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1.
Int J Mol Sci ; 24(19)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37834149

RESUMEN

Fluorescence lifetime measurements of blood or plasma offer valuable insights into the microenvironment and molecular interactions of fluorophores, particularly concerning albumin. Neutrophil- and hypoxia-induced oxidative stress in COVID-19 pneumonia patients leads to hyperinflammation, various oxidative modifications of blood proteins, and potential alterations in the fluorescence lifetime of tryptophan-containing proteins, especially albumin. The objective of this study was to investigate the efficacy of time-resolved fluorescence spectroscopy of blood and plasma as a prompt diagnostic tool for the early diagnosis and severity assessment of COVID-19-associated pneumonia. This study examined a cohort of sixty COVID-19 patients with respiratory symptoms. To investigate whether oxidative stress is the underlying cause of the change in fluorescence lifetime, human serum albumin was treated with chloramine T. The time-resolved spectrometer Life Spec II (Edinburgh Instruments Ltd., Livingston, UK), equipped with a sub-nanosecond pulsed 280 nm diode, was used to measure the fluorescence lifetime of blood and plasma. The findings revealed a significant reduction in the fluorescence lifetime of blood (diluted 200 times) and plasma (diluted 20 times) at 360 nm in COVID-19 pneumonia patients compared with their respective values recorded six months post-infection and those of healthy individuals. Significant negative correlations were observed between the mean fluorescence lifetime of blood and plasma at 360 nm and several severity biomarkers and advanced oxidation protein products, while a positive correlation was found with albumin and the albumin-globulin ratio. The time-resolved fluorescence spectroscopy method demonstrates the potential to be used as a preliminary screening technique for identifying patients who are at risk of developing severe complications. Furthermore, the small amount of blood required for the measurements has the potential to enable a rapid fingerstick blood test.


Asunto(s)
COVID-19 , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico , Espectrometría de Fluorescencia/métodos , Proteínas Sanguíneas , Albúminas , Inflamación , Prueba de COVID-19
2.
Int J Mol Sci ; 24(19)2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37834401

RESUMEN

Several studies have indicated that COVID-19 can lead to alterations in blood rheology, including an increase in red blood cell aggregation. The precise mechanisms behind this phenomenon are not yet fully comprehended. The latest findings suggest that erythrocyte aggregation significantly influences microcirculation, causes the formation of blood clots in blood vessels, and even damages the endothelial glycocalyx, leading to endothelial dysfunction. The focus of this research lies in investigating the cellular factors influencing these changes in aggregation and discussing potential causes and implications in the context of COVID-19 pathophysiology. For this purpose, the aggregation of erythrocytes in a group of 52 patients with COVID-19 pneumonia was examined in a 70 kDa Dextran solution, which eliminates the influence of plasma factors. Using image analysis, the velocities and sizes of the formed aggregates were investigated, determining their porosity. This study showed that the process of erythrocyte aggregation in COVID-19 patients, independent of plasma factors, leads to the formation of more compact, denser, three-dimensional aggregates. These aggregates may be less likely to disperse under circulatory shear stress, increasing the risk of thrombotic events. This study also suggests that cellular aggregation factors can be responsible for the thrombotic disorders observed long after infection, even when plasma factors have normalized. The results and subsequent broad discussion presented in this study can contribute to a better understanding of the potential complications associated with increased erythrocyte aggregation.


Asunto(s)
COVID-19 , Agregación Eritrocitaria , Humanos , Dextranos , Eritrocitos/fisiología , Plasma
3.
Int J Mol Sci ; 23(17)2022 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-36077496

