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1.
Small ; : e2312261, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733225

RESUMO

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy.

2.
J Clin Med ; 12(21)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37959415

RESUMO

BACKGROUND: The integration of continuous glucose monitoring systems with insulin infusion pumps has shown improved glycemic control, with improvements in hyperglycemia, hypoglycemia, Hb1Ac, and greater autonomy in daily life. These have been most studied in adults and there are currently not many articles published in the pediatric population that establish their correlation with age of debut. METHODS: Prospective, single-study. A total of 28 patients (mean age 12 ± 2.43 years, 57% male, duration of diabetes 7.84 ± 2.46 years) were included and divided into two groups according to age at T1D onset (≤4 years and >4 years). Follow-up for 3 months, with glucometric variables extracted at different cut-off points after the start of the closed-loop (baseline, 1 month, 3 months). RESULTS: Significant improvement was evidenced at 1 month and 3 months after closed-loop system implantation, with better glycemic control in the older age group at baseline at TIR (74.06% ± 6.37% vs. 80.33% ± 7.49% at 1 month, p < 0.003; 71.87% ± 6.58% vs. 78.75% ± 5.94% at 3 months, p < 0.009), TAR1 (18.25% ± 4.54% vs. 14.33% ± 5.74% at 1 month, p < 0.006; 19.87% ± 5.15% vs. 14.67% ± 4. 36% at 3 months, p < 0.009) and TAR2 (4.75% ± 2.67% vs. 2.75% ± 1.96% at 1 month, p = 0.0307; 5.40% ± 2.85% vs. 3% ± 2.45% at 3 months, p < 0.027). CONCLUSIONS: the use of automated systems such as the MiniMedTM780G system brings glucometric results closer to those recommended by consensus, especially in age at T1D onset >4 years. However, the management in pediatrics continues to be a challenge even after the implementation of these systems, especially in terms of hyperglycemia and glycemic variability.

3.
J Diabetes ; 15(8): 699-708, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37337407

RESUMO

BACKGROUND: In recent years, technological advances in the field of diabetes have revolutionized the management, prognosis, and quality of life of diabetes patients and their environment. The aim of our study was to evaluate the impact of implementing the MiniMed 780G closed-loop system in a pediatric and adolescent population previously treated with a continuous subcutaneous insulin infusion pump and intermittent glucose monitoring. METHODS: Data were collected from 28 patients with type 1 diabetes aged 6 to 17 years, with a follow-up of 6 months. We included both glucometric and quality of life variables, as well as quality of life in primary caregivers. Metabolic control variables were assessed at baseline (before system change) and at different cutoff points after initiation of the closed-loop system (48 hours, 7 days, 14 days, 21 days, 1 month, 3 months, 6 months). RESULTS: Time in range 70-180 mg/dL increased from 59.44% at baseline to 74.29% in the first 48 hours after automation of the new system, and this improvement was maintained at the other cutoff points, as was time in hyperglycemia 180-250 mg/dL (24.44% at baseline to 18.96% at 48 hours) and >250 mg/dL (11.71% at baseline to 3.82% at 48 hours). CONCLUSIONS: Our study showed an improvement in time in range and in all time spent in hyperglycemia from the first 48 hours after the automation of the system, which was maintained at 6 months.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Humanos , Adolescente , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Glicemia , Automonitorização da Glicemia , Qualidade de Vida , Insulina/uso terapêutico , Sistemas de Infusão de Insulina
4.
Heliyon ; 9(1): e13045, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685472

RESUMO

For the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, clinical manifestations are broad and highly heterogeneous for both sexes. We aimed to determine how biological sex and age impact immune gene expression, particularly influencing the humoral neutralizing antibody (NAb) response and the cytokine production in coronavirus disease 2019 (COVID-19) subjects. The immune gene expression, according to biological sex and age, was assessed using the genome wide expression profile of blood proteins from healthy individuals using the Genotype Tissue Expression (GTEx) database. Moreover, anti-SARS-CoV-2 neutralizing antibody titers and cytokine levels were determined in blood samples from 141 COVID-19 individuals from Medellín, Colombia. Among subjects with COVID-19, males had statistically significantly higher median NAb titers and serum concentrations of interleukin-6 and CC chemokine ligand 3 than females. Overall, our findings point out a more robust innate immune response in women that could help recognize and restrain the virus faster than in men.

