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BACKGROUND: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma. METHODS: In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150 × 106 to 450 × 106 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses). RESULTS: Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)-negative status (<10-5 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion. CONCLUSIONS: Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.).
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Imunoterapia Adotiva , Mieloma Múltiplo/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Síndrome da Liberação de Citocina/etiologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Imunoterapia Adotiva/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Intervalo Livre de Progressão , RecidivaRESUMO
BACKGROUND: Preclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multiple myeloma. METHODS: In this phase 1 study involving patients with relapsed or refractory multiple myeloma, we administered bb2121 as a single infusion at doses of 50×106, 150×106, 450×106, or 800×106 CAR-positive (CAR+) T cells in the dose-escalation phase and 150×106 to 450×106 CAR+ T cells in the expansion phase. Patients had received at least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes. The primary end point was safety. RESULTS: Results for the first 33 consecutive patients who received a bb2121 infusion are reported. The data-cutoff date was 6.2 months after the last infusion date. Hematologic toxic effects were the most common events of grade 3 or higher, including neutropenia (in 85% of the patients), leukopenia (in 58%), anemia (in 45%), and thrombocytopenia (in 45%). A total of 25 patients (76%) had cytokine release syndrome, which was of grade 1 or 2 in 23 patients (70%) and grade 3 in 2 patients (6%). Neurologic toxic effects occurred in 14 patients (42%) and were of grade 1 or 2 in 13 patients (39%). One patient (3%) had a reversible grade 4 neurologic toxic effect. The objective response rate was 85%, including 15 patients (45%) with complete responses. Six of the 15 patients who had a complete response have had a relapse. The median progression-free survival was 11.8 months (95% confidence interval, 6.2 to 17.8). All 16 patients who had a response (partial response or better) and who could be evaluated for minimal residual disease (MRD) had MRD-negative status (≤10-4 nucleated cells). CAR T-cell expansion was associated with responses, and CAR T cells persisted up to 1 year after the infusion. CONCLUSIONS: We report the initial toxicity profile of a BCMA-directed cellular immunotherapy for patients with relapsed or refractory multiple myeloma. Antitumor activity was documented. (Funded by Bluebird Bio and Celgene; CRB-401 ClinicalTrials.gov number, NCT02658929.).
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Antígeno de Maturação de Linfócitos B/antagonistas & inibidores , Imunoterapia Adotiva , Mieloma Múltiplo/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Adulto , Idoso , Relação CD4-CD8 , Feminino , Humanos , Imunoterapia Adotiva/efeitos adversos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Intervalo Livre de Progressão , Linfócitos T/metabolismoRESUMO
AIM: To compare the safety and efficacy of bexagliflozin administered as monotherapy at three dosage strengths over a 12-week period to patients with type 2 diabetes who were either naïve to pharmacotherapy or were previously prescribed one oral hypoglycaemic agent and underwent a 6-week period of medication abstinence. METHODS: Adults with type 2 diabetes (n = 292) having an HbA1c of between 7.0% and 8.5% were randomized to receive one of three dosage strengths of bexagliflozin (5, 10 or 20 mg) or placebo. The primary endpoint was the change from baseline to week 12 in the %HbA1c. Secondary endpoints included the changes from baseline in fasting plasma glucose (FPG), systolic blood pressure and diastolic blood pressure, body mass and fraction of patients achieving an HbA1c of <7%. RESULTS: The mixed model repeated measure estimates of the placebo-adjusted change in %HbA1c from baseline to week 12 for the 5, 10 and 20 mg groups were -0.55% (95% CI: -0.76%, -0.34%, P < 0.0001), -0.68% (95% CI: -0.89%, -0.47%, P < 0.0001) and -0.80% (95% CI: -1.01%, -0.59%, P < 0.0001), respectively. Significant and dose-dependent placebo-adjusted mean reductions from baseline to week 12 in FPG and body mass were observed. The fraction of subjects achieving an HbA1c of <7% was significantly greater in the 20 mg bexagliflozin group. The incidence of adverse events was similar for participants in all active arms (42.3%) compared with the rate measured in those receiving placebo (40.3%). CONCLUSIONS: Bexagliflozin confers substantial and dose-dependent benefits on subjects with type 2 diabetes and has an acceptable safety profile. Further evaluation of bexagliflozin for the control of type 2 diabetes in adults is warranted.
