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1.
Int Microbiol ; 26(1): 69-79, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36001166

RESUMO

BACKGROUND: The aim of this study was to evaluate (i) the prevalence of subjects with a positive sperm culture (SC) for bacteria in subjects with or without genitourinary tract inflammation (GTI); (ii) the actual distribution of the species analysed, according to Gram stain; (iii) the impact on sperm parameters; and (iv) the actual bacterial susceptibility to antibiotics. METHODS: A total of 930 subjects (18-55) years, were retrospectively studied. All the patients underwent SC and in the case of positive tests (CFU > 106), a microbiological susceptibility analysis. The subjects studied were subdivided into group A (n = 452), with subjective signs of GTI; group B (n = 478), male partners of infertile couples; and group C, 30 healthy normospermic subjects. In group B and in the control group, a semen analysis was performed. RESULTS: Overall, the prevalence of positive SC was 21.5% (200/930). The prevalence of positive SC in group A (113/200; 56.5%) was significantly higher vs. group B (87/200; 43.5%; p = 0.01) and control group (1/30; 3.3%; p = 0.0001). In subjects with GTI, the prevalence of asthenozoospermic (96/285; 33.7%) and oligo-asthenozoospermic (98/285; 34.4%) was significantly higher vs. normospermic, oligo-astheno-teratozoospermic, oligozoospermic and azoospermic subjects (22/285 (7.7%), 48/285 (16.8%), 15/285 (5.3%) and 6/285 (2.1%), respectively; p = 0.001). Finally, Enterococcus faecalis (Gram-positive) and Escherichia coli (Gram-negative) showed the highest prevalence of antibiotic resistance. CONCLUSIONS: The prevalence of positive SC is higher in GTI subjects; however, the SC could also be positive in subjects without GTI. Commonly used antibiotics have an increasing risk of being useless for the treatment of bacterial infections. Finally, the diagnosis of GTIs is important also for male fertility.


Assuntos
Infertilidade Masculina , Humanos , Masculino , Infertilidade Masculina/diagnóstico , Sêmen , Prevalência , Estudos Retrospectivos , Espermatozoides , Bactérias
2.
Clin Chem Lab Med ; 61(4): 662-665, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36656995

RESUMO

Precision Medicine is a reality in selected medical areas, as oncology, or in excellent healthcare structures, but it is still far to reach million patients who could benefit from this medical concept. Here, we sought to highlight how the time is ripe to achieve horizontal delivery to a significant larger audience of patients, represented by the poly-treated patients. Combination therapies are frequent (especially in the elderly, to treat comorbidities) and are related to decreased drug safety and efficacy, disease's exacerbation, additional treatments, hospitalization. But the recent development and validation of bioinformatic tools, aimed to automatic evaluation and optimization of poly-therapies, according to the unique individual characteristics (including genotype), is ready to change the daily approach to pharmacological prescription.


Assuntos
Atenção à Saúde , Medicina de Precisão , Humanos , Idoso , Pacientes , Hospitalização
3.
Sleep Breath ; 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37843681

RESUMO

OBJECTIVES: To investigate the vascular networks of the retina and choroid using optical coherence tomography angiography (OCTA) to identify early biomarkers of obstructive sleep apnea (OSA) severity and to evaluate correlations with blood levels of oxidative stress. STUDY DESIGN: Patients with OSA were diagnosed based on video-polysomnography (PSG) and blood samples were collected to evaluate oxidative stress markers: total antioxidant status (TAS), biological antioxidant potential (BAP) test, Diacron reactive oxygen metabolites (d-ROMs) test. The eyes of children with OSA were evaluated and compared with eyes of healthy age-matched children. OCTA imaging was carried out to evaluate the choroidal and retinal vascular network density indices. RESULTS: A total of 31 children with OSA were recruited and compared with 10 healthy children. Choriocapillaris flow area decreased (p = 0.006) and superficial capillary plexus vessel density increased (p=0.01) with increasing severity of OSA. Children with OSA showed significant differences in TAS and d-ROMs test when compared to normal pediatric values (p<0.05). In calculating the correlations between PSG, oxidative stress, and OCTA variables, there was a negative correlation between choriocapillaris flow area and apnea hypopnea index (AHI) (p = 0.02, r2 -0.5) and between choriocapillaris flow area and the d-ROMs test (p 0.03; r2 0.5). CONCLUSIONS: The severity of OSA was associated with the choroidal and retinal capillary vascular networks. The correlation of the choriocapillaris flow area with AHI and the d-ROMs test indicates the connection of the choroidal microvasculature with the number of obstructive apnea and hypopnea events and oxidative stress.