5.
Front Immunol ; 13: 1007068, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451829

RESUMO

Background: The COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up. Methods: A cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively. Results: Older age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19+ cells at day 0 was observed in hospitalized and ICU patients compared to asymptomatic and symptomatic groups. Likewise, the frequency of plasmablasts was significantly increased at the first sample in the ICU group compared to the asymptomatic group, but then waned over time. The frequency of naïve B cells decreased at days 7 and 30 compared to day 0 in hospitalized and ICU patients. The neutralizing antibody titers were higher as the severity of COVID-19 increased; in asymptomatic individuals, it was strongly correlated with the percentage of IgM+ switched memory B cells, and a moderate correlation was found with plasmablasts. Conclusion: The humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Masculino , Imunidade Humoral , Pandemias , Anticorpos Neutralizantes
6.
Endocrinol Diabetes Nutr (Engl Ed) ; 69(8): 561-565, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36347794

RESUMO

INTRODUCTION: Analysis of the impact on severe hypoglycaemia and direct costs of the introduction of the FreeStyle Libre sensor in paediatric population with type 1 Diabetes Mellitus. MATERIAL AND METHODS: Ambispective single-centre study to assess the impact on severe hypoglycaemia and direct costs, focusing on consumption of materials, in paediatric population with type 1 Diabetes Mellitus before and after introduction of the FreeStyle Libre 1 sensor. RESULTS: A significant decrease was found in episodes of severe hypoglycaemia, with 4.2 episodes of severe hypoglycaemia per 100 patients under follow-up versus 0.25 episodes per 100 patients a year after introduction of the system. This represents a cost difference for severe hypoglycaemia, estimated at €6559.52 before introduction and €409.97 after introduction of the FreeStyle Libre sensor. We found a decrease in the daily consumption of capillary blood glucose strips, which translates as a decrease in the cost of materials and helps mitigate the cost of the sensor. The cost in materials for the patient with FreeStyle Libre was €185.13 per patient and year higher than conventional control with capillary blood glucose strips.


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Criança , Humanos , Glicemia , Hipoglicemiantes/uso terapêutico , Custos de Cuidados de Saúde
7.
J Clin Med ; 11(2)2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-35053981

RESUMO

AIMS: To evaluate the relationship between daily sensor scan rates and changes in HbA1c and hypoglycemia in children. METHODS: We enrolled 145 paediatric T1D patients into a prospective, interventional study of the impact of the FreeStyle Libre 1 system on measures of glycemic control. RESULTS: HbA1c was higher at lower scan rates, and decreased as the scan rate increased to 15-20 scans, after which it rose at higher scan rates. An analysis of the change in hypoglycemia, based on the number of daily sensor scans, showed there was a significant correlation between daily scan rates and hypoglycemia. Subjects with higher daily scan rates reduced all levels of hypoglycaemia. CONCLUSIONS: HbA1c is higher at lower scan rates, and decreases as scan rate increases. Reductions in hypoglycemia were evident in subjects with higher daily scan rates.

8.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1407803

RESUMO

Resumen El virus de la hepatitis E (VHE) es uno de los principales agentes etiológicos de hepatitis entérica en el mundo. En países en vía de desarrollo, la seroprevalencia oscila entre 20 y 50% y en países desarrollados entre 4,4 y 21%. Clínicamente los casos de infección por VHE en individuos inmunocompetentes cursan como una hepatitis viral aguda auto limitada; por el contrario, en mujeres embarazadas, individuos receptores de trasplantes de órganos e individuos que conviven con el virus de la inmunodeficiencia humana (VIH), la infección puede manifestarse como una hepatitis crónica y grave. En América Latina, sólo Brasil y Argentina reportan cifras en individuos que conviven con el VIH. Se requieren más estudios en nuestra región que permitan determinar la prevalencia del VHE en individuos inmunosuprimidos, donantes de sangre y población general para adoptar medidas que garanticen un diagnóstico oportuno, acceso a la atención y el control de la transmisión.


