Anemia ferropénica en el embarazo: esquema de sulfato ferroso intermitente en comparación con el continuo / Iron deficiency anaemia in pregnancy: comparison of intermittent versus continuous ferrous sulphate regimen

Resumen OBJETIVO: Comparar las concentraciones de hemoglobina en embarazadas con anemia por deficiencia de hierro que recibieron un tratamiento intermitente en comparación con el continuo de 200 mg de sulfato ferroso por vía oral. Además, comparar la frecuencia de efectos secundarios del tratamiento intermitente con el continuo. MATERIALES Y MÉTODOS: Ensayo clínico, aleatorizado, no cegado, efectuado en la Unidad Médica de Alta Especialidad Hospital de Ginecoobstetricia 4 Luis Castelazo Ayala, IMSS, en pacientes de 18 a 35 años atendidas entre los meses de enero a marzo del 2023 con 30 o más semanas de embarazo, diagnóstico de anemia ferropénica (definida operativamente solo con una biometría hemática inferior a 11 g/dL, con hipocromía y microcitosis), sin antecedentes de enfermedad crónico-degenerativa. El análisis estadístico se procesó en el programa SPSS v21, la distribución y características de la muestra con análisis univariado, seguido de un análisis bivariado con t de Student y diferencia de medias. Se consideró con significación estadística el valor de p < 0.05. RESULTADOS: Se estudiaron 32 pacientes: 16 con esquema continuo y 16 con el intermitente. Ambos grupos con incremento de 1 g/dL entre la hemoglobina inicial y final (p < 0.01), con una diferencia de medias entre el aumento de los grupos con p = 0.4. Con disminución significativa de la epigastralgia y la náusea. CONCLUSIONES: El tratamiento intermitente con sulfato ferroso incrementa las concentraciones de hemoglobina igual que un esquema continuo, pero con menos efectos adversos.

Abstract OBJECTIVE: To compare hemoglobin concentrations in pregnant women with iron deficiency anemia who received intermittent versus continuous treatment with 200 mg oral ferrous sulfate. In addition, to compare the incidence of side effects of intermittent versus continuous treatment. MATERIALS AND METHODS: Randomized, non-blinded, clinical trial conducted at the Unidad Médica de Alta Especialidad Hospital de Ginecoobstetricia 4 Luis Castelazo Ayala, IMSS, in patients aged 18 to 35 years attended between January and March 2023 with 30 or more weeks of pregnancy, diagnosis of iron deficiency anemia (operationally defined only with a blood biometry lower than 11 g/dL, with hypochromia and microcytosis), without a history of chronic degenerative disease. Statistical analysis was performed in SPSS v21 program, distribution and characteristics of the sample with univariate analysis, followed by bivariate analysis with Student's t and mean difference. A value of p < 0.05 was considered statistically significant. RESULTS: Thirty-two patients were studied: 16 with continuous and 16 with intermittent regimen. Both groups with increase of 1 g/dL between initial and final hemoglobin (p < 0.01), with a mean difference between groups increase with p = 0.4. With significant reduction in epigastralgia and nausea. CONCLUSIONS: Intermittent treatment with ferrous sulfate increases hemoglobin concentrations.

Nivel de conocimiento y adhesión al tratamiento de pacientes con anemia gestacional / Level of knowledge and adherence to treatment in patients with gestational anemia

Resumen OBJETIVO: Determinar la relación entre el nivel de conocimiento y la adhesión al régimen prescrito de sulfato ferroso y ácido fólico para prevenir o tratar la anemia gestacional en pacientes atendidas en un hospital público del Perú. MATERIAL Y MÉTODOS: Estudio observacional, descriptivo, de serie de casos, transversal y prospectivo llevado a cabo entre febrero y abril de 2022 en pacientes en el puerperio inmediato con diagnóstico de anemia gestacional establecido dos meses antes del término del embarazo. Se evaluaron los conocimientos mediante un cuestionario y la adhesión mediante la prueba de Morisky-Green-Levine, ambos instrumentos validados y fiables. El análisis estadístico se procesó en el programa STATA; se utilizaron χ2 de Pearson y el modelo lineal generalizado de la familia de Poisson con varianza robusta y nivel de confianza del 95%. RESULTADOS: Se estudiaron 217 pacientes; 2 de cada 10 tenían diagnóstico de anemia gestacional y cumplían el tratamiento. En conjunto, el 71.89% de las participantes tenía un conocimiento adecuado de la importancia del tratamiento con sulfato ferroso y ácido fólico, y el 23.96% alcanzó un nivel intermedio. La relación entre el nivel de conocimientos y el apego se aproximó a la significación estadística (p = 0.05 RPa:1.63; IC95%: 0.99-2.71), establecida mediante análisis ajustado. El conocimiento de la importancia del tratamiento antianémico para la madre multiplicó por tres la prevalencia de la adherencia (p = 0.04; RPa: 3.17; IC95%: 1.04-9.72). CONCLUSIÓN: El conocimiento por parte de las madres de la importancia del tratamiento antianémico aumentó significativamente la adherencia.

