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1.
Pharmacology ; 109(3): 147-155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432197

RESUMO

INTRODUCTION: The prevalence of potential drug-drug interactions (pDDIs) is becoming a major safety concern, as it has been previously linked to a significant number of adverse drug events and could have serious consequences for patients, including death. This is especially relevant for patients with chronic renal failure, as they are particularly vulnerable to drug-drug interactions. The aim of this study was to evaluate the prevalence and associated factors of pDDIs in patients receiving chronic peritoneal dialysis. METHODS: An observational, cross-sectional study was conducted on consecutive peritoneal dialysis patients attending four tertiary care hospitals for regular monthly examination. The primary outcome was the number of pDDIs identified using Lexicomp. Potential predictors were determined using multiple linear regression. RESULTS: Total number of patients included in the study was 140. The results showed that pDDIs were highly prevalent, especially in patients who use antiarrhythmics (p = 0.001), have diabetes mellitus (p = 0.001), recently started peritoneal dialysis (p = 0.003), or have higher number of prescribed drugs (p < 0.001). Number of prescribed drugs (p < 0.001) remained a significant predictor of high-risk pDDIs in addition to the female gender (p = 0.043). CONCLUSION: Clinicians should be particularly cautious when prescribing multiple medications to high-risk patients, such as peritoneal dialysis patients, to mitigate the risk of drug-drug interactions and associated adverse health outcomes.


Assuntos
Interações Medicamentosas , Diálise Peritoneal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Fatores de Risco , Idoso , Adulto , Falência Renal Crônica/terapia , Prevalência , Polimedicação
2.
Med Princ Pract ; 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37734333

RESUMO

OBJECTIVES: We hypothesized the existence of distinct phenotype-based groups within the very heterogeneous population of patients of heart failure with preserved ejection fraction (HFpEF) and using an unsupervised hierarchical clustering applied to plasma concentration of various biomarkers. We sought to characterize them as "biomarker phenotypes" and to conclude differences in their overall characteristics. SUBJECTS AND METHODS: A cross-sectional study was conducted on 75 patients with HFpEF. An agglomerative hierarchical clustering was performed using the concentrations of cardiac remodeling biomarkers, BNP and cystatin C. RESULTS: According to the obtained heat map of this analysis, we concluded two distinctive biomarker phenotypes within the HFpEF. The "remodeled phenotype" presented with significantly higher concentrations of cardiac remodeling biomarkers and cystatin C (p < 0.001), higher prevalence of myocardial infarction (p = 0.047), STEMI (p = 0.045), atrial fibrillation (p = 0.047) and anemia: lower erythrocytes count (p=0.037), hemoglobin concentration (p = 0.034) and hematocrit (p = 0.046), compared to "non-remodeled phenotype". Echocardiography showed that patients within "remodeled phenotype" had significantly increased parameters of left ventricular remodeling: left ventricular mass index (p < 0.001), left ventricular mass (p = 0.001), diameters of the interventricular septum (p = 0.027) and posterior wall (p = 0.003) and function alterations, intermediate pauses duration >2.0 seconds (p < 0.006). CONCLUSION: Unsupervised hierarchical clustering applied to plasma concentration of various biomarkers in patients with HFpEF enables the identification of two biomarker phenotypes, significantly different in clinical characteristics and cardiac structure and function, whereas one phenotype particularly relates to patients with reduced ejection fraction. These findings imply distinct underlying pathophysiology within a unique cohort of HFpEF.

3.
Pharmacology ; 108(1): 1-7, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36446348

RESUMO

INTRODUCTION: Inappropriate prescribing is common in patients with end-stage kidney disease, especially in those over 65 years of age. Our study aimed to reveal potentially inappropriate drug prescribing in patients on peritoneal dialysis (PD) and explore factors associated with this phenomenon. METHODS: The research was designed as an observational, cross-sectional study on a convenient sample of 145 consecutive patients with PD who attended the four tertiary-care hospitals in Serbia. The main outcome was the extent of inappropriate prescribing, as assessed by the medication appropriateness index, and potential predictors were tested by multiple linear regression. RESULTS: Inappropriate prescribing was a widespread phenomenon among patients on PD. The main factors that promote inappropriate prescribing in this subgroup of patients on kidney replacement therapy are comorbidities (p = 0.000), increased body weight (p = 0.022), a number of prescribed drugs (p = 0.000), and arterial hypertension on examination (p = 0.030). On the other hand, drinking alcohol and higher systolic blood pressure were associated with a lower inappropriate prescribing. CONCLUSION: In order to prevent the occurrence of inappropriate prescribing and its severe health or economic consequences, clinicians should pay special attention when prescribing new drugs to high-risk patients.