RESUMEN

Oxidative stress induced by neutrophils and hypoxia in COVID-19 pneumonia leads to albumin modification. This may result in elevated levels of advanced oxidation protein products (AOPPs) and advanced lipoxidation end-products (ALEs) that trigger oxidative bursts of neutrophils and thus participate in cytokine storms, accelerating endothelial lung cell injury, leading to respiratory distress. In this study, sixty-six hospitalized COVID-19 patients with respiratory symptoms were studied. AOPPs-HSA was produced in vitro by treating human serum albumin (HSA) with chloramine T. The interaction of malondialdehyde with HSA was studied using time-resolved fluorescence spectroscopy. The findings revealed a significantly elevated level of AOPPs in COVID-19 pneumonia patients on admission to the hospital and one week later as long as they were in the acute phase of infection when compared with values recorded for the same patients 6- and 12-months post-infection. Significant negative correlations of albumin and positive correlations of AOPPs with, e.g., procalcitonin, D-dimers, lactate dehydrogenase, aspartate transaminase, and radiological scores of computed tomography (HRCT), were observed. The AOPPs/albumin ratio was found to be strongly correlated with D-dimers. We suggest that oxidized albumin could be involved in COVID-19 pathophysiology. Some possible clinical consequences of the modification of albumin are also discussed.


Asunto(s)
Productos Avanzados de Oxidación de Proteínas , COVID-19 , Productos Avanzados de Oxidación de Proteínas/metabolismo , Albúminas/metabolismo , Humanos , Oxidación-Reducción , Estrés Oxidativo
4.
Molecules ; 26(14)2021 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-34299418

RESUMEN

The present review summarizes scientific reports from between 2010 and 2019 on the use of capillary electrophoresis to quantify active constituents (i.e., phenolic compounds, coumarins, protoberberines, curcuminoids, iridoid glycosides, alkaloids, triterpene acids) in medicinal plants and herbal formulations. The present literature review is founded on PRISMA guidelines and selection criteria were formulated on the basis of PICOS (Population, Intervention, Comparison, Outcome, Study type). The scrutiny reveals capillary electrophoresis with ultraviolet detection as the most frequently used capillary electromigration technique for the selective separation and quantification of bioactive compounds. For the purpose of improvement of resolution and sensitivity, other detection methods are used (including mass spectrometry), modifiers to the background electrolyte are introduced and different extraction as well as pre-concentration techniques are employed. In conclusion, capillary electrophoresis is a powerful tool and for given applications it is comparable to high performance liquid chromatography. Short time of execution, high efficiency, versatility in separation modes and low consumption of solvents and sample make capillary electrophoresis an attractive and eco-friendly alternative to more expensive methods for the quality control of drugs or raw plant material without any relevant decrease in sensitivity.


Asunto(s)
Electroforesis Capilar/métodos , Preparaciones Farmacéuticas/análisis , Fitoquímicos/análisis , Plantas Medicinales/química
5.
Molecules ; 26(17)2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34500689

RESUMEN

2-Arylidene-indan-1,3-done derivatives have very different properties, thanks to which they find various applications in science, medicine, and industry. Selected derivatives show antiviral, antibacterial, and anti-inflammatory activity. This paper presents a procedure for the synthesis of a series of indan-1,3-dione derivatives that present antiproliferative activity. The aim of the work was to develop a method of simple synthesis and purification, evaluate the fulfillment of the Lipinski's and Veber's rule, and determine the potential scope of application of the obtained series of compounds. The structure of the synthesized compounds was confirmed, and their lipophilicity was determined using experimental and computational methods. Their antiproliferative activity against selected cell lines was tested in accordance with the MTT protocol; the ability to bind to albumin was tested, and the parameters related to the toxicity of substances in silico were determined. The selected compounds which showed antiproliferative activity were strongly bound to albumin and, in most cases, met the Lipinski's and Veber's rule. Thus, the obtained results suggest that 2-arylidene-indan-1,3-done derivatives appear to be good candidates for drugs with a potential leading structure for further development.