4.
Int J Mol Sci ; 24(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37628884

RESUMO

Improper drug prescription is a main cause of both drug-related harms (inefficacy and toxicity) and ineffective spending and waste of the healthcare system's resources. Nowadays, strategies to support an improved, informed prescription process may benefit from the adequate use of pharmacogenomic testing. Using next-generation sequencing, we analyzed the genomic profile for three major cytochromes P450 (CYP2C9, CYP2C19, CYP2D6) and studied the frequencies of dysfunctional isozymes (e.g., poor, intermediate, or rapid/ultra-rapid metabolizers) in a cohort of 298 Italian subjects. We found just 14.8% of subjects with a fully normal set of cytochromes, whereas 26.5% of subjects had combined cytochrome dysfunction (more than one isozyme involved). As improper drug prescription is more frequent, and more burdening, in polytreated patients, since drug-drug interactions also cause patient harm, we discuss the potential benefits of a more comprehensive PGX testing approach to support informed drug selection in such patients.


Assuntos
Citocromo P-450 CYP2D6 , Prescrições de Medicamentos , Humanos , Citocromo P-450 CYP2C9/genética , Perfil Genético , Sequenciamento de Nucleotídeos em Larga Escala
5.
Medicina (Kaunas) ; 59(5)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37241135

RESUMO

Background and Objectives: The aim of this study was to evaluate the impact of medications on oxidative stress, inflammatory biomarkers and semen characteristics in males with idiopathic infertility. Materials and Methods: In this observational case-control clinical study, 50 men with idiopathic infertility were enrolled, of whom 38 (the study group) were on pharmacological treatment and 12 made up the control group. The study group was clustered according to the medications (Group A: anti-hypertensive, n = 10; Group B: thyroxine, n = 6; Group C: non-steroidal anti-inflammatory drugs, n = 13; Group D: miscellaneous, n = 6; Group E: lipid-lowering drugs, n = 4). Semen analyses were performed according to WHO 2010 guidelines. Interleukins (IL)-10, IL-1 beta, IL-4, IL-6, Tumor Necrosis Factor- alpha (TNF-alpha) and IL-1 alpha were determined using a solid-phase sandwich immunoassay. The diacron reactive oxygen metabolites, d-ROMs test, was performed by means of a colorimetric determination of reactive oxygen metabolites and measured with a spectrophotometer. Beta-2-microglobulin and cystatin-C were measured with an immunoturbidimetric analyzer. Results: No differences between the study and control groups for age and macroscopic and microscopic semen characteristics were found, nor were any differences found after clustering according to the drug categories. IL-1 alpha and IL-10 were significantly lower in the study group compared with the control group; IL-10 was significantly lower in groups A, B, C and D compared with the control group. Furthermore, a direct correlation between IL-1 alpha, IL-10 and TNF-alpha and leukocytes was found. Conclusions: Despite the sample size limitations, the data suggest a correlation between drug use and activation of the inflammatory response. This could clarify the pathogenic mechanism of action for several pharmacological classes on male infertility.


Assuntos
Infertilidade Masculina , Sêmen , Masculino , Humanos , Interleucina-1alfa/metabolismo , Fator de Necrose Tumoral alfa/análise , Interleucina-10/metabolismo , Infertilidade Masculina/tratamento farmacológico , Estresse Oxidativo , Oxigênio/metabolismo
6.
Blood Purif ; 51(2): 155-162, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33910194