Abstract The hepatitis E virus (HEV) is one of the main etiological agents of enteric hepatitis in the world. In developing countries its sero-prevalence ranges from 20 to 50% and in developed countries from 4.4% to 21%. Clinically, cases of HEV infection in immunocompetent individuals present as self-limited acute viral hepatitis; conversely, in pregnant women, transplanted individuals, and individuals living with the human immunodeficiency virus (HIV), the infection can manifest as chronic and severe hepatitis. In Latin America, only Brazil and Argentina report figures for individuals living with HIV. More studies are required in our region to determine the prevalence of HEV in immunosuppressed individuals, blood donors, and the general population to adopt measures that guarantee timely diagnosis, access to care, and control of transmission.

9.
Ultrason Sonochem ; 73: 105500, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33689978

RESUMO

Degradation of seven relevant pharmaceuticals with different chemical structures and properties: acetaminophen (ACE), cloxacillin (CXL), diclofenac (DCF), naproxen (NPX), piroxicam (PXC), sulfacetamide (SAM) and cefadroxil (CDX), in distilled water and mineral water by ultrasound was studied herein. Firstly, proper conditions of frequency and acoustic power were determined based on the degradation ability of the system and the accumulation of sonogenerated hydrogen peroxide (24.4 W and 375 kHz were found as the suitable conditions for the sonochemical treatment of the pharmaceuticals). Under such conditions, the pharmaceuticals degradation order in distilled water was: PXC > DCF ~ NPX > CXL > ACE > SAM > CDX. In fact, the initial degradation rate showed a good correlation with the Log P parameter, most hydrophobic compounds were eliminated faster than the hydrophilic ones. Interestingly, in mineral water, the degradation of those hydrophilic compounds (i.e., ACE, SAM and CDX) was accelerated, which was attributed to the presence of bicarbonate ions. Afterwards, mineral water containing six different initial concentrations (i.e., 0.331, 0.662, 3.31, 16.55, 33.1, and 331 µM) of selected pharmaceuticals was sonicated, the lowest concentration (0.331 µM) always gave the highest degradation of the pollutants. This result highlights the great ability of the sonochemical process to treat bicarbonate-rich waters containing pollutants at trace levels, as pharmaceuticals. Finally, the addition of ferrous ions to the sonochemical system to generate a sono-Fenton process resulted in an acceleration of degradation in distilled water but not in mineral water. This was attributed to the scavenging of sonogenerated HO• by bicarbonate anion, which decreases H2O2 accumulation, thus limiting the Fenton reaction.


Assuntos
Águas Minerais/análise , Preparações Farmacêuticas/química , Ondas Ultrassônicas , Poluentes Químicos da Água/química , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Preparações Farmacêuticas/análise , Poluentes Químicos da Água/análise
13.
Front Pediatr ; 8: 397, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793527

RESUMO

Background: Kawasaki disease (KD) is an acute febrile illness that largely affects young children before 5 years of age. Younger children with KD are reported to have a higher prevalence of coronary artery abnormalities. Little is known about infants in the first 3 months of age diagnosed with KD. Methods: A retrospective study was conducted at the National Institute of Pediatrics in Mexico City from 1995 to 2019. Clinical features, laboratory results and cardiac outcomes were recorded. Infants in the first 3 months of age were compared with older patients. Wilcoxon-Mann-Whitney analysis was performed for continuous variables and Fisher's exact test for categorical variables. Results: Six hundred and eighty-eight cases of KD were included in this study. Fourteen cases were diagnosed in the first three months of age. Heart failure and KD shock-syndrome was found in five cases (35.7%). Giant coronary artery aneurysms were found in six cases in the younger group (42.9%). Conclusions: Diagnosis of KD in children younger than 3 months of age is rare. In most cases, an incomplete presentation contributed to a delay diagnosis, treatment, and complications. Younger patients with KD have an increased risk of presenting cardiac complications, including giant coronary artery aneurysms, shock, and death.