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Diabetes Mellitus Tipo 2 , Adulto , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Piranos , Resultado do TratamentoRESUMO
Nitrogen (N) deficiency is one of the major stresses that crops are exposed to. It is plausible to suppose that a stress condition can induce a memory in plants that might prime the following generations. Here, an experimental setup that considered four successive generations of N-sufficient and N-limited Arabidopsis was used to evaluate the existence of a transgenerational memory. The results demonstrated that the ability to take up high amounts of nitrate is induced more quickly as a result of multigenerational stress exposure. This behavior was paralleled by changes in the expression of nitrate responsive genes. RNAseq analyses revealed the enduring modulation of genes in downstream generations, despite the lack of stress stimulus in these plants. The modulation of signaling and transcription factors, such as NIGTs, NFYA and CIPK23 might indicate that there is a complex network operating to maintain the expression of N-responsive genes, such as NRT2.1, NIA1 and NIR. This behavior indicates a rapid acclimation of plants to changes in N availability. Indeed, when fourth generation plants were exposed to N limitation, they showed a rapid induction of N-deficiency responses. This suggests the possible involvement of a transgenerational memory in Arabidopsis that allows plants to adapt efficiently to the environment and this gives an edge to the next generation that presumably will grow in similar stressful conditions.
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Arabidopsis/fisiologia , Nitrogênio/deficiência , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Anotação de Sequência Molecular , Nitratos/metabolismo , Raízes de Plantas/metabolismo , Fatores de TempoRESUMO
INTRODUCTION: During malaria infection, both parasite and host are under the effects of oxidative stress due to the increased production of reactive oxygen species, which can induce DNA damage by its genotoxic effects. OBJECTIVE: To evaluate genotoxic effects in human lymphocytes in a cohort of patients with malaria from Medellin and Quibdó. METHODS: We performed an observational cross sectional study in 100 individuals with malaria and 100 healthy controls. Patients infected with Plasmodium consulting the Institute Colombiano of Medicina Tropical of Medellin and the Hospital Ismael Roldán Valencia of Quibdó were included. Genotoxic effects (genetic damage) was analysed by electrophoresis using alkaline single cell gel (Commet assay). RESULTS: The average of tail length of malaria samples (26.9±9.8) was significantly higher than of controls (14.8±3.2) (p<0.01). CONCLUSION: In our study population, malaria infection was associated with increased genotoxicity, while other variables such as smoking, antimalarial treatment, and occupation were not.
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Dano ao DNA/genética , Linfócitos/parasitologia , Malária Falciparum/genética , Malária Vivax/genética , Estresse Oxidativo/genética , Estudos de Casos e Controles , Colômbia , Estudos Transversais , Feminino , Humanos , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Masculino , Plasmodium falciparum , Plasmodium vivax , Fatores de Risco , FumarRESUMO
Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months). The primary endpoint was safety outcomes, and secondary endpoints included overall response rate (ORR), complete response (CR) and very good partial response (VGPR). The study met its primary endpoint with low rates of grade 3/grade 4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). ORR was 75.8%; 64.5% achieved VGPR or better and 38.7% achieved CR or stringent CR. Among exploratory endpoints, median duration of response, progression-free survival (PFS) and overall survival were 10.3, 8.8 and 34.2 months, respectively, and ide-cel expansion in blood and bone marrow correlated with clinical efficacy and postinfusion reduction of soluble BCMA. Patients with PFS ≥ 18 months had more naive and less exhausted T cells in apheresis material and improved functional T cell phenotype in the drug product compared with those with less durable responses. These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response. Clinicaltrials.gov identifier : NCT02658929 .
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Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/terapia , Antígeno de Maturação de Linfócitos B , Seguimentos , Síndrome da Liberação de CitocinaRESUMO
[This corrects the article DOI: 10.3389/fimmu.2018.02355.].