RESUMO

INTRODUCTION: Cardiovascular events (CVE) remain the leading cause of mortality in hemodialysis (HD) patients. The ability to assess the risk of short-term CVE is of great importance. Soluble suppression of tumorogenicity-2 (sST2) is a novel biomarker that better stratifies risk of CVE than troponins in patients with heart failure. Few studies have investigated the role of sST2 in the HD population. The aim of this single-center study was to assess the predictive ability of sST2 on CVE in comparison to high-sensitive cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) in HD patients. METHODS: This study used a prospective, observational cohort design. We enrolled 40 chronic HD patients asymptomatic for chest pain and without recent history of acute coronary syndrome. We tested sST2 pre-/post-HD, hs-cTnI, and BNP. Demographic/dialytic/echocardiographic data were evaluated. We recorded the number of CVE for 12 months. The patients were classified into 2 groups: those who developed CVE and those who did not. RESULTS: Ten of the 40 patients (25%) developed CVE during a 12-month follow-up. Increased sST2 levels (p < 0.0001) as well as hs-cTnI and BNP are predictive of CVE. When analyzing biomarkers as binary variables for values above or below the normal range, the correlation remained significant only for sST2 (p = 0.001). A small variation in sST2 levels before and after HD sessions was found (-2.1 ng/mL). sST2 was correlated with left ventricular (LV) echocardiographic data: LV mass index (p = 0.0001), LV ejection fraction (p = 0.01), and diastolic bulging of septum (p = 0.015). BNP and sST2 combination increased the prediction of CVE in a statistical model. CONCLUSION: Our study confirms that sST2 is useful for stratifying CV risk in the HD population. sST2 can be evaluated simply as a dichotomous value higher or lower than the normal range, making it easily interpretable. Dialysis and residual diuresis did not affect significantly sST2. A multimarker approach that incorporates sST2 and BNP may improve the prediction of CVE.


Assuntos
Proteína 1 Semelhante a Receptor de Interleucina-1 , Diálise Renal , Biomarcadores , Humanos , Peptídeo Natriurético Encefálico , Prognóstico , Estudos Prospectivos , Diálise Renal/efeitos adversos
7.
Int J Mol Sci ; 23(22)2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36430399

RESUMO

Deficiency of dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene, is associated with severe toxicity induced by the anti-cancer drug 5-Fluorouracil (5-FU). DPYD genotyping of four recommended polymorphisms is widely used to predict toxicity, yet their prediction power is limited. Increasing availability of next generation sequencing (NGS) will allow us to screen rare variants, predicting a larger fraction of DPD deficiencies. Genotype−phenotype correlations were investigated by performing DPYD exon sequencing in 94 patients assessed for DPD deficiency by the 5-FU degradation rate (5-FUDR) assay. Association of common variants with 5-FUDR was analyzed with the SNPStats software. Functional interpretation of rare variants was performed by in-silico analysis (using the HSF system and PredictSNP) and literature review. A total of 23 rare variants and 8 common variants were detected. Among common variants, a significant association was found between homozygosity for the rs72728438 (c.1974+75A>G) and decreased 5-FUDR. Haplotype analysis did not detect significant associations with 5-FUDR. Overall, in our sample cohort, NGS exon sequencing allowed us to explain 42.5% of the total DPD deficiencies. NGS sharply improves prediction of DPD deficiencies, yet a broader collection of genotype−phenotype association data is needed to enable the clinical use of sequencing data.


Assuntos
Deficiência da Di-Hidropirimidina Desidrogenase , Di-Hidrouracila Desidrogenase (NADP) , Humanos , Di-Hidrouracila Desidrogenase (NADP)/genética , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Deficiência da Di-Hidropirimidina Desidrogenase/diagnóstico , Deficiência da Di-Hidropirimidina Desidrogenase/genética , Fluoruracila/efeitos adversos , Fluoruracila/metabolismo , Floxuridina , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/metabolismo , Éxons
8.
J Transl Med ; 19(1): 139, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794925

RESUMO

BACKGROUND: Low T3 syndrome is frequent in patients admitted to intensive care units for critical illness and pneumonia. It has been reported also in patients with COVID-19, Hodgkin disease and chronic lymphocytic leukemia. We analyzed the clinical relevance of Low T3 syndrome in COVID-19 patients and, in particular, in those with associated hematological malignancies. METHODS: Sixty-two consecutive patients, hospitalized during the first wave of SARS-CoV-2 outbreak in Sant'Andrea University Hospital in Rome, were subdivided in 38 patients (Group A), showing low levels of FT3, and in 24 patients (Group B), with normal FT3 serum values. During the acute phase of the disease, we measured serum, radiologic and clinical disease severity markers and scores, in search of possible correlations with FT3 serum values. In addition, in 6 COVID-19 patients, 4 with Low T3 syndrome, including 2 with a hematological malignancy, and 2 with normal FT3 values, we performed, high-dimensional single-cell analysis by mass cytometry, multiplex cytokine assay and gene expression profiling in peripheral blood mononuclear cells (PBMC). RESULTS: Low FT3 serum values were correlated with increased Absolute Neutrophil Count, NLR and dNLR ratios and with reduced total count of CD3+, CD4+ and CD8+ T cells. Low FT3 values correlated also with increased levels of inflammation, tissue damage and coagulation serum markers as well as with SOFA, LIPI and TSS scores. The CyTOF analysis demonstrated reduction of the effector memory and terminal effector subtypes of the CD4+ T lymphocytes. Multiplex cytokine assay indicates that mainly IL-6, IP-10 and MCAF changes are associated with FT3 serum levels, particularly in patients with coexistent hematological malignancies. Gene expression analysis using Nanostring identified four genes differently expressed involved in host immune response, namely CD38, CD79B, IFIT3 and NLRP3. CONCLUSIONS: Our study demonstrates that low FT3 serum levels are associated with severe COVID-19. Our multi-omics approach suggests that T3 is involved in the immune response in COVID-19 and coexistent hematological malignancy and new possible T3 target genes in these patients have been identified.