Abstract OBJECTIVE: To determine the relationship between the level of knowledge and adherence to the prescribed regimen of ferrous sulfate and folic acid to prevent or treat gestational anemia in patients attended in a public hospital in Peru. MATERIALS AND METHODS: Observational, descriptive, case series, cross-sectional and prospective study carried out between February and April 2022 in patients in the immediate postpartum period with a diagnosis of gestational anemia established two months before the end of pregnancy. Knowledge was assessed by means of a questionnaire and adherence by means of the Morisky-Green-Levine test, both validated and reliable instruments. Statistical analysis was performed with the STATA program; Pearson's χ2 and the generalized linear model of the Poisson family with robust variance and 95% confidence level were used. RESULTS: A total of 217 patients were studied; 2 out of 10 had a diagnosis of gestational anemia and were compliant with treatment. Overall, 71.89% of the participants had adequate knowledge of the importance of treatment with ferrous sulfate and folic acid, and 23.96% reached an intermediate level. The relationship between the level of knowledge and adherence was close to statistical significance (p = 0.05 RPa:1.63; 95%CI: 0.99-2.71), established by adjusted analysis. Understanding the importance of antianemic treatment for the mother increased the prevalence of adherence threefold (p = 0.04; RPa: 3.17; 95%CI: 1.04-9.72). CONCLUSION: Mothers' knowledge of the importance of antianemic treatment significantly increased adherence.

Use of antianemics in prenatal care: A population cohort from a capital city in the North region of Brazil.

Anemia during pregnancy is a significant risk factor for adverse maternal and fetal outcomes, including preterm birth, low birth weight, and maternal mortality. In Brazil, anemia prevention and treatment programs are available, but regional variations in prevalence and factors associated with antianemic drug use remain understudied. The objective was to identify the prevalence of gestational anemia and the factors associated with the use of antianemic drugs during pregnancy in a cross-sectional population-based study carried out in Rio Branco, AC. To do so, we planned a cross-sectional, population-based study with a total of 1190 postpartum women who gave birth between April 6 and July 10, 2015, were interviewed about demographic, socioeconomic, reproductive, and prenatal care factors. The prevalence of anemia during pregnancy was found to be 13.8 %, with 93.2 % of women using antianemic drugs, such as ferrous sulfate and folic acid. Factors positively associated with antianemic drug use were higher education (elementary school II RCajust = 2.46; 95 %, CI: 1.01-6.13; high school RCajust = 2.61; 95 %, CI: 1.11-6.12), primiparity (ACadjust = 1.69; 95 %, CI: 0.98-3.74), 6 to 8 prenatal consultations (ACjust = 2.16; 95, CI%: 1.15-4.05), and planned pregnancy (ARjust = 1.94; 95 %, CI: 1.05-3.74). Food security during pregnancy was inversely associated. These findings suggest that while anemia prevention and treatment programs exist, more targeted strategies are needed, particularly for women with lower socioeconomic status, to improve maternal and fetal health outcomes.

Efectividad de la administración de hierro en forma semanal y diaria para la prevención de anemia por deficiencia de hierro en lactantes / Effectiveness of weekly and daily iron administration for the prevention of iron deficiency anemia in infants

Introducción. La deficiencia de hierro (DH) es la carencia nutricional más prevalente y la principal causa de anemia en lactantes. Existe consenso en la suplementación diaria con hierro como estrategia de prevención; también se demostró que la suplementación semanal es eficaz, pero la evidencia en lactantes es escasa. El objetivo fue comparar la efectividad de la administración diaria de hierro frente a la semanal para la prevención de la anemia por DH del lactante. Población y métodos. Ensayo clínico controlado y aleatorizado. Lactantes atendidos en un centro de salud público, sin anemia a los 3 meses de edad, aleatorizados en tres grupos: suplementación diaria (1 mg/kg/día), semanal (4 mg/kg/semana) o sin suplementación (grupo control con lactancia materna exclusiva [LME]). Se evaluó anemia y DH a los 3 y 6 meses. Se registró grado de adherencia y efectos adversos. Los datos se analizaron con el software R versión 4.0.3. Resultados. Participaron 227 lactantes. A los 6 meses el grupo de lactantes con LME sin suplementación (control) presentó prevalencias de DH y anemia por DH (ADH) mayores que los grupos intervenidos (diario y semanal). DH: 40,5 % vs. 13,5 % y 16,7 % (p = 0,002); ADH: 33,3 % vs. 7,8 % y 10 % (p < 0,001). No hubo diferencias entre los grupos diario y semanal. Tampoco hubo diferencias en el porcentaje de alta adherencia a la suplementación (50,6 % diaria vs. 57,1 % semanal), ni en los efectos adversos. Conclusiones. No se hallaron diferencias significativas en la efectividad entre la administración diaria y semanal para la prevención de ADH del lactante.

Introduction. Iron deficiency (ID) is the most prevalent nutritional deficiency and the main cause of anemia in infants. There is consensus on daily iron supplementation as a preventive strategy; and weekly iron supplementation has also been shown to be effective, but evidence in infants is scarce. The objective of this study was to compare the effectiveness of daily versus weekly iron administration for the prevention of ID anemia (IDA) in infants. Population and methods. Randomized, controlled clinical trial. Infants seen at a public health center, without anemia at 3 months of age, were randomized into 3 groups: daily supplementation (1 mg/kg/ day), weekly supplementation (4 mg/kg/week), or no supplementation (control group with exclusive breastfeeding [EB]). Anemia and ID were assessed at 3 and 6 months old. Adherence and adverse events were recorded. Data were analyzed using the R software, version 4.0.3. Results. A total of 227 infants participated. At 6 months, the group of infants with EB without supplementation(control) had a higher prevalence of ID and IDA than the intervention groups (daily and weekly). ID: 40.5% versus 13.5% and 16.7% (p = 0.002); IDA: 33.3% versus 7.8% and 10% (p < 0.001). There were no differences between the daily and weekly supplementation groups. There were also no differences in the percentage of high adherence to supplementation (50.6% daily versus 57.1% weekly) or adverse events. Conclusions. No significant differences in effectiveness were observed between daily and weekly administration for the prevention of infant IDA.

