RESUMEN
OBJECTIVES: Dibenzyl trisulfide (DTS) has been reported to have cytotoxic and anti-inflammatory effects. It also affects erythrocyte deformability. We investigated the effects of DTS on the p50 of the oxygen haemoglobin dissociation curve. METHODS: Blood samples from 10 healthy male volunteers with normal haemoglobin AA were exposed to 50, 100, 200 and 400 ng/mL, respectively, of DTS. A hemox-analyzer was used to obtain the p50 values. RESULTS: The mean p50 value for the control samples was 25.89 ± 2.18 mm Hg. The values for the samples exposed to 50, 100, 200 and 400 ng/mL were 23.53 ± 1.81 mm Hg, 22.62 ± 1.61 mm Hg, 21.88 ± 1.67 mm Hg and 21.68 ± 1.88 mm Hg, respectively. CONCLUSIONS: DTS caused a significant (p<0.001) reduction in p50 values indicating a shift of the oxygen- haemoglobin dissociation curve to the left in all the samples compared with control, suggesting that the administration of DTS could result in decrease in oxygen supply to tissues.
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Compuestos de Bencilo/farmacología , Eritrocitos/efectos de los fármacos , Hemoglobinas/efectos de los fármacos , Oxígeno/metabolismo , Sulfuros/farmacología , Relación Dosis-Respuesta a Droga , Hematócrito , Humanos , Concentración de Iones de Hidrógeno , Masculino , Presión Parcial , Temperatura , Adulto JovenRESUMEN
INTRODUCTION: Patients with acute coronary syndrome usually receive dual antiplatelet therapy (DAPT) (usually clopidogrel + aspirin) prior to coronary catheterization, and approximately 10% of these patients require coronary artery bypass grafting (CABG). DAPT has favorable effects on prevention of thrombus formation, but it can have deleterious effects on surgical hemostasis. Anaemia, if present, gives additional risk to such patients. The aim of this study was to examine if DAPT affects postoperative bleeding in patients with haemoglobin levels above 110 g/L, who underwent urgent or emergent CABG, less than five days after stopping DAPT therapy. METHODS: Data were collected prospectively on 122 CABG patients, operated by a surgical team from March 2008 to August 2013. Patients were stratified into two groups: group 1 received DAPT within 5 days of CABG (n=65), and group 2 where DAPT was discontinued for more than 5 days prior to CABG (n=57). All patients were diagnosed with acute coronary syndrome preoperatively, and all of them had haemoglobin levels above 110 g/L. Patients who needed reoperation, combined procedures, or off-pump revascularization were excluded. RESULTS: There was no hospital mortality. Mean chest tube losses after the surgical revascularization did not differ significantly, but group 1 received a higher quantity of transfused red blood cells and platelets. CONCLUSION: Urgent and emergent surgical revascularization using extracorporeal circulation in patients with acute coronary syndrome whose preoperative haemoglobin levels are above 110 g/L is a safe and effective procedure. We suggest that, where indicative, one may perform CABG in less than 5 days after the clopidogrel discontinuation.
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Síndrome Coronario Agudo/cirugía , Aspirina/administración & dosificación , Clopidogrel/administración & dosificación , Puente de Arteria Coronaria/métodos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Hemorragia Posoperatoria/prevención & control , Anciano , Femenino , Hemoglobinas/efectos de los fármacos , Humanos , Masculino , Estudios Prospectivos , ReoperaciónRESUMEN
Abstract Introduction: Patients with acute coronary syndrome usually receive dual antiplatelet therapy (DAPT) (usually clopidogrel + aspirin) prior to coronary catheterization, and approximately 10% of these patients require coronary artery bypass grafting (CABG). DAPT has favorable effects on prevention of thrombus formation, but it can have deleterious effects on surgical hemostasis. Anaemia, if present, gives additional risk to such patients. The aim of this study was to examine if DAPT affects postoperative bleeding in patients with haemoglobin levels above 110 g/L, who underwent urgent or emergent CABG, less than five days after stopping DAPT therapy. Methods: Data were collected prospectively on 122 CABG patients, operated by a surgical team from March 2008 to August 2013. Patients were stratified into two groups: group 1 received DAPT within 5 days of CABG (n=65), and group 2 where DAPT was discontinued for more than 5 days prior to CABG (n=57). All patients were diagnosed with acute coronary syndrome preoperatively, and all of them had haemoglobin levels above 110 g/L. Patients who needed reoperation, combined procedures, or off-pump revascularization were excluded. Results: There was no hospital mortality. Mean chest tube losses after the surgical revascularization did not differ significantly, but group 1 received a higher quantity of transfused red blood cells and platelets. Conclusion: Urgent and emergent surgical revascularization using extracorporeal circulation in patients with acute coronary syndrome whose preoperative haemoglobin levels are above 110 g/L is a safe and effective procedure. We suggest that, where indicative, one may perform CABG in less than 5 days after the clopidogrel discontinuation.