Assuntos
COVID-19/complicações , Síndromes do Eutireóideo Doente/complicações , Neoplasias Hematológicas , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/genética , Humanos , Itália , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Análise de Célula Única , Tri-Iodotironina/sangue
9.
Ann Vasc Surg ; 56: 240-245, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30339898

RESUMO

BACKGROUND: ST2 represents an interesting biomarker associated with the progression of atherosclerotic disease. METHODS: This study aims to detect different ST2 serum concentrations, and intraplaque ST2 expression, in patients with symptomatic and asymptomatic carotid artery stenosis. RESULTS: The analysis of ST2 expression in the atheromatous plaque did not show any significant difference between symptomatic and asymptomatic patients (39.61 ± 35.97 vs. 38.49 ± 35.26; P = ns). ST2 serum concentrations of asymptomatic and symptomatic patients were statistically different with a concentration of 11.04 ± 8.95 ng/mL and 13.91 ± 8.01 ng/mL, respectively (P = 0.037). We observed statistical difference in serum ST2 levels between asymptomatic and symptomatic patients for cerebrovascular acute disease. No differences have been obtained in intraplaque ST2 expression. CONCLUSIONS: Soluble serum ST2 levels can be a useful biomarker to identify patients at risk for cerebrovascular events.


Assuntos
Estenose das Carótidas/sangue , Transtornos Cerebrovasculares/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Idoso , Doenças Assintomáticas , Biomarcadores/sangue , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/etiologia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Masculino , Placa Aterosclerótica , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Regulação para Cima
10.
Clin Immunol ; 195: 18-27, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30036638

RESUMO

Immunogenicity of 13-valent pneumococcal polysaccharide (PnPS) conjugate vaccine (PCV13) was evaluated in 38 rheumatoid arthritis patients under immunosuppressive treatment and 20 healthy controls (HC). Antibodies to all PnPS and diphtheria-toxin analogue conjugate protein were measured pre- (T0), 1 (T1), 6 (T2), 12 (T3) months post-immunization. Patients and HC had similar response to individual PnPS. Mean antibody levels to all PnPS but one doubled at T1 compared with T0, with T3 persistence for only 8-7/13 PnPS. Baseline antibody levels was inversely associated with the rate of responders at T1 (T1/T0≥2) to 11/13 PnPS. Few subjects reached protective IgG levels against some serotypes frequently isolated in Italian patients with invasive pneumococcal disease. Antibody response was not influenced by therapy, except the one to PS7F, which was reduced by tumor necrosis factor-α-inhibitors. Vaccination increased also anti-diphtheria IgG. Despite this study substantially confirmed the PCV13 immunogenicity in immunocompromised patients, it also revealed some limitations.


Assuntos
Artrite Reumatoide/imunologia , Corynebacterium diphtheriae/fisiologia , Difteria/imunologia , Infecções Pneumocócicas/imunologia , Vacinas Pneumocócicas/imunologia , Idoso , Anticorpos Antibacterianos/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Feminino , Humanos , Imunidade Humoral , Hospedeiro Imunocomprometido , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Pneumocócicas/epidemiologia , Polissacarídeos Bacterianos/imunologia , Vacinação
11.
Int J Mol Sci ; 19(10)2018 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-30261687

RESUMO

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/microbiologia , Disbiose/etiologia , Etanercepte/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Disbiose/microbiologia , Etanercepte/farmacologia , Etanercepte/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Clin Immunol ; 181: 60-66, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28625884