Asunto(s)
Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Humanos , Preparaciones Farmacéuticas , Relación Estructura-Actividad
6.
Int J Mol Sci ; 21(23)2020 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-33260768

RESUMEN

A new series of hybrid compounds with tropinone and thiazole rings in the structure was designed and synthesized as potential anticancer agents. They were tested against human multiple myeloma (RPMI 8226), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), and mouse skin melanoma (B16-F10) cell lines. Toxicity was tested on human normal skin fibroblasts (HSF) and normal colon fibroblasts (CCD-18Co). The growth inhibition mechanism of the most active derivative was analyzed through investigation of its effect on the distribution of cell cycle phases and ability to induce apoptosis and necrosis in RPMI 8226 and A549 cancer cells. The tyrosinase inhibitory potential was assessed, followed by molecular docking studies. Compounds 3a-3h show high anticancer activity against MDA-MB-231 and B16-F10 cell lines with IC50 values of 1.51-3.03 µM. Moreover, the cytotoxic activity of the investigated compounds against HSF and CCD-18Co cells was 8-70 times lower than against the cancer cells or no toxicity was shown in our tests, with derivative 3a being particularly successful. The mechanism of action of compound 3a in RPMI 8226 cell was shown to be through induction of cell death through apoptosis. The derivatives show ability to inhibit the tyrosinase activity with a mixed mechanism of inhibition. The final molecular docking results showed for IC50 distinct correlation with experiment.


Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Teoría Funcional de la Densidad , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa/antagonistas & inhibidores , Tropanos/síntesis química , Tropanos/farmacología , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quimioinformática , Humanos , Concentración 50 Inhibidora , Ratones , Electricidad Estática , Termodinámica
7.
Gen Physiol Biophys ; 37(6): 647-655, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30338760

RESUMEN

The aim of this study was to investigate the effect of oxidative stress on drug binding affinity, free and bound fraction. The fluorescence anisotropy method was used to examine the interactions of commercial human serum albumin (HSA) and human plasma proteins with ochratoxin A (OTA) or carboxylate form of camptothecin (CPT-C). In-vitro method revealed significant reduction in bound fraction of drugs to HSA oxidized by chloramine T. Oxidative stress was determined by measuring the plasma level of advanced oxidation protein products (AOPP). A significant positive correlation between the AOPP and the plasma free fraction of tested drugs in thirty healthy patients was also found. The oxidative stress monitoring by AOPP is very important for improvement of dosage of drugs highly bound to albumin and with narrow therapeutic index. As a result of severe oxidative stress, the drug pharmacokinetics and therapeutic effects are prone to change. This study highlights the issues of therapeutic drug monitoring and it can explain the behaviour of drugs in pathological situations.


Asunto(s)
Estrés Oxidativo , Proteínas Sanguíneas , Polarización de Fluorescencia , Humanos , Oxidación-Reducción
8.
Acta Pol Pharm ; 73(1): 29-34, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27008798

RESUMEN

The study can be useful for understanding the interaction of camptothecin with human serum albu- min. There are two forms of camptothecin (the carboxylate form (CPT-C) and the lactone form (CPT-L)) but only the lactone one is pharmacologically active. It was reported earlier that in the presence of HSA, the active lactone form of camptothecin changes to inactive carboxylate form and it reduces the antitumor activities of camptothecin. However, those studies were performed at physiological pH (7.4) and with non-oxidized and non-glycosylated albumin. The aim of this study was to investigate the effect of oxidative stress, glycosylation, pH changes and competitor drugs on inactivation of lactone form of camptothecin in albumin solution using measurements of fluorescence anisotropy spectroscopy. It was tried to prove that in vivo camptothecin may be present in higher amount in lactone form than previously thought. Due to a reduction of pH value, a decreased rate of hydrolysis from CPT-L to CPT-C was observed. It was found in vitro a significant reduction in bound fraction of CPT-C to HSA oxidized by chloramine T or glycosylated by glucose. Moreover, as a result of block- ing binding of CPT-C to HSA by competitive compound (flurbiprofen), a decrease in the fluorescence anisotropy of the HSA-CPT complex was found. This study opens the way to review an application of CPT and its derivatives in therapy.