Assuntos
Prescrição Inadequada , Diálise Peritoneal , Humanos , Prescrição Inadequada/prevenção & controle , Estudos Transversais , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados , Diálise Peritoneal/efeitos adversos
4.
Front Cardiovasc Med ; 8: 691513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395559

RESUMO

Background: Renalase has been implicated in chronic heart failure (CHF); however, nothing is known about renalase discriminatory ability and prognostic evaluation. The aims of the study were to assess whether plasma renalase may be validated as a predictor of ischemia in CHF patients stratified to the left ventricular ejection fraction (LVEF) and to determine its discriminatory ability coupled with biomarkers representing a range of heart failure (HF) pathophysiology: brain natriuretic peptide (BNP), soluble suppressor of tumorigenicity (sST2), galectin-3, growth differentiation factor 15 (GDF-15), syndecan-1, and cystatin C. Methods: A total of 77 CHF patients were stratified according to the LVEF and were subjected to exercise stress testing. Receiver operating characteristic curves were constructed, and the areas under curves (AUC) were determined, whereas the calibration was evaluated using the Hosmer-Lemeshow statistic. A DeLong test was performed to compare the AUCs of biomarkers. Results: Independent predictors for ischemia in the total HF cohort were increased plasma concentrations: BNP (p = 0.008), renalase (p = 0.012), sST2 (p = 0.020), galectin-3 (p = 0.018), GDF-15 (p = 0.034), and syndecan-1 (p = 0.024), whereas after adjustments, only BNP (p = 0.010) demonstrated predictive power. In patients with LVEF <45% (HFrEF), independent predictors of ischemia were BNP (p = 0.001), renalase (p < 0.001), sST2 (p = 0.004), galectin-3 (p = 0.003), GDF-15 (p = 0.001), and syndecan-1 (p < 0.001). The AUC of BNP (0.837) was statistically higher compared to those of sST2 (DeLong test: p = 0.042), syndecan-1 (DeLong: p = 0.022), and cystatin C (DeLong: p = 0.022). The AUCs of renalase (0.753), galectin-3 (0.726), and GDF-15 (0.735) were similar and were non-inferior compared to BNP, regarding ischemia prediction. In HFrEF patients, the AUC of BNP (0.980) was statistically higher compared to those of renalase (DeLong: p < 0.001), sST2 (DeLong: p < 0.004), galectin-3 (DeLong: p < 0.001), GDF-15 (DeLong: p = 0.001), syndecan-1 (DeLong: p = 0.009), and cystatin C (DeLong: p = 0.001). The AUC of renalase (0.814) was statistically higher compared to those of galectin-3 (DeLong: p = 0.014) and GDF-15 (DeLong: p = 0.046) and similar to that of sST2. No significant results were obtained in the patients with LVEF >45%. Conclusion: Plasma renalase concentration provided significant discrimination for the prediction of ischemia in patients with CHF and appeared to have similar discriminatory potential to that of BNP. Although further confirmatory studies are warranted, renalase seems to be a relevant biomarker for ischemia prediction, implying its potential contribution to ischemia-risk stratification.

