Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 300
Filtrar
1.
Vet Res Commun ; 48(3): 1941-1947, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38499909

RESUMO

The aim of this study was to molecularly investigate the presence of antimicrobial resistance genes (ARGs) in organ samples from 11 Apennine wolves (Canis lupus italicus) collected in Central Italy. Samples from lung, liver, spleen, kidney, tongue and intestine were investigated by PCRs targeting the following genes: tet(A), tet(B), tet(C), tet(D), tet(E), tet(G), tet(K), tet(L), tet(M), tet(O), tetA(P), tet(Q), tet(S), tet(X), sul1, sul2, sul3, blaCTX-M, blaSHV, blaTEM and mcr-1. A PCR positivity was highlighted for 13 out of the 21 tested genes; no positive results were obtained for tet(C), tet(D), tet(E), tet(G), sul3, blaCTX, blaSHV and mcr-1 genes. All 11 animals sampled showed positivity for one or more resistance genes. The results confirm the potential role of the wolf as an indicator and/or vector of antimicrobial-resistant bacteria or ARGs.


Assuntos
Lobos , Animais , Itália , Lobos/microbiologia , Lobos/genética , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Animais Selvagens , Reação em Cadeia da Polimerase/veterinária , Genes Bacterianos
2.
Vet Res Commun ; 47(4): 2351-2355, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37436553

RESUMO

In recent years an increasing interest has been focused on the contribution of wildlife in ecology and evolution of the antimicrobial resistance (AMR). The aim of this study was to molecularly investigate the presence of antimicrobial resistance genes (ARGs) in organ samples from a golden jackal (Canis aureus) found dead in the Marche region (Central Italy). Samples from lung, liver, spleen, kidney, and intestine were investigated by PCRs targeting the following genes: tet(A), tet(B), tet(C), tet(D), tet(E), tet(G), tet(K), tet(L), tet(M), tet(O), tet(S), tet(P), tet(Q), tet(X), sul1, sul2, sul3, blaCTX-M, blaSHV, blaTEM, and mcr-1 to mcr-10. One or more ARGs were detected in all organs tested, except the spleen. Specifically, the lung and liver were positive for tet(M) and tet(P), the kidney for mcr-1 and the intestine for tet(A), tet(L), tet(M), tet(O), tet(P), sul3 and blaTEM-1. These results, according to the opportunistic foraging strategy of the jackal, confirm its potential role as a good bioindicator of AMR environmental contamination.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Chacais , Itália
3.
Clin Nutr ; 41(12): 3055-3060, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34049750

RESUMO

BACKGROUND & AIMS: After prolonged hospitalization, the assessment of nutritional status and the identification of adequate nutritional support is of paramount importance. In this observational study, we aimed at assessing the presence of a malnutrition condition in SARS-Cov2 patients after the acute phase and the effects of a multidisciplinary rehabilitation program on nutritional and functional status. METHODS: We recruited 48 patients (26 males/22 females) admitted to our Rehabilitation Unit after discharge from acute Covid Hospitals in northern Italy with negative swab for SARS-Cov2. We used the Global Leadership Initiative on Malnutrition (GLIM) criteria to identify patients with different degrees of malnutrition. Patients underwent a 3 to 4-week individual multidisciplinary rehabilitation program consisting of nutritional intervention (energy intake 27to30 kcal/die/kg and protein intake 1-1.3 g/die/kg), exercise for total body conditioning and progressive aerobic exercise with cycle- and arm-ergometer (45 min, 5 days/week). At admission and discharge from our Rehabilitation Unit, body composition and phase angle (PhA) (BIA101 Akern), muscle strength (handgrip, HG) and physical performance (Timed-Up-and-Go, TUG) were assessed. RESULTS: At admission in all patients the mean weight loss, as compared to the habitual weight, was -12.1 (7.6)%, mean BMI was 25.9 (7.9) kg/m2, mean Appendicular Skeletal Muscle Index (ASMI) was 6.6 (1.7) kg/m2 for males and 5.4 (1.4) kg/m2 for females, mean phase angle was 2.9 (0.9)°, mean muscle strength (HG) was 21.1 (7.8) kg for males and 16.4 (5.9) kg for females, mean TUG value was 23.7 (19.2) s. Based on GLIM criteria 29 patients (60% of the total) showed a malnutrition condition. 7 out of those 29 patients (24%) presented a mild/moderate grade and 22 patients (76%) a severe grade. After a rehabilitation program of an average duration of 25 days (range 13-46) ASMI increased, with statistically significant differences only in females (p = 0.001) and HG improved only in males (p = 0.0014). In all of the patients, body weight did not change, CRP/albumin (p < 0.05) and TUG (p < 0.001) were reduced and PhA increased (p < 0.01). CONCLUSIONS: We diagnosed a malnutrition condition in 60% of our post SARS-Cov2 patients. An individualized nutritional intervention with adequate energy and protein intake combined with tailored aerobic and strengthening exercise improved nutritional and functional status.