Asunto(s)
Camptotecina/química , Albúmina Sérica/química , Polarización de Fluorescencia , Concentración de Iones de Hidrógeno , Espectrometría de Fluorescencia
9.
Am J Addict ; 24(1): 24-9, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25823632

RESUMEN

BACKGROUND AND OBJECTIVES: Despite buprenorphine's promise as a novel therapy for opioid dependence, little is known about its clinical adoption. We characterized trends in ambulatory use of buprenorphine in the United States. METHODS: Cross-sectional, descriptive analyses of buprenorphine utilization from 2003 to 2013 using the IMS Health National Disease and Therapeutic Index, a nationally representative audit of ambulatory care. The primary unit of analysis was an office visit where buprenorphine was used for opioid dependence (treatment visit). RESULTS: Between 2003 and 2013, there was significant uptake of buprenorphine in ambulatory treatment visits, from 0.16 million [M] (95% confidence interval [CI] 0.10-0.20) visits in 2003 to 2.1M (CI 1.9-2.3M) treatment visits during 2013. Approximately 90% involved the use of brand name combination buprenorphine/naloxone (Suboxone), although this percentage decreased modestly to 80% by the last quarter of 2013. Buprenorphine prescribing increased among all specialties, but the proportion accounted for by primary care physicians increased significantly from 6.0% in 2003 to 63.5% in 2013 and decreased among psychiatrists from 92.2% to 32.8% over the same time period. CONCLUSIONS: The use of buprenorphine products to treat opioid dependence has increased significantly in the past 10 years and has shifted to greater use by primary care physicians, indicating a rapidly changing face of opioid maintenance therapy in the United States.


Asunto(s)
Atención Ambulatoria/tendencias , Buprenorfina/uso terapéutico , Utilización de Medicamentos/tendencias , Analgésicos Opioides/uso terapéutico , Combinación Buprenorfina y Naloxona/uso terapéutico , Estudios Transversales , Femenino , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Estados Unidos
10.
Am J Addict ; 23(1): 48-52, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24313241

RESUMEN

BACKGROUND: Long-term consumption of opioid compounds, even after withdrawal, affects serum biochemical parameters. Investigating these alterations is a new approach in substance abuse studies. METHOD: This study investigated clinical laboratory results in men who are currently active, recently abstinent and non-heroin users. Participants (N = 240) of this matched cohort study included heroin dependent men referred for abstinence treatment, volunteer men who did not abuse opioids matched for age, sex, body mass index, and educational level (control group). The groups were further sub-divided for analysis into (a) continuous heroin users for more than 2 years (N = 70), the dependent group; (b) heroin abusers with 1 month abstinence period (N = 70), identified as ex-heroin dependents; and (c) a matched, non-dependent control group (N = 100). All participants were tested for fasting blood sugar (FBS), sodium, potassium, calcium, uric acid (UA), blood urea nitrogen (BUN), creatinine, total cholesterol, triglycerides (TGs), total protein, fibrinogen, and prothrombin. RESULTS: Compared to the control group, ex-heroin dependents showed decreased FBS and significantly higher sodium, creatinine, and cholesterol levels. Compared to the heroin dependent group, the ex-heroin dependents showed significant differences in FBS, sodium, calcium, creatinine, UA, and thrombin time. No significant differences were noted between ex-heroin dependents and controls in potassium, calcium, UA, BUN, TGs, total protein, and thrombin time. CONCLUSION: These results demonstrate altered laboratory markers in long-term heroin dependents as well as ex-heroin dependents and suggest the need for further identification, population distribution, and etiological understanding of these biomarkers in individuals who have abused heroin.


Asunto(s)
Biomarcadores/sangre , Dependencia de Heroína/sangre , Síndrome de Abstinencia a Sustancias/sangre , Adulto , Glucemia , Proteínas Sanguíneas , Nitrógeno de la Urea Sanguínea , Calcio/sangre , Estudios de Casos y Controles , Colesterol/sangre , Creatinina/sangre , Fibrinógeno/análisis , Humanos , Masculino , Persona de Mediana Edad , Potasio/sangre , Proteínas , Protrombina/análisis , Sodio/sangre , Triglicéridos/sangre , Ácido Úrico/sangre
11.
Am J Emerg Med ; 32(5): 421-31, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24560834