5.
Mol Cell Biochem ; 476(11): 4167-4175, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34327604

RESUMO

The aim of our study was to investigate the effects of one-month consumption of polyphenol-rich standardized Aronia melanocarpa extract (SAE) on redox status in anemic hemodialysis patients. The study included 30 patients (Hb < 110 g/l, hemodialysis or hemodiafiltration > 3 months; > 3 times week). Patients were treated with commercially available SAE in a dose of 30 ml/day, for 30 days. After finishing the treatment blood samples were taken to evaluate the effects of SAE on redox status. Several parameters of anemia and inflammation were also followed. After the completion of the treatment, the levels of superoxide anion radical and nitrites significantly dropped, while the antioxidant capacity improved via elevation of catalase and reduced glutathione. Proven antioxidant effect was followed by beneficial effects on anemia parameters (increased hemoglobin and haptoglobin concentration, decreased ferritin and lactate dehydrogenase concentration), but SAE consumption didn't improve inflammatory status, except for minor decrease in C-reactive protein. The consumption of SAE regulates redox status (reduce the productions of pro-oxidative molecules and increase antioxidant defense) and has beneficial effects on anemia parameters. SAE could be considered as supportive therapy in patients receiving hemodialysis which are prone to oxidative stress caused by both chronic kidney disease and hemodialysis procedure. Additionally, it could potentially be a good choice for supplementation of anemic hemodialysis patients. TRN: NCT04208451 December 23, 2019 "retrospectively registered".


Assuntos
Anemia/dietoterapia , Inflamação/dietoterapia , Photinia/química , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Diálise Renal/métodos , Anemia/metabolismo , Anemia/patologia , Antioxidantes/administração & dosagem , Feminino , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Oxirredução , Resultado do Tratamento
6.
Tohoku J Exp Med ; 250(4): 233-242, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32295985

RESUMO

Soluble suppressor of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor (GDF)-15 and syndecan-1 represent biomarkers of cardiac remodeling, involved in heart failure (HF) progression. We hypothesize that their plasma concentrations, together with brain natriuretic peptide (BNP), are different in HF stratified by ejection fraction (EF), demonstrating correlations with echocardiographic parameters that indicate left ventricular (LV) hypertrophy; LV mass index (LVMI) and posterior wall and septum diameters. HF patients (n = 77) were classified according to EF: reduced EF < 40% (HFrEF), mid-range EF = 40-49% (HFmrEF), preserved EF > 50% (HFpEF). We found that plasma concentrations of four cardiac remodeling biomarkers were highest in HFrEF and lowest in HFpEF, p < 0.001. In HFpEF, remodeling biomarkers independently correlated with LVMI: sST2 (p = 0. 002), galectin-3 (p < 0.001), GDF-15 (p = 0.011), and syndecan-1 (p = 0.006), whereas galectin-3 correlated after multivariable adjustments (p = 0.001). Independent correlates of septum and posterior wall diameters, in HFpEF, were sST2 (p = 0.019; p = 0.026), galectin-3 (p = 0.011; p = 0.009), GDF-15 (p = 0.007; p = 0.001), and syndecan-1 (p = 0.005; p = 0.002). In HFrEF, only sST2, adjusted, correlated with LVMI (p = 0.010), whereas BNP correlated with LVMI (p = 0.002) and EF (p = 0.001). GDF-15 correlated with diastolic dysfunction in HFpEF (p = 0.046) and HFrEF (p = 0.024). Cardiac remodeling biomarkers are potential circulating indicators of LV hypertrophy in HFpEF, which may ensure timely recognition of disease progression among high-risk patients.


Assuntos
Biomarcadores/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/fisiopatologia , Volume Sistólico/fisiologia , Remodelação Ventricular , Estudos de Casos e Controles , Ecocardiografia , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão
7.
Curr Med Res Opin ; 36(6): 909-919, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32297799