14.
Nutr. hosp ; 37(2): 321-326, mar.-abr. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-190597

RESUMO

INTRODUCCIÓN: la valoración de los menús hospitalarios debe realizarse periódicamente para adecuarlos a las necesidades de los pacientes. El yogur líquido de leche de cabra podría tener ventajas nutricionales en comparación con el de vaca. OBJETIVOS: evaluar la satisfacción de los pacientes con el menú hospitalario y con la incorporación del yogur líquido de leche de cabra, suministrado como postre en el menú hospitalario, en comparación con un postre lácteo de vaca. MATERIAL Y MÉTODOS: se realizó una encuesta de satisfacción con el menú hospitalario y con el postre (yogur de cabra no edulcorado frente a postre lácteo de vaca edulcorado (yogur o arroz con leche)) a pacientes ingresados con dietas basales. RESULTADOS: se analizaron 214 encuestas. El 43,9 % de los encuestados fueron mujeres. La edad media fue de 62,1 ± 15,8 años y la estancia media de los pacientes de 14,1 ± 20,1 días. La aceptación del menú hospitalario se valoró como buena por un alto porcentaje de los encuestados (temperatura, 90,9 %; preparación, 75,6 %; presentación, 88,9 %; horario, 73,7 %). La satisfacción global con el almuerzo (de 1 a 10) fue de 7,5 ± 2,1 en los pacientes que tomaron yogur líquido de leche de cabra frente a 7,4 ± 2,2 en los que tomaron el postre lácteo de vaca (NS); con el postre fue de 6,1 ± 3,2 frente a 7,9 ± 2,5 (p < 0,000), respectivamente. CONCLUSIONES: la satisfacción global con el menú hospitalario fue alta y la aceptación del postre de yogur líquido de cabra fue menor que la observada con el postre lácteo de vaca. La ausencia de edulcorantes en el primero pudo influir en los resultados


INTRODUCTION: an assessment of hospital menus should be regularly performed to suit the needs of patients. Drinkable goat milk yogurt could have nutritional advantages over the cow's milk variety. OBJECTIVES: to evaluate the satisfaction of patients with the hospital menu and with the inclusion therein of drinkable goat milk yogurt as a dessert as compared to a cow milk dessert. MATERIAL AND METHODS: a satisfaction survey for the hospital menu and its included dessert (non-sweetened goat milk yogurt vs a sweetened cow's milk dessert (yogurt or rice pudding)) was conducted in patients admitted with baseline diets. RESULTS: in all, 214 responses were analyzed: 43.9 % of respondents were women. Mean age was 62.1 ± 15.8 years, and average patient stay was 14.1 ± 20.1 days. Acceptance of the hospital menu was rated as good in a high percentage of respondents (temperature, 90.9 %; preparation, 75.6 %; presentation, 88.9 %; time schedule, 73.7 %). Overall satisfaction with the lunch meal (1 to 10) was 7.5 ± 2.1 in patients who took the drinkable goat milk yogurt vs 7.4 ± 2.2 in those who took the cow's milk dessert (NS); satisfaction with the dessert was 6.1 ± 3.2 vs 7.9 ± 2.5 (p < 0.000), respectively. CONCLUSIONS: overall satisfaction with the hospital menu was high, and the acceptance of the liquid goat milk yogurt was lower than that observed for the cow's milk dessert. The absence of sweeteners in the former may have influenced the results obtained


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Serviço Hospitalar de Nutrição , Iogurte , Valor Nutritivo , Necessidades Nutricionais , Planejamento de Cardápio/normas , Inquéritos Nutricionais , Estudos Transversais , Laticínios
15.
Nutr Hosp ; 37(2): 321-326, 2020 Apr 16.
Artigo em Espanhol | MEDLINE | ID: mdl-32124621

