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1.
Lupus ; 32(12): 1409-1417, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37840528

RESUMO

BACKGROUND: Pregnancy in SLE continues to be a challenge. The neutrophil-to-lymphocyte ratio (NLR) and chemerin are predictors of preeclampsia in the general population; however, their role as predictors of maternal-fetal complications in pregnant SLE patients has not been analyzed. OBJECTIVE: To investigate the prognostic value of NLR and serum chemerin, to predict maternal-fetal complications in pregnant SLE patients, and compare both biomarkers among three study groups. METHODS: Design: Analytical cross-sectional study of cases and controls with the following study groups: systemic lupus erythematosus (SLE), preeclampsia, and healthy. NLR and chemerin serum were determined between 20 and 25 weeks of gestation. Patients were evaluated every 4-6 weeks until pregnancy resolution. Maternal and fetal outcomes were registered. We employed Receiver Operating Characteristic (ROC) curves to validate prognostic values. RESULTS: Seventy pregnant patients were included: 20 with SLE, 20 with preeclampsia, and 30 healthy pregnant women; NLR values were 4 (2.3-5.6) in SLE, 6 (4.6-9.2) in preeclampsia, and 2.8 (2.1-2.9) in the group of healthy women (p = .0001). Chemerin levels were: 26 (15.3-56.2) in SLE, 96 (37.3-146.2) in preeclampsia, and 24.6 ng/mL (15.3-47.4) in the healthy group (p = .007) Maternal complications were observed in 11 (55%), 20 (100%), and 8 (26%) per group, respectively. Thrombocytopenia was the most frequent complication in all pregnant women, followed by hypertensive disorders. Fetal complications were registered in 12 (60%), 16 (80%), and 2 (6.7%), respectively. Congenital malformations and prematurity were the most frequent fetal complications. NLR had good diagnostic accuracy in predicting maternal-fetal complications (AUROC 0.715) p = .015, CI 95% 0.56-0.86, cut-off point level: 2.9, sensitivity 61%, specificity 78%, positive predictive value (PPV) 65%, negative predictive value (NPV) 75%. Regarding chemerin, a cut-off point level >43 ng/mL had a sensitivity of 75%, specificity of 72% AUROC 0.75, p = .001, CI 95% 0.61-0.89, PPV 51.7% NPV 87.8%, meaning that 51.7% of patients with chemerin levels >43 ng/mL have or will have preeclampsia. CONCLUSION: The NLR may help predict maternal-fetal complications in SLE pregnancy, constituting a marker of subclinical inflammation. Chemerin levels may be associated with preeclampsia. These biomarkers could improve the care of SLE patients with timely intervention of potential complications during pregnancy.


Assuntos
Lúpus Eritematoso Sistêmico , Pré-Eclâmpsia , Complicações na Gravidez , Humanos , Gravidez , Feminino , Lúpus Eritematoso Sistêmico/diagnóstico , Resultado da Gravidez/epidemiologia , Prognóstico , Neutrófilos , Estudos Transversais , Complicações na Gravidez/diagnóstico , Biomarcadores , Linfócitos , Estudos Retrospectivos
2.
Environ Res ; 235: 116681, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37474087

RESUMO

BACKGROUND: This study aimed to estimate airborne nicotine concentrations and nicotine, cotinine, and tobacco-specific nitrosamines (TSNAs) in settled dust from private cars in Spain and the UK. METHODS: We measured vapor-phase nicotine concentrations in a convenience sample of 45 private cars from Spain (N = 30) and the UK (N = 15) in 2017-2018. We recruited non-smoking drivers (n = 20), smoking drivers who do not smoke inside the car (n = 15), and smoking drivers who smoke inside (n = 10). Nicotine, cotinine, and three TSNAs (NNK, NNN, NNA) were also measured in settled dust in a random subsample (n = 20). We computed medians and interquartile ranges (IQR) of secondhand smoke (SHS) and thirdhand smoke (THS) compounds according to the drivers' profile. RESULTS: 24-h samples yielded median airborne nicotine concentrations below the limit of quantification (LOQ) (IQR:

Assuntos
Nitrosaminas , Poluição por Fumaça de Tabaco , Nicotina/análise , Cotinina , Poluição por Fumaça de Tabaco/análise , Poeira , Nitrosaminas/análise
3.
Environ Res ; 219: 115118, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36566961