RESUMEN

OBJECTIVES: To describe changes in the prevalence and severity of pain and prescribing of non-opioid analgesics in US emergency departments (EDs) from 2000 to 2010. METHODS: Analysis of serial cross-sectional data regarding ED visits from the National Hospital Ambulatory Medical Care Survey. Visits were limited to patients ≥18 years old without malignancy. Outcome measures included annual volume of visits among adults with a primary symptom or diagnosis of pain, annual rates of patient-reported pain severity, and predictors of non-opioid receipt for non-malignant pain. RESULTS: Rates of pain remained stable, representing approximately 45% of visits from 2000 through 2010. Patients reported pain as their primary symptom twice as often as providers reported a primary pain diagnosis (40% vs 20%). The percentage of patients reporting severe pain increased from 25% (95% confidence intervals [CI] 22%-27%) in 2003 to 40% (CI 37%-42%) in 2008. From 2000 to 2010, the proportion of pain visits treated with pharmacotherapies increased from 56% (CI 53%-58%) to 71% (CI 69%-72%), although visits treated exclusively with non-opioids decreased 21% from 28% (CI 27%-30%) to 22% (CI 20%-23%). The adjusted odds of non-opioid rather than opioid receipt were greater among visits for patients 18 to 24 years old (odds ratio [OR] 1.35, CI 1.24-1.46), receiving fewer medicines (OR 2.91, CI 2.70-3.15) and those with a diagnosis of mental illness (OR 2.24, CI 1.99-2.52). CONCLUSIONS: Large increases in opioid utilization in EDs have coincided with reductions in the use of non-opioid analgesics and an unchanging prevalence of pain among patients.


Asunto(s)
Analgésicos/uso terapéutico , Servicio de Urgencia en Hospital , Manejo del Dolor/métodos , Dolor/epidemiología , Dolor/prevención & control , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Prevalencia , Estados Unidos/epidemiología
12.
J Clin Med ; 13(7)2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38610786

RESUMEN

Background: Molecular classification, tumor diameter, Ki67 expression, and brachytherapy administration still act as the most potent potential predictors of breast cancer recurrence and overall survival. Methods: Over the period of 23 months, we included in the study 92 invasive breast cancer (IBrC) patients initially diagnosed at the Clinical Ward of Breast Cancer and Reconstructive Surgery, Oncology Center in Bydgoszcz, Poland. The probability of disease-free survival (DFS) and overall survival (OS) in relation to potential prognostic factors for the patients were determined using a Kaplan-Meier analysis, and univariate and multivariate Cox regression analyses evaluated the predictive factors of IBrC patients. The investigation of the potential prognostic model's accuracy was analyzed using the ROC curve. Results: Patients with tumor size < 2 cm, Ki67 expression < 20%, luminal-A molecular subtype, and extra-dose brachytherapy boost administration displayed the most favorable prognosis according to breast cancer disease-free survival and overall survival. The estimated 5 year probability of DFS and OS rates in women with tumor diameter < 2 cm were 89% and 90%, respectively. In tumor diameter > 2 cm, the estimated 5 year probability of DFS was 73% and OS was 76%. Interestingly, the tumor diameter of 1.6 cm with a specificity of 60.5% and a sensitivity of 75% occurred as the best threshold point to differentiate patients with cancer recurrence from those without cancer progression. Conclusions: Our study provides essential information on the clinicopathological profile and future outcomes of early stage IBrC patients. Furthermore, the tumor diameter cut-off value of 1.6 cm discriminating between disease recurrence and those without disease progression patients represents an innovative direction for further research.