Assuntos
COVID-19 , Desnutrição , Masculino , Feminino , Humanos , Estado Nutricional , RNA Viral , Força da Mão , SARS-CoV-2 , Desnutrição/diagnóstico , Desnutrição/etiologia
5.
Int Nurs Rev ; 67(3): 420-426, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32700371

RESUMO

BACKGROUND: Job satisfaction is important for increasing nurse retention rates. However, there is little research examining whether there is an association between nationality and job satisfaction among nurses. AIM: To examine whether there is an association between nationality and nurse job satisfaction. METHODS/DESIGN: A cross-sectional survey design was utilized, and 743 nurses from three major government hospitals in Saudi Arabia participated in the survey. Job satisfaction was measured using McCloskey/Mueller Satisfaction Scale. Data were collected between May 2014 and February 2015. RESULTS: Compared with Saudi nurses, expatriate nurses had overall lower job satisfaction after controlling for other predictors. While expatriates were less satisfied than Saudi nurses about extrinsic rewards and family-work balance, however, Saudi nurses were less satisfied than expatriate nurses about their professional opportunities, praise and recognition, and co-worker relationships. CONCLUSION: For some subscales, Saudi nurses were more satisfied than expatriate nurses, while for other subscales, the opposite was true. Nationality should be included in job satisfaction studies in countries with migrant workforces, as nationality-based differences may have been present but masked in earlier international studies by aggregating satisfaction across national groups. IMPLICATIONS FOR NURSING & HEALTH POLICY: Policy makers in Saudi Arabia and other countries with migrant nursing workforces should have effective induction programmes that help newly employed nurses - migrant and local - clearly understand their jobs, roles and responsibilities. Policy makers must have sufficient evidence to modify the reward system to ensure fairness and equality for all.


Assuntos
Diversidade Cultural , Etnicidade/psicologia , Satisfação no Emprego , Recursos Humanos de Enfermagem Hospitalar/psicologia , Adulto , Estudos Transversais , Etnicidade/estatística & dados numéricos , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Arábia Saudita , Inquéritos e Questionários
6.
Neotrop Entomol ; 49(2): 213-226, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916201

RESUMO

Ground beetles (Coleoptera: Carabidae) are among the early colonisers of recently deglaciated terrains. While patterns of carabid colonisation along forelands of retreating glaciers have been thoroughly investigated in temperate climates, information remains scarce in tropical mountains. This study aimed to describe for the first time the carabid beetle species assemblages along the chronosequence of two tropical Andean glaciers (Antisana and Carihuairazo, Ecuador). Shannon index, taxonomic distinctness and species assemblage composition did not reveal deterministic and directional patterns. Only the principal coordinate analysis performed on the Antisana dataset showed that some species had a clear preference for terrains deglaciated for more than 200 years. Our results showed that equatorial glacier forelands are colonised by pioneer species that persist from the recently deglaciated terrains (less than 25 years) to terrains deglaciated since more than 200 years. This pattern fits the 'addition and persistence model' of high-latitude glacier forelands, rather than the 'species replacement model' of the Alps. The pioneer species observed are high-altitude specialists adapted to constantly cold environments, but not specifically ice-related. In the current context of climate warming, pioneer and cold-adapted species living near the glaciers of equatorial mountains are therefore only threatened by the 'summit trap' risk, unlike in temperate regions, as they are not strictly linked to the glacier microclimate.