RESUMO

Objective: Heart failure (HF) represents a huge socio-economic burden. It has been demonstrated, experimentally, that renalase, a newly discovered protein, prevents cardiac hypertrophy and adverse remodeling, which is seen in HF. We postulated the following aims: to investigate associations of renalase with biomarkers of cardiac remodeling: galectin-3, soluble suppression of tumorigenicity, (sST2), growth differentiation factor 15 (GDF-15) and syndecan-1, myocardial stretch (BNP) and cardio-renal axis (cystatin C) in HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) to determine whether renalase, in combination with left ventricular ejection fraction (LVEF), represents a risk factor for plasma elevation in biomarkers.Methods: We classified HF patients (n = 76) according to LVEF (preserved/reduced), applied a median plasma renalase (113 ng/mL) as a cut-off value (low/high) and created four subgroups of HF patients: HFpEF/low renalase (n = 19), HFrEF/low renalase (n = 19), HFrEF/high renalase (n = 32) and HFpEF/high renalase (n = 6). A control group (n = 35) consisted of healthy volunteers.Results: Plasma concentrations of evaluated biomarkers were determined using an ELISA technique and were highest in HF patients with reduced EF (p < .001, respectively), and renalase's positive correlations were obtained relating to all biomarkers: galectin-3 (r = 0.913; p < .001), sST2 (r = 0.965; p < .001), GDF-15 (r = 0.887; p < .001), syndecan-1 (r = 0.922; p < .001), BNP (r = 0.527; p < .001) and cystatin C (r = 0.844; p < .001) and strong and negative correlation with LVEF (r = -0.456, p < .001). Increased renalase, regardless of the EF (preserved/reduced), was shown to be an independent risk factor for an increase in all evaluated cardiac remodeling biomarkers, p < .001, respectively. However, increased renalase and reduced EF was the only independent risk factor for BNP and cystatin C elevation, p < .001, respectively. Results after multivariable adjustments (age/gender) were identical.Conclusion: When elevated plasma renalase and HF are present, regardless of EF being reduced or preserved, that represents a significant risk factor for increase in cardiac remodeling biomarker plasma concentrations. However, only elevated renalase and reduced EF demonstrated significance as a risk factor for BNP and cystatin C plasma elevation. Renalase may be considered a promising molecule for the improved predictive abilities of conventional biomarkers and is worthy of further investigation.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Monoaminoxidase/sangue , Volume Sistólico/fisiologia , Remodelação Ventricular/fisiologia , Idoso , Biomarcadores/sangue , Doença Crônica , Feminino , Fator 15 de Diferenciação de Crescimento/sangue , Insuficiência Cardíaca/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Função Ventricular Esquerda
8.
Int Urol Nephrol ; 50(1): 63-70, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29052086

RESUMO

The objective of this prospective follow-up trial was to ascertain whether the urinary kidney injury molecule-1 (uKIM-1) associates with tumor tissue (tKIM-1) expression and with the pathological characteristics of clear renal cell carcinoma (cRCC) in radically nephrectomized (RN) and/or in partially nephrectomized (PN) patients with cRCC, pre- and postoperatively. This clinical study included 40 patients subjected to RN/PN (cRCC group) and 30 healthy volunteers (control group). Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine. Immunohistochemical staining (monoclonal anti-human anti-TIM-1/KIM-1/HAVCR antibody) was used for semiquantitative analysis of the tKIM-1 expression and expressed as a score (% KIM-1 positively stained tubules). Both markers were interpreted in terms of the tumor characteristics comprising tumor size, Fuhrman grade, pathological (pT) stage, tumor/nodes/metastasis (TNM) stage, lymphovascular invasion and type of surgery RN/PN. Preoperative uKIM-1 was significantly higher in the cRCC group compared to controls, such as uKIM-1 was statistically higher in RN than in PN patients. Postoperatively, uKIM-1 decreased to control values. Expression of tKIM-1 was documented in all nephrectomized patients. Significant associations were achieved between uKIM-1 and tKIM-1 and with considered tumor characteristics, especially with tumor size and grade. Based on the accomplished associations, we found uKIM-1 as a highly sensitive marker for cRCC diagnosis. The clinical trial registration number: 1110-2012.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/secundário , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Túbulos Renais/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/urina , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/urina , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Renais/cirurgia , Neoplasias Renais/urina , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Nefrectomia/métodos , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Carga Tumoral
9.
J BUON ; 22(1): 162-169, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28365950