13.
Cancers (Basel) ; 16(5)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38473424

RESUMEN

Breast cancer (BrC) is a highly prevalent tumour among women. The high incidence and mortality rate of BrC prompts researchers to search for new markers that will provide information on the possible impact of the therapy on the risk of cancer-related events. This study aimed to investigate whether the level of advanced oxidation protein products (AOPPs) may have a potential impact on disease-free (DFS) and overall survival (OS) in BrC patients with early-stage cancer. Additionally, we tried to assess the relationship between AOPPs and angiogenic parameters. In this study, the pre- and post-treatment AOPP levels were examined in the serum of 70 newly diagnosed BrC women. The receiver operating characteristic curve identified pre- and post-treatment AOPPs to be above 9.37 µM and 10.39 µM, respectively, as the best cut-off values to predict the risk of cancer relapse. Additionally, Kaplan-Meier survival analysis indicated that pre- and post-treatment AOPPs above 9.37 µM and 10.39 µM were associated with significantly poorer OS. The uni- and multivariate Cox regression analysis highlighted that lower levels of pre- and post-treatment AOPPs were associated with a longer duration without relapse or cancer-related death. A positive correlation between concentrations of pre-treatment AOPPs and vascular endothelial growth factor A, and negative correlations with levels of soluble forms of vascular endothelial growth factor receptor type 1 and 2, were found. In conclusion, AOPPs appear to have an important role in predicting cancer-related events and may potentially serve as a simple prognostic marker in clinical practice.

14.
Med Care ; 51(10): 870-8, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24025657

RESUMEN

BACKGROUND: Escalating rates of prescription opioid use and abuse have occurred in the context of efforts to improve the treatment of nonmalignant pain. OBJECTIVE: The aim of the study was to characterize the diagnosis and management of nonmalignant pain in ambulatory, office-based settings in the United States between 2000 and 2010. DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional and multivariate regression analyses of the National Ambulatory Medical Care Survey (NAMCS), a nationally representative audit of office-based physician visits, were conducted. MEASURES: (1) Annual visit volume among adults with primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3) receipt of prescription opioid or nonopioid pharmacologic therapy in visits for new musculoskeletal pain. RESULTS: Primary symptoms or diagnoses of pain consistently represented one-fifth of visits, varying little from 2000 to 2010. Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%, whereas nonopioid analgesic prescribing remained unchanged (26%-29% of visits). One-half of new musculoskeletal pain visits resulted in pharmacologic treatment, although the prescribing of nonopioid pharmacotherapies decreased from 38% of visits (2000) to 29% of visits (2010). After adjusting for potentially confounding covariates, few patient, physician, or practice characteristics were associated with a prescription opioid rather than a nonopioid analgesic for new musculoskeletal pain, and increases in opioid prescribing generally occurred nonselectively over time. CONCLUSIONS: Increased opioid prescribing has not been accompanied by similar increases in nonopioid analgesics or the proportion of ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives to prescription opioids may be underutilized as a means of treating ambulatory nonmalignant pain.


Asunto(s)
Atención Ambulatoria/estadística & datos numéricos , Analgésicos no Narcóticos/uso terapéutico , Analgésicos Opioides/uso terapéutico , Utilización de Medicamentos/estadística & datos numéricos , Dolor/diagnóstico , Dolor/tratamiento farmacológico , Medicamentos bajo Prescripción/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Visita a Consultorio Médico/estadística & datos numéricos , Dolor/epidemiología , Pautas de la Práctica en Medicina , Estados Unidos/epidemiología , Adulto Joven
15.
J Mol Graph Model ; 113: 108144, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35168146