Effectiveness of weekly and daily iron administration for the prevention of iron deficiency anemia in infants. / Efectividad de la administración de hierro en forma semanal y diaria para la prevención de anemia por deficiencia de hierro en lactantes.

Introduction. Iron deficiency (ID) is the most prevalent nutritional deficiency and the main cause of anemia in infants. There is consensus on daily iron supplementation as a preventive strategy; and weekly iron supplementation has also been shown to be effective, but evidence in infants is scarce. The objective of this study was to compare the effectiveness of daily versus weekly iron administration for the prevention of ID anemia (IDA) in infants. Population and methods. Randomized, controlled clinical trial. Infants seen at a public health center, without anemia at 3 months of age, were randomized into 3 groups: daily supplementation (1 mg/kg/day), weekly supplementation (4 mg/kg/week), or no supplementation (control group with exclusive breastfeeding [EB]). Anemia and ID were assessed at 3 and 6 months old. Adherence and adverse events were recorded. Data were analyzed using the R software, version 4.0.3. Results. A total of 227 infants participated. At 6 months, the group of infants with EB without supplementation (control) had a higher prevalence of ID and IDA than the intervention groups (daily and weekly). ID: 40.5% versus 13.5% and 16.7% (p = 0.002); IDA: 33.3% versus 7.8% and 10% (p < 0.001). There were no differences between the daily and weekly supplementation groups. There were also no differences in the percentage of high adherence to supplementation (50.6% daily versus 57.1% weekly) or adverse events. Conclusions. No significant differences in effectiveness were observed between daily and weekly administration for the prevention of infant IDA.

Introducción. La deficiencia de hierro (DH) es la carencia nutricional más prevalente y la principal causa de anemia en lactantes. Existe consenso en la suplementación diaria con hierro como estrategia de prevención; también se demostró que la suplementación semanal es eficaz, pero la evidencia en lactantes es escasa. El objetivo fue comparar la efectividad de la administración diaria de hierro frente a la semanal para la prevención de la anemia por DH del lactante. Población y métodos. Ensayo clínico controlado y aleatorizado. Lactantes atendidos en un centro de salud público, sin anemia a los 3 meses de edad, aleatorizados en tres grupos: suplementación diaria (1 mg/kg/día), semanal (4 mg/kg/semana) o sin suplementación (grupo control con lactancia materna exclusiva [LME]). Se evaluó anemia y DH a los 3 y 6 meses. Se registró grado de adherencia y efectos adversos. Los datos se analizaron con el software R versión 4.0.3. Resultados. Participaron 227 lactantes. A los 6 meses el grupo de lactantes con LME sin suplementación (control) presentó prevalencias de DH y anemia por DH (ADH) mayores que los grupos intervenidos (diario y semanal). DH: 40,5 % vs. 13,5 % y 16,7 % (p = 0,002); ADH: 33,3 % vs. 7,8 % y 10 % (p < 0,001). No hubo diferencias entre los grupos diario y semanal. Tampoco hubo diferencias en el porcentaje de alta adherencia a la suplementación (50,6 % diaria vs. 57,1 % semanal), ni en los efectos adversos. Conclusiones. No se hallaron diferencias significativas en la efectividad entre la administración diaria y semanal para la prevención de ADH del lactante.

Hexachlorocyclohexane chemical remediation of a contaminated site in Argentina.

This work describes the complete decontamination of three parcels of a dump site located in Lomas de Zamora county, Buenos Aires province (Argentina) heavily polluted with hexachorocyclohexane (HCH), where phytoremediation, successful in the surrounding areas, was ineffective. HCH contained in contaminated soil (10 g/kg average) was oxidized with sodium persulfate activated with citric acid chelated Fe(II). This chemical remediation process required treatment in situ in each parcel of approximately 10900 tons total of soil that were mechanically removed and initially mixed with 1750 tons of sodium persulfate. The mixture was then transferred to the excavation site, and 105 tons of ferrous sulfate and 35 tons of citric acid were finally added. The process, started in January 2011 and completed in February 2016, was very effective since chemical remediation average efficiency in the three parcels was higher than 99.99%. To the best of our knowledge this work is the first demonstration that persulfate oxidation activated with citric acid chelated Fe(II) can be successfully applied for field remediation of a relatively large area.

Evaluation of pentoxifylline and ferrous sulfate for treatment of lower limb venous ulcers.

BACKGROUND: Venous ulcers (VU) are the most advanced stage of chronic venous disease (CVD) of the lower limbs. They are frequently associated with episodes of hemorrhage that can provoke chronic anemia (CA), delaying healing. There are no studies in the literature analyzing the prevalence of CA among patients with VU of the lower limbs and few studies have analyzed use of pentoxifylline to treat VU of the lower limbs. OBJECTIVES: To evaluate the prevalence of CA in patients with lower limb VU and responses to treatment with ferrous sulfate (SF) compared with a combination of SF plus pentoxifylline as adjuvant treatment for VU of the lower limbs. METHODS: A total of 67 patients with lower limb VU were recruited from a Lymphedema and Angiodysplasia Clinic at the Hospital das Clínicas, Recife, PE, Brazil. After initial clinical and laboratory assessments, patients diagnosed with CA were randomized into one of two groups: a control group, given SF (900 mg/day oral route), or a study group, treated with SF (900 mg/day oral route) and pentoxifylline (1,200 mg/day). All were reassessed after 90 days. RESULTS: Twenty-seven patients (40%) had CA. After treatment, increases were observed in hemoglobin and hematocrit levels, iron kinetics had improved, and both depth and area of VU had reduced in both groups, without statistically significant differences. CONCLUSIONS: A high prevalence of anemia was detected in the study population. The combination of SF and pentoxifylline was not more effective than SF alone for adjuvant treatment of VU of the lower limbs.