RESUMO

OBJECTIVE: Smoke-free policies are effective in preventing secondhand smoke (SHS) exposure, but their adoption at home remains largely voluntary. This study aimed to quantify SHS exposure in homes with residents who smoke in Europe according to households' characteristics, tobacco consumption habits, and national contextual factors. METHODS: Cross-sectional study (March 2017-September 2018) based on measurements of air nicotine inside 162 homes with residents who smoke from nine European countries. We installed passive samplers for seven consecutive days to monitor nicotine concentrations. Through self-administered questionnaires, we collected sociodemographic information and the number of individuals who smoke, smoking rules, frequency, location, and quantity of tobacco use in households. Country-level factors included the overall score in the Tobacco Control Scale 2016, the smoking prevalence, and self-reported SHS exposure prevalence. Nicotine concentrations were analyzed as continuous and dichotomous variables, categorized based on the limit of quantification of 0.02 µg/m3. RESULTS: Overall, median nicotine concentration was 0.85 µg/m3 (interquartile range (IQR):0.15-4.42), and there was nicotine presence in 93% of homes. Participants reported that smoking was not permitted in approximately 20% of households, 40% had two or more residents who smoked, and in 79% residents had smoked inside during the week of sampling. We found higher nicotine concentrations in homes: with smell of tobacco smoke inside (1.45 µg/m3 IQR: 0.32-6.34), where smoking was allowed (1.60 µg/m3 IQR: 0.68-7.63), with two or more residents who smoked (2.42 µg/m3 IQR: 0.58-11.0), with more than 40 cigarettes smoked (2.92 µg/m3 IQR: 0.97-10.61), and where two or more residents smoked inside (4.02 µg/m3 IQR: 1.58-11.74). Household nicotine concentrations were significantly higher in countries with higher national smoking prevalence and self-reported SHS exposure prevalence (p < 0.05). CONCLUSIONS: SHS concentrations in homes with individuals who smoke were approximately twenty times higher in homes that allowed smoking compared to those reporting smoke-free household rules. Evidence-based interventions promoting smoke-free homes should be implemented in combination with strengthening other MPOWER measures.


Assuntos
Poluição por Fumaça de Tabaco , Humanos , Poluição por Fumaça de Tabaco/análise , Nicotina/análise , Estudos Transversais , Europa (Continente) , Fumar
4.
BMC Nurs ; 22(1): 149, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37143072

RESUMO

BACKGROUND: Falls are among the most common and serious adverse events for hospitalised patients. In-hospital falls pose a major medical and economic challenge for public health worldwide. Nevertheless, the issue is often addressed without regard to certain relevant variables such as the time of the fall. The aim of this study was to determine the effect of the implementation of a nurse-led intervention based on the temporal patterns of falls and their aetiology on the occurrence of falls. METHODS: A mixed-method research design was carried out in three phases: a) a longitudinal prospective study (audits, chronobiological analyses and implementation of a multicentre nurse-led intervention based on temporal patterns of falls); b) a retrospective study of fall records; and c) a qualitative study based on focus groups. The protocol was published in 2021. RESULTS: A difference was observed in the number of fall records before and after the chronopreventive intervention (retrospective: 64.4% vs. 35.6%; p < 0,001). According to the interrupted series analysis, considering the influence of the COVID-19 pandemic, a reduction in falls of 2.96% (95% CI 1.70%-4.17%) was observed. The concepts of falls, the COVID-19 pandemic and the causes of non-registration have emerged as categories for qualitative analysis. CONCLUSIONS: A multicentric nurse-led program based on tailored organisational, educational and behavioural chronopreventive measures seems to lead to a reduction in the number of in-hospital falls. The findings of the present study, highlighting the implementation of chronopreventive measures, can serve as a basis for future health policies. TRIAL REGISTRATION: The project was registered on the Clinical Trials Registry NCT04367298 (29/04/2020).