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Dendritic cells (DCs) are the most potent antigen-presenting cells able to trigger the adaptive immune response to specific antigens. When non-self-antigens are captured, DCs switch from an "immature" to a "mature" state to fulfill their function. Among the several surface proteins involved in DCs maturation, the role of aquaporins (AQPs) is still poorly understood. Here we investigated the expression profile of Aqps in murine bone marrow derived dendritic cells (BMDCs). Among the Aqps analyzed, Aqp9 was the most expressed by DCs. Its expression level was significantly upregulated 6 h following LPS exposure. Chemical inhibition of Aqp9 led to a decreased inflammatory cytokines secretion. BMDCs from AQP9-KO mice release lower amount of inflammatory cytokines and chemokines and increased release of IL-10. Despite the reduced release of inflammatory cytokines, Aqp9-KO mice were not protected from DSS induced colitis. All together, our data indicate that AQP9 blockade can be an efficient strategy to reduce DCs inflammatory response but it is not sufficient to protect from acute inflammatory insults such as DSS induced colitis.
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BACKGROUND: The importance of hemoproteins for life lies largely in their iron-mediated chemical properties. In the human body, there are about 4 g of iron, a precious resource preserved by sophisticated recycling mechanisms. Iron is also important for pathogen growth, so it is not surprising that immune cells developed mechanisms to reduce iron availability in cases of inflammation. In healthy conditions, macrophages degrade hemoproteins and export iron, while if inflammation develops, they retain cytoplasmic iron to reduce extracellular iron concentrations. Iron-rich macrophages possess a stronger inflammatory ability, which explains the chronic inflammatory response observed in states of iron overload. Inflammatory bowel syndromes are often characterized by intestinal blood loss and consequent anemia, but iron-supplementation therapies may exacerbate the inflammatory response. In chronically transfused patients iron overload is frequently observed; the iron can become toxic and in excess, even fatal if not treated with iron-chelating drugs. CONCLUSION: In the present review, we discuss the importance of iron homeostasis in states of health and inflammation, focusing on iron and iron-chelation treatment for IBD patients. Oral administration of natural ironchelating chemicals may be an effective adjuvant therapy for IBD patients, acting on numerous aspects of chronic inflammatory syndromes.
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Adjuvantes Imunológicos/uso terapêutico , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Humanos , Inflamação/imunologia , Inflamação/patologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologiaRESUMO
INTRODUCTION: Cerebral venous sinus thrombosis represents 0.5 - 1% of all cerebrovascular diseases. OBJECTIVE: The aim of this study was to determine the epidemiological, clinical, and imaging features of the disease, as well as the outcomes of patients with cerebral venous sinus thrombosis, and to explore the characteristics associated with unfavorable patient outcomes. MATERIALS AND METHODS: In this cross-sectional, retrospective study, the medical records of 37 patients with cerebral venous sinus thrombosis were analyzed. RESULTS: Eighty-six percent of the patients were women, and the mean patient age was 41 years. The most frequently reported symptom was headache (86.5%); headache was the single presenting symptom in 40.5% of the patients. Sixty-eight percent of the patients had at least one risk factor, the most frequent of which was obesity (24.3%). A total of 43.2% of the patients had no focal neurological findings. The most common finding on computerized tomography (CT) was hyperdense venous sinuses; on Magnetic Resonance Imaging (MRI), the most common finding was venous infarction. On average, 2.27±1.3 sinuses were involved; most frequently, the transverse venous sinuses were affected. The average hospital stay was 7.8±3.6 days. At hospital discharge, the outcomes were favorable in 92% of the patients, and the mortality rate was 5.4%. CONCLUSIONS: Cerebral venous sinus thrombosis is a different type of cerebrovascular disorder, with distinct epidemiology, risk factors, clinical presentations and functional outcomes. The diagnosis is based on clinical suspicion because of the unspecific clinical presentation of the disease.