Randomized Trial of Oral Iron and Diet Advice versus Diet Advice Alone in Young Children with Nonanemic Iron Deficiency.

OBJECTIVE: To compare the effects of 2 treatment options on neurodevelopmental and laboratory outcomes in young children with nonanemic iron deficiency. STUDY DESIGN: A blinded, placebo-controlled, randomized trial of children 1-3 years with nonanemic iron deficiency (hemoglobin ≥110 g/L, serum ferritin <14 µg/L) was conducted in 8 primary care practices in Toronto, Canada. Interventions included ferrous sulfate or placebo for 4 months; all parents received diet advice. The primary outcome was the Early Learning Composite (ELC) using the Mullen Scales of Early Learning (mean 100, SD 15). Secondary outcomes included serum ferritin. Measurements were obtained at baseline and 4 and 12 months. Sample size was calculated to detect a between-group difference of 6-7 points in ELC. RESULTS: At enrollment (n = 60), mean age was 24.2 (SD 7.4) months and mean serum ferritin was 10.0 (SD 2.4) µg/L. For ELC, the mean between-group difference at 4 months was 1.1 (95% CI -4.2 to 6.5) and at 12 months was 4.1 (95% CI -1.9 to 10.1). For serum ferritin, at 4 months, the mean between-group difference was 16.9 µg/L (95% CI 6.5 to 27.2), and no child randomized to ferrous sulfate had a serum ferritin <14 µg/L (0% vs 31%, P = .003). CONCLUSIONS: For young children with nonanemic iron deficiency, treatment options include oral iron and/or diet advice. We remain uncertain about which option is superior with respect to cognitive outcomes; however, adding ferrous sulfate to diet advice resulted in superior serum ferritin outcomes after 4 months. Shared decision-making between practitioners and parents may be considered when selecting either option. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01481766.

Avaliação da pentoxifilina e do sulfato ferroso no tratamento da úlcera varicosa dos membros inferiores / Evaluation of pentoxifylline and ferrous sulfate for treatment of lower limb venous ulcers

Resumo Contexto A úlcera varicosa (UV) é o estágio mais avançado da doença venosa crônica (DVC) dos membros inferiores (MMII), frequentemente associada a episódios de hemorragia que podem provocar anemia crônica (AC) e retardar a sua cicatrização. Não há, na literatura, trabalhos que avaliem a prevalência da AC nos portadores de UV dos MMII, e poucos trabalhos analisam o uso da pentoxifilina no tratamento das UV dos MMII. Objetivos Avaliar a prevalência da AC nos pacientes portadores de UV de MMII e a resposta terapêutica ao sulfato ferroso (SF) e a associação da pentoxifilina com SF no tratamento adjuvante das UV dos MMII. Métodos Foram avaliados 67 pacientes portadores de UV de MMII atendidos no ambulatório de Cirurgia Vascular do Hospital das Clínicas, Recife, PE. Após as avaliações clínica e laboratorial iniciais, os pacientes diagnosticados com AC foram randomizados em dois grupos: o grupo controle, que recebeu SF (900 mg/dia via oral), e o grupo de estudo, tratado com SF (900 mg/dia via oral) e pentoxifilina (1.200 mg/dia). Todos foram reavaliados após 90 dias. Resultados Entre os pacientes avaliados, 27 (40%) apresentavam AC. Após o tratamento, foram observados aumento dos níveis de hemoglobina e de hematócrito e melhora das taxas da cinética do ferro, assim como a diminuição da profundidade e da área das UV em ambos os grupos, sem diferença estatística. Conclusões Foi encontrada alta prevalência de anemia na população estudada. A associação do SF com a pentoxifilina não se mostrou mais eficaz do que o emprego isolado do SF no tratamento adjuvante da UV dos MMII.

Abstract Background Venous ulcers (VU) are the most advanced stage of chronic venous disease (CVD) of the lower limbs. They are frequently associated with episodes of hemorrhage that can provoke chronic anemia (CA), delaying healing. There are no studies in the literature analyzing the prevalence of CA among patients with VU of the lower limbs and few studies have analyzed use of pentoxifylline to treat VU of the lower limbs. Objectives To evaluate the prevalence of CA in patients with lower limb VU and responses to treatment with ferrous sulfate (SF) compared with a combination of SF plus pentoxifylline as adjuvant treatment for VU of the lower limbs. Methods A total of 67 patients with lower limb VU were recruited from a Lymphedema and Angiodysplasia Clinic at the Hospital das Clínicas, Recife, PE, Brazil. After initial clinical and laboratory assessments, patients diagnosed with CA were randomized into one of two groups: a control group, given SF (900 mg/day oral route), or a study group, treated with SF (900 mg/day oral route) and pentoxifylline (1,200 mg/day). All were reassessed after 90 days. Results Twenty-seven patients (40%) had CA. After treatment, increases were observed in hemoglobin and hematocrit levels, iron kinetics had improved, and both depth and area of VU had reduced in both groups, without statistically significant differences. Conclusions A high prevalence of anemia was detected in the study population. The combination of SF and pentoxifylline was not more effective than SF alone for adjuvant treatment of VU of the lower limbs.

Iron recovery from the coarse fraction of basic oxygen furnace sludge. Part I: optimization of acid leaching conditions.