5.
Nat Mater ; 20(4): 503-510, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33510445

RESUMO

Despite progress in solid-state battery engineering, our understanding of the chemo-mechanical phenomena that govern electrochemical behaviour and stability at solid-solid interfaces remains limited compared to at solid-liquid interfaces. Here, we use operando synchrotron X-ray computed microtomography to investigate the evolution of lithium/solid-state electrolyte interfaces during battery cycling, revealing how the complex interplay among void formation, interphase growth and volumetric changes determines cell behaviour. Void formation during lithium stripping is directly visualized in symmetric cells, and the loss of contact that drives current constriction at the interface between lithium and the solid-state electrolyte (Li10SnP2S12) is quantified and found to be the primary cause of cell failure. The interphase is found to be redox-active upon charge, and global volume changes occur owing to partial molar volume mismatches at either electrode. These results provide insight into how chemo-mechanical phenomena can affect cell performance, thus facilitating the development of solid-state batteries.

6.
Blood Purif ; 51(1): 87-90, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33853066

RESUMO

We present the case of a patient with subarachnoid hemorrhage (SAH) secondary to a ruptured cerebral aneurysm and a refractory shock with high doses of vasopressors without a proven source of infection. This patient received therapy with high-volume hemofiltration plus adsorption, resolving the hemodynamic deterioration and with good neurological evolution. Our clinical case proposes that extracorporeal therapies may have a feasibility role in the management of complications of SAH.


Assuntos
Hemofiltração , Hemorragia Subaracnóidea/terapia , Hemofiltração/instrumentação , Humanos , Interleucina-6/sangue , Aneurisma Intracraniano/sangue , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/complicações
7.
Rev Med Chil ; 150(11): 1540-1544, 2022 Nov.
Artigo em Espanhol | MEDLINE | ID: mdl-37358181

RESUMO

Liver transplantation is the only effective therapy to reduce the high mortality associated with acute liver failure and acute on chronic liver failure (ACLF). Single-pass albumin dialysis (SPAD) is an extracorporeal supportive therapy used as a bridge to liver transplantation or regeneration. We report a 44-year-old man with alcoholic cirrhosis admitted for critical COVID-19 pneumonia that evolves with ACLF. SPAD technique was performed completing six sessions, with a reduction of bilirubin and ammonia levels. He evolved with severe respiratory failure and refractory septic shock, dying. SPAD is a safe and efficient technique aimed to eliminate liver toxins, preventing multiorgan damage interrupting the process known as the "autointoxication hypothesis". It is easy to implement in any critical patient unit and has lower costs than other extracorporeal liver support therapies.


Assuntos
Insuficiência Hepática Crônica Agudizada , COVID-19 , Transplante de Fígado , Masculino , Humanos , Adulto , Diálise Renal/métodos , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/terapia , COVID-19/complicações , Albuminas/uso terapêutico
8.
Rev Med Chil ; 150(2): 266-270, 2022 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-36156655

RESUMO

Sepsis is one of the leading causes of death in critically ill patients with COVID-19 and blood purification therapies have a role to immunomodulate the excessive inflammatory response and improve clinical results. One of the devices designed for these therapies is the oXiris® filter, allowing to perform renal replacement therapy combined with selective adsorption of endotoxins and cytokines. We report a 55-year-old male with COVID who developed a septic shock secondary to a sepsis caused by Pseudomona aeruginosa, refractory to the usual management. A veno-venous continuous hemofiltration was started using the oXiris® filter for 48 hours. Subsequently, there was an improvement in clinical perfusion parameters and a reduction in inflammatory markers. The patient was discharged from the intensive care one month later.


Assuntos
COVID-19 , Sepse , Choque Séptico , COVID-19/complicações , Citocinas , Endotoxinas , Humanos , Masculino , Pessoa de Meia-Idade , Sepse/complicações , Choque Séptico/complicações , Choque Séptico/terapia
9.
Rev Med Chil ; 150(2): 147-153, 2022 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-36156639