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Humanos , Masculino , Femenino , Anciano , Inhibidores de Agregación Plaquetaria/administración & dosificación , Aspirina/administración & dosificación , Puente de Arteria Coronaria/métodos , Hemorragia Posoperatoria/prevención & control , Síndrome Coronario Agudo/cirugía , Clopidogrel/administración & dosificación , Reoperación , Hemoglobinas/efectos de los fármacos , Estudios ProspectivosRESUMEN
BACKGROUND: Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy. METHODS: One-hundred sixteen pediatric ESA-naïve subjects (aged 1-18 years) with CKD stages 3-5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2 years. RESULTS: In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0-12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases. CONCLUSIONS: Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl.
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Anemia/tratamiento farmacológico , Darbepoetina alfa/administración & dosificación , Hematínicos/administración & dosificación , Insuficiencia Renal Crónica/complicaciones , Adolescente , Anemia/etiología , Niño , Preescolar , Darbepoetina alfa/efectos adversos , Método Doble Ciego , Esquema de Medicación , Europa (Continente) , Femenino , Hematínicos/efectos adversos , Hemoglobinas/análisis , Hemoglobinas/efectos de los fármacos , Humanos , Lactante , Masculino , México , Calidad de Vida , Diálisis Renal , Insuficiencia Renal Crónica/tratamiento farmacológico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
ABSTRACT BACKGROUND AND OBJECTIVES: The use of tranexamic acid in primary total knee replacement surgeries has been the subject of constant study. The strategies to reduce bleeding are aimed at reducing the need for blood transfusion due to the risks involved. In this study we evaluated the use of tranexamic acid in reducing bleeding, need for blood transfusion, and prevalence of postoperative deep vein thrombosis in primary total knee replacement. METHOD: 62 patients undergoing primary total knee replacement were enrolled in the study, from June 2012 to May 2013, and randomized to receive a single dose of 2.5 g of intravenous tranexamic acid (Group TA) or saline (Group GP), 5 min before opening the pneumatic tourniquet, respectively. Hemoglobin, hematocrit, and blood loss were recorded 24 h after surgery. Deep vein thrombosis was investigated during patient's hospitalization and 15 and 30 days after surgery in review visits. RESULTS: There was no demographic difference between groups. Group TA had 13.89% decreased hematocrit (p = 0.925) compared to placebo. Group TA had a decrease of 12.28% (p = 0.898) in hemoglobin compared to Group GP. Group TA had a mean decrease of 187.35 mL in blood loss (25.32%) compared to group GP (p = 0.027). The number of blood transfusions was higher in Group GP (p = 0.078). Thromboembolic events were not seen in this study. CONCLUSION: Tranexamic acid reduced postoperative bleeding without promoting thromboembolic events.
RESUMO JUSTIFICATIVA E OBJETIVOS: O uso do ácido tranexâmico, em cirurgias de artroplastia total primária de joelho, tem sido objeto de constante estudo. As estratégias para redução de sangramento visam à redução da necessidade de transfusão de sangue devido aos riscos que apresentam. Neste estudo, propomos a avaliação do uso do ácido tranexâmico na redução do sangramento, na necessidade de transfusão de sangue e na prevalência de trombose venosa profunda (TVP) pós-operatória em artroplastia total primária de joelho. MÉTODO: Foram estudados 62 pacientes submetidos à artroplastia primária total de joelho, de junho de 2012 a maio de 2013, randomizados para receber ácido tranexâmico 2,5 g endovenoso (grupo AT), em dose única, ou soro fisiológico (grupo GP), cinco minutos antes da abertura do torniquete pneumático, respectivamente. Foram feitas dosagens de hemoglobina e hematócrito e medida a perda sanguínea 24 horas após a cirurgia. A TVP foi pesquisada durante a internação do paciente, 15 e 30 dias após a cirurgia nas consultas de revisão. RESULTADOS: Não houve diferenças demográficas entre os grupos estudados. O grupo GT apresentou queda do hematócrito 13,89% (p = 0,925) comparado com o grupo placebo. O grupo GT apresentou diminuição de 12,28% (p = 0,898) da hemoglobina comparado com o grupo GP. O grupo GT apresentou uma diminuição média de 187,35 ml nas perdas sanguíneas (25,32%) quando comparado com o grupo GP (p = 0,027). O número de transfusões sanguíneas foi maior no grupo GP (p = 0,078). Eventos tromboembólicos não foram evidenciados neste estudo. CONCLUSÕES: O ácido tranexâmico diminuiu o sangramento pós-operatório sem promover eventos tromboembólicos.
