Maternal iron kinetics and maternal-fetal iron transfer in normal-weight and overweight pregnancy.

BACKGROUND: Inflammation during pregnancy may aggravate iron deficiency (ID) by increasing serum hepcidin and reducing iron absorption. This could restrict iron transfer to the fetus, increasing risk of infant ID and its adverse effects. OBJECTIVES: We aimed to assess whether iron bioavailability and/or iron transfer to the fetus is impaired in overweight/obese (OW) pregnant women with adiposity-related inflammation, compared with normal-weight (NW) pregnant women. METHODS: In this prospective study, we followed NW (n = 43) and OW (n = 40) pregnant women who were receiving iron supplements from the 14th week of gestation to term and followed their infants to age 6 mo. We administered 57Fe and 58Fe in test meals mid-second and mid-third trimester, and measured tracer kinetics throughout pregnancy and infancy. RESULTS: In total, 38 NW and 36 OW women completed the study to pregnancy week 36, whereas 30 NW and 27 OW mother-infant pairs completed the study to 6 mo postpartum. Both groups had comparable iron status, hemoglobin, and serum hepcidin throughout pregnancy. Compared with the NW, the OW pregnant women had 1) 43% lower fractional iron absorption (FIA) in the third trimester (P = 0.033) with median [IQR] FIA of 23.9% [11.4%-35.7%] and 13.5% [10.8%-19.5%], respectively; and 2) 17% lower maternal-fetal iron transfer from the first tracer (P = 0.051) with median [IQR] maternal-fetal iron transfer of 4.8% [4.2%-5.4%] and 4.0% [3.6%-4.6%], respectively. Compared with the infants born to NW women, infants born to OW women had lower body iron stores (BIS) with median [IQR] 7.7 [6.3-8.8] and 6.6 [4.6-9.2] mg/kg body weight at age 6 mo, respectively (P = 0.024). Prepregnancy BMI was a negative predictor of maternal-fetal iron transfer (ß = -0.339, SE = 0.144, P = 0.025) and infant BIS (ß = -0.237, SE = 0.026, P = 0.001). CONCLUSIONS: Compared with NW, OW pregnant women failed to upregulate iron absorption in late pregnancy, transferred less iron to their fetus, and their infants had lower BIS. These impairments were associated with inflammation independently of serum hepcidin.This trial was registered at clinicaltrials.gov as NCT02747316.

Human papillomavirus type 18 E5 oncoprotein cooperates with E6 and E7 in promoting cell viability and invasion and in modulating the cellular redox state.

BACKGROUND: High-risk human papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer. Among them, types 16 and 18 are the most prevalent worldwide. The HPV genome encodes three oncoproteins (E5, E6, and E7) that possess a high transformation potential in culture cells when transduced simultaneously. In the present study, we analysed how these oncoproteins cooperate to boost key cancer cell features such as uncontrolled cell proliferation, invasion potential, and cellular redox state imbalance. Oxidative stress is known to contribute to the carcinogenic process, as reactive oxygen species (ROS) constitute a potentially harmful by-product of many cellular reactions, and an efficient clearance mechanism is therefore required. Cells infected with HR-HPVs can adapt to oxidative stress conditions by upregulating the formation of endogenous antioxidants such as catalase, glutathione (GSH), and peroxiredoxin (PRX). OBJECTIVES: The primary aim of this work was to study how these oncoproteins cooperate to promote the development of certain cancer cell features such as uncontrolled cell proliferation, invasion potential, and oxidative stress that are known to aid in the carcinogenic process. METHODS: To perform this study, we generated three different HaCaT cell lines using retroviral transduction that stably expressed combinations of HPV-18 oncogenes that included HaCaT E5-18, HaCaT E6/E7-18, and HaCaT E5/E6/E7-18. FINDINGS: Our results revealed a statistically significant increment in cell viability as measured by MTT assay, cell proliferation, and invasion assays in the cell line containing the three viral oncogenes. Additionally, we observed that cells expressing HPV-18 E5/E6/E7 exhibited a decrease in catalase activity and a significant augmentation of GSH and PRX1 levels relative to those of E5, E6/E7, and HaCaT cells. MAIN CONCLUSIONS: This study demonstrates for the first time that HPV-18 E5, E6, and E7 oncoproteins can cooperate to enhance malignant transformation.