RESUMO

BACKGROUND: Therapeutic Plasma Exchange (TPE) is a procedure in which plasma and harmful macromolecules are separated from the rest of the blood components by centrifugation or filtration through membranes and are replaced with solutions with albumin and/or plasma. AIM: To communicate our experience using TPE by filtration. MATERIAL AND METHODS: Review of records of 655 TPE sessions performed in 102 patients aged 50 ± 18 years (64% women). The requirement of renal replacement therapy (RRT) and seven days and one year mortality were recorded. RESULTS: Forty five percent of patients had hypertension or diabetes. The main indications for TPE were pulmonary-renal syndrome (PRS) (62%) and antibody mediated graft rejection (29%), followed by neurological diseases (36%). Fifteen percent of patients required RRT for one year. Mortality at seven days and one year was 20 and 30%, respectively. Out of the total of deaths associated with kidney diseases, 88% corresponded to PRS and ANCA vasculitis. The main complications were thrombocytopenia in 41%, hypocalcemia in 18%, and hypotension in 16%. CONCLUSIONS: In our experience, TPE by filtration is a safe technique, with mild and preventable complications. Despite this, the reported mortality is high, which reflects the severity of the diseases that motivated the indication for TPE.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Troca Plasmática , Albuminas , Feminino , Glomerulonefrite , Hemorragia , Humanos , Pneumopatias , Masculino , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Estudos Retrospectivos
10.
Environ Res ; 200: 111355, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34022230

RESUMO

OBJECTIVE: Due to partial or poorly enforced restrictions secondhand tobacco smoke (SHS) is still present in outdoor hospitality venues in many European countries. This study aimed to assess SHS concentrations in outdoor hospitality venues across Europe and identify contextual exposure determinants. METHODS: Cross-sectional study. We measured airborne nicotine and evidence of tobacco use in terraces of bars, cafeterias, and pubs from 11 European countries in 2017-2018. Sites were selected considering area-level socioeconomic indicators and half were visited during nighttime. We noted the smell of smoke, presence of smokers, cigarette butts, ashtrays, and number of physical covers. Contextual determinants included national smoke-free policies for the hospitality sector, the Tobacco Control Scale score (2016), and the national smoking prevalence (2017-2018). We computed medians and interquartile ranges (IQR) of nicotine concentrations and used multivariate analyses to characterize the exposure determinants. RESULTS: Nicotine was present in 93.6% of the 220 sites explored. Overall concentrations were 0.85 (IQR:0.30-3.74) µg/m3 and increased during nighttime (1.45 IQR:0.65-4.79 µg/m3), in enclosed venues (2.97 IQR:0.80-5.80 µg/m3), in venues with more than two smokers (2.79 IQR:1.03-6.30 µg/m3), in venues in countries with total indoor smoking bans (1.20 IQR:0.47-4.85 µg/m3), and in venues in countries with higher smoking prevalence (1.32 IQR:0.49-5.34 µg/m3). In multivariate analyses, nicotine concentrations were also positively associated with the observed number of cigarette butts. In venues with more than two smokers, SHS levels did not significantly vary with the venues' degree of enclosure. CONCLUSIONS: Our results suggest that current restrictions in outdoor hospitality venues across Europe have a limited protective effect and justify the adoption of total smoking bans in outdoor areas of hospitality venues.


Assuntos
Poluição do Ar em Ambientes Fechados , Política Antifumo , Poluição por Fumaça de Tabaco , Poluição do Ar em Ambientes Fechados/análise , Estudos Transversais , Europa (Continente) , Nicotina/análise , Restaurantes , Poluição por Fumaça de Tabaco/análise
11.
Blood Purif ; 50(4-5): 575-577, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33264786

RESUMO

We present the case of a patient who suffered from acute respiratory distress syndrome caused by pneumonia associated with COVID-19 and cytokine release syndrome. This patient received a high-volume hemofiltration plus adsorption, solving the hemodynamic deterioration, pulmonary infiltrates, and gas exchange. Our clinical case proposes that the extracorporeal therapies can have a role in the management of severe COVID-19.


Assuntos
COVID-19/terapia , Estado Terminal/terapia , Síndrome da Liberação de Citocina/prevenção & controle , Hemofiltração , Hemoperfusão , SARS-CoV-2 , Injúria Renal Aguda/etiologia , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , COVID-19/complicações , COVID-19/diagnóstico por imagem , Terapia Combinada , Síndrome da Liberação de Citocina/etiologia , Citocinas/sangue , Progressão da Doença , Quimioterapia Combinada , Hemoperfusão/métodos , Humanos , Hiperpotassemia/etiologia , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Vasoconstritores/uso terapêutico , Tratamento Farmacológico da COVID-19
12.
Acta Derm Venereol ; 99(12): 1078-1084, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31453631