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Humanos , Masculino , Femenino , Anciano , Complicaciones Posoperatorias/prevención & control , Ácido Tranexámico/uso terapéutico , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Hemorragia Posoperatoria/prevención & control , Artroplastia de Reemplazo de Rodilla , Antifibrinolíticos/uso terapéutico , Transfusión Sanguínea/estadística & datos numéricos , Hemoglobinas/efectos de los fármacos , Trombosis de la Vena/prevención & control , Hematócrito/estadística & datos numéricos , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVES: The use of tranexamic acid in primary total knee replacement surgeries has been the subject of constant study. The strategies to reduce bleeding are aimed at reducing the need for blood transfusion due to the risks involved. In this study we evaluated the use of tranexamic acid in reducing bleeding, need for blood transfusion, and prevalence of postoperative deep vein thrombosis in primary total knee replacement. METHOD: 62 patients undergoing primary total knee replacement were enrolled in the study, from June 2012 to May 2013, and randomized to receive a single dose of 2.5g of intravenous tranexamic acid (Group TA) or saline (Group GP), 5min before opening the pneumatic tourniquet, respectively. Hemoglobin, hematocrit, and blood loss were recorded 24h after surgery. Deep vein thrombosis was investigated during patient's hospitalization and 15 and 30 days after surgery in review visits. RESULTS: There was no demographic difference between groups. Group TA had 13.89% decreased hematocrit (p=0.925) compared to placebo. Group TA had a decrease of 12.28% (p=0.898) in hemoglobin compared to Group GP. Group TA had a mean decrease of 187.35mL in blood loss (25.32%) compared to group GP (p=0.027). The number of blood transfusions was higher in Group GP (p=0.078). Thromboembolic events were not seen in this study. CONCLUSION: Tranexamic acid reduced postoperative bleeding without promoting thromboembolic events.
Asunto(s)
Antifibrinolíticos/uso terapéutico , Artroplastia de Reemplazo de Rodilla , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Complicaciones Posoperatorias/prevención & control , Hemorragia Posoperatoria/prevención & control , Ácido Tranexámico/uso terapéutico , Anciano , Transfusión Sanguínea/estadística & datos numéricos , Femenino , Hematócrito/estadística & datos numéricos , Hemoglobinas/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Trombosis de la Vena/prevención & controlRESUMEN
BACKGROUND: The objective of this study was to compare the effect of once weekly iron supplementation (IS) versus twice weekly, on hemoglobin (Hb) levels and anemia prevalence. METHODS: In this cluster-randomized clinical trial study, we evaluated infants aged 6-18 months. Length of intervention: 16 weeks. Infants were cluster randomized to either 25 mg elemental iron once weekly (Group-A) or twice weekly (Group-B). Primary outcome variables were change in Hb concentration and anemia prevalence. Two biochemical evaluations were performed to determine Hb concentrations, before and after intervention. RESULTS: For Group-A, at baseline, mean Hb concentration was 10.8 ± 1.18 g/dl and after intervention 11.2 ± 1.07 g/dl,p = 0.12; anemia prevalence was 52.5% at baseline and 37.5% after intervention,p = 0.18; Group-B, mean baseline Hb was 10.7 ± 1.04 g/dl, and 11.3 ± 0.91 g/dl after intervention,p = 0.002; anemia prevalence reduced from 57.9 to 36.8%. CONCLUSIONS: Both once and twice weekly IS increased mean Hb concentration; however, twice weekly supplementation provided more significant results.
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Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/prevención & control , Compuestos Ferrosos/administración & dosificación , Hemoglobinas/efectos de los fármacos , Hierro de la Dieta/administración & dosificación , Anemia Ferropénica/epidemiología , Brasil/epidemiología , Análisis por Conglomerados , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Ferritinas/sangre , Hemoglobinas/análisis , Humanos , Lactante , Masculino , Prevalencia , Factores Socioeconómicos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Anemia diminishes oxygen transport in the body, resulting in potentially irreversible growth and developmental consequences for children. Limited evidence for determinants of anemia exists for school-aged children. We conducted a cluster randomized controlled trial in Haiti from 2012 to 2013 to test the efficacy of a fortified school snack. Children (N = 1,047) aged 3-13 years were followed longitudinally at three time points for hemoglobin (Hb) concentrations, anthropometry, and bioelectrical impedance measures. Dietary intakes, infectious disease morbidities, and socioeconomic and demographic factors were collected at baseline and endline. Longitudinal regression modeling with generalized least squares and logit models with random effects identified anemia risk factors beyond the intervention effect. At baseline, 70.6% of children were anemic and 2.6% were severely anemic. Stunting increased the odds of developing anemia (adjusted odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.05-2.08) and severe anemia (adjusted OR: 2.47, 95% CI: 1.30-4.71). Parent-reported vitamin A supplementation and deworming were positively associated with Hb concentrations, whereas fever and poultry ownership showed a negative relationship with Hb concentration and increased odds of severe anemia, respectively. Further research should explore the full spectrum of anemia etiologies in school children, including genetic causes.