In this study, a new reuse process of the coarse fraction of basic oxygen furnace (BOF) sludge based on iron recovery by the ferrous sulfate production was proposed. This study was based on three main steps: (i) characterization of the steel waste, (ii) evaluation and optimization of the recycling process, and (iii) characterization of ferrous sulfate produced. Acid leaching was used to solubilize the iron for obtaining ferrous sulfate heptahydrate. The ferrous sulfate crystallization was performed by adding anhydrous ethanol (EtOH). A multivariate optimization for iron leaching and ferrous sulfate precipitation in the same solution was employed. This optimization consisted of screening steps using a full factorial design followed by optimization. The coarse fraction of BOF sludge was predominantly composed of iron in metallic form (82.5%, dry weight). The sulfuric acid concentration and leaching time had significant effects on Fe(II) solubilization. The desirability function predicted the following optimized conditions: 20% (v/v) sulfuric acid solution, 200 min of leaching time, 7.00 g of waste, and 110 mL of anhydrous EtOH, producing 19.60 g of ferrous sulfate heptahydrate (yield of 70.8%). The characterization of ferrous sulfate was performed by X-ray diffraction, scanning electron microscopy coupled to energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. The characterization of the ferrous sulfate produced evidenced the effectiveness of the optimized process condition. Graphical abstract.

Effects of iron supplementation versus dietary iron on the nutritional iron status: Systematic review with meta-analysis of randomized controlled trials.

This meta-analysis compared the effects of dietary intervention versus iron supplementation on biochemical parameters related to the iron nutritional status in humans. The PubMed, CENTRAL, LILACS, SCIELO, OPENGREY.EU and ClinicalTrials.gov databases were searched for randomized clinical trials that assigned individuals to a dietary intervention or to an iron supplementation regimen, for 12 weeks or more. The primary outcome was the hemoglobin concentration, and secondary outcomes were ferritin, RDW, mean corpuscular volume, soluble transferrin receptor, total iron binding capacity, serum iron, and transferrin saturation. From the 6095 records identified, twelve studies were included, six with children, five with adolescents/adults, and one with pregnant women. In the subgroup of studies that included anemic/iron deficient children, supplementation significantly increased the hemoglobin concentration (weighted mean difference (WMD): 3.19 g/L [95% CI: 1.31, 5.07]) and induced a significantly greater reduction of the soluble transferrin receptor (WMD: -0.46 mg/L [95% CI: -0.70, -0, 21]), when compared to dietary intervention. It also induced a greater reduction of the total binding capacity of iron in adolescents/adults (WMD: -6.96 µmol/L [95% CI: -12.70, -1.21]). Supplementation showed a better effect on hemoglobin recovery in anemic/iron deficient children, while no differences were observed between supplementation and dietary intervention in treating adolescents/adults.

Oxidative Stress and Genomic Damage Induced In Vitro in Human Peripheral Blood by Two Preventive Treatments of Iron Deficiency Anemia.

Iron deficiency is the most prevalent nutritional deficiency and the main cause of anemia worldwide. Since children aged 6-24 months are among the most vulnerable groups at risk, daily supplementation with ferrous sulfate is recommended by the Argentine Society of Pediatrics as preventive treatment of anemia. However, a single weekly dose would have fewer adverse side effects and has been therefore proposed as an alternative treatment. Ferrous sulfate is known by its pro-oxidative properties, which may lead to increased oxidative stress as well as lipid, protein, and DNA damage. We analyzed the effect of daily and weekly preventive treatment of iron deficiency anemia (IDA) on cell viability, oxidative stress, chromosome, and cytomolecular damage in peripheral blood cultured in vitro. The study protocol included the following: untreated negative control; bleomycin, hydrogen peroxide, or ethanol-treated positive control; daily 0.14 mg ferrous sulfate-supplemented group; and weekly 0.55 mg ferrous sulfate-supplemented group. We assessed cell viability (methyl-thiazolyl-tetrazolium and neutral red assays), lipid peroxidation (thiobarbituric acid reactive substances assay), antioxidant response (superoxide dismutase and catalase enzyme analysis), chromosome damage (cytokinesis-blocked micronucleus cytome assay), and cytomolecular damage (comet assay). Lipid peroxidation, antioxidant response, and chromosome and cytomolecular damage decreased after weekly ferrous sulfate supplementation (p < 0.05), suggesting less oxygen free radical production and decreased oxidative stress and genomic damage. Such a decrease in oxidative stress and genomic damage in vitro positions weekly supplementation as a better alternative for IDA treatment. Further studies in vivo would be necessary to corroborate whether weekly supplementation could improve IDA preventive treatment compliance in children.

Screening of medium constituents for clavulanic acid production by Streptomyces clavuligerus

ABSTRACT Clavulanic acid is a β-lactam compound with potent inhibitory activity against β-lactamases. Studies have shown that certain amino acids play essential roles in CA biosynthesis. However, quantitative evaluations of the effects of these amino acids are still needed in order to improve CA production. Here, we report a study of the nutritional requirements of Streptomyces clavuligerus for CA production. Firstly, the influence of the primary nitrogen source and the salts composition was investigated. Subsequently, soybean protein isolate was supplemented with arginine (0.0-3.20 g L-1), threonine (0.0-1.44 g L-1), ornithine (0.0-4.08 g L-1), and glutamate (0.0-8.16 g L-1), according to a two-level central composite rotatable design. A medium containing ferrous sulfate yielded CA production of 437 mg L-1, while a formulation without this salt produced only 41 mg L-1 of CA. This substantial difference suggested that Fe2+ is important for CA biosynthesis. The experimental design showed that glutamate and ornithine negatively influenced CA production while arginine and threonine had no influence. The soybean protein isolate provided sufficient C5 precursor for CA biosynthesis, so that supplementation was unnecessary. Screening of medium components, together with experimental design tools, could be a valuable way of enhancing CA titers and reducing the process costs.