RESUMO

INTRODUCTION: Introduction: an assessment of hospital menus should be regularly performed to suit the needs of patients. Drinkable goat milk yogurt could have nutritional advantages over the cow's milk variety. Objectives: to evaluate the satisfaction of patients with the hospital menu and with the inclusion therein of drinkable goat milk yogurt as a dessert as compared to a cow milk dessert. Material and methods: a satisfaction survey for the hospital menu and its included dessert (non-sweetened goat milk yogurt vs a sweetened cow's milk dessert (yogurt or rice pudding)) was conducted in patients admitted with baseline diets. Results: in all, 214 responses were analyzed: 43.9% of respondents were women. Mean age was 62.1 ± 15.8 years, and average patient stay was 14.1 ± 20.1 days. Acceptance of the hospital menu was rated as good in a high percentage of respondents (temperature, 90.9%; preparation, 75.6%; presentation, 88.9%; time schedule, 73.7%). Overall satisfaction with the lunch meal (1 to 10) was 7.5 ± 2.1 in patients who took the drinkable goat milk yogurt vs 7.4 ± 2.2 in those who took the cow's milk dessert (NS); satisfaction with the dessert was 6.1 ± 3.2 vs 7.9 ± 2.5 (p < 0.000), respectively. Conclusions: overall satisfaction with the hospital menu was high, and the acceptance of the liquid goat milk yogurt was lower than that observed for the cow's milk dessert. The absence of sweeteners in the former may have influenced the results obtained.


INTRODUCCIÓN: Introducción: la valoración de los menús hospitalarios debe realizarse periódicamente para adecuarlos a las necesidades de los pacientes. El yogur líquido de leche de cabra podría tener ventajas nutricionales en comparación con el de vaca. Objetivos: evaluar la satisfacción de los pacientes con el menú hospitalario y con la incorporación del yogur líquido de leche de cabra, suministrado como postre en el menú hospitalario, en comparación con un postre lácteo de vaca. Material y métodos: se realizó una encuesta de satisfacción con el menú hospitalario y con el postre (yogur de cabra no edulcorado frente a postre lácteo de vaca edulcorado (yogur o arroz con leche)) a pacientes ingresados con dietas basales. Resultados: se analizaron 214 encuestas. El 43,9% de los encuestados fueron mujeres. La edad media fue de 62,1 ± 15,8 años y la estancia media de los pacientes de 14,1 ± 20,1 días. La aceptación del menú hospitalario se valoró como buena por un alto porcentaje de los encuestados (temperatura, 90,9%; preparación, 75,6%; presentación, 88,9%; horario, 73,7%). La satisfacción global con el almuerzo (de 1 a 10) fue de 7,5 ± 2,1 en los pacientes que tomaron yogur líquido de leche de cabra frente a 7,4 ± 2,2 en los que tomaron el postre lácteo de vaca (NS); con el postre fue de 6,1 ± 3,2 frente a 7,9 ± 2,5 (p < 0,000), respectivamente. Conclusiones: la satisfacción global con el menú hospitalario fue alta y la aceptación del postre de yogur líquido de cabra fue menor que la observada con el postre lácteo de vaca. La ausencia de edulcorantes en el primero pudo influir en los resultados.


Assuntos
Dietoterapia/métodos , Leite , Satisfação do Paciente , Adulto , Idoso , Animais , Bovinos , Dieta , Feminino , Cabras , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
16.
J Med Chem ; 62(23): 10664-10675, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31702921

RESUMO

We report the discovery of new 4-hydroxyphenyl phosphonium salt derivatives active in the submicromolar range (EC50 from 0.04 to 0.28 µM, SI > 10) against the protozoan parasite Leishmania donovani. The pharmacokinetics and in vivo oral efficacy of compound 1 [(16-(2,4-dihydroxyphenyl)-16-oxohexadecyl)triphenylphosphonium bromide] in a mouse model of visceral leishmaniasis were established. Compound 1 reduced the parasite load in spleen (98.9%) and liver (95.3%) of infected mice after an oral dosage of four daily doses of 1.5 mg/kg. Mode of action studies showed that compound 1 diffuses across the plasma membrane, as designed, and targets the mitochondrion of Leishmania parasites. Disruption of the energetic metabolism, with a decrease of intracellular ATP levels as well as mitochondrial depolarization together with a significant reactive oxygen species production, contributes to the leishmanicidal effect of 1. Importantly, this compound was equally effective against antimonials and miltefosine-resistant clinical isolates of Leishmania infantum, indicating its potential as antileishmanial lead.