Assuntos
Distribuição Animal , Besouros/classificação , Camada de Gelo , Animais , Clima , Equador
7.
Photodiagnosis Photodyn Ther ; 26: 284-286, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30991109

RESUMO

P. aeruginosa is a gram-negative bacterium present in nosocomial infections with high morbidity and mortality. This microorganism is frequently resistant to antibiotics, leading to clinical complications. In the present report, we described a clinical case of a patient with severe oral lesions caused by P. aeruginosa, which was refractory to antibiotics treatment and presented positive clinical outcomes after some sessions of antimicrobial photodynamic inactivation (API) mediated by methylene blue dye. We discuss the potential of API for P. aeruginosa refractory infections and possible resistance mechanisms of this microorganism to different API protocols.


Assuntos
Azul de Metileno/uso terapêutico , Doenças da Boca/tratamento farmacológico , Doenças da Boca/microbiologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Adulto , Anti-Infecciosos/uso terapêutico , Feminino , Humanos , Pseudomonas aeruginosa
8.
Biochem Pharmacol ; 144: 52-62, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28782526

RESUMO

Trabectedin and its analogue lurbinectedin are effective drugs used in the treatment of ovarian cancer. Since the presence of ascites is a frequent event in advanced ovarian cancer we asked the question whether ascites could modify the activity of these compounds against ovarian cancer cells. The cytotoxicity induced by trabectedin or lurbinectedin against A2780, OVCAR-5 cell lines or primary culture of human ovarian cancer cells was compared by performing treatment in regular medium or in ascites taken from either nude mice or ovarian cancer patients. Ascites completely abolished the activity of lurbinectedin at up to 10nM (in regular medium corresponds to the IC90), strongly reduced that of trabectedin, inhibited the cellular uptake of lurbinectedin and, to a lesser extent, that of trabectedin. Since α1-acid glycoprotein (AGP) is present in ascites at relatively high concentrations, we tested if the binding of the drugs to this protein could be responsible for the reduction of their activity. Adding AGP to the medium at concentration range of those found in ascites, we reproduced the anticytotoxic effect of ascites. Erythromycin partially restored the activity of the drugs, presumably by displacing them from AGP. Equilibrium dialysis experiments showed that both drugs bind AGP, but the affinity of binding of lurbinectedin was much greater than that of trabectedin. KD values are 8±1.7 and 87±14nM for lurbinectedin and trabectedin, respectively. The studies intimate the possibility that AGP present in ascites might reduce the activity of lurbinectedin and to a lesser extent of trabectedin against ovarian cancer cells present in ascites. AGP plasma levels could influence the distribution of these drugs and thus they should be monitored in patients receiving these compounds.


Assuntos
Ascite/metabolismo , Carbolinas/metabolismo , Dioxóis/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/metabolismo , Orosomucoide/metabolismo , Neoplasias Ovarianas/metabolismo , Tetra-Hidroisoquinolinas/metabolismo , Animais , Antineoplásicos Alquilantes/metabolismo , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Carbolinas/farmacologia , Carbolinas/uso terapêutico , Linhagem Celular Tumoral , Dioxóis/farmacologia , Dioxóis/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Camundongos , Camundongos Nus , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ligação Proteica/fisiologia , Tetra-Hidroisoquinolinas/farmacologia , Tetra-Hidroisoquinolinas/uso terapêutico , Trabectedina , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
9.
J R Army Med Corps ; 161 Suppl 1: i26-i33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26419524