RESUMO

The aim of this 12-week randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of a probiotic mixture in the reduction of psoriasis severity. Ninety 18-70-year-old adults with plaque psoriasis were randomized into probiotic and placebo groups. At 12-week follow-up, 66.7% of patients in the probiotic group and 41.9% in the placebo group showed a reduction in Psoriasis Area and Severity Index of up to 75% (p < 0.05). A clinically relevant difference was observed in Physician Global Assessment index: 48.9% in the probiotic group achieved a score of 0 or 1, compared with 30.2% in the placebo group. The results of follow-up 6 months after the end of the study showed a lower risk of relapse after the intake of the probiotic mixture. Analysis of gut microbiota confirmed the efficacy of the probiotic in modulation of the microbiota composition.


Assuntos
Microbioma Gastrointestinal , Probióticos/administração & dosagem , Psoríase/terapia , Administração Oral , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/efeitos adversos , Psoríase/diagnóstico , Psoríase/imunologia , Psoríase/microbiologia , Recidiva , Indução de Remissão , Espanha , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
J Electrocardiol ; 53: 8-12, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30576931

RESUMO

BACKGROUND: There are several approaches widely used in the localization of the responsible artery in inferior myocardial infarction. However, the existing papers show differences in the point where the ST segment is measured. The purpose of our investigation is to analyse the influence of the point at which elevation of the ST segment is measured on the results of these algorithms. METHODS: We analysed the 12­lead electrocardiograms of 90 consecutive patients with inferior myocardial infarction. The ST segment elevation or depression was measured at the J-point and at 80 ms, and three algorithms were applied to predict the culprit artery with both measurements. Sensitivity, specificity, the area under the curve, and the kappa index of agreement were analysed to compare each algorithm at the J-point and at 80 ms. RESULTS: The area under the curve was better at the J-point than at 80 ms in two algorithms (0.696 vs. 0.635, p < 0.043, and 0.754 vs. 0.661, p < 0.045) and did not change in one. Agreement between the J-point and 80 ms was suboptimal in all three algorithms (0.71, 0.65, and 0.58). CONCLUSIONS: The result of different algorithms to detect the culprit artery in inferior STEMI patients can change significantly depending on the point where ST elevation or depression is measured.


Assuntos
Vasos Coronários/fisiopatologia , Eletrocardiografia , Infarto Miocárdico de Parede Inferior/fisiopatologia , Idoso , Algoritmos , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
14.
Environ Res ; 164: 340-345, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29567419

RESUMO

INTRODUCTION: Questionnaires are widely used to assess secondhand smoke (SHS) exposure. However, the validity of self-reported SHS exposure indicators has been rarely assessed. We aimed to assess correlations, sensitivity, specificity, and predictive values between self-reported SHS exposure indicators and airborne nicotine concentrations. METHODS: We performed a cross-sectional study with a convenience sample of 175 homes in Barcelona and Santiago de Compostela, Spain. Airborne nicotine samples were collected from participants' homes and a self-administered questionnaire was completed on SHS exposure in the home. Spearman correlations coefficients and sensitivity, specificity and predictive values were assessed between self-reported SHS exposure indicators and nicotine concentrations in the home. RESULTS: All self-reported SHS exposure indicators correlated moderately strongly with airborne nicotine concentrations (Spearman correlations coefficient ranging from 0.58 to 0.65). Moreover, sensitivities and negative predictive values between self-reported indicators and the presence of nicotine in the home were below 66.4% while specificities and positive predictive values were over 78.4%. The "number of people usually smoking in the home" showed the best results (rs = 0.65, p < 0.001; sensitivity = 50.4%, specificity = 95.2%, PPV = 95.0, NPV = 51.3). CONCLUSIONS: The self-reported SHS indicators assessed in this study showed moderate and strong correlations, low sensitivities, and high specificities. Among them, the best results were obtained with the "number of people usually smoking in the home".


