SQC - Artigos publicados em revistas indexadas na Pubmed/Medline
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- Advanced Glycation End Products Evolution after Pancreas-Kidney Transplantation: Plasmatic and Cutaneous AssessmentsPublication . Martins, L.; Oliveira, J.; Vizcaíno, J.; Fonseca, R.; Gouveia, C.; Silva, D.; Castro-Henriques, A.; Noronha, I.; Rodrigues, A.Diabetes mellitus leads to increased Advanced Glycation End Products (AGE) production, which has been associated with secondary diabetic complications. Type 1 diabetic patients undergoing pancreas-kidney transplantation (SPKT) can restore normoglycemia and renal function, eventually decreasing AGE accumulation. We aimed to prospectively study AGE evolution after SPKT. Circulating AGE were assessed in 20 patients, at time 0 (T0), 3 months (T3), 6 months (T6), and 12 months (T12) after successful SPKT. Global AGE and carboxymethyllysine (CML) were analyzed, as well as advanced oxidation protein products (AOPP). Skin biopsies were obtained at T0 and T12. Immunohistochemistry with anti-AGE antibody evaluated skin AGE deposition. AGE mean values were 16.8 ± 6.4 μg/mL at T0; 17.1 ± 3.8 μg/mL at T3; 17.5 ± 5.6 μg/mL at T6; and 16.0 ± 5.2 μg/mL at T12. CML mean values were 0.94 ± 0.36 ng/mL at T0; 1.11 ± 0.48 ng/mL at T3; 0.99 ± 0.42 ng/mL at T6; and 0.78 ± 0.38 ng/mL at T12. AOPP mean values were 130.1 ± 76.8 μMol/L at T0; 137.3 ± 110.6 μMol/L at T3; 116.4 ± 51.2 μMol/L at T6; and 106.4 ± 57.9 μMol/L at T12. CML variation was significant (P = 0.022); AOPP variation was nearly significant (P = 0.076). Skin biopsies evolved mostly from a cytoplasmic diffuse to a peripheral interkeratinocytic immunoreaction pattern; in 7 cases, a reduction in AGE immunoreaction intensity was evident at T12. In conclusion, glycoxidation markers decrease, plasmatic and on tissues, may start early after SPKT. Studies with prolonged follow-up may confirm these data.
- Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterolPublication . Fonseca, Liliana; Paredes, Sílvia; Ramos, Helena; Oliveira, José Carlos; Palma, IsabelBackground: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. Methods: A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. Results: In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). Conclusions: These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients' evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.
- Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative MetabolitePublication . Duarte, D.; Amaro, F.; Silva, I.; Silva, D.; Fresco, P.; Oliveira, José Carlos; REGUENGO, HENRIQUE; Gonçalves, J.; Vale, N.Carbidopa is used for the treatment of Parkinson's disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa.
- Does Cystatin C have a role as metabolic surrogate in peritoneal dialysis beyond its association with residual renal function?Publication . Leal Moreira, Carla; Cunha, Liliana; Correia, Sofia; Silva, Filipa; Castro, Ana; Tavares, Joana Manuel; Carvalho, Maria João; Oliveira, José Carlos; Santos, Maria Olivia; Cabrita, Antonio; Rodrigues, AnabelaIntroduction: It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes. Aim: To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients. Methods: Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m2. Results: Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease (p = 0.28), nor with glycated hemoglobin (p = 0.19) or c-reactive protein (p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease (p = 0.038); neither cystatin C (p = 0.096) nor minimal residual renal function (p = 0.756) reached a significant association with cardiovascular disease. Conclusions: In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.
- First Trimester Aneuploidy Screening Program for Preeclampsia Prediction in a Portuguese Obstetric PopulationPublication . Teixeira, C.; Tejera, E.; Martins, H.; Pereira, A.; Costa-Pereira, A:; Rebelo, I.Objective. To evaluate the performance of a first trimester aneuploidy screening program for preeclampsia (PE) prediction in a Portuguese obstetric population, when performed under routine clinical conditions. Materials and Methods. Retrospective cohort study of 5672 pregnant women who underwent routine first trimester aneuploidy screening in a Portuguese university hospital from January 2009 to June 2013. Logistic regression-based predictive models were developed for prediction of PE based on maternal characteristics, crown-rump length (CRL), nuchal translucency thickness (NT), and maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) and free beta-subunit of human chorionic gonadotropin (free β-hCG). Results. At a false-positive rate of 5/10%, the detection rate for early-onset (EO-PE) and late-onset (LO-PE) PE was 31.4/45.7% and 29.5/35.2%, respectively. Although both forms of PE were associated with decreased PAPP-A, logistic regression analysis revealed significant contributions from maternal factors, free β-hCG, CRL, and NT, but not PAPP-A, for prediction of PE. Conclusion. Our findings support that both clinical forms of EO-PE and LO-PE can be predicted using a combination of maternal history and biomarkers assessed at first trimester aneuploidy screening. However, detection rates were modest, suggesting that models need to be improved with additional markers not included in the current aneuploidy screening programs.