Time Trends in Age at Menarche and Related Non-Communicable Disease Risk during the 20th Century in Mexico.

Developed countries have shown a time trend towards a younger age at menarche (AAM), which is associated with increased risk of later obesity and non-communicable diseases. This study aimed to assess whether a time trend in AAM is associated with disease risk in Mexican women (n = 30,826), using data from the Mexican National Health Survey (2000). Linear and log binomial regression was used for nutritional and disease outcomes, while Welch⁻ANOVA was used to test for a time trend. AAM (in years) decreased over time (p < 0.001), with a maximal difference of 0.99 years between the 1920s (13.6 years) and 1980s (12.6 years ). AAM was negatively associated with weight (ß = -1.01 kg; 95% CI -1.006, -1.004) and body mass index (BMI) (ß = -1.01 kg/m²; -1.007, -1.006), and positively with height (ß = 0.18 cm; 0.112, 0.231). AAM was associated with diabetes (RR = 0.95; 0.93, 0.98) and hypercholesterolemia (RR = 0.93; 0.90, 0.95), but not with hypertension, breast cancer or arthritis. In Mexico, AAM decreased significantly during the 20th century. AAM was inversely associated with adult weight and BMI, and positively with height. Women with a later AAM had a lower risk of diabetes and hypercholesterolemia.

Greater blood volume and Hb mass in obese women quantified by the carbon monoxide-rebreathing method affects interpretation of iron biomarkers and iron requirements.

BACKGROUND/OBJECTIVE: Iron deficiency (ID) is common in overweight and obese individuals (OW/OB) but the mechanism is uncertain. Greater blood volume (BV) in OW/OB may increase hemoglobin (Hb) mass and iron requirements, and confound iron biomarkers by hemodilution. Quantification of BV/PV changes in OW/OB is challenging and a formula to estimate BV/PV based on anthropometric indices would be valuable. In normal weight (NW) and OW/OB women, we aimed at: (1) measure BV and assess whether differences in BV affect concentrations and total circulating mass of Hb and iron biomarkers; (2) develop an algorithm describing BV in OW/OB. SUBJECTS/METHODS: In a cross-sectional study, we measured BV in NW, OW, and OB non-anemic women (n = 62) by using the carbon monoxide-rebreathing method, body composition by dual energy X-ray absorptiometry, and iron and inflammatory status. RESULTS: OW and OB women had 11 and 16% higher mean BV and PV compared to NW (P < 0.05), respectively. In OW/OB compared to NW, total circulating masses of IL-6, hepcidin, Hb, and sTfR were higher, while total mass of serum iron was lower (for all, P < 0.05). An equation including height, body mass and lean mass to estimate BV in all BMI groups (R2 = 0.76). CONCLUSION: An equation based on anthropometric indices provides a good estimate of increased BV in OW/OB women. In OW/OB women, there is an increase in Hb mass that likely increases iron requirements for erythropoiesis and circulating TfR mass. At the same time, higher hepcidin concentrations may lower serum iron mass. Both these mechanisms may increase risk for ID in OW/OB women.

Información sobre la seguridad de los medicamentos que consumen los pacientes de la Obra Social Universitaria, en Córdoba Argentina / Información sobre la seguridad de los medicamentos que consumen los pacientes de la Obra Social Universitaria, en Córdoba Argentina / Information about safety of drugs taken by patients who have university health insurance, in Córdoba, Argentina