Assuntos
Antiprotozoários/química , Antiprotozoários/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Animais , Antiprotozoários/síntese química , Fragmentação do DNA , Descoberta de Drogas , Resistência a Medicamentos , Feminino , Leishmania donovani/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Espécies Reativas de Oxigênio , Relação Estrutura-Atividade
17.
Eur J Med Chem ; 180: 28-40, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31299585

RESUMO

Among neglected tropical diseases, leishmaniasis is one of the most relevant with an estimated 30,000 deaths annually. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost; therefore, new safer and shorter treatments are needed for this disease. Here we report on the synthesis of novel 4-amino-7-chloroquinoline-based compounds with leishmanicidal activity, together with deeper insight into the mechanism of action of our previously published hit compound 1. New derivatives showed comparable activity to 1 against both promastigote and intracellular amastigote forms of Leishmania infantum, with IC50 < 1 µM. Furthermore, we have determined that compound 1 induced a decrease of intracellular ATP levels, as well as a mitochondrial depolarization, together with an alteration of plasma membrane permeability and a significant ROS production. The inhibition of the energy metabolism of Leishmania plays an important role in the leishmanicidal mechanism of this compound. In all, these results support the consideration of compound 1 for the future development of new leishmanicidal drugs.


Assuntos
Aminoquinolinas/farmacologia , Antiprotozoários/farmacologia , Leishmania infantum/efeitos dos fármacos , Aminoquinolinas/síntese química , Aminoquinolinas/química , Antiprotozoários/síntese química , Antiprotozoários/química , Relação Dose-Resposta a Droga , Metabolismo Energético , Leishmania infantum/metabolismo , Estrutura Molecular , Testes de Sensibilidade Parasitária , Relação Estrutura-Atividade
18.
Biomedica ; 38(3): 363-378, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30335242

RESUMO

Introduction. Breast reconstruction, either immediate or delayed, is part of the treatment of breast cancer. Each country and health system pays for and evaluates these procedures in different ways. Thus, it is important to determine which strategy is most cost-effective in Colombia. Objective: To evaluate the cost-utility of breast cancer treatment with immediate reconstruction compared with delayed reconstruction. Materials and methods: We used a decision tree model and a one-year time horizon from the perspective of the third-party payer; the cost data were taken from the Colombian Instituto de Seguros Sociales 2001 rate manual plus a 30% adjustment according to the methodology of the Instituto de Evaluación Tecnológica en Salud, IETS, and the billing model of the Centro Javeriano de Oncología at the Hospital Universitario San Ignacio. The transition probabilities and profits were obtained from medical specialists, patients, and the medical literature. We also conducted univariate and probabilistic sensitivity analyses. Results: The expected costs per capita were COP$ 26,710,605 (USD$ 11,165) for the immediate reconstruction and COP$ 26,459,557 (USD$ 11,060) for the deferred reconstruction. Immediate reconstruction generated an incremental cost of COP$ 251,049 (USD$ 105) and 0.75 quality-adjusted life years (QALY), while deferred reconstruction generated 0.63 QALYs, with an incremental cost-utility ratio of COP$ 2,154,675 per QALY (USD$ 901). Conclusions: The cost per QALY did not exceed the acceptability threshold of the Gross Domestic Product (GDP) per capita. The costs for the first year were similar. Both techniques are favorable for the Colombian health system, but the utility reported by patients and the literature is greater with the immediate reconstruction.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Colômbia , Análise Custo-Benefício , Custos e Análise de Custo , Árvores de Decisões , Feminino , Humanos , Reembolso de Seguro de Saúde , Mamoplastia/economia , Mamoplastia/psicologia , Mastectomia , Modelos Econômicos , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Tempo
19.
J Clin Transl Endocrinol ; 12: 8-12, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29892561