RESUMO

INTRODUCTION: Little empirical evidence exists to identify the impact that a partner's absence or presence has on the mother's decision-making and her consequential help-seeking behaviour when her child is unwell. METHODS: This study used a qualitative design in three phases using focus groups and interviews to explore Army mothers' help-seeking behaviour as a lone parent when their child was unwell during the out-of-hours period. Thirty-one parents from a British Army garrison were interviewed. RESULTS: The findings demonstrated that Army life created a combination of stressors for Army mothers, which altered their help-seeking behaviour when their child was unwell. When their partner was available, mothers contacted health services as a last resort, once all other avenues had been exhausted. However, in contrast, in their partners' absence, they were contacted as a first resort. CONCLUSION: An algorithm was generated from the findings, which illustrates the importance of ascertaining whether the mother is alone at the time of the consultation. Increased emotional vulnerability intensified the need for reassurance and affected a mother's decision-making ability. Primary healthcare staff should ascertain whether mothers are currently lone parents at an early stage of their assessment, as this may influence the entire consultation.


Assuntos
Tomada de Decisões , Militares/psicologia , Mães/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Pais Solteiros/psicologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adulto , Plantão Médico , Criança , Pré-Escolar , Feminino , Grupos Focais , Humanos , Lactente , Pesquisa Qualitativa , Reino Unido
10.
Leuk Res ; 39(8): 846-52, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26145790

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders, with very different prognosis in given individuals; age and comorbidities are emerging as relevant patient-related factors influencing clinical outcome in MDS. Our aim was to evaluate the impact of age, comorbidities and disease severity (IPSS and IPSS-R prognostic scores) in a "real-life" series of MDS patients. METHODS: 318 patients with available assessment of comorbidities at diagnosis and consecutively registered into the Registro Ligure delle Mielodisplasie were analyzed. Comorbidities were evaluated according to HCT-CI and MDS-CI comorbidity indexes. Overall survival (OS) and the probability of death among patients who did not develop acute myeloid leukemia (NLD cumulative incidence) were analyzed. RESULTS: Comorbidities were seen in 177 (55.7%) patients. An older age (>75 y) had a significant negative impact on OS (p=0.008). HCT-CI was not associated with OS. MDS-CI was of prognostic significance (p=0.001), but the association was limited to pts with IPSS or IPSS-R "lower-risk". In multivariate analysis, MDS-CI remained an independent factor associated with OS and with an increased risk of NLD both when controlling for IPSS (p=0.019 and p=0.001, respectively) and for IPSS-R (p=0.048 and p=0.002, respectively). CONCLUSIONS: Evaluation of age and comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporated to current prognostic scores.


Assuntos
Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
11.
Ann Oncol ; 26(1): 185-192, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25361995

RESUMO

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Esplenomegalia/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Baço/patologia , Adulto Jovem
12.
Clin Vaccine Immunol ; 21(9): 1357-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24990906

RESUMO

Ninety-one serum samples from 51 hematology patients with bacteremia infections were tested for (1,3)-ß-d-glucan (BG). Eleven samples (15%) from 7 patients (14%) were positive for BG. Of these 7 patients with positive BG results, 4 (8%) had invasive aspergillosis and 3 (6%) had no invasive fungal disease. Bacteremia was an unlikely cause of the false-positive BG results.


Assuntos
Reações Falso-Positivas , Neoplasias Hematológicas/complicações , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/patologia , Soro/química , beta-Glucanas/sangue , Humanos , Proteoglicanas
13.
Nat Commun ; 5: 4161, 2014 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-24946715

RESUMO

The energetics of metal/molecular semiconductor interfaces plays a fundamental role in organic electronics, determining the performance of very diverse devices. So far, information about the energy level alignment has been most commonly gained by spectroscopy techniques that typically require experimental conditions far from the real device operation. Here we demonstrate that a simple three-terminal device allows the acquisition of spectroscopic information about the metal/molecule energy alignment in real operative condition. As a proof of principle, we employ the proposed device to measure the energy barrier height between different clean metals and C60 molecules and we recover typical results from photoemission spectroscopy. The device is designed to inject a hot electron current directly into the molecular level devoted to charge transport, disentangling the contributions of both the interface and the bulk to the device total resistance, with important implications for spintronics and low-temperature physics.