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Anemia/prevención & control , Suplementos Dietéticos , Alimentos Fortificados , Hemoglobinas/análisis , Adolescente , Anemia/complicaciones , Anemia/tratamiento farmacológico , Anemia/epidemiología , Antropometría , Composición Corporal , Peso Corporal , Niño , Preescolar , Dietoterapia , Impedancia Eléctrica , Femenino , Trastornos del Crecimiento/complicaciones , Haití/epidemiología , Hemoglobinas/efectos de los fármacos , Humanos , Estudios Longitudinales , Masculino , Estado Nutricional , Factores de Riesgo , Vitamina A/administración & dosificaciónRESUMEN
OBJECTIVE: Assess drinking water fortification with iron and/or ascorbic acid as a strategy to control iron-deficiency anemia and iron deficiency. METHODS: Randomized blind clinical study, fortifying drinking water to 153 pre-school children during 3 months, with iron and ascorbic acid (A), ascorbic acid (B) or plain water (C). Hemoglobin (Hb), mean corpuscular volume (MCV) and ferritin were measured. RESULTS: Within the groups, Hb raised in all three groups, MCV in A and B and ferritin in A. The difference between time points 0 and 1 was significant between A and B for Hb, when A and B were compared with C for MCV and when A was compared with either B or C for ferritin. CONCLUSIONS: Water fortification is efficient in controlling iron deficiency and anemia. Iron stores' recovery depends on a more effective offer of iron. Water fortification must be preceded by a careful assessment of the previous nutritional status.
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Anemia Ferropénica/prevención & control , Ácido Ascórbico/administración & dosificación , Guarderías Infantiles , Agua Potable , Alimentos Fortificados , Hemoglobinas/análisis , Hierro/administración & dosificación , Anemia Ferropénica/epidemiología , Brasil/epidemiología , Preescolar , Método Doble Ciego , Femenino , Hemoglobinas/efectos de los fármacos , Humanos , Deficiencias de Hierro , Masculino , Evaluación Nutricional , Estado Nutricional , Prevalencia , Resultado del Tratamiento , Vitaminas/administración & dosificaciónRESUMEN
BACKGROUND: Relationships among Schistosoma haematobium, anemia, and iron deficiency have been documented, and all have been found to be associated with a decline in school attendance and lower performance. OBJECTIVE: To assess the effect of single or combined iron and multiple micronutrients and/or praziquantel on school attendance and achievement in randomly selected 7- to 12-year-old anemic children with documented S. haematobium infection (n = 406) in Mali over a 3-month period. METHODS: Schistosomiasis infection was diagnosed by the presence of schistosome eggs in the urine. Venous blood samples (5 mL) were drawn from an antecubital vein for hemoglobin assessment. Children were randomly assigned to one of four treatment groups: praziquantel alone, praziquantel + iron, praziquantel + multiple micronutrients, and praziquantel + multiple micronutrients + iron. School attendance was defined by the number of days the child was absent from class. Achievement was defined by the child's overall school grades. RESULTS: Changes within treatment groups from baseline to the end of study were found for attendance (p < .001) but not for achievement (p > .05). Significant supplement treatments by age group interactions were found in 7- to 9-year-old children for attendance. Further exploration of treatment effects in this age group showed that only iron treatment's main effect was significant on attendance (p = .049) and was of borderline significance on school grades (p = .08). CONCLUSIONS: Combined praziquantel and iron treatment improved children's school attendance and performance better than praziquantel alone, particularly among younger children.