RESUMO

PURPOSE: Considering the contradictory literature data about the role of nitric oxide (NO) in colon carcinogenesis, the purpose of this study was to examine the changes of L-arginine metabolites in colon cancer and surrounding tissue as possible molecular markers of tumor behavior after surgery and the possibility of NO synthesis modulation in new individualized therapeutic strategies. METHODS: The study encompassed 50 patients who underwent surgery for colorectal cancer (CRC). The three tissue specimens were taken by surgery (tumor, adjacent and healthy tissue) and the concentrations of NO2+NO3, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) were determined in the tissue specimens. RESULTS: The results proved higher NO2+NO3 concentrations in adjacent tissue compared to the tumor, implicating high angiogenic potential of the tumor-surrounding tissue, which could have clinical importance in the assessment of the probability of tumor local recurrence and metastasis. Increased ADMA concentrations in tumor tissue associated with low NO levels, could lead to new therapeutic strategies directed to the use of inhibitors of NO synthesis as ideal candidates for molecular therapy of CRC. ADMA concentration in adjacent tissue was an independent predictor of distant metastasis. CONCLUSIONS: The obtained results suggest that determination of the examined biomarkers in CRC and adjacent tissue samples could give useful information about tumor proliferative and angiogenic potential, which in turn could enable individualization of therapy and the choice of proper adjuvant therapy in patients with CRC.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Óxido Nítrico/biossíntese , Arginina/análogos & derivados , Arginina/análise , Biomarcadores Tumorais/análise , Neoplasias Colorretais/patologia , Humanos
10.
Srp Arh Celok Lek ; 144(3-4): 232-9, 2016.
Artigo em Sérvio | MEDLINE | ID: mdl-27483573

RESUMO

`Hematologic malignancies (leukemia, lymphoma, multiple myeloma, et al.), as well as solid tumours (renal, liver, lung, ovarian, etc.), can lead to acute or chronic renal failure.The most common clinical manifestation is acute renal failure within the tumour lysis syndrome (TLS). It is characterized by specific laboratory and clinical criteria in order to prove that kidney disorders result from cytolysis of tumour cells after chemotherapy regimen given, although on significantly fewer occasions it is likely to occur spontaneously or after radiotherapy. Essentially, failure is the disorder of functionally conserved kidney or of kidney with varying degrees of renal insufficiency, which render the kidney impaired and unable to effectively eliminate the end products of massive cytolysis and to correct the resulting disorders: hyperuricemia, hyperkalemia, hypocalcaemia, hyperphosphatemia, and others. The risk of TLS depends on tumour size, proliferative potential of malignant cells, renal function and the presence of accompanying diseases and disorders. Hydration providing adequate diuresis and administration of urinary suppressants (allopurinol, febuxostat) significantly reduce the risk of developing TLS. If prevention of renal impairment isn't possible, the treatment should be supplemented with hemodynamic monitoring and pharmacological support, with the possible application of recombinant urate-oxidase enzyme (rasburicase). Depending on the severity of azotemia and hydroelectrolytic disorders, application of some of the methods of renal replacement therapy may be considered.


Assuntos
Injúria Renal Aguda/terapia , Síndrome de Lise Tumoral/terapia , Injúria Renal Aguda/etiologia , Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Hidratação , Humanos , Hiperpotassemia/etiologia , Hiperpotassemia/terapia , Hiperfosfatemia/etiologia , Hiperfosfatemia/terapia , Hiperuricemia/etiologia , Hiperuricemia/terapia , Hipocalcemia/etiologia , Hipocalcemia/terapia , Terapia de Substituição Renal , Síndrome de Lise Tumoral/complicações , Urato Oxidase/uso terapêutico
11.
Vojnosanit Pregl ; 73(3): 266-72, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27295912

RESUMO

BACKGROUND/AIM: Kidney injury molecule-1 (KIM-1) and aquaporin-1 (AQP-1) are potential early urinary biomarkers of clear renal cell carcinoma (cRCC). The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy) in patients with cRCC. METHODS: Urinary concentrations of urinary KIM-1 (uKIM-1) and urinary AQP-1 (uAQP-1) were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. RESULTS: The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ? 1.120 ng/mg urinary creatinine (Ucr)] were significantly greater compared with controls (healthy volunteers) (0.210 +/- 0.082 ng/mgUcr) (p = 0.0227). Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 +/- 0.099 ng/mgUcr vs 0.210 + 0.082 ng/mgUcr, respectively). The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 +/- 0.092 ng/mgUcr) compared with the control group (0.202 +/- 0.078 ng/mgUcr) (p = 0.0014). Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. CONCLUSION: uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy.