Assuntos
Exposição Ambiental , Autorrelato , Poluição por Fumaça de Tabaco , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina , Espanha , Inquéritos e Questionários , Adulto Jovem
15.
Tob Control ; 27(4): 399-406, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28822971

RESUMO

BACKGROUND: The introduction of 'smoke-free laws' has reduced the population's exposure to second-hand smoke (SHS), although SHS is still an issue in homes and other public places. Children are vulnerable to its health effects, and their greatest exposure occurs at home. OBJECTIVES: To assess airborne nicotine concentration of the living room and children's bedroom of homes with children under 13 years of age, and to analyse factors associated with these levels. METHODS: We conducted a cross-sectional study in Barcelona in 2015-2016, selecting a convenience sample from families with at least one child under 13 years of age. The sample comprised 50 families with smokers and 50 without. We measured airborne nicotine concentrations in the living room and children's bedroom, and, using a questionnaire administered to the parents, collected information about smoking habits at home. RESULTS: Homes without smokers showed nicotine concentrations below the limit of detection (<0.02 µg/m3), while those with at least one smoker showed 0.16 µg/m3 in the living room and 0.12 µg/m3 in the bedroom. When smoking was allowed inside home, these values increased to 1.04 and 0.48 µg/m3, respectively. Moreover, nicotine concentrations in both rooms were strongly correlated (r=0.89), and higher nicotine levels were associated with the number of cigarettes smoked in the living room, smoking rules, the number of smokers living at home and tobacco smell. CONCLUSIONS: Homes with smokers present SHS in the living room and in the children's bedroom. Therefore, programmes focused on reducing children's SHS exposure are urgently needed.


Assuntos
Poluição do Ar em Ambientes Fechados/análise , Exposição Ambiental/análise , Habitação/estatística & dados numéricos , Nicotina/análise , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/análise , Adulto , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pais , Espanha/epidemiologia , Adulto Jovem
16.
Nanotechnology ; 28(1): 015102, 2017 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-27893441

RESUMO

Bacterial inclusion bodies are non-toxic, mechanically stable and functional protein amyloids within the nanoscale size range that are able to naturally penetrate into mammalian cells, where they deliver the embedded protein in a functional form. The potential use of inclusion bodies in protein delivery or protein replacement therapies is strongly impaired by the absence of specificity in cell binding and penetration, thus preventing targeting. To address this issue, we have here explored whether the genetic fusion of two tumor-homing peptides, the CXCR4 ligands R9 and T22, to an inclusion body-forming green fluorescent protein (GFP), would keep the interaction potential and the functionality of the fused peptides and then confer CXCR4 specificity in cell binding and further uptake of the materials. The fusion proteins have been well produced in Escherichia coli in their full-length form, keeping the potential for fluorescence emission of the partner GFP. By using specific inhibitors of CXCR4 binding, we have demonstrated that the engineered protein particles are able to penetrate CXCR4+ cells, in a receptor-mediated way, without toxicity or visible cytopathic effects, proving the availability of the peptide ligands on the surface of inclusion bodies. Since no further modification is required upon their purification, the biological production of genetically targeted inclusion bodies opens a plethora of cost-effective possibilities in the tissue-specific intracellular transfer of functional proteins through the use of structurally and functionally tailored soft materials.


Assuntos
Amiloide/administração & dosagem , Amiloide/química , Corpos de Inclusão/química , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Amiloide/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Escherichia coli/metabolismo , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Corpos de Inclusão/metabolismo , Peptídeos/administração & dosagem , Peptídeos/química , Peptídeos/metabolismo , Receptores CXCR4/administração & dosagem , Receptores CXCR4/química , Receptores CXCR4/metabolismo , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo
17.
J Enzyme Inhib Med Chem ; 31(1): 53-62, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25690043

RESUMO

The enzyme type 5 17ß-hydroxysteroid dehydrogenase 5 (17ß-HSD5) catalyzes the transformation of androstenedione (4-dione) to testosterone (T) in the prostate. This metabolic pathway remains active in cancer patients receiving androgen deprivation therapy. Since physicians seek to develop advantageous and better new treatments to increase the average survival of these patients, we synthesized several different dehydroepiandrosterone derivatives. These compounds have a pyrazole or imidazole function at C-17 and an ester moiety at C-3 and were studied as inhibitors of 17ß-HSD5. The kinetic parameters of this enzyme were determined for use in inhibition assays. Their pharmacological effect was also determined on gonadectomized hamsters treated with Δ(4)-androstenedione (4-dione) or testosterone (T) and/or the novel compounds. The results indicated that the incorporation of a heterocycle at C-17 induced strong 17ß-HSD5 inhibition. These derivatives decreased flank organ diameter and prostate weight in castrated hamsters treated with T or 4-dione. Inhibition of 17ß-HSD5 by these compounds could have therapeutic potential for the treatment of prostate cancer and benign prostatic hyperplasia.