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Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/epidemiologia , Adulto , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer's disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive effects of encenicline in healthy volunteers. METHODS: A single ascending-dose study assessed the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of encenicline in healthy male volunteers. Subjects received a single 1-, 3.5-, 7-, 20-, 60-, or 180-mg oral solution dose of encenicline or placebo. A second single-dose, randomized, open-label, 3-period, crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile. FINDINGS: In the first study, encenicline was well tolerated and dose-proportional increases in C(max) (mean range 0.59-100 ng/mL) and AUC0-∞ (mean range 45.6-8890 ng·h/mL) were observed over a 1- to 180-mg dose range. Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose. In the second study, encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90% confidence intervals of the treatment ratios for both comparisons (ie, capsule to solution and fed to fasted) for Cmax and AUC being within 80% to 125%. A 30% to 40% higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33% higher weight of the male subjects. No clinically relevant safety profile or tolerability effects of encenicline were observed. IMPLICATIONS: Encenicline was well tolerated at single doses up to 180 mg, and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system. Oral capsule and solution were bioequivalent and were not affected by food. Although a sex effect on pharmacokinetic profile was observed, it was attributable to weight differences. Clinical Trial Registration at EudraCT: 2006-005623-42 and EudracT: 2008-000029-20.
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Agonistas Nicotínicos/farmacocinética , Quinuclidinas/farmacocinética , Tiofenos/farmacocinética , Administração Oral , Adulto , Disponibilidade Biológica , Cápsulas , Cognição/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Jejum , Feminino , Interações Alimento-Droga , Voluntários Saudáveis , Humanos , Masculino , Agonistas Nicotínicos/administração & dosagem , Agonistas Nicotínicos/efeitos adversos , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversos , Receptores Nicotínicos , Fatores Sexuais , Equivalência Terapêutica , Tiofenos/administração & dosagem , Tiofenos/efeitos adversosRESUMO
Introducción. La trombosis de senos venosos cerebrales representa entre 0,5 y 1 % de las enfermedades cerebrovasculares en adultos, y sus factores de riesgo son diferentes a los del resto de dichas enfermedades. Objetivo. Determinar la epidemiología, las características clínicas e imaginológicas, así como los resultados en pacientes con trombosis de senos venosos cerebrales, y explorar los aspectos asociados con los puntajes desfavorables en la escala modificada de Rankin. Materiales y métodos. Se llevó a cabo un estudio retrospectivo de corte transversal en el Instituto Neurológico de Colombia entre marzo de 2006 y junio de 2011, periodo en el que se analizaron las historias clínicas de 37 pacientes con diagnóstico confirmado por neuroimágenes. Resultados. El 86,5 % de los pacientes eran mujeres, con una edad promedio de 41 años. El síntoma más frecuente fue la cefalea (86,5 %), el cual se presentó como único síntoma en el 40,5 % de los casos. El 68 % tenía, por lo menos, un antecedente de riesgo para trombosis de senos venosos cerebrales, siendo el más frecuente la obesidad (24,3 %), seguido del uso de anticonceptivos hormonales (21,9 %). El examen neurológico fue normal en el 43,2 %. El hallazgo más frecuente en la tomografía fue la hiperdensidad de los senos venosos (33 %) y, en la resonancia magnética, el infarto venoso (37,5 %). El promedio de senos comprometidos fue de 2,27+1,3, siendo más frecuente el compromiso de los transversos. La estancia hospitalaria promedio fue de 7,8+3,6 días. El 92 % de los pacientes presentaba resultados funcionales favorables al dárseles de alta. La mortalidad hospitalaria fue de 5,4 % y se relacionó directamente con la trombosis de senos venosos cerebrales. Conclusiones. La trombosis de senos venosos cerebrales difiere de los otros tipos de enfermedad cerebrovascular en cuanto a su perfil epidemiológico, factores de riesgo, presentación clínica y pronóstico. Es una condición que exige un alto grado de sospecha diagnóstica, pues su presentación clínica es inespecífica.