Assuntos
Aquaporina 1/urina , Biomarcadores Tumorais/urina , Carcinoma de Células Renais/urina , Neoplasias Renais/urina , Glicoproteínas de Membrana/urina , Adulto , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos de Casos e Controles , Feminino , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Nefrectomia , Estudos Prospectivos , Receptores Virais , Carga Tumoral
12.
Comput Biol Med ; 63: 187-95, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26093786

RESUMO

Circulating tumor cells (CTCs) are known to be a harbinger of cancer metastasis. The CTCs are known to circulate as individual cells or as a group of interconnected cells called CTC clusters. Since both single CTCs and CTC clusters have been detected in venous blood samples of cancer patients, they needed to traverse at least one capillary bed when crossing from arterial to venous circulation. The diameter of a typical capillary is about 7µm, whereas the size of an individual CTC or CTC clusters can be greater than 20µm and thus size exclusion is believed to be an important factor in the capillary arrest of CTCs - a key early event in metastasis. To examine the biophysical conditions needed for capillary arrest, we have developed a custom-built viscoelastic solid-fluid 3D computational model that enables us to calculate, under physiological conditions, the maximal CTC diameter that will pass through the capillary. We show that large CTCs and CTC clusters can successfully cross capillaries if their stiffness is relatively small. Specifically, under physiological conditions, a 13µm diameter CTC passes through a 7µm capillary only if its stiffness is less than 500Pa and conversely, for a stiffness of 10Pa the maximal passing diameter can be as high as 140µm, such as for a cluster of CTCs. By exploring the parameter space, a relationship between the capillary blood pressure gradient and the CTC mechanical properties (size and stiffness) was determined. The presented computational platform and the resulting pressure-size-stiffness relationship can be employed as a tool to help study the biomechanical conditions needed for capillary arrest of CTCs and CTC clusters, provide predictive capabilities in disease progression based on biophysical CTC parameters, and aid in the rational design of size-based CTC isolation technologies where CTCs can experience large deformations due to high pressure gradients.


Assuntos
Capilares/patologia , Capilares/fisiopatologia , Simulação por Computador , Modelos Cardiovasculares , Células Neoplásicas Circulantes/patologia , Humanos , Metástase Neoplásica
14.
Srp Arh Celok Lek ; 143(1-2): 83-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25845258

RESUMO

INTRODUCTION: Granulomatosis with polyangitis (Wegener's) is an antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, which commonly involves the upper and lower respiratory tracts and kidneys. Central nervous system involvement is reported in less than 11%, and rarely present at onset. CASE OUTLINE: We report the case of a 41-year-old male patient with a high disease activity, large organ involvement, as well as central nervous system manifestations presented at onset.Treatment with intravenous pulse methylprednisolone, followed by the pulsed doses of cyclophosphamide was induced. After 6 months of cyclophosphamide pulse therapy a remission was achieved. Next, azathioprine was used for maintenance during the next 18 months.There were no disease flares during 24-month follow-up. CONCLUSION: Granulomatosis with polyangitis (Wegener's) with large organ involvement, affecting the central nervous system structures require a rapid diagnosis and intensive medication treatment in order to prevent or reduce irreversible damage. Our experience confirms the findings reported in the literature that the severe forms of the disease are associated with increased probability of achieving remission, which reflects increased responsiveness of such patients to immunosuppressant therapy.


Assuntos
Granulomatose com Poliangiite/diagnóstico , Adulto , Anticorpos Anticitoplasma de Neutrófilos , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Masculino , Metilprednisolona/uso terapêutico , Sistema Nervoso
15.
Med Glas (Zenica) ; 9(2): 174-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22926347

RESUMO

Kidney transplantation offers better quality of life in comparison to patient dialysis. Patients with endogenous creatinine clearance 30 mL/min/1.73m2 are introduced into the kidney transplant program. Every patient should be assessed for a degree of eligibility for the kidney transplant procedure. Basic principles of eligibility assessment include: patient education, assessment of patient's motivation level, medical risk assessment, as well as evaluation of psychosocial status and the level of family support. Medical risk assessment involves establishing the etiology of the primary kidney disease, cardiovascular status assessment, viral status assessment, risk assessment for renal graft thrombosis, screening for early malignancy detection, assessment of mineral metabolism and bone tissue disorders, and immunological risk assessment. Identification of patients with highest degree of kidney transplant eligibility shall decrease morbidity and mortality, reduce medical costs and improve the quality of life for these patients.