Objetivos: Describir la información sobre la seguridad de los medicametos que cosumen los pacientes afiliados a la Obra Social Universitaria y conocer sí los pacientes tenían interés en recibir información sobre estos medicamentos. Métodos: Estudio descriptivo, observacional y de corte transversal, con una muestra no probabilística (por conveniencia) de n=81 de los pacientes que acudieron a dispensar su medicamento a la farmacia central de la Obra Social Universitaria, se utilizó un cuestionario validado. Resultados: El 64% de los encuestados fueron del sexo masculino, con una media de edad de 57,22 ± 1,36. El 63% alcanzó un nivel de instrucción universitario, siendo el 36% jubilado, además el 32% de los encuestados solicito información sobre el medicamento que consumía. En los aspectos evaluados por el cuestionario como el conocimiento sobre las precauciones respecto al medicamento, el 83% respondió de manera incorrecta o dijo no conocer ninguna precaución.

Objectives: To describe information about the safety of medicine taken by patients who have the university health insurance and know if these patients were interested in receiving this information. Methods: Descriptive, observational, cross-sectional study with nonprobabilistic sample (for convenience) of n=81 of patients who went to the University Health Insurance central chemist to be dispensed their medicine; a validated questionnaire was used. Results: 64 % of the respondents were male with average age of 57.22 ± 1.36, 63% reached university level of education, 36% were retired, besides, 32% requested information on the drugs they were taking. In aspects evaluated in the questionnaire such as knowledge about precautions regarding the drug, 83% answered incorrectly or said they did not know about any precaution.

Objetivos: Descrever as informações sobre a segurança dos medicamentos consumidos pelos pacientes afiliados ao Serviço Social da Universidade e saber se eles estavam interessados em receber informações sobre esses medicamentos Métodos: Estudo descritivo, observacional e transversal, através de uma amostra não probabilística (por conveniência) de n = 81 dos pacientes que adquiriram seus medicamentos na farmácia central do Serviço Social da Universidade, foi utilizado um questionário validado. Resultados: 64% dos entrevistados eram do sexo masculino, com média 57,22 ± 1,36. 63% atingiram um nível de ensino superior, 36% aposentados e 32% dos entrevistados solicitaram informações sobre os medicamentos que usavam. Nos aspetos avaliados pelo questionário, como conhecimento sobre as precauções em relação à medicação, 83% responderam incorretamente ou afirmaram não conhecer qualquer precaução.

The effects of fat loss after bariatric surgery on inflammation, serum hepcidin, and iron absorption: a prospective 6-mo iron stable isotope study.

BACKGROUND: Iron deficiency is common in obese subjects. This may be due to an increase in serum hepcidin and a decrease in iron absorption from adiposity-related inflammation. OBJECTIVE: We evaluated whether weight and fat loss in obese subjects would decrease inflammation and serum hepcidin and thereby improve iron absorption. DESIGN: We performed a 6-mo prospective study in obese [body mass index (in kg/m2) ≥35 and <45] adults who had recently undergone laparoscopic sleeve gastrectomy. At 2 and 8 mo postsurgery, subjects consumed a test drink with 6 mg 57Fe as ferrous sulfate and were intravenously infused with 100 µg 58Fe as iron citrate. We then compared erythrocyte incorporation of iron isotopic labels, changes in body composition, iron status, hepcidin, and inflammation at each time point. RESULTS: Forty-three subjects were studied at baseline, and 38 completed the protocol (32 women and 6 men). After 6 mo, total body fat, interleukin IL-6, and hepcidin were significantly lower (all P < 0.005). In iron-deficient subjects (n = 17), geometric mean (95% CI) iron absorption increased by 28% [from 9.7% (6.5%, 14.6%) to 12.4% (7.7%, 20.1%); P = 0.03], whereas in iron-sufficient subjects (n = 21), absorption did not change [5.9% (4.0%, 8.6%) and 5.6% (3.9%, 8.2%); P = 0.81]. CONCLUSION: Adiposity-related inflammation is associated with a reduction in the normal upregulation of iron absorption in iron-deficient obese subjects, and this adverse effect may be ameliorated by fat loss. This protocol was approved by the ethics committees of Wageningen University, ETH Zurich, the University of Monterrey, and the Federal Commission for the Protection against Sanitary Risks, and registered at clinicaltrials.gov as NCT01347905.