Introduction: Cerebral venous sinus thrombosis represents 0.5 - 1% of all cerebrovascular diseases. Objective: The aim of this study was to determine the epidemiological, clinical, and imaging features of the disease, as well as the outcomes of patients with cerebral venous sinus thrombosis, and to explore the characteristics associated with unfavorable patient outcomes. Materials and methods: In this cross-sectional, retrospective study, the medical records of 37 patients with cerebral venous sinus thrombosis were analyzed. Results: Eighty-six percent of the patients were women, and the mean patient age was 41 years. The most frequently reported symptom was headache (86.5%); headache was the single presenting symptom in 40.5% of the patients. Sixty-eight percent of the patients had at least one risk factor, the most frequent of which was obesity (24.3%). A total of 43.2% of the patients had no focal neurological findings. The most common finding on computerized tomography (CT) was hyperdense venous sinuses; on Magnetic Resonance Imaging (MRI), the most common finding was venous infarction. On average, 2.27±1.3 sinuses were involved; most frequently, the transverse venous sinuses were affected. The average hospital stay was 7.8±3.6 days. At hospital discharge, the outcomes were favorable in 92% of the patients, and the mortality rate was 5.4%. Conclusions: Cerebral venous sinus thrombosis is a different type of cerebrovascular disorder, with distinct epidemiology, risk factors, clinical presentations and functional outcomes. The diagnosis is based on clinical suspicion because of the unspecific clinical presentation of the disease.
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Adulto , Feminino , Humanos , Masculino , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/epidemiologia , Estudos Transversais , Imageamento por Ressonância Magnética , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Introduction: During malaria infection, both parasite and host are under the effects of oxidative stress due to the increased production of reactive oxygen species, which can induce DNA damage by its genotoxic effects. Objective: To evaluate genotoxic effects in human lymphocytes in a cohort of patients with malaria from Medellin and Quibdó. Methods: We performed an observational cross sectional study in 100 individuals with malaria and 100 healthy controls. Patients infected with Plasmodium consulting the Institute Colombiano of Medicina Tropical of Medellin and the Hospital Ismael Roldán Valencia of Quibdó were included. Genotoxic effects (genetic damage) was analysed by electrophoresis using alkaline single cell gel (Commet assay). Results: The average of tail length of malaria samples (26.9 ± 9.8) was significantly higher than of controls (14.8 ± 3.2) (p < 0.01). Conclusion: In our study population, malaria infection was associated with increased genotoxicity, while other variables such as smoking, antimalarial treatment, and occupation were not.
Introducción: Durante la infección de la malaria, tanto el parásito como el hospedero están bajo los efectos de estrés oxidativo, dado que se aumenta la producción de especies reactivas del oxígeno, las cuales pueden inducir daños en el ADN debido a su gran efecto genotóxico. Objetivo: Evaluar el efecto genotóxico en linfocitos humanos en una cohorte de pacientes con malaria de Medellín y Quibdó. Métodos: Se realizó un estudio observacional transversal en 100 personas con malaria y 100 controles sanos. Se incluyeron pacientes infectados con Plasmodium, que consultaron en el Instituto Colombiano de Medicina Tropical de Medellín y el Hospital Ismael Roldán Valencia de Quibdó. Se realizó una valoración transversal del efecto (daño genético) mediante electro-foresis en gel de células individuales (ensayo Cometa). Resultados: El promedio de longitud de la cola de los pacientes (26,9 ± 9,8) fue significativamente mayor que la media de los controles sanos (14,8 ± 3,2) (p < 0,01). Conclusión: Se evidenció en la población de estudio que la infección por malaria generó genotoxicidad, no así variables como tabaquismo, tratamiento antimalárico y ocupación.
