were calculated for every two-year period between 1996 and 2003. RESULTS AND CONCLUSIONS: The crude incidence rate was 227.2 (C.I.95% 221.9-232.7) per 100,000 women and 54.4 (C.I. 95% 51.9-57.1) per 100,000 men. The prevalence of first hospitalization was very high and varied widely by geographic area. Two possible explanations for such wide variation between areas include differences in exposure to risk factors for CTS and in the diagnostic criteria used. The increasing prevalence over time was only partly explained by an increase in work-related cases. The development of standardized diagnostic criteria would improve understanding of the effect of workplace exposures on CTS. The number of new cases per year in Piedmont was estimated at 1,500, much higher than the compensation claims related to CTS. Health education campaigns addressed to general practitioners on compensation law could improve reporting to the workers' compensation board.


Assuntos
Síndrome do Túnel Carpal/epidemiologia , Adolescente , Adulto , Síndrome do Túnel Carpal/cirurgia , Feminino , Registros Hospitalares , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência
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