Assuntos
Definição da Elegibilidade , Transplante de Rim , Humanos , Medição de Risco , Listas de Espera
16.
Srp Arh Celok Lek ; 140(3-4): 221-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22650111

RESUMO

INTRODUCTION: Insulinomas are the most common endocrine tumours of the pancreas. They are more frequent in females, and they are commonly less than 2 cm in diameter. If conservative treatment of typical clinical symptoms fails, detailed diagnostic procedures are necessary and surgical treatment is indicated.The aim of this report was to emphasize the need of pancreatic resection when insulinoma is poorly visualized during surgery and when it is not possible to perform intraoperative ultrasonography. CASE OUTLINE: A 27-year-old female patient suffered from hypoglycaemic episodes during physical efforts and fasting periods. After examination, diagnostic procedures and preoperative preparation, laparoscopic surgery was performed. The tumour was less than 10 mm in diameter, and it could not be visualized during laparoscopic exploration. The body and the tail of the pancreas were mobilized using ultrasound scissors and the resection was performed by two Endo GIA staplers. The surgical specimen was removed in an endo-bag. The postoperative course was without complications and the glycemic level was normalized. Macroscopic examination of the resected specimen showed a solitary, poorly demarcated, dark grey lesion, 0.8 cm in diameter, with a solid consistence in comparison with the surrounding gland tissue. Histological examination showed a poorly demarcated, subcapsular tissue in this area, consisting of uniform, irregular, cubic and short cylindrical cells, organized in clusters with pseudoglandular and "zellballen" formations. CONCLUSION: In case when the insulinoma is so small in size that it cannot be visualized during operation, pancreas resection is a surgical procedure of choice. Laparoscopic surgery is preferred because of less postoperative complications and faster recovery.


Assuntos
Insulinoma/cirurgia , Laparoscopia , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Feminino , Humanos , Adulto Jovem
17.
Med Pregl ; 63(9-10): 674-80, 2010.
Artigo em Sérvio | MEDLINE | ID: mdl-21446098

RESUMO

INTRODUCTION Cardiovascular disease is a leading cause of death among hemodialysis patients. SECONDARY HYPERPARATHYROIDISM: Secondary hyperparathyroidism is one of the main factors for the development of cardiovascular complications among these patients. A high concentration of parathormone, hypercalcemia, hyperphosphatemia and high calcium x phosphate product among dialysis patients play a crucial role in the development of vascular (calcification of coronary artery) and valvular calcifications. DISCUSSION AND CONCLUSION With every new patient on hemodialysis it is necessary to see if there is a vascular/valvular calcification in order to single out the patients at risk of progression of coronary artery calcification and to use non-calcium containing binder phosphate in due time. Non-calcium containing binder phosphate, new active vitamin D agents and calcimimetics prevent the development of secondary hyperparathyroidism as well as cardiovascular complications and decrease the rate of cardiovascular morbidity and mortality of these patients.


Assuntos
Doenças Cardiovasculares/etiologia , Hiperparatireoidismo Secundário/complicações , Diálise Renal , Calcinose/etiologia , Humanos , Hiperparatireoidismo Secundário/metabolismo , Falência Renal Crônica/terapia , Fatores de Risco
18.
Int J Artif Organs ; 32(3): 173-9, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19440993

RESUMO

INTRODUCTION: Aortic valve calcification (AVC) accelerates development of aortic valve stenosis and cardiovascular complications. Hyperphosphatemia is one of the key risk factors for aortic valve calcification. AIM: The aim of this study was to evaluate the prevalence of AVC in patients on regular hemodialysis and to assess the impact of different factors on its appearance. METHOD: The study investigated a total of 115 patients treated in the Hemodialysis Department of the Urology and Nephrology Clinic at the Kragujevac Clinical Center in Serbia. The variables investigated were: serum albumin, C-reactive protein (CRP), homocysteine, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), Apolipoprotein A-I (Apo A-I), Apolipoprotein B (Apo B) and lipoprotein (a), calcium, phosphate and parathormone, and calcium-phosphorus product (Ca x P). Patients were evaluated by echocardiography for AVC. Statistical analysis included univariate and multivariate logistic regression analysis. RESULTS: Univariate regression analysis showed that serum phosphate levels and Ca x P are the most important risk factors for AVC (p<0.001). Multivariate logistic regression analysis revealed that hyperphosphatemia is an independent risk factor for AVC (p<0.001). CONCLUSION: Hyperphosphatemia is an independent risk factor for aortic valve calcification.