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Anemia/tratamiento farmacológico , Suplementos Dietéticos , Hierro de la Dieta/uso terapéutico , Micronutrientes/uso terapéutico , Esquistosomiasis Urinaria/tratamiento farmacológico , Absentismo , Animales , Niño , Femenino , Hemoglobinas/análisis , Hemoglobinas/efectos de los fármacos , Humanos , Modelos Lineales , Masculino , Malí/epidemiología , Análisis Multivariante , Recuento de Huevos de Parásitos , Praziquantel/uso terapéutico , Prevalencia , Estudios Prospectivos , Schistosoma haematobium/efectos de los fármacos , Esquistosomiasis Urinaria/sangre , Esquistosomiasis Urinaria/epidemiología , Instituciones AcadémicasRESUMEN
BACKGROUND: Anemia, neutropenia, and thrombocytopenia are commonly observed in HIV-infected patients. This study was undertaken to evaluate the prevalence of cytopenias and their association with CD4 count. Furthermore, the association of hemoglobin concentration with mortality was also investigated. METHODS: We reviewed the data of 701 HIV-infected patients followed at our institution. Blood cell counts, hemoglobin concentration, CD4 count, and viral load were recorded. We also recorded the mortality rate after 1 year in the groups with CD4 <200/µl and ≥ 200/µl according to hemoglobin concentration. RESULTS: Of the total patients, 37.5% had anemia; 61.1% (110/180) were in the low CD4 group and 29.4% (153/521) were in the high CD4 group (p<0.01). Mean neutrophil counts were 2.610 × 10(9)/l and 3.204 × 10(9)/l in the low CD4 and high CD4 groups, respectively (p<0.01); mean platelet counts were 218.639 × 10(9)/l and 234.807 × 10(9)/l for the low CD4 and the high CD4 groups, respectively (p=0.03). Patients whose hemoglobin concentration was below the median value had a higher death rate in both the low CD4 (14 vs. 4 deaths, p=0.013) and high CD4 (8 vs. 1 death, p=0.0158) groups. CONCLUSIONS: We found an association between CD4 count and hemoglobin level, neutrophil count, and platelet count, and that anemia was independently associated with a higher mortality.
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Infecciones por VIH/sangre , VIH-1/aislamiento & purificación , Enfermedades Hematológicas/epidemiología , Adolescente , Adulto , Anciano , Anemia/complicaciones , Anemia/epidemiología , Fármacos Anti-VIH/farmacología , Recuento de Células Sanguíneas , Brasil/epidemiología , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , VIH-1/genética , Enfermedades Hematológicas/complicaciones , Hemoglobinas/análisis , Hemoglobinas/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Neutropenia/complicaciones , Neutropenia/epidemiología , ARN Viral/sangre , Estudios Retrospectivos , Trombocitopenia/complicaciones , Trombocitopenia/epidemiología , Carga Viral , Adulto Joven , Zidovudina/farmacologíaRESUMEN
Plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. During this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. In this context, a group of azole antimycotics, clotrimazole (CTZ), ketoconazole (KTZ) and fluconazole (FCZ), were investigated for their abilities to inhibit ß-hematin synthesis (IßHS) and hemoglobin proteolysis (IHbP) in vitro. The ß-hematin synthesis was recorded by spectrophotometry at 405 nm and the hemoglobin proteolysis was determined by SDS-PAGE 12.5%, followed by densitometric analysis. Compounds were also assayed in vivo in a malaria murine model. CTZ and KTZ exhibited the maximal effects inhibiting both biochemical events, showing inhibition of ß-hematin synthesis (IC50 values of 12.4 ± 0.9 µM and 14.4 ± 1.4 µM respectively) and inhibition of hemoglobin proteolysis (80.1 ± 2.0% and 55.3 ± 3.6%, respectively). There is a broad correlation to the in vivo results, especially CTZ, which reduced the parasitemia (%P) of infected-mice at 4th day post-infection significantly compared to non-treated controls (12.4 ± 3.0% compared to 26.6 ± 3.7%, p = 0.014) and prolonged the survival days post-infection. The results indicated that the inhibition of the hemoglobin metabolism by the azole antimycotics could be responsible for their antimalarial effect.
Asunto(s)
Antimaláricos/farmacología , Clotrimazol/farmacología , Fluconazol/farmacología , Hemoproteínas/biosíntesis , Cetoconazol/farmacología , Malaria/parasitología , Plasmodium berghei/efectos de los fármacos , Animales , Electroforesis en Gel de Poliacrilamida , Hemoglobinas/efectos de los fármacos , Hemoglobinas/metabolismo , Hemólisis/efectos de los fármacos , Malaria/sangre , Malaria/tratamiento farmacológico , Masculino , Ratones , Ratones Endogámicos BALB C , Plasmodium berghei/fisiologíaRESUMEN
Plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. During this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. In this context, a group of azole antimycotics, clotrimazole (CTZ), ketoconazole (KTZ) and fluconazole (FCZ), were investigated for their abilities to inhibit ß-hematin synthesis (IßHS) and hemoglobin proteolysis (IHbP) in vitro. The ß-hematin synthesis was recorded by spectrophotometry at 405 nm and the hemoglobin proteolysis was determined by SDS-PAGE 12.5 percent, followed by densitometric analysis. Compounds were also assayed in vivo in a malaria murine model. CTZ and KTZ exhibited the maximal effects inhibiting both biochemical events, showing inhibition of β-hematin synthesis (IC50 values of 12.4 ± 0.9 µM and 14.4 ± 1.4 µM respectively) and inhibition of hemoglobin proteolysis (80.1 ± 2.0 percent and 55.3 ± 3.6 percent, respectively). There is a broad correlation to the in vivo results, especially CTZ, which reduced the parasitemia ( percentP) of infected-mice at 4th day post-infection significantly compared to non-treated controls (12.4 ± 3.0 percent compared to 26.6 ± 3.7 percent, p = 0.014) and prolonged the survival days post-infection. The results indicated that the inhibition of the hemoglobin metabolism by the azole antimycotics could be responsible for their antimalarial effect.