Screening of medium constituents for clavulanic acid production by Streptomyces clavuligerus

Clavulanic acid is a beta-lactam compound with potent inhibitory activity against beta-lactamases. Studies have shown that certain amino acids play essential roles in CA biosynthesis. However, quantitative evaluations of the effects of these amino acids are still needed in order to improve CA production. Here, we report a study of the nutritional requirements of Streptomyces clavuligerus for CA production. Firstly, the influence of the primary nitrogen source and the salts composition was investigated. Subsequently, soybean protein isolate was supplemented with arginine (0.03.20 g L-1), threonine (0.01.44 g L-1), ornithine (0.04.08 g L-1), and glutamate (0.08.16 g L-1), according to a two-level central composite rotatable design. A medium containing ferrous sulfate yielded CA production of 437 mg L-1, while a formulation without this salt produced only 41 mg L-1 of CA. This substantial difference suggested that Fe2+ is important for CA biosynthesis. The experimental design showed that glutamate and ornithine negatively influenced CA production while arginine and threonine had no influence. The soybean protein isolate provided sufficient C5 precursor for CA biosynthesis, so that supplementation was unnecessary. Screening of medium components, together with experimental design tools, could be a valuable way of enhancing CA titers and reducing the process costs.(AU)

Generación de radicales libres por efecto de vitamina C sobre un jarabe antianémico de sulfato ferroso / Generation of free radicals by the effect of vitamin C on a ferrous sulfate antianemic syrup

Objetivo: Determinar el efecto que ejerce la vitamina C sobre el sulfato ferroso, principio activo de un jarabe antianémico. Materiales y métodos: La reacción que se produce entre el sulfato ferroso de un jarabe antianémico y la vitamina C se determinó al aplicar la técnica de descomposición de la desoxirribosa, que evalúa la formación de malondialdehído por acción de radicales libres. Resultados: En un medio de ensayo constituido por tampón fosfato 50 mM (pH 7,4), el jarabe antianémico de sulfato ferroso a una concentración 1,080 mM reaccionó con la vitamina C en concentraciones comprendidas entre 5,0 x 10-6 mM y 0,5 mM, generando radicales libres que disminuyen cuando se utiliza una concentración de vitamina C de 5,0 x 10-2 mM mientras que a una concentración 0,5 mM, se eleva. Cuando se usa sulfato ferroso en condiciones similares se aprecia un incremento de la generación de radicales libres que alcanza un valor máximo a una concentración de vitamina C de 5,0 x 10-6 mM que se mantiene invariable a concentraciones de dos órdenes de magnitud mayor y, ulteriormente, decrece a concentraciones más elevadas. La vitamina C a una concentración 1,0 mM reacciona con el sulfato ferroso utilizado en concentraciones comprendidas entre 0,270 y 2,160 mM describiendo una curva de tipo hiperbólica. En cambio, el jarabe de sulfato ferroso, utilizado en las mismas concentraciones, mostró un elevado incremento a bajas concentraciones de tipo no lineal pero que tuvo una respuesta lineal a partir de la concentración 0,540 mM del jarabe, respuesta que fue mayor a la alcanzada por el sulfato ferroso disuelto en agua destilada. Conclusiones: La vitamina C reacciona con el jarabe de sulfato ferroso y genera radicales libres, esta respuesta depende de las concentraciones relativas de sulfato ferroso, vitamina C y de los excipientes del jarabe.

Objective: To determine the effect of vitamin C on ferrous sulfate, the active ingredient of an antianemic syrup. Materials and methods: The reaction between the ferrous sulfate contained in an antianemic syrup and vitamin C was determined using the decomposition technique of deoxyribose, which evaluates the formation of malondialdehyde by the action of free radicals. Results: In an assay medium consisting of 50 mM phosphate buffer (pH 7.4), the ferrous sulfate antianemic syrup at a concentration of 1.080 mM reacted with vitamin C at concentrations between 5.0 x 10-6 mM and 0.5 mM, generating levels of free radicals that decrease when vitamin C is used at a concentration of 5.0 x 10-2 mM, and increase at a concentration of 0.5 mM. When ferrous sulfate is used under similar conditions, an increase in the generation of free radicals is observed, which reaches a maximum value with vitamin C at a concentration of 5.0 x 10-6 mM, remains unchanged at concentrations of two orders of magnitude higher, and subsequently decreases at higher concentrations. Vitamin C at a concentration of 1.0 mM reacts with ferrous sulfate used at concentrations between 0.270 and 2.160 mM, describing a hyperbolic curve. In contrast, ferrous sulfate syrup used at the same concentrations showed a high increase at low non-linear concentrations, but a linear response from the 0.540 mM concentration of the syrup, a response that was higher than that reached by the ferrous sulfate dissolved in distilled water. Conclusions: Vitamin C reacts with ferrous sulfate syrup generating free radicals. This response depends on the relative concentrations of ferrous sulfate, vitamin C and syrup excipients.

Screening of medium constituents for clavulanic acid production by Streptomyces clavuligerus.

Clavulanic acid is a ß-lactam compound with potent inhibitory activity against ß-lactamases. Studies have shown that certain amino acids play essential roles in CA biosynthesis. However, quantitative evaluations of the effects of these amino acids are still needed in order to improve CA production. Here, we report a study of the nutritional requirements of Streptomyces clavuligerus for CA production. Firstly, the influence of the primary nitrogen source and the salts composition was investigated. Subsequently, soybean protein isolate was supplemented with arginine (0.0-3.20gL-1), threonine (0.0-1.44gL-1), ornithine (0.0-4.08gL-1), and glutamate (0.0-8.16gL-1), according to a two-level central composite rotatable design. A medium containing ferrous sulfate yielded CA production of 437mgL-1, while a formulation without this salt produced only 41mgL-1 of CA. This substantial difference suggested that Fe2+ is important for CA biosynthesis. The experimental design showed that glutamate and ornithine negatively influenced CA production while arginine and threonine had no influence. The soybean protein isolate provided sufficient C5 precursor for CA biosynthesis, so that supplementation was unnecessary. Screening of medium components, together with experimental design tools, could be a valuable way of enhancing CA titers and reducing the process costs.