Assuntos
Valva Aórtica , Calcinose/etiologia , Doenças das Valvas Cardíacas/etiologia , Hiperfosfatemia/complicações , Diálise Renal/efeitos adversos , Adulto , Idoso , Valva Aórtica/diagnóstico por imagem , Biomarcadores/sangue , Calcinose/diagnóstico por imagem , Calcinose/epidemiologia , Cálcio/sangue , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/epidemiologia , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Prevalência , Medição de Risco , Fatores de Risco , Sérvia/epidemiologia , Fatores de Tempo , Ultrassonografia
19.
Dalton Trans ; (7): 887-94, 2008 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-18259621

RESUMO

A series of copper(I) complexes with a sterically hindered, bidentate ligand, BL iPr, derived from an N-heterocyclic carbene precursor have been isolated, characterized and their reactivity studied. The ethylene-bridged bis(imidazolin-2-imine) ligand (BL iPr) provides strongly donating N-donor atoms for the stabilization of a copper(I) metal center, priming it for reactivity. The complexes [(BL iPr)Cu(XyNC)]PF6 (4) and [(BL iPr)CuCl] (5) were characterized by X-ray crystallography and exhibit trigonal coordination at the copper centers. The reactivity of [(BL iPr)Cu]SbF6 toward dioxygen was studied at low temperature, indicating formation of a thermally sensitive intermediate with intense UV/Vis features and an isotope-sensitive vibration at 625 cm(-1) (599 cm(-1) with 18 O2). The intermediate is assigned as containing the bis(mu-oxo)dicopper(III) core, [2](PF6)2, and the related, stable hydroxo form was crystallized as [{(BL iPr)Cu}2(mu-OH)2](PF6)2, [3](PF6)2. The reactivity of 5 as a catalyst for the ATR polymerization of styrene was assessed in terms of reaction kinetics and polymer properties, with low PDI values achieved for polymers with molecular weights up to 30 000 g mol(-1).


Assuntos
Cobre/química , Etilenos/química , Compostos Heterocíclicos de Anel em Ponte/síntese química , Imidazolinas/síntese química , Compostos Organometálicos/síntese química , Compostos Heterocíclicos de Anel em Ponte/química , Imidazolinas/química , Estrutura Molecular , Compostos Organometálicos/química
20.
Vojnosanit Pregl ; 65(12): 871-5, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19160979

RESUMO

INTRODUCTION/AIM: Occlusive disease of lower limb arteries have been so far traditionally best treated with bypass surgery, but we want to find minimally invasive approach that should be at least as good as conventional surgery, and hopefully better. The aim of this study was to evaluate SMART Control stents (Cordis, J&J) in Trans Atlantic Society Consensus (TASC) B and C femoropopliteal lesions during one-year follow-up. METHODS: Retrospective nonrandomized analysis included forty arteries in consecutive 40 patients who were stented with SMART Control stents. Primary patency at 12-month verified with Duplex Ultrasound and Acute Brachial Index (ABI) as well as freedom from Target Vessel Revascularization (TVR) were primary endpoints. RESULTS: Primary technical success at stent implantation was 100%. Mean ABI values were preprocedurally 0.50, postprocedurally 0.83, at one month 0.86, at six months 0.84, at one year 0.78. After one year 39 stents were patent (97.5%). CONCLUSION: Excellent performance of the stent from technical point of view and a midterm results in vessel patency, as well as the absence of need for TVR were achieved. Yet, life expectancy in this cohort group of patients demands longer follow up data to draw a definite sustained positive conclusion.


Assuntos
Angioplastia com Balão , Artéria Femoral , Artéria Poplítea , Stents , Adulto , Idoso , Arteriopatias Oclusivas/diagnóstico por imagem , Arteriopatias Oclusivas/terapia , Feminino , Artéria Femoral/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Poplítea/diagnóstico por imagem , Radiografia , Grau de Desobstrução Vascular
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