RESUMO
BACKGROUND: The functional characteristics of circulating angiogenic cells (CACs) are impaired in congestive heart failure (CHF) patients, suggesting that CAC dysfunction could contribute to CHF pathogenesis. However, the underlying mechanisms are only partly unraveled. No data are currently available regarding telomere/telomerase system in CACs of CHF patients. METHODS: CACs were obtained from 80 subjects: 40 healthy control subjects (CTR) [median age (IQR), 80 (76-85 yrs)] and 40 patients affected by post-ischemic cardiomyopathy CHF [median age (IQR), 82 (77-89)]. CAC and leukocyte telomere length, assessed as T/S ratio, and telomerase (TERT) activity were determined in all the enrolled subjects. Specificity and sensitivity of CAC and leukocyte T/S in discriminating between CHF and CTR were evaluated using Receiver Operator Characteristic (ROC) curve analysis and reported as AUC values. CD34+/VEGFR2+ number and pro-inflammatory cytokines plasma levels, such as IL-6 and TNF-α, were also measured. RESULTS: CAC T/S and TERT activity were significantly reduced in CHF patients compared to CTR subjects. In leukocytes, only a significant T/S reduction was observed. AUC values were higher for CAC T/S with respect to leukocyte T/S (AUC=0.89, and AUC=0.73, P<0.01, respectively). In multivariate analysis, leukocyte T/S, CAC T/S, CAC TERT activity and NT-proBNP levels were confirmed as parameters significantly associated with CHF. CD34+/VEGFR2+ number, IL-6 and TNF-α plasma levels were significantly increased in CHF patients. CONCLUSIONS: CACs from CHF patients are characterized by telomere/telomerase system impairment, providing new insight into the clinical relevance of CACs in CHF pathogenesis.
Assuntos
Células , Insuficiência Cardíaca/sangue , Neovascularização Fisiológica , Telomerase/fisiologia , Telômero/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , MasculinoAssuntos
Estenose da Valva Aórtica/terapia , Cateterismo Cardíaco , Implante de Prótese de Valva Cardíaca/métodos , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/diagnóstico , Cateterismo Cardíaco/instrumentação , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/instrumentação , Humanos , Desenho de Prótese , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
HPV-DNA testing has entered in clinical practice. Three important questions remain controversial: 1) which is the best HPV-DNA technology? 2) Which age group should be targeted? 3) Is HPV-DNA testing predictive of disease outcome? The answers to these queries represent the endpoints of this study. The population of this retrospective study consisted of 272 women, each one having: baseline cytological diagnosis of Low-grade Squamous Intraepithelial Lesion (LSIL); baseline HPV-DNA reports by Hybrid Capture 2 (HC2) and MY09/11 consensus primers PCR; follow-up duration over 3-years; cytological report of disease status at follow-up time. Firstly, we assessed the concordance and the performances of both HPV-DNA testing, then we correlated, respectively HPV-DNA results and age of patients to disease outcome. DNA testing methods agreed in 83.4 percent of cases (K=0.66). Baseline HPV-DNA result was not significantly associated to disease outcome (p=0.06). Within HPV-DNA positive group, we found no evidence of correlation between age and LSIL prognosis (p=0.89). Confining the analysis to age-stratified HPV-DNA negative women, the differences were statistically significant (p=0.01). In conclusion, HPVDNA testing gives no information about the real behaviour of cervical abnormalities. These findings suggest the demand for additive markers, reflecting the risk of progression, in prevention strategy and clinical approach.
Assuntos
Colo do Útero/patologia , DNA Viral/análise , Papillomaviridae/isolamento & purificação , Esfregaço Vaginal , Adolescente , Adulto , Fatores Etários , Colo do Útero/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , Estudos RetrospectivosAssuntos
Hipertensão/genética , Síndrome Metabólica/genética , Obesidade/genética , Fatores de Transcrição TCF/genética , Adulto , Alelos , Análise de Variância , Distribuição de Qui-Quadrado , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de RiscoRESUMO
Type-specific persistent infection with Human Papillomavirus (HPV) is a significant risk factor for the development of cervical diseases. Persistent infection could be further refined by a sequencing approach to detect early cervical lesions that are at high risk of developing an invasive squamous cervical cancer. The aim of the present study is to investigate the clinical utility of detecting mRNA transcripts of HPV oncogenes E6/E7 by using a Real-time NASBA technology (mRNA test) and to identify women with low-grade cytological disease but with an increased risk of developing high-grade cervical abnormalities or invasive squamous cervical cancer. Our preliminary results show that E6/E7 is detected in only a subset of HR-HPV-positive cases. Since viral persistence is considered to be the true precursor of neoplastic progression, only the detection of E6/E7 mRNA can identify the infection which is more likely to persist and induce neoplasia in future. For these reasons we believe that this test would be useful for the characterization of women with HR-HPV DNA positivity who should be effectively treated because at high-risk of developing a high grade cervical lesion or an invasive squamous cervical cancer.
Assuntos
Alphapapillomavirus/genética , DNA Viral/metabolismo , Infecções por Papillomavirus/diagnóstico , RNA Mensageiro/metabolismo , Triagem , Doenças do Colo do Útero/diagnóstico , Feminino , Humanos , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Doenças do Colo do Útero/virologiaRESUMO
In the foetal human ovary, diameters of oocyte and follicle, as well as those of oocyte and nucleus, are found to be positively and linearly correlated with each other. Follicle diameter and number of granulosa cells also show a positive and linear relationship. Finally, in all ovaries examined, from 5 months after conception onwards, small antral follicles were assessed.