RESUMEN

The positively charged products of Cisplatin hydrolysis can form bonds with Guanine and Adenine, showing the ability to crosslink with nucleobases within the double helical DNA, and leading to apoptosis of the neoplastic cell. It has been proved that the presence of chemicals other than nucleobases, compound of aromatic rings with a nitrogen lone pair on the ring, such as B vitamins, may have a competitive character in relation to a chemotherapeutic drug. A theoretical study confirms the stability of bonds formed not only between Cisplatin and Guanine/Adenine but also Cisplatin and B vitamins, namely Thiamine (vit.B1), Niacin (vit.B3), Riboflavin (vit.B2) and Pyridoxal phosphate (vit.B6). That is why it seems to be justified to conduct the research on the physicochemical, thermochemical and optical properties of mono and diaqua complexes of Cisplatin with nucleobases and B vitamins. Equally important is carrying out such research as spectroscopic measurements, bond order analysis and vibrational analysis of the studied complexes. The complexation reaction is spontaneous and thermodynamically favored with the high electronegativity value, a shift of the electron density from the metal zone towards organic compounds, a reduction the value of gap parameter and a shift of the maximum absorbance ΔλABS towards longer wavelengths. Moreover, the performed density variation upon photoexcitation showed the contributions from HOMO→LUMO transition, where the maximum of the absorption band shifts towards shorter wavelengths compared to the cisPt derivatives, thereby lowering the photoexcitation energy. The formation of complexes causes the reduction of energy gap (ΔEgap) values and show higher kinetic stability with high values of gap. The bonding energies between Cisplatin and the target molecules were performed. Cisplatin forms the strongest bonds with Guanine and Pyridoxal phosphate (vit.B6). The vibrations of Pt-N7 bond in complexes occur in the low range of frequencies with low intensities. Only in case of nucleobases appeared vibrations of Pt-N7 in high frequencies. The highest intensity is shown by symmetry and asymmetry stretching vibrations of H-O(H2O) bonds in the high range of frequencies. The vibrations related with ammonium groups (NH3) of great importance appear in the medium and high range of frequencies. The complexes with Guanine show the highest intensities. A theoretical IR spectra were studied. The obtained calculated IR spectra for native nucleobases and vitamins from B group were compared with their experimental FT-IR. So the conducted research provides theoretical knowledge in practical terms regarding the physicochemical and spectral properties of the formed Cisplatin complexes with both nucleobases and B vitamins. Theoretical and partially experimental studies of the molecular and electronic structure or prediction of spectroscopic characteristics are quite useful for better understanding of the reactivity of this drug with physiological target molecules.


Asunto(s)
Cisplatino , Complejo Vitamínico B , Cisplatino/química , Guanina , Teoría Cuántica , Espectroscopía Infrarroja por Transformada de Fourier , Espectrometría Raman , Vibración , Complejo Vitamínico B/uso terapéutico
16.
Sci Rep ; 12(1): 9012, 2022 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-35637245

RESUMEN

The aim of this study was to examine the usefulness of time-resolved fluorescence spectroscopy in the evaluation of the oxidative processes in human plasma. To investigate the impact of oxidative stress on the fluorescence of plasma, five studied markers (thiobarbituric acid-reactive substances, ischemia modified albumin, carbonyl groups, hydrogen peroxide, advanced oxidation protein products) were chosen as oxidative damage approved markers. Our method presents several advantages over traditional methods as it is a direct, non-time-consuming, repeatable, and non-invasive technique that requires only simple pre-treatment of samples without additional reagents and the sample size needed for analysis is small. In principle, each modification of the protein in plasma can be expected to modify its fluorescence properties and hence its lifetime or intensity. The study involved 59 blood donors with no evidence of disease. The research was conducted at excitation wavelengths of 280 nm and 360 nm, and emission was measured at wavelengths of 350 nm and 440 nm, respectively. Our results, although preliminary, suggest that the application of fluorescence measurements can be considered as an effective marker of oxidative stress. Regression analyses showed that a notable growth in fluorescence intensity at 440 nm and a simultaneous decrease in fluorescence intensity and mean fluorescence lifetime at 350 nm are associated with higher levels of oxidative stress.


Asunto(s)
Estrés Oxidativo , Albúmina Sérica , Biomarcadores , Humanos , Oxidación-Reducción , Espectrometría de Fluorescencia/métodos
17.
Sci Rep ; 12(1): 19751, 2022 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-36396711

RESUMEN

The aim of this study was to investigate the aggregation of red blood cells (RBCs) suspended in dextran solution at various levels of molecular mass. Dextran solutions at molecular mass 40, 70, 100 and 500 kDa at concentration from 2 to 5 g/dL were used to suspend the RBCs. The radius and velocity of sedimenting RBC aggregates were investigated using image analysis. The radius and sedimentation velocity of aggregates increased initially, then decreased after achieving maxima. The maximal velocity of RBC aggregates showed a bell-shaped dependence on dextran molecular mass and concentration, whereas maximal radius showed monotonic increase with both factors. Difference between aggregate and solution density was estimated using aggregate radius and sedimentation velocity and dextran solution viscosity, and was consistent across most molecular mass and concentration levels. This allowed to calculate the porosity of aggregates and to show that it monotonically decreased with the increase in the solution density, caused by the increase in the dextran concentration. The results provide insight into the RBC aggregation process in solutions of proteins of different size, reflecting various pathological conditions. The currently reported data can be potentially applied to specific pathophysiological conditions giving an interpretation that is not yet fully discussed in the literature.