RESUMO

INTRODUCTION: Degludec (IDeg) is an ultralong-acting insulin, with stable pharmacodynamic profile which leads to lower fluctuations in glucose levels. The effect of IDeg has not been specifically assessed in patients with unstable diabetes, defined as increased glycemic variability (GV). METHODS: A prospective before-after pilot study was conducted, including patients managed at Hospital Universitario San Ignacio in Bogotá, Colombia. The impact of the switch from a Glargine or Detemir insulin to a basal insulin regimen with IDeg for 12 weeks on GV measured by continuous glucose monitoring, on A1c levels, and on the incidence of episodes of global and nocturnal hypoglycemia was assessed in a group of patients with (coefficient of variation >34%) or without increased basal GV using a Generalised Estimating Equation (GEE) analysis. RESULTS: 60 patients with basal bolus therapy and history of hypoglycemia were included. 18 patients had High GV (HGV). In this group a significant reduction of 11.1% of CV (95% CI: 6.3, 15.9, p = 0.01) was found. GEE analysis confirmed a higher impact over time on patients with HGV (p < 0.001). The percentage of patients with at least 1 episode of hypoglycemia decreased from 66.6% to 22.2% (p = 0.02) and from 37.14% to 5.71% (p < 0.01) for global and nocturnal hypoglycemia, respectively. Changes were not significant in patients with low GV. A reduction of A1c was observed in both groups (p < 0.001). CONCLUSIONS: The results suggest that treatment with IDeg reduces GV, A1c levels and the incidence of global and nocturnal hypoglycemia events in patients with HGV, but not in patients with low GV.

20.
Placenta ; 61: 39-47, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29277270

RESUMO

INTRODUCTION: Human decidual stromal cells (DSCs) play a key role in maternal-fetal interactions. Precursors of DSCs (preDSCs) localize around vessels in both the endometrium and decidua. Previous studies suggested a relationship between preDSCs and pericytes because these cells share a perivascular location, alpha smooth muscle actin (α-SM actin) expression and the ability to contract under the effects of cytokines. METHODS: To further study this relationship, we established 15 human preDSC lines and 3 preDSC clones. The preDSC lines and clones were tested by flow cytometry with a panel of 29 monoclonal antibodies, 14 of which are pericyte markers. The expression of angiogenic factors was determined by RT-PCR, chemotactic activity was studied with the migration assay, and cell contractility was evaluated with the collagen cell contraction assay. Confocal microscopy was used to study decidual sections. RESULTS: Under the effect of progesterone and cAMP, these lines decidualized in vitro: the cells became rounder and secreted prolactin, a marker of physiological DSC differentiation (decidualization). The antigen phenotype of these preDSC lines and clones was fully compatible with that reported for pericytes. PreDSC lines displayed pericyte characteristics: they expressed angiogenic factors and showed chemotactic and cytokine-induced contractile activity. Confocal microscopic examination of decidual sections revealed the expression of antigens detected in preDSC lines: α-SM actin colocalized with CD146, CD140b, MFG-E8, nestin, and STRO-1 (all of which are pericyte markers) in cells located around the vessels, a distinctive location of preDSCs and pericytes. DISCUSSION: Taken together, our results show that preDSCs are pericyte-like cells.


Assuntos
Indutores da Angiogênese/metabolismo , Quimiotaxia , Decídua/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Pericitos/metabolismo , Células Estromais/metabolismo , Adolescente , Biomarcadores/metabolismo , Desdiferenciação Celular , Diferenciação Celular , Linhagem Celular , Movimento Celular , Forma Celular , Tamanho Celular , Células Cultivadas , Células Clonais , Decídua/citologia , Decídua/imunologia , Feminino , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Pericitos/citologia , Pericitos/imunologia , Gravidez , Células Estromais/citologia , Células Estromais/imunologia , Adulto Jovem
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