In overweight and obese women, dietary iron absorption is reduced and the enhancement of iron absorption by ascorbic acid is one-half that in normal-weight women.

BACKGROUND: Iron deficiency is common in overweight and obese individuals. This deficiency may be due to adiposity-related inflammation that increases serum hepcidin and decreases dietary iron absorption. Because hepcidin reduces iron efflux from the basolateral enterocyte, it is uncertain whether luminal enhancers of dietary iron absorption such as ascorbic acid can be effective in overweight and obese individuals. OBJECTIVE: In this study, we compared iron absorption from a meal with ascorbic acid (+AA) and a meal without ascorbic acid (-AA) in women in a normal-weight group (NW) with those in overweight and obese groups combined (OW/OB). DESIGN: Healthy, nonanemic women [n = 62; BMI (in kg/m(2)): 18.5-39.9] consumed a stable-isotope-labeled wheat-based test meal -AA and a wheat-based test meal +AA (31.4 mg ascorbic acid). We measured iron absorption and body composition with the use of dual-energy X-ray absorptiometry, blood volume with the use of a carbon monoxide (CO)-rebreathing method, iron status, inflammation, and serum hepcidin. RESULTS: Inflammatory biomarkers (all P < 0.05) and hepcidin (P = 0.08) were lower in the NW than in the OW/OB. Geometric mean (95% CI) iron absorptions in the NW and OW/OB were 19.0% (15.2%, 23.5%) and 12.9% (9.7%, 16.9%) (P = 0.049), respectively, from -AA meals and 29.5% (23.3%, 38.2%) and 16.6% (12.8%, 21.7%) (P = 0.004), respectively, from +AA meals. Median percentage increases in iron absorption for -AA to +AA meals were 56% in the NW (P < 0.001) and 28% in OW/OB (P = 0.006). Serum ferritin [R(2) = 0.22; ß = -0.17 (95% CI: -0.25, -0.09)], transferrin receptor [R(2) = 0.23; ß = 2.79 (95% CI: 1.47, 4.11)], and hepcidin [R(2) = 0.13; ß = -0.85 (95% CI: -1.41, -0.28)] were significant predictors of iron absorption. CONCLUSIONS: In overweight and obese women, iron absorption is two-thirds that in normal-weight women, and the enhancing effect of ascorbic acid on iron absorption is one-half of that in normal-weight women. Recommending higher intakes of ascorbic acid (or other luminal enhancers of iron absorption) in obese individuals to improve iron status may have a limited effect. This trial was registered at clinicaltrials.gov as NCT01884506.

[Agrobacterium rubi strains from blueberry plants are highly diverse]. / Diversidad de cepas de Agrobacterium rubi aisladas de arándanos.

The diversity of a collection of Agrobacterium rubi strains isolated from blueberries from different regions of Argentina was studied by conventional microbiological tests and molecular techniques. Results from biochemical and physiological reactions, as well as from rep-PCR and RFLP analysis of PCR-amplified 23S rDNA showed high phenotypic and genotypic intraspecific variation.

Diversidad de cepas de Agrobacterium rubi aisladas de arándanos / Agrobacterium rubi strains from blueberry plants are highly diverse

Se estudió la diversidad de una colección de cepas de Agrobacterium rubi aisladas de arándanos provenientes de distintas regiones de la República Argentina estableciendo su grado de heterogeneidad mediante pruebas microbiológicas clásicas y técnicas de biología molecular. Los resultados obtenidos en las pruebas bioquímicas y fisiológicas, así como mediante rep-PCR y RFLP del gen 23S ADNr, demostraron una alta variabilidad intraespecífica, tanto fenotípica como genotípica

The diversity of a collection of Agrobacterium rubi strains isolated from blueberries from different regions of Argentina was studied by conventional microbiological tests and molecular techniques. Results from biochemical and physiological reactions, as well as from rep-PCR and RFLP analysis of PCR-amplified 23S rDNA showed high phenotypic and genotypic intraspecific variation

Evaluación del método epsilométrico Etest para la determinación de la sensibilidad a tetraciclina en Paenibacillus larvae, agente causal de la loque americana de las abejas / [Evaluation of the Epsilometer (Etest) method for the detection of tetracycline susceptibility in Paenibacillus larvae, the causal agent of American foulbrood disease of honeybees].