14.
Leukemia ; 28(3): 642-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24220274

RESUMO

We conducted a phase II, noncomparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m(2)) for 2 consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to six cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% confidence of interval (CI), 57-84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0-95.7%) and the progression-free survival (PFS) was 49.6% (95% CI, 35.9-68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade ≥3 neutropenia was observed in 61.7% of patients; however, grade ≥3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high-risk clinical and biological features.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Cloridrato de Bendamustina , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Compostos de Mostarda Nitrogenada/administração & dosagem , Recidiva
16.
J Sports Med Phys Fitness ; 52(3): 229-36, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22648460

RESUMO

AIM: The aim of this study, based on the interaction between two aerobic and anaerobic metabolisms with a parallel production of both aerobic and anaerobic ATP, was to develop a high intensity training programme and increase the aerobic contribution. We examined the applicability of a 16-week training programme with an ergospirometer treadmill and field tests on eight water polo players. METHODS: Tests/retests of repeated exercises to 90V (90% of maximum personal speed over 100 m freestyle) and Speed Endurance Training (SET) after eight weeks were developed. A one-way blocked ANOVA with random blocks was used and each player represented a particular block with two before-after treatments with the aim of reducing error by subtracting both the variance due to the difference between the treatments and that due to the difference between the blocks. RESULTS: A reduction (15.2%) in blood lactate was observed in response to the same absolute workload (before-after). Furthermore the anaerobic contribution to VO2max (ESCAna, Estimated Anaerobic Contribution) after eight weeks of training at 90maxV and the anaerobic contribution to VO2max (ESCAna) after speed endurance training (SET) were very significant (P<0.004) with a reduction in the anaerobic contribution of 16%. The results of the field tests show that there was a very significant reduction (P<0.001) in lactate between 90maxV and maximal aerobic power velocity (MAPv) of 24%. CONCLUSION: With 90maxV and SET, space was gained towards those velocities, which had previously required a considerable anaerobic contribution. In this way match speed was increased.


Assuntos
Desempenho Atlético/fisiologia , Educação Física e Treinamento/métodos , Resistência Física/fisiologia , Esportes , Limiar Anaeróbio/fisiologia , Análise de Variância , Teste de Esforço , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Aptidão Física/fisiologia , Água , Adulto Jovem
18.
Leukemia ; 26(5): 943-50, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22033492

RESUMO

Phosphoinositide-phospholipase C (PI-PLC) beta1 can be considered a specific target for demethylating therapy in high-risk myelodysplastic syndrome (MDS) patients, as azacitidine treatment has been associated with a PI-PLCbeta1-specific promoter demethylation, and induction of PI-PLCbeta1 gene and protein expression. However, little is known about the molecular effect of azacitidine in low-risk MDS or the functional mechanisms linked with azacitidine effect on PI-PLCbeta1 promoter. In the present study, we further investigated the role of epigenetic regulation of PI-PLCbeta1, mainly focusing on the structure of the PI-PLCbeta1 promoter. We first examined the effect of azacitidine on PI-PLCbeta1 promoter methylation and gene expression in low-risk MDS. Moreover, we studied the expression of key molecules associated with the nuclear inositide signaling pathways, such as cyclin D3. By applying a chromatin immunoprecipitation method, we also studied the correlation between the demethylating effect of azacitidine and the degree of recruitment to PI-PLCbeta1 promoter of some transcription factors implicated in hematopoietic stem cell proliferation and differentiation, as well as of the methyl-CpG-binding domain proteins, which specifically interact with methylated DNA. Taken together, our results hint at a specific involvement of PI-PLCbeta1 in epigenetic mechanisms, and are particularly consistent with the hypothesis of a role for PI-PLCbeta1 in azacitidine-induced myeloid differentiation.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Epigênese Genética , Síndromes Mielodisplásicas/tratamento farmacológico , Fosfatidilinositóis/metabolismo , Fosfolipase C beta/metabolismo , Transdução de Sinais , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Metilação de DNA , Primers do DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Síndromes Mielodisplásicas/enzimologia , Síndromes Mielodisplásicas/patologia , Fosfolipase C beta/genética , Regiões Promotoras Genéticas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...