Los parásitos del género Plasmodium degradan la hemoglobina hospedera obteniendo aminoácidos libres para su síntesis proteica. Durante este evento, unidades de hemo libre tóxicas cristalizan espontáneamente formando un pigmento no tóxico denominado ß-hematina. En este trabajo, se investigó la capacidad de un grupo de azoles antimicóticos: clotrimazol (CTZ), ketoconazol (KTZ) y fluconazol (FCZ), en inhibir la síntesis de ß-hematina y la proteólisis de la globina. La síntesis de ß-hematina se registro por espectrofotometría a 405 nm y la proteólisis de la hemoglobina se determino por SDS-PAGE 15 por ciento seguido por análisis densitométrico de las bandas de hemoglobina intactas. Los compuestos fueron también ensayados in vivo en un modelo de malaria murina. CTZ y KTZ inhibieron la síntesis de ß-hematina con CI50 entre 10 y 15 µM y bloquearon la proteólisis de la hemoglobina (80.01 ± 2.04 por ciento y 55.33 ± 3.57 por ciento, respectivamente). En relación directa con los resultados encontrados in vitro, el CTZ redujo la parasitemia de ratones infectados en forma significativa, así como prolongó lo días de sobrevivencia post-infección en comparación con animales controles no tratados. Se sugiere así que la inhibición del metabolismo de la hemoglobina por los antimicóticos azólicos pudiera ser el mecanismo responsable de su actividad antimalárica.
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Animales , Masculino , Ratones , Antimaláricos/farmacología , Clotrimazol/farmacología , Fluconazol/farmacología , Hemoproteínas/biosíntesis , Cetoconazol/farmacología , Malaria/parasitología , Plasmodium berghei/efectos de los fármacos , Electroforesis en Gel de Poliacrilamida , Hemoglobinas/efectos de los fármacos , Hemoglobinas/metabolismo , Hemólisis/efectos de los fármacos , Ratones Endogámicos BALB C , Malaria/sangre , Malaria/tratamiento farmacológico , Plasmodium berghei/fisiologíaRESUMEN
Median lethal concentration (LC(50)) and sublethal effects of the commercial endosulfan formulation Zebra Ciagro(®) on the fish Cichlasoma dimerus were studied. The 96-h LC(50) was estimated as 17.7 µg/L. In order to investigate sublethal effects, fish were exposed to 25% and 50% LC(1) (3.4 and 6.8 µg/L, respectively). Endosulfan (ED) significantly increased the hemoglobin concentration and white blood cell count after 96 h. Differential leukocytes count was also altered, due to an increase in the percentage of neutrophils in exposed fish. The hepatopancreatic tissue of fish under ED treatment showed a decrease in aspartate aminotransferase and alanine aminotransferase and an increase in alkaline phosphatase. Lipid peroxidation levels in the 6.8-µg/L ED-containing group were higher than those in control fish for all organs tested (gills, hepatopancreas, and brain).
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Cíclidos , Endosulfano/toxicidad , Monitoreo del Ambiente/métodos , Insecticidas/toxicidad , Estrés Fisiológico/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Alanina Transaminasa/efectos de los fármacos , Alanina Transaminasa/metabolismo , Fosfatasa Alcalina/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Animales , Aspartato Aminotransferasas/efectos de los fármacos , Aspartato Aminotransferasas/metabolismo , Encéfalo/efectos de los fármacos , Endosulfano/análisis , Branquias/efectos de los fármacos , Hemoglobinas/análisis , Hemoglobinas/efectos de los fármacos , Insecticidas/análisis , Dosificación Letal Mediana , Recuento de Leucocitos , Hígado/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Contaminantes Químicos del Agua/análisisRESUMEN
Iron deficiency and visceral leishmaniasis are serious problems of public health. The aim of this study was to evaluate the effect of iron deficiency, induced by the iron chelator desferrioxamine, on the course of the infection by Leishmania chagasi in BALB/c mice. Our data show that the iron chelator caused significant reduction in hemoglobin concentration of treated mice and reduction in parasite load in spleen and liver. Significant differences were not observed in the production of IFN-gamma and IL-4 among the experimental groups. In conclusion, the data reported in this paper suggest that iron deficiency may favor the host. If there is not enough iron available to the parasite, its multiplication may be reduced and infection attenuated.