American foulbrood (AFB) is a bacterial disease caused by the spore-forming, grampositive bacterium Paenibacillus larvae, which affects honeybee broods worldwide. The aim of this work was to compare the Epsilometer test (Etest) to the agar dilution method for testing a collection of 22 P. larvae strains to tetracycline by using MYPGP and Iso- Sensitest agars. Results showed that a categorical agreement of 100

was found when using Iso-Sensitest, while a categorical agreement of 86.36

was found (with 3 minor errors) when MYPGP was tested. In conclusion, the Etest could be a rapid and reliable method for testing MIC values of tetracycline in P. larvae only when used in combination with Iso-Sensitest agar. Nevertheless, these results should be confirmed with future studies involving a larger number of isolates.

Métodos para la detección de Agrobacterium a partir de muestras de material vegetal, suelo y agua / Methods for the detection of Agrobacterium from plant, soil and water samples

El género Agrobacterium incluye especies ftopatógenas que inducen la formación de agallas en el cuello o la proliferación de raíces en cabellera en más de 600 especies de dicotiledóneas, y especies no patógenas cuyo hábitat natural es el suelo. Como no es posible erradicar a las especies patógenas y habida cuenta de que más del 80 % de las infecciones puede provenir de viveros, es importante evitar la diseminación de la enfermedad. Por ello, el objetivo de este trabajo ha sido desarrollar técnicas sensibles y precisas que, aisladamente o combinadas, permitan detectar la presencia de especies y biovares de Agrobacterium a partir de muestras de material vegetal, suelo y agua. Se comprobó que con la estrategia combinada de realizar aislamientos en los medios semiselectivos D1, D1-M y YEM-RCT; PCR multiplex sobre el gen 23S ADNr; PCR específca sobre los genes virC1 y virC2 y bioensayos en plántulas de pimiento cv. California Wonder y en hojas cortadas de kalanchoe, se reduce la posibilidad de obtener falsos negativos y/o falsos positivos. Por lo expuesto, esta combinación de técnicas constituye una herramienta adecuada para el diagnóstico de cepas patógenas de Agrobacterium a partir de distintos tipos de muestras.

The genus Agrobacterium includes phytopathogenic bacteria that induce the development of root crown galls and/or aerial galls at the base of the stem or hairy roots on more than 600 species of plants belonging to 90 dicotyledonous families and non-pathogenic species. These bacteria being natural soil inhabitants are particularly diffcult to eradicate, which is a problem in nurseries where more than 80% of infections occur. Since early detection is crucial to avoid the inadvertent spread of the disease, the aim of this work was to develop sensitive and precise identifcation techniques by using a set of semi-selective and differential culture media in combination with a specifc PCR to amplify a partial sequence derived from the virC operon, as well as a multiplex PCR on the basis of 23SrDNA sequences, and biological assays to identify and differentiate species and biovars of Agrobacterium obtained either from soil, water or plant samples. The combination of the different assays allowed us to reduce the number of false positive and negative results from bacteria isolated from any of the three types of samples. Therefore, the combination of multiplex PCR, specifc PCR, isolations in semi-selective D1, D1-M and YEM-RCT media combined with bioassays on cut leaves of Kalanchoe and seedlings of California Wonder pepper cultivar constitute an accurate tool to detect species and biovars of Agrobacterium for diagnostic purposes.

Sharply higher rates of iron deficiency in obese Mexican women and children are predicted by obesity-related inflammation rather than by differences in dietary iron intake.