Asunto(s)
Dextranos , Agregación Eritrocitaria , Agregación Eritrocitaria/fisiología , Peso Molecular , Eritrocitos , Recuento de Eritrocitos
18.
J Clin Med ; 11(17)2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-36079011

RESUMEN

A method of rapidly pointing out the risk of developing persistent pulmonary fibrosis from a sample of blood is extraordinarily needed for diagnosis, prediction of death, and post-infection prognosis assessment. Collagen scar formation has been found to play an important role in the lung remodeling following SARS-CoV-2 infection. For this reason, the concentration of collagen degradation products in plasma may reflect the process of lung remodeling and determine the extent of fibrosis. According to our previously published results of an in vitro study, an increase in the concentration of type III collagen degradation products in plasma resulted in a decrease in the fluorescence lifetime of plasma at a wavelength of 450 nm. The aim of this study was to use time-resolved fluorescence spectroscopy to assess pulmonary fibrosis, and to find out if the lifetime of plasma fluorescence is shortened in patients with COVID-19. The presented study is thus far the only one to explore the fluorescence lifetime of plasma in patients with COVID-19 and pulmonary fibrosis. The time-resolved spectrometer Life Spec II with the sub-nanosecond pulsed 360 nm EPLED® diode was used in order to measure the fluorescence lifetime of plasma. The survival analysis showed that COVID-19 mortality was associated with a decreased mean fluorescence lifetime of plasma. The AUC of mean fluorescence lifetime in predicting death was 0.853 (95% CI 0.735−0.972, p < 0.001) with a cut-off value of 7 ns, and with 62% sensitivity and 100% specificity. We observed a significant decrease in the mean fluorescence lifetime in COVID-19 non-survivors (p < 0.001), in bacterial pneumonia patients without COVID-19 (p < 0.001), and in patients diagnosed with idiopathic pulmonary fibrosis (p < 0.001), relative to healthy subjects. Furthermore, these results suggest that the development of pulmonary fibrosis may be a real and serious problem in former COVID-19 patients in the future. A reduction in the mean fluorescence lifetime of plasma was observed in many patients 6 months after discharge. On the basis of these data, it can be concluded that a decrease in the mean fluorescence lifetime of plasma at 450 nm may be a risk factor for mortality, and probably also for pulmonary fibrosis in hospitalized COVID-19 patients.

19.
Foods ; 11(16)2022 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-36010451

RESUMEN

Three Salmonella enterica strains were used in the study (serovars: S. enteritidis, S. typhimurim and S. virchow). This study evaluated the efficacy of radiant catalytic ionization (RCI) and ozonation against Salmonella spp. on eggshell (expressed as log CFU/egg). The egg surface was contaminated three different bacterial suspension (103 CFU/mL, 105 CFU/mL and 108 CFU/mL) with or without poultry manure. Experiments were conducted at 4 °C and 20 °C in three different time period: 30 min, 60 min and 120 min. Treatment with RCI reduced Salmonella numbers from 0.26 log CFU/egg in bacterial suspension 108 CFU/mL, 4 °C and 20 °C, with manure for 30 min to level decrease in bacteria number below the detection limit (BDL) in bacterial suspension 105 CFU/mL, 20 °C, with or without manure for 120 min. The populations of Salmonella spp. on eggs treated by ozonizer ranged from 0.20 log CFU/egg in bacteria suspension 108 CFU/mL, 20 °C, with manure for 30 min to 2.73 log CFU/egg in bacterial suspension 105 CFU/mL, 20 °C, with manure for 120 min. In all treatment conditions contamination with poultry manure decrease effectiveness the RCI and ozonation. In summary, RCI technology shows similar effectiveness to the ozonation, but it is safer for poultry plant workers and consumers.

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