Asunto(s)
Anemia Ferropénica/complicaciones , Leishmania infantum , Leishmaniasis Visceral/complicaciones , Anemia Ferropénica/inducido químicamente , Animales , Citocinas/biosíntesis , Deferoxamina/toxicidad , Femenino , Hemoglobinas/efectos de los fármacos , Hemoglobinas/metabolismo , Leishmania infantum/efectos de los fármacos , Leishmania infantum/crecimiento & desarrollo , Leishmaniasis Visceral/parasitología , Leishmaniasis Visceral/patología , Hígado/efectos de los fármacos , Hígado/parasitología , Hígado/patología , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Sideróforos/toxicidad , Bazo/efectos de los fármacos , Bazo/parasitología , Bazo/patologíaRESUMEN
The aim of the present study was to evaluate the chronic toxicity of ethanol low blood levels in malnourished rats. Female Wistar rats (220 g) were subjected to either an ad libitum diet (W, well-nourished, n=10) or food restriction (M, malnourished, n=10). Water (WW and MW) or ethanol solution (W5% and M5%) was offered to half of each nutritional group (n=5) as the only fluid source. The treatment was continued for two months. After sacrifice, blood biochemical parameters and macroscopic, histologic and morphometric evaluation of the liver were performed. Results indicated that: Ethanol consumption was higher in malnourished rats and minimized body weight loss in malnourished rats, while it decreased the body weight gain in well-nourished ones. Behavioral ethanol intoxication was more severe in malnourished rats. Malnutrition decreased hematocrit and hemoglobin but, on the other hand, ethanol was a protective factor of that effect (hemoglobin: MW 10.6 mg/dl / ME 13.02 mg/dl, p< 0.05). Ethanol increased the relative liver weight of both well-nourished and malnourished rats. Ethanol intake minimized iron pigment, collagen area and binuclear hepatocyte/ field increased by malnutrition. These data are in accordance with previous reports which showed ethanol as an important source of calories and, even chronically, ethanol still attenuates the effects of malnutrition.
Asunto(s)
Etanol/toxicidad , Hígado/efectos de los fármacos , Desnutrición/fisiopatología , Animales , Etanol/administración & dosificación , Etanol/sangre , Femenino , Hematócrito , Hemoglobinas/análisis , Hemoglobinas/efectos de los fármacos , Hígado/patología , Desnutrición/sangre , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Chemiluminescence assay was suitable for rapid determination of alterations caused by chloramphenicol (Ch) in blood. The new aspects observed indicated oxidative stress with: (a) biphasic response of reactive oxidant species (ROS) with different concentration of Ch; (b) increase of carbonyl residues and advanced oxidation protein products in blood as a consequence of oxidative stress; (c) oxidation of haemoglobin with rise of oxyhaemoglobin; protein and haemoglobin oxidation was more pronounced in the samples that exhibited high stimuli of ROS; and (d) the ferrous reduction antioxidant potential (FRAP) was the lowest in the maximum ROS-producer sample, which exhibited the lowest consumption of FRAP in response to Ch treatment. The present investigation could contribute to a rapid detection of persons with elevated susceptibility to Ch previously to its application in chemotherapy.
Asunto(s)
Antibacterianos/toxicidad , Cloranfenicol/toxicidad , Mediciones Luminiscentes/métodos , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/administración & dosificación , Biomarcadores/metabolismo , Cloranfenicol/administración & dosificación , Relación Dosis-Respuesta a Droga , Hemoglobinas/efectos de los fármacos , Hemoglobinas/metabolismo , Humanos , Técnicas In Vitro , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Oxihemoglobinas/efectos de los fármacos , Oxihemoglobinas/metabolismo , Proteínas/efectos de los fármacos , Proteínas/metabolismoRESUMEN
The aim of the present study was to evaluate the chronic toxicity of ethanol low blood levels in malnourished rats. Female Wistar rats (220 g) were subjected to either an ad libitum diet (W, well-nourished, n=10) or food restriction (M, malnourished, n=10). Water (WW and MW) or ethanol solution (W5 percent and M5 percent) was offered to half of each nutritional group (n=5) as the only fluid source. The treatment was continued for two months. After sacrifice, blood biochemical parameters and macroscopic, histologic and morphometric evaluation of the liver were performed. Results indicated that: Ethanol consumption was higher in malnourished rats and minimized body weight loss in malnourished rats, while it decreased the body weight gain in well-nourished ones. Behavioral ethanol intoxication was more severe in malnourished rats. Malnutrition decreased hematocrit and hemoglobin but, on the other hand, ethanol was a protective factor of that effect (hemoglobin: MW 10.6 mg/dl / ME 13.02 mg/dl, p< 0.05). Ethanol increased the relative liver weight of both well-nourished and malnourished rats. Ethanol intake minimized iron pigment, collagen area and binuclear hepatocyte/ field increased by malnutrition. These data are in accordance with previous reports which showed ethanol as an important source of calories and, even chronically, ethanol still attenuates the effects of malnutrition.