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Feminino , Humanos , Masculino , Dano ao DNA/genética , Linfócitos/parasitologia , Malária Falciparum/genética , Malária Vivax/genética , Estresse Oxidativo/genética , Estudos de Casos e Controles , Colômbia , Estudos Transversais , Malária Falciparum/tratamento farmacológico , Malária Vivax/tratamento farmacológico , Plasmodium falciparum , Plasmodium vivax , Fatores de Risco , FumarRESUMO
Introducción. La sensibilidad de las pruebas convencionales (examen directo, cultivo) para el diagnóstico de la onicomicosis (25 a 80%), representa un problema para la decisión terapéutica del dermatólogo. Objetivo. Determinar la exactitud diagnóstica de la muestra de la lámina ungular en pacientes con diagnóstico clínico de onicomicosis. Metodología. Es un estudio prospectivo de pruebas diagnósticas en 50 pacientes con sospecha de onicomicosis. Se tomó muestra de la lámina ungular con cortaúñas estéril en el área de onicólisis para pruebas micológicas (KOHcultivo) y de histopatología (hematoxilina y eosina y ácido peryódico de Schiff), y muestra de detritos mediante raspado del lecho para prueba micológica. La toma de muestras y el procesamiento de las pruebas se realizaron en laboratorios de referencia y se interpretaron de manera ciega e independiente. La muestra de detritos se consideró la prueba estándar. Resultados. Se observó compromiso de los pies en 90% de los pacientes, 86,6% con afectación del primer dedo. La prueba micológica de detritos fue positiva en 80% de los casos, encontrándose estructuras micóticas en el examen directo en 72% y aislamiento al cultivo en 64%. En la lámina ungular, la sensibilidad fue de 87,5% y la especificidad de 80%; el cociente de probabilidades positivo fue 4,4. Cinco muestras positivas con la tinción PAS fueron negativas en la prueba estándar. La sensibilidad neta aumentó a 95% mediante el análisis de las pruebas en paralelo de la lámina ungular. La mayoría de los aislamientos fueron especies de Candida (77,3% en detritos y 75,9% en la lámina ungular), y C. parapsilosis fue el aislamiento más frecuente. Conclusión. Se propone la muestra de la lámina ungular para pruebas micológicas y tinción de PAS, como complemento a la muestra de detritos para el diagnóstico de onicomicosis.
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Dermatoses do Pé , Onicomicose/diagnósticoRESUMO
Objetivo: evaluar los niveles séricos de 25 hidroxivitamina D (25-OH vitamina D) en mujeres no menopáusicas, menopáusicas y posmenopáusicas, y su relación con algunos factores de riesgo. Materiales y métodos: estudio analítico de cohorte transversal, realizado en 113 mujeres elegidas consecutivamente en la consulta externa de una institución de tercer nivel de complejidad. Se conformaron tres grupos: grupo A, premenopáusicas de 20 a 30 años (n=40); grupo B, menopáusicas de 45 a 55 años (n=40); y grupo C, posmenopáusicas >65 años (n=33). Se comparó el nivel de 25-OH vitamina D en suero a través del estudio ELISA, y su relación con factores como tabaquismo, exposición solar y actividad física en los últimos tres meses. Resultados: el 76% de las mujeres tenían niveles bajos de 25-OH vitamina D (<25 nmol/L). En el 80% de las mujeres del grupo A, se encontraron niveles bajos de esta vitamina comparado con el 77,5% del grupo B y el 69,7% del grupo C (p=0,57). Hubo diferencias significativas entre las medianas de los valores de 25-OH vitamina D en el grupo B al compararlas con el grupo A y C. El análisis de factores de riesgo para una disminución de los niveles séricos de 25-OH vitamina D no mostró diferencias significativas. Conclusiones: a pesar de estar ubicados en un área geográfica tropical, existen niveles séricos bajos de 25-OH vitamina D en las mujeres de los grupos de edad evaluados.
Objective: evaluating 25-hydroxy vitamin D (25OH vitamin D) serum levels in non-menopausal, menopausal and postmenopausal in females and their relationship with dome risk factors. Materials and methods: this was an analytical, cross-sectional study of 113 females chosen consecutively when attending external consultation at a third-level hospital. Three groups were formed: group A, pre-menopausal aged 20-30 (n=40); group B, menopausal aged 45-55 (n=40); and group C, postmenopausal aged >65 (n=33) The levels of 25-OH vitamin D were compared in serum by ELISA and the relationship with smoking, exposure to the sun and physical activity during the last three months. Results: 76% of the females had low 25-OH vitamin D (<25 nmol/L) levels; 80% of the females in group A had low levels compared to 77.5% from group B and 69.7% from group C (p=0.57). There were significant differences between the means of group Bs 25-OH vitamin D values compared to those of group A and C. Analysis of risk factors for reducing 25-OH vitamin D serum levels revealed no significant differences. Conclusions: in spite of our geographical location in the tropics, females from age groups evaluated in this study had low 25-OH vitamin D levels.