BACKGROUND: Obese individuals may be at increased risk of iron deficiency (ID), but it is unclear whether this is due to poor dietary iron intakes or to adiposity-related inflammation. OBJECTIVE: The aim of this study was to examine the relations between body mass index (BMI), dietary iron, and dietary factors affecting iron bioavailability, iron status, and inflammation [C-reactive protein (CRP)] in a transition country where obesity and ID are common. DESIGN: Data from the 1999 Mexican Nutrition Survey, which included 1174 children (aged 5-12 y) and 621 nonpregnant women (aged 18-50 y), were analyzed. RESULTS: The prevalence of obesity was 25.3% in women and 3.5% in children. The prevalence of ID was significantly (P < 0.05) higher in obese women and children compared with normal-weight subjects [odds ratios (95% CIs): 1.92 (1.23, 3.01) and 3.96 (1.34, 11.67) for women and children, respectively]. Despite similar dietary iron intakes in the 2 groups, serum iron concentrations were lower in obese women than in normal-weight women (62.6 ± 29.5 compared with 72.4 ± 34.6 µg/dL; P = 0.014), and total-iron-binding capacity was higher in obese children than in normal-weight children (399 ± 51 compared with 360 ± 48 µg/dL; P < 0.001). CRP concentrations in obese women and children were 4 times those of their normal-weight counterparts (P < 0.05). CRP but not iron intake was a strong negative predictor of iron status, independently of BMI (P < 0.05). CONCLUSIONS: The risk of ID in obese Mexican women and children was 2-4 times that of normal-weight individuals at similar dietary iron intakes. This increased risk of ID may be due to the effects of obesity-related inflammation on dietary iron absorption. Thus, ID control efforts in Mexico may be hampered by increasing rates of adiposity in women and children.

[Methods for the detection of Agrobacterium from plant, soil and water samples]. / Métodos para la detección de Agrobacterium a partir de muestras de material vegetal, suelo y agua.

The genus Agrobacterium includes phytopathogenic bacteria that induce the development of root crown galls and/or aerial galls at the base of the stem or hairy roots on more than 600 species of plants belonging to 90 dicotyledonous families and non-pathogenic species. These bacteria being natural soil inhabitants are particularly difficult to eradicate, which is a problem in nurseries where more than 80% of infections occur. Since early detection is crucial to avoid the inadvertent spread of the disease, the aim of this work was to develop sensitive and precise identification techniques by using a set of semi-selective and differential culture media in combination with a specific PCR to amplify a partial sequence derived from the virC operon, as well as a multiplex PCR on the basis of 23SrDNA sequences, and biological assays to identify and differentiate species and biovars of Agrobacterium obtained either from soil, water or plant samples. The combination of the different assays allowed us to reduce the number of false positive and negative results from bacteria isolated from any of the three types of samples. Therefore, the combination of multiplex PCR, specific PCR, isolations in semi-selective D1, D1-M and YEM-RCT media combined with bioassays on cut leaves of Kalanchoe and seedlings of California Wonder pepper cultivar constitute an accurate tool to detect species and biovars of Agrobacterium for diagnostic purposes.

Does obesity increase risk for iron deficiency? A review of the literature and the potential mechanisms.

Increasing obesity is a major global health concern while at the same time iron-deficiency anemia remains common worldwide. Although these two conditions represent opposite ends of the spectrum of over- and under-nutrition, they appear to be linked: overweight individuals are at higher risk of iron deficiency than normal-weight individuals. Potential explanations for this association include dilutional hypoferremia, poor dietary iron intake, increased iron requirements, and/or impaired iron absorption in obese individuals. Recent evidence suggests obesity-related inflammation may play a central role through its regulation of hepcidin. Hepcidin levels are higher in obese individuals and are linked to subclinical inflammation; this may reduce iron absorption and blunt the effects of iron fortification. Thus, low iron status in overweight individuals may result from a combination of nutritional (reduced absorption) and functional (increased sequestration) iron deficiency. In this review, we focus on subclinical inflammation in obesity, and its effect on hepcidin levels, as the most plausible explanation for the link between iron deficiency and obesity.