Asunto(s)
Animales , Femenino , Ratas , Etanol/toxicidad , Hígado/efectos de los fármacos , Desnutrición/fisiopatología , Etanol/administración & dosificación , Etanol/sangre , Hematócrito , Hemoglobinas/análisis , Hemoglobinas/efectos de los fármacos , Hígado/patología , Desnutrición/sangre , Tamaño de los Órganos/efectos de los fármacos , Ratas Wistar , Factores de TiempoRESUMEN
BACKGROUND: Universal fortification of staple foods with iron has been widely promoted as a cost-effective strategy to reduce iron deficiency in developing-country populations. Nonetheless, relatively few efficacy trials have been reported to date to demonstrate impact on iron status. The Ultra Rice technology provides a means of delivering fortificant iron via rice. OBJECTIVE: The objective of this study was to test the efficacy of rice fortified with microencapsulated, micronized iron pyrophosphate to improve the iron status of women in Mexico in a randomized, controlled intervention trial. METHODS: Nonpregnant, nonlactating women 18 to 49 years of age were recruited from six factories. The women received a daily portion of cooked rice 5 days per week for a period of 6 months, before and after which iron status indicators were determined in venous blood samples. RESULTS: The average intake of iron from the fortificant was 13 mg/day. Mean plasma ferritin concentration and estimated body iron stores were significantly higher, and transferrin receptors were lower, in the iron-fortified rice group following the intervention. Mean hemoglobin concentration also increased in the treatment group, but the increase was significant only when the analysis was restricted to those with baseline hemoglobin < 12.8 g/dL. The absolute reduction in anemia and iron deficiency was 10.3 and 15.1 percentage points, respectively. Total iron intake from fortificant was a significant covariate of change in body iron stores. The overall prevalence of anemia was reduced by 80%. CONCLUSIONS: Fortification of rice with iron using this technology is an efficacious strategy for preventing iron deficiency.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Alimentos Fortificados , Hemoglobinas/metabolismo , Hierro de la Dieta/uso terapéutico , Estado Nutricional , Oryza , Adolescente , Adulto , Anemia Ferropénica/sangre , Anemia Ferropénica/epidemiología , Anemia Ferropénica/prevención & control , Difosfatos/administración & dosificación , Difosfatos/uso terapéutico , Femenino , Ferritinas/sangre , Hemoglobinas/efectos de los fármacos , Humanos , Hierro/administración & dosificación , Hierro/uso terapéutico , Hierro de la Dieta/administración & dosificación , México/epidemiología , Persona de Mediana Edad , Prevalencia , Receptores de Transferrina/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: In developing countries there is high prevalence of iron deficiency anemia, which causes negative impact on growth, development and quality of life for infant population. Currently several strategies are being elaborated and tested to tackle this problem. OBJECTIVE: To measure anemia prevalence in preschool children. To evaluate fortification effectiveness with 5 or 10 mg of elemental iron/daily added to school meals by increasing hemoglobin levels in anemic children. METHODS: Double-blind, cluster randomized intervention study with 728 students from public network. Blood count was taken at beginning of study, to evaluate anemia prevalence, those anemic were selected for intervention, after intervention new blood count was taken to evaluate fortification effectiveness. Ferrous Sulphate was added in individual dosage of 5 or 10 mg of elemental iron/daily to usual school meal. From 35 schools 3 were randomized to receive 5 mg/daily (group A) and 3 to receive 10 mg/daily (group B). Hemoglobin and hematocrit averages before and after intervention were compared in each group and between them. RESULTS: In group A, the anemia prevalence reduced 34.9 to 12.4%, and in group B 39.0 to 18.7%. In both groups a significant increase in hemoglobin was observed: in group A from 10.1 to 11.5 g/dl (p < 0.01) and in group B from 10.0 to 11.0 g/dl (p < 0.01). There was no statistically significant difference in final levels of hemoglobin among groups. CONCLUSIONS: Both dosages of elemental iron were equally effective in increasing hemoglobin levels, and reducing anemia prevalence. Fortification of school meals was shown to be an effective, low cost and easy to manage intervention.