RESUMO

Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently indicated vaccinations as possibly responsible for autoimmunity/lymphoproliferation development. Multiply vaccinated Italian military personnel (group 1, operating in Italy, group 2, operating in Lebanon) were followed-up for nine months to monitor possible post-vaccine autoimmunity/lymphoproliferation onset. No serious adverse event was noticed in both groups. Multivariate analysis of intergroup differences only showed a significant association between lymphocyte increase and tetanus/diphtheria vaccine administration. A significant post-vaccine decrease in autoantibody positivity was observed. Autoantibodies were also studied by microarray analysis of self-proteins in subjects exposed to ≥4 concurrent vaccinations, without observing significant difference among baseline and one and nine months post-vaccine. Moreover, HLA-A2 subjects have been analyzed for the possible CD8T-cell response to apoptotic self-epitopes, without observing significant difference between baseline and one month post-vaccine. Multiple vaccinations in young adults are safe and not associated to autoimmunity/lymphoproliferation onset during a nine-month-long follow-up.


Assuntos
Doenças Autoimunes/epidemiologia , Transtornos Linfoproliferativos/epidemiologia , Militares/estatística & dados numéricos , Vacinas/uso terapêutico , Adolescente , Adulto , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Anticorpos Antinucleares/imunologia , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Eletroforese das Proteínas Sanguíneas , Vacina contra Varicela/uso terapêutico , Vacina contra Difteria e Tétano/uso terapêutico , Feminino , Seguimentos , Vacinas contra Hepatite A/uso terapêutico , Vacinas contra Hepatite B/uso terapêutico , Humanos , Imunoglobulinas/sangue , Vacinas contra Influenza/uso terapêutico , Itália/epidemiologia , Transtornos Linfoproliferativos/imunologia , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/uso terapêutico , Vacinas Meningocócicas/uso terapêutico , Vacina Antipólio de Vírus Inativado/uso terapêutico , Estudos Prospectivos , Fator Reumatoide/imunologia , Fatores de Risco , Vacinas Tíficas-Paratíficas/uso terapêutico , Adulto Jovem
13.
Invest New Drugs ; 34(4): 399-406, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26994617

RESUMO

Inhibitors of kinesin spindle protein Eg5 are characterized by pronounced antitumor activity. Our group has recently synthesized and screened a library of 1,3,4-thiadiazoline analogues with the pharmacophoric structure of K858, an Eg5 inhibitor. We herein report the effects of K858 on four different breast cancer cell lines: MCF7 (luminal A), BT474 (luminal B), SKBR3 (HER2 like) and MDA-MB231 (basal like). We demonstrated that K858 displayed anti-proliferative activity on every analyzed breast cancer cell line by inducing apoptosis. However, at the same time, we showed that K858 up-regulated survivin, an anti-apoptotic molecule. We then performed a negative regulation of survivin expression, with the utilization of wortmannin, an AKT inhibitor, and obtained a significant increase of K858-dependent apoptosis. These data demonstrate that K858 is a potent inhibitor of replication and induces apoptosis in breast tumor cells, independently from the tumor phenotype. This anti-proliferative response of tumor cells to K858 can be limited by the contemporaneous over-expression of survivin; consequently, the reduction of survivin levels, obtained with AKT inhibitors, can sensitize tumor cells to K858-induced apoptosis.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Proteínas Inibidoras de Apoptose/metabolismo , Cinesinas/antagonistas & inibidores , Tiadiazóis/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Survivina
14.
Tumour Biol ; 37(3): 3379-87, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26449821