Suplementação de sulfato ferroso na gestação e anemia gestacional: uma revisão de literatura / Ferrous sulfate supplementation in pregnancy and gestational anemia: a systematic review

Este estudo objetivou realizar uma revisão da literatura sobre a influência da suplementação de ferro na prevenção da anemia ferropriva na gestação e seus efeitos associados na saúde do binômio mãe e feto. Para tanto, foram consultadas as bases de dados PUBMED, MEDLINE, SCIELO com os descritores "anemia", "pregnancy" e "ferrous sulfate", e selecionados os estudos que avaliavam os benefícios, malefícios e/ou a necessidade da suplementação ferrosa durante a gestação. Dos duzentos e um (201) artigos selecionados, onze (11) se enquadravam nos critérios. Dentre esses, quatro (04) abordaram apenas aspectos positivos, quatro (04) somente a perspectiva negativa e três (03) apresentaram ambos os lados. Ademais, oito (08) artigos fizeram ressalvas que contrapõem o atual modelo de uso rotineiro no Brasil, evidenciando que a suplementação individual de ferro seja preferida à rotineira. Isso porque, embora a anemia seja apontada como geradora de abortos espontâneos, restrição de crescimento intrauterino, parto pré-termo, pré-eclâmpsia, dentre outros, a suplementação também pode gerar efeitos negativos, os quais são resultantes tanto da hemoconcentração ­ em função do aumento expressivo dos níveis de hemoglobina ­ quanto dos efeitos colaterais da suplementação, como náuseas, vômitos, dor abdominal e constipação. Ainda, não houveram diferenças nos valores de hemoglobina e de prevalência de anemia significantes nos estudos avaliados, nem desfechos clinicamente relevantes em gestantes não anêmicas que receberam profilaxia com sulfato ferroso. Desse modo, o uso individualizado de acordo com cada paciente é mais plausível, pois a forma rotineira negligencia aspectos individuais, como a melhor frequência de uso, a demanda e os efeitos colaterais.

This study aimed to realize a literature review about the influence of iron supplementation on the prevention of iron deficiency anemia in pregnancy and its associated effects on the health of the mother and fetus binomial. Therefore, were consulted the databases PUBMED, MEDLINE and SCIELO with the descriptors "anemia", "pregnancy" and "ferrous sulfate", selecting the studies that evaluated the benefits, harms and/or the necessity of ferrous supplementation during pregnancy. Of the two hundred and one (201) selected articles, eleven (11) fit the criteria. Among these, four (04) addressed only positive aspects, four (04) only negative perspective and three (03) presented both sides. In addition, eight (08) articles made caveats that counterpose the current model of routine use in Brazil, evidencing that individual iron supplementation is preferred to routine. This because, although anemia is pointed as generating spontaneous abortions, intrauterine growth restriction, preterm delivery, preeclampsia, among others, supplementation can also generate negative effects, both of which result from hemoconcentration ­as a function of increased hemoglobin levels- as well as the side effects of supplementation, such as nausea, vomiting, abdominal pain and constipation. Furthermore, there were no significant differences in hemoglobin values and prevalence of anemia in the studies evaluated nor clinically relevant outcomes in non-anemic pregnant women who received prophylaxis with ferrous sulfate yet. In this way, the individualized use according to each patient is more plausible, since the routine way neglects individual aspects, such as the best frequency of use, the demand and the side effects.

The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate / Estado de maturação do nervo auditivo e tronco encefálico em ratos expostos a acetato de chumbo e suplementados com sulfato ferroso

Abstract Introduction The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood. Objective To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate. Methods 30 weanling male rats (Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400 mg/L) and supplemented with ferrous sulfate (20 mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry. Results We verified that the concentration of Pb in blood and in brainstem presented a high correlation (r = 0.951; p < 0.0001). Both concentrations of lead acetate affected the maturation state of the auditory system, being the maturation slower in the regions corresponding to portion of the auditory nerve (wave I) and cochlear nuclei (wave II). The ferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100 mg/L), but not for the group exposed to the higher concentration (400 mg/L). Conclusion This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect.

Resumo Introdução A literatura relatou a associação entre o chumbo e os efeitos auditivos, com base em estudos clínicos e experimentais. No entanto, não há consenso em relação aos efeitos do chumbo no sistema auditivo, ou sua correlação com a concentração do metal no sangue. Objetivo Investigar o estado de maturação do sistema auditivo, especificamente do nervo auditivo e do tronco encefálico, em ratos expostos ao acetato de chumbo e suplementados com sulfato ferroso. Método 30 ratos machos desmamados (Rattus norvegicus, Wistar) foram distribuídos em seis grupos de cinco animais e expostos a uma de duas concentrações de acetato de chumbo (100 ou 400 mg/L) e suplementados com sulfato ferroso (20 mg/kg). O estado de maturação do nervo auditivo e do tronco encefálico foi analisado pelo Potencial Evocado Auditivo do Tronco Encefálico antes e após a exposição ao chumbo. A concentração de chumbo no sangue e tronco encefálico foi analisada utilizando-se Espectrometria de Massa com Plasma Indutivamente Acoplado. Resultados Verificamos que as concentrações de Pb no sangue e no tronco encefálico apresentaram alta correlação (r = 0,951, p < 0,0001). Ambas as concentrações de acetato de chumbo afetaram o estado de maturação do sistema auditivo, a maturação foi mais lenta nas regiões correspondentes à porção do nervo auditivo (onda I) e dos núcleos cocleares (onda II). A suplementação com sulfato ferroso reduziu significativamente a concentração de chumbo no sangue e no tronco encefálico no grupo exposto à menor concentração de chumbo (100 mg/L), mas não para o grupo exposto à maior concentração (400 mg/L). Conclusão Esse estudo indica que o acetato de chumbo pode ter efeitos deletérios na maturação do nervo auditivo e do tronco encefálico (região do núcleo coclear), como detectado pelos potenciais evocados auditivos do tronco encefálico, e que o sulfato ferroso pode diminuir parcialmente esse efeito.