Assuntos
17-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Desidroepiandrosterona/farmacologia , Inibidores Enzimáticos/farmacologia , Imidazóis/farmacologia , Pirazóis/farmacologia , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Cricetinae , Desidroepiandrosterona/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Imidazóis/química , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Próstata/enzimologia , Pirazóis/química , Relação Estrutura-Atividade
18.
Opt Express ; 23(10): 13589-604, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-26074608

RESUMO

This paper presents a novel algorithm for phase extraction based on the computation of the Euclidean distance from a point to an ellipse. The idea consists in extracting the intensities from a data row or column in three interferograms to form points of intensity and then fitting them to an ellipse by the method of least squares. The Euclidean distance for each intensity point is computed to find a parametric phase whose value is associated to the object phase. The main advantage of the present method is to avoid the use of tangent function, reducing the error in the desired phase computation.

19.
Anal Bioanal Chem ; 407(9): 2455-62, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25701414

RESUMO

High-resolution tandem mass spectrometry by collision-induced dissociation with a linear ion trap-Orbitrap has been performed on marine dissolved organic matter (DOM). Product ion spectra of selected precursor ions (m/z 359-375) have been acquired to obtain structural information, after method development. To evaluate the performance of the method, the Suwannee River fulvic acid (SRFA) reference standard was also analyzed. By reconstructing the individual product ion spectrum of marine DOM, several fragments were assigned to the different precursor ions indicating the presence of carboxyl, hydroxyl, lactones, quinones, esters, and structures more similar to lignin-degraded molecules. On the basis of these findings, coastal marine DOM molecules, although structurally homogeneous, might be more rich in diversity of functional groups than previously described.

20.
JSES Rev Rep Tech ; 4(1): 53-60, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38323209

RESUMO

Background: Open reduction and internal fixation with plate is one of the most widely used treatments for distal third humeral shaft fractures. The purpose of this study was to report the outcomes of the treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve. Methods: We performed an observational, retrospective, consecutive, monocentric, continuous multioperator study. We reviewed 22 distal third humeral shaft fractures treated with posterior MIPO in our institution with an extra-articular distal humerus plate from 2018 to 2021. Inclusion was limited to functionally independent patients with displaced fractures involving the junction of the middle and distal thirds of the humerus and minimum 12-month follow-up for implant removal. We assessed clinical outcomes including range of motion; QuickDASH score; Mayo Elbow Performance Score; and Constant-Murley score. Results: The average follow-up period of the sample was 31.7 ± 11.6 months (range, 15.7-51.3 months). The average elbow flexion and extension were 146.4° ± 7.3° (range, 120°-150°) and -0.7° ± 3.3° (range, -15° to 0°), respectively. The average shoulder anterior flexion, elevation, and abduction were 178.6° ± 3.6° (range, 170°-180°), 179.1° ± 2.9° (range, 170°-180°), and 140.9° ± 14.8° (range, 110°-160°), respectively. The average external rotation was 88.6° ± 6.4 (range, 65°-90°). The mean visual analog scale score for pain was 1.0 ± 1.6 (range, 0-5) and the mean Mayo Elbow Performance Score was 90.5 ± 9.9 (range, 70-100). The mean QuickDASH and Constant-Murley scores were 4.7 ± 6.8 (range, 0-20.5) and 95.5 ± 5.1 (range, 81-100), respectively. Two patients presented with relevant compromise of radial nerve motor function postoperatively (M3 and M2; the more compromised was preoperative injury). All patients recovered radial nerve neuropraxia within six weeks postoperatively. All fractures achieved union. The average anteroposterior and lateral axis were 175.0 ± 3.6 (168.0°-180.0°) and 177.5 ± 2.0 (173.0°-180.0°), respectively. No superficial or deep infection was reported. No cases of re-displacement of fracture, implant failure, or any other implant-related complication in follow-up were reported. No patient required plate withdrawal. Conclusion: The results of this study demonstrate that the posterior MIPO technique is a reliable option for treating distal third shaft humeral fractures. The radial nerve must be identified and protected in all cases to prevent palsy.

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