RESUMO

Anti-neoplastic chemotherapy can determine various side effects, including cardiotoxicity, and no real guidelines for its early detection and management have been developed. The aim of this study is to find some plasmatic markers able to identify breast cancer patients that are at greater risk of developing cardiovascular complications during chemotherapy, in particular heart failure. A prospective study on 100 breast cancer patients with mean age of 66 years in adjuvant treatment with anthracyclines, taxanes, and trastuzumab was performed. Patients underwent cardiological examination before starting treatment (T0) and at 3 months (T1), 6 months (T2), and 1 year (T3) after treatment. Evaluation of serum cardiac markers and N-terminal pro-brain natriuretic peptide (NT-proBNP) was performed at T0, T1, T2, and T3, simultaneously to electrocardiogram and echocardiogram, showing a significant increase in NT-proBNP concentration (p > 0.0001) at T1, T2, and T3, before left ventricular ejection fraction decrease became evident. Human epidermal growth factor receptor 2 (HER2)-negative patients were more susceptible to mild hematological cardiotoxicity, while HER2-positive patients were more susceptible to severe cardiotoxicity. A significant correlation between NT-proBNP increased values after chemotherapy and prediction of mortality at 1 year was evidenced. From our experience, serum biomarker detection was able to support an early diagnosis of cardiac damage, also in the absence of left ventricular ejection fraction decrease. Therefore, the evaluation of specific plasmatic markers for cardiac damage is more sensitive than echocardiography in the early diagnosis of chemotherapy-related cardiotoxicity; furthermore, it can also add a prognostic value on outcome.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Coração/efeitos dos fármacos , Idoso , Biomarcadores/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Creatina Quinase Forma MB/sangue , Eletrocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Receptor ErbB-2/análise , Troponina T/sangue , Função Ventricular Esquerda
15.
Tumour Biol ; 37(2): 2603-11, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26392111

RESUMO

Breast cancer is characterized by molecular heterogeneity, and four major breast cancer subtypes have been identified, each characterized by significant differences in survival, prognosis, and response to therapy. We have studied the effects of docetaxel treatment on apoptosis and survivin expression in four breast cancer cell lines: MCF7 (luminal A: estrogen receptor-positive and progesterone receptor-positive, ErbB2-negative), BT474 (luminal B: estrogen receptor/progesterone receptor/ErbB2-positive), SKBR3 (HER2-like: estrogen receptor/progesterone receptor-negative, ErbB2-positive), and MDA-MB231 (basal-like: estrogen receptor/progesterone receptor/ErbB2-negative). We demonstrated that docetaxel-induced apoptosis and survivin upregulation (MCF7 p = 0.002, BT474 p = 0.001, SKBR3 p = 0.001) in luminal A/B and HER2-like cells, while it induced mainly necrosis and a lower rate of survivin upregulation (MDA-MB231 p = 0.035) in basal-like cells. Wortmannin, a p-Akt inhibitor, was able to revert surviving upregulation and, at the same time, induced an increase of docetaxel-dependent apoptosis, suggesting that reduced levels of survivin can sensitize tumor cells to apoptosis. These data show that the analyzed breast cancer cell lines respond differently to docetaxel, depending on their receptor expression profile and molecular phenotype. Yet, these data confirm that one of the pathways involved in taxane-related chemoresistance is the upregulation of survivin. Further studies on the molecular mechanisms of chemoresistance and on the different modalities of apoptosis induced by chemotherapeutic agents are requested to better understand how cancer cells evade cell death, in order to design new kind of anticancer agents and survivin could represent a future target for this kind of research.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Proteínas Inibidoras de Apoptose/genética , Taxoides/farmacologia , Regulação para Cima/genética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Linhagem Celular Tumoral , Docetaxel , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Fenótipo , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Survivina , Regulação para Cima/efeitos dos fármacos
16.
Clin Chem Lab Med ; 52(10): 1465-72, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24803611

RESUMO

BACKGROUND: Procalcitonin (PCT) is currently the most studied infection biomarker and its blood levels seem to mirror the severity of illness and outcome. PCT is widely used together with other biomarkers, such as white blood cells (WBC) count and C reactive protein (CRP), in order to guide antibiotic therapy. This study aimed to verify the diagnostic and prognostic power of WBC, CRP and PCT in patients with suspected infection in emergency department (ED). METHODS: A total of 513 patients presenting to the ED with signs/symptoms of local infections or sepsis were enrolled. APACHEII score and in-hospital death were recorded. Patients were subdivided into quartiles by age, and the biomarkers were measured at baseline. Receiver operating characteristics (ROC) curves for evaluating diagnostic and prognostic role of PCT, CRP and WBC were calculated for each variable alone and combined. RESULTS: When compared each other for PCT, CRP, and WBC there was no significant difference between the four subgroups. A direct correlation between PCT and WBC was found in the II, III, and IV quartiles (the highest correlation, r=0.34, p<0.0003). PCT alone or when combined with WBC showed the best diagnostic and prognostic power at ROC analysis. CONCLUSIONS: Our data demonstrate that WBC, but more CRP and PCT are reliable diagnostic and prognostic biomarkers, when considered in combination and with severity clinical score. PCT confirms its stronger usefulness as a diagnostic marker of sepsis. A multi-diagnostic tools approach is fundamental to perform a correct and rapid diagnosis of infection and sepsis in ED.