The maturation state of the auditory nerve and brainstem in rats exposed to lead acetate and supplemented with ferrous sulfate.

INTRODUCTION: The literature has reported the association between lead and auditory effects, based on clinical and experimental studies. However, there is no consensus regarding the effects of lead in the auditory system, or its correlation with the concentration of the metal in the blood. OBJECTIVE: To investigate the maturation state of the auditory system, specifically the auditory nerve and brainstem, in rats exposed to lead acetate and supplemented with ferrous sulfate. METHODS: 30 weanling male rats (Rattus norvegicus, Wistar) were distributed into six groups of five animals each and exposed to one of two concentrations of lead acetate (100 or 400mg/L) and supplemented with ferrous sulfate (20mg/kg). The maturation state of the auditory nerve and brainstem was analyzed using Brainstem Auditory Evoked Potential before and after lead exposure. The concentration of lead in blood and brainstem was analyzed using Inductively Coupled Plasma-Mass Spectrometry. RESULTS: We verified that the concentration of Pb in blood and in brainstem presented a high correlation (r=0.951; p<0.0001). Both concentrations of lead acetate affected the maturation state of the auditory system, being the maturation slower in the regions corresponding to portion of the auditory nerve (wave I) and cochlear nuclei (wave II). The ferrous sulfate supplementation reduced significantly the concentration of lead in blood and brainstem for the group exposed to the lowest concentration of lead (100mg/L), but not for the group exposed to the higher concentration (400mg/L). CONCLUSION: This study indicate that the lead acetate can have deleterious effects on the maturation of the auditory nerve and brainstem (cochlear nucleus region), as detected by the Brainstem Auditory Evoked Potentials, and the ferrous sulphate can partially amend this effect.

Iniquidade na suplementação de sulfato ferroso entre gestantes no sul do Brasil / Inequality in iron sulfate supplementation among pregnant women in Southern Brazil

RESUMO: Introdução: O uso de sulfato ferroso é recomendado a todas as gestantes a partir da vigésima semana de gestação até o terceiro mês após o parto. Objetivo: Avaliar a cobertura de sulfato ferroso entre as gestantes e diferenciais de acordo com variáveis demográficas e socioeconômicas. Metodologia: Estudo transversal de base populacional com mulheres que tiveram filhos em Rio Grande, Rio Grande do Sul, no período de 01 de janeiro a 31 de dezembro de 2013. A cobertura de sulfato ferroso foi avaliada de acordo com idade e escolaridade materna, renda familiar e tipo de assistência médica no pré-natal. A análise estatística incluiu teste do χ2 de Pearson e regressão de Poisson. Resultados: Foram entrevistadas 2.685 puérperas (97% das mulheres elegíveis). A cobertura de sulfato ferroso foi de 63%. As maiores diferenças relativas foram entre os grupos extremos de escolaridade materna (50%) e em relação ao tipo de assistência médica no pré-natal (72%). Mulheres com idade entre 13 e 19 anos mostraram-se significativamente associadas ao uso do suplemento (RP = 1,16; IC95% 1,08 - 1,25) quando comparadas às mulheres com idade ≥ 30 anos. Quem utilizou o serviço público no pré-natal esteve mais fortemente associado ao desfecho quando comparado com quem utilizou o sistema privado (RP = 1,61; IC95% 1,49 - 1,74). Conclusão: São incomuns situações no setor de saúde em que os grupos menos favorecidos são privilegiados. Esses achados são raros e indicam a presença de iniquidade de forma contrária ao esperado. O suplemento deve considerar todas as mulheres, em especial as mais velhas, com maior escolaridade e de melhor nível socioeconômico.

ABSTRACT: Introduction: The use of ferrous sulfate is recommended for all pregnant women from the 20th week of gestation to the 3rd month after delivery. Objective: To evaluate the coverage of ferrous sulfate among pregnant women and differentials according to demographic and socioeconomic variables. Method: A cross-sectional population-based study with women who had children in Rio Grande, Rio Grande do Sul, Brazil, from January 1st to December 31st, 2013. Ferrous sulfate coverage was assessed according to maternal age, schooling, family income, and type of prenatal care. Statistical analysis included Pearson's χ2 test and Poisson regression. Results: 2,685 postpartum women (97% of the total) were interviewed and the ferrous sulfate coverage was 63%. The largest relative differences were between the extreme maternal schooling groups (50%) and the type of medical care in prenatal care (72%). Women aged between 13 and 19 years were significantly associated with the use of supplement (RP = 1.16; 95%CI 1.08 - 1.25) when compared to women aged ≥ 30 years. Those who used the public service in prenatal care were more strongly associated with the outcome when compared to those who used the private system (PR = 1.61; 95%CI 1.49 - 1.74). Conclusion: Considering that there are unusual situations in the health sector in which disadvantaged groups are privileged, these findings are rare and indicate the presence of inequality in a way that is opposite to what was expected. The supplement should consider all women, especially older women, with higher education and better socioeconomic status.