- Hepatocyte growth factor signalizes peritoneal membrane failure in peritoneal dialysisPublication . Bernardo, A.; Oliveira, J.; Santos, O.; Carvalho, M.; Cabrita, A.; Rodrigues, A.BACKGROUND: Hepatocyte growth factor (HGF) counteracts peritoneal fibrosis in animal models and in-vitro studies, but no study explored effluent HGF in peritoneal dialysis (PD) patients with ultrafiltration failure (UFF). Our aim was to assess the relationship between effluent HGF with UF profile, free water transport (FWT) and small-solute transport. METHODS: We performed 4-hour, 3.86% PET with additional UF measurement at 60 minutes in 68 PD patients. MTACcreatinine, FWT, small-pore ultrafiltration, and effluent HGF were quantified. RESULTS: Effluent HGF negatively correlated with UF (r=-0.80, p=0.009) and FWT (r=-0.69, p=0.04). Patients with UFF had higher dialysate HGF (103 pg/mL vs 77 pg/mL, p=0.018) and, although not statistically significant, those with FWT compromise had also higher dialysate HGF compared with subgroup of UFF without FWT compromise (104 pg/mL vs 88 pg/mL, p=0.08). FWT≤45% without clinical UFF was documented in some patients who also had increased effluent HGF. CONCLUSIONS: Dialysate HGF concentration is significantly higher among patients with UFF, specially, if FWT is impaired, being a sign of peritoneal membrane deterioration.
- Importance of immunogenicity testing for cost-effective management of psoriasis patients treated with adalimumabPublication . Mota, F.; Neves, E.; Oliveira, J.; Selores, M.; Torres, T.INTRODUCTION: Up to 30% of patients treated with anti-tumor necrosis factor drugs do not respond adequately, and up to 50% lose response over time. Immunogenicity is now known to be one of the main causes of this loss of response. METHODS: Serum levels of adalimumab and anti-drug antibodies (ADAs) were measured in 19 patients with psoriasis. RESULTS: Eighty-nine percent of the patients were responders (Psoriasis Area Severity Index (PASI) > 75) and 11% were partial responders (PASI 50-75). The serum levels of adalimumab were lower than the cutoff in both of the partial responders and the ADAs were high, whereas the other 17 patients had adalimumab levels above the cutoff and low ADA levels. Both partial responders were obese and none of them were taking methotrexate. Both patients switched to ustekinumab, and a PASI 90 response was observed after 16 weeks. CONCLUSION: Immunogenicity is a risk of biological drugs. In this work, the detection of low levels of adalimumab and high levels of ADAs using a sandwich ELISA correlated with loss of clinical response. Testing immunogenicity and the drug pharmacokinetics of biological drugs in psoriasis patients will probably be part of the daily management of these patients in the future.
- Influence of spironolactone on matrix metalloproteinase-2 in acute decompensated heart failurePublication . Ferreira, J.; Santos, M.; Oliveira, J.; Marques, I.; Bettencourt, P.; Cyrne-Carvalho, H.Matrix metalloproteinases (MMPs) are a family of enzymes important for the resorption of extracellular matrices, control of vascular remodeling and repair. Increased activity of MMP2 has been demonstrated in heart failure, and in acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has been demonstrated along with successful treatment.
- Molecular epidemiology of imipenem‐resistant Acinetobacter haemolyticus and Acinetobacter baumannii isolates carrying plasmidmediated OXA‐40 from a Portuguese hospital.Publication . QUINTEIRA, S.; GROSSO, F.; RAMOS, H.; PEIXE, L.Antimicrob Agents Chemother. 2007 Sep;51(9):3465-6. Epub 2007 Jul 2. Molecular epidemiology of imipenem-resistant Acinetobacter haemolyticus and Acinetobacter baumannii isolates carrying plasmid-mediated OXA-40 from a Portuguese hospital. Quinteira S, Grosso F, Ramos H, Peixe L. PMID: 17606684 [PubMed - indexed for MEDLINE]
- PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital PracticePublication . Ferreira, Abigail; Martins, Helena; Oliveira, José Carlos; Lapa, Rui; Vale, NunoThe importance of closely observing patients receiving antibiotic therapy, performing therapeutic drug monitoring (TDM), and regularly adjusting dosing regimens has been extensively demonstrated. Additionally, antibiotic resistance is a contemporary concerningly dangerous issue. Optimizing the use of antibiotics is crucial to ensure treatment efficacy and prevent toxicity caused by overdosing, as well as to combat the prevalence and wide spread of resistant strains. Some antibiotics have been selected and reserved for the treatment of severe infections, including amikacin, gentamicin, tobramycin, and vancomycin. Critically ill patients often require long treatments, hospitalization, and require particular attention regarding TDM and dosing adjustments. As these antibiotics are eliminated by the kidneys, critical deterioration of renal function and toxic effects must be prevented. In this work, clinical data from a Portuguese cohort of 82 inpatients was analyzed and physiologically based pharmacokinetic (PBPK) modeling and simulation was used to study the influence of different therapeutic regimens and parameters as biological sex, body weight, and renal function on the biodistribution and pharmacokinetic (PK) profile of these four antibiotics. Renal function demonstrated the greatest impact on plasma concentration of these antibiotics, and vancomycin had the most considerable accumulation in plasma over time, particularly in patients with impaired renal function. Thus, through a PBPK study, it is possible to understand which pharmacokinetic parameters will have the greatest variation in a given population receiving antibiotic administrations in hospital context.