Assuntos
Proteína C-Reativa/metabolismo , Calcitonina/sangue , Serviço Hospitalar de Emergência , Contagem de Leucócitos , Precursores de Proteínas/sangue , Sepse/sangue , Sepse/diagnóstico , Idoso , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Feminino , Humanos , Masculino , Prognóstico , Reprodutibilidade dos Testes
17.
Clin Chem Lab Med ; 52(10): 1499-505, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24887961

RESUMO

BACKGROUND: Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). METHODS: Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. RESULTS: The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. CONCLUSIONS: This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Galectina 3/metabolismo , Hipertensão/metabolismo , Hipertensão/patologia , Miocárdio/patologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Eletrocardiografia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade
18.
Clin Chem Lab Med ; 52(10): 1457-64, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24803610

RESUMO

BACKGROUND: With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients' risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea. METHODS: We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed. RESULTS: A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum-minimum): 31 (0-905) versus 8 (0-13) pmol/L. Median copeptin value at admission was 42 (0-905) pmol/L in acute heart failure patients and 20 (0-887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001). CONCLUSIONS: In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.


Assuntos
Dispneia/sangue , Dispneia/diagnóstico , Glicopeptídeos/sangue , Admissão do Paciente/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Idoso , Dispneia/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Determinação de Ponto Final , Feminino , Humanos , Masculino , Readmissão do Paciente , Prognóstico
19.
Am J Emerg Med ; 32(4): 334-41, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24559907

RESUMO

INTRODUCTION: Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency department patients with dyspnea. METHODS: To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF). RESULTS: Five hundred one patients were enrolled. Procalcitonin and MR-proADM values at admission and at 72 hours were significantly (P < .001) predictive for 30-day mortality: baseline PCT with an area under the curve (AUC) of 0.70 and PCT at 72 hours with an AUC of 0.61; baseline MR-proADM with an AUC of 0.62 and MR-proADM at 72 hours with an AUC of 0.68. As for 90-day mortality, both PCT and MR-proADM baseline and 72 hours values showed a significant (P < .0001) predictive ability: baseline PCT with an AUC of 0.73 and 72 hours PCT with an AUC of 0.64; baseline MR-proADM with an AUC of 0.66 and 72 hours MR-proADM with an AUC of 0.71. In AHF, group biomarkers predicted rehospitalization and mortality at 90 days, whereas in AHF + NO AHF group, they predict mortality at 30 and 90 days. CONCLUSIONS: In patients admitted for dyspnea, assessment of PCT plus MR-proADM improves risk stratification and management. Combined use of biomarkers is able to predict in the total cohort both rehospitalization and death at 30 and 90 days.


Assuntos
Adrenomedulina/sangue , Calcitonina/sangue , Dispneia/sangue , Dispneia/mortalidade , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Pneumopatias/sangue , Pneumopatias/mortalidade , Precursores de Proteínas/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Peptídeo Relacionado com Gene de Calcitonina , Serviço Hospitalar de Emergência , Feminino , Mortalidade Hospitalar , Humanos , Itália/epidemiologia , Masculino , Admissão do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco
20.
Nutrients ; 16(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38257147

RESUMO

School is one of the main settings where it is useful to guarantee health promotion actions, as it is well known that diet and eating habits that are shaped in the early stages of life are maintained through adulthood. The objective of this study was to carry out the "Healthy Snack" project to promote nutritional education in primary schools in the Province of Belluno in the 2022-2023 school year, in which 925 students were enrolled, and to evaluate the intervention in terms of changes in eating habits during their school breaks. Following the workshops performed by the healthcare workers (HCWs), medals were awarded, taking into account the quality of the participating students' mid-morning snacks, considering the food pyramid. The results collected in the annual survey period were related to the type and quantity of snacks consumed at school, and allowed students to gain a final score, comparing the period before and after the educational intervention to demonstrate the effectiveness of the actions promoted by HCWs and the increased nutritional quality of meals. In light of this evidence, public health strategies must continue to emphasize the importance of implementing health promotion interventions and actions aimed at children in order to prevent weight gain in this age group, and the potential development of cardiometabolic pathologies over their lifetime.


Assuntos
Distinções e Prêmios , Lanches , Criança , Humanos , Refeições , Instituições Acadêmicas , Comportamento Alimentar
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