Dual strategy to improve the oral bioavailability of efavirenz employing nanomicelles and curcumin as a bio-enhancer.

The present investigation was focused on the development of Soluplus®-based nanomicelles (NMs) (10 % w/v) loaded with Efavirenz (EFV) (5 mg/mL) and Curcumin (natural bio-enhancer) (CUR) (5, 10 and 15 mg/mL) to improve the oral bioavalability of EFV. Micellar formulations were obtained employing an acetone-diffusion technique. Apparent aqueous solubility was increased up to ∼1250-fold and 25,000-fold for EFV and CUR, respectively. Drug-loaded nanoformulations showed an excellent colloidal stability with unimodal size distribution and PDI values < 0.30. In vitro drug release was 41.5 % (EFV) and 2.6 % (CUR) from EFV-CUR-NMs over 6 h in simulated gastrointestinal fluids. EFV-CUR-loaded NMs resulted as safe nanoformulations according to the in vitro cytocompatibility assays in Caco-2 cells. Furthermore, CUR bio-enhancer activity was demonstrated for those nanoformulations. A CUR concentration of 15 mg/mL produced a significant (p < 0.05) increment (2.64-fold) of relative EFV oral bioavailability. Finally, the active role of the lymphatic system in the absorption process of EFV, after its oral administration was assessed in a comparative pharmacokinetic study in presence and absence of cycloheximide, a lymphatic transport inhibitor. Overall our EFV-CUR-NMs denoted their potential as a novel nanotechnological platform, representing a step towards an optimized "nano-sized" therapy for AIDS patients.

Helicobacter pylori and corpus gastric pathology are associated with lower serum ghrelin.

AIM: To evaluate the association of Helicobacter pylori (H. pylori), cagA genotype, and type of gastric pathology with ghrelin, leptin and nutritional status. METHODS: Fasted dyspeptic adults (18-70 years) referred for an upper digestive endoscopy were enrolled in this cross-sectional study. Height and weight were assessed for body mass index (BMI) calculation. A sociodemographic survey was administered and nutrient intake was evaluated with 24 h dietary recalls. Serum total ghrelin and leptin levels were analyzed by enzyme-linked immunosorbent assay. 13C-Urea Breath Test was performed and four gastric biopsies were obtained during endoscopy for histopathology and H. pylori DNA amplification and genotyping. Data analysis was performed using χ2, Mann-Whitney U, Kruskal-Wallis tests, Spearman's correlation and linear regression. RESULTS: One hundred and sixty-three patients (40.8 ± 14.0 years), 98/65 females/males, were included. Overall, persistent H. pylori prevalence was 53.4% (95%CI: 45.7%-65.8%). Neither nutrient intake nor BMI differed significantly between H. pylori positive and negative groups. Serum ghrelin was significantly lower in infected patients [median 311.0 pg/mL (IQR 230.0-385.5)] than in uninfected ones [median 355.0 pg/mL (IQR 253.8-547.8)] (P = 0.025), even after adjusting for BMI and gender (P = 0.03). Ghrelin levels tended to be lower in patients carrying cagA positive strains both in the antrum and the corpus; however, differences with those carrying cagA negative strains did not reach statistical significance (P = 0.50 and P = 0.49, respectively). In addition, the type and severity of gastric pathology in the corpus was associated with lower serum ghrelin (P = 0.04), independently of H. pylori status. Conversely, leptin levels did not differ significantly between infected and uninfected patients [median 1.84 ng/mL (0.80-4.85) vs 1.84 ng/mL (0.50-5.09), (P = 0.51)]. CONCLUSION: H. pylori infection and severity of gastric corpus pathology are associated with lower serum ghrelin. Further studies could confirm a lower ghrelin prevalence in cagA-positive patients.

Pilocarpine-Induced Status Epilepticus Is Associated with P-Glycoprotein Induction in Cardiomyocytes, Electrocardiographic Changes, and Sudden Death.

Sudden unexpected death in epilepsy (SUDEP) is the major cause of death in those patients suffering from refractory epilepsy (RE), with a 24-fold higher risk relative to the normal population. SUDEP risk increases with seizure frequency and/or seizure-duration as in RE and Status Epilepticus (SE). P-glycoprotein (P-gp), the product of the multidrug resistant ABCB1-MDR-1 gene, is a detoxifying pump that extrudes drugs out of the cells and can confer pharmacoresistance to the expressing cells. Neurons and cardiomyocytes normally do not express P-gp, however, it is overexpressed in the brain of patients or in experimental models of RE and SE. P-gp was also detected after brain or cardiac hypoxia. We have previously demonstrated that repetitive pentylenetetrazole (PTZ)-induced seizures increase P-gp expression in the brain, which is associated with membrane depolarization in the hippocampus, and in the heart, which is associated with fatal SE. SE can produce hypoxic-ischemic altered cardiac rhythm (HIACR) and severe arrhythmias, and both are related with SUDEP. Here, we investigate whether SE induces the expression of hypoxia-inducible transcription factor (HIF)-1α and P-gp in cardiomyocytes, which is associated with altered heart rhythm, and if these changes are related with the spontaneous death rate. SE was induced in Wistar rats once a week for 3 weeks, by lithium-pilocarpine-paradigm. Electrocardiograms, HIF-1α, and P-gp expression in cardiomyocytes, were evaluated in basal conditions and 72 h after SE. All spontaneous deaths occurred 48 h after each SE was registered. We observed that repeated SE induced HIF-1α and P-gp expression in cardiomyocytes, electrocardiographic (ECG) changes, and a high rate of spontaneous death. Our results suggest that the highly accumulated burden of convulsive stress results in a hypoxic heart insult, where P-gp expression may play a depolarizing role in cardiomyocyte membranes and in the development of the ECG changes, such as QT interval prolongation, that could be related with SUDEP. We postulate that this mechanism could explain, in part, the higher SUDEP risk in patients with RE or SE.

Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil®.

Doxorubicin (DOX) is used as a "first-line" antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus®, Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery. Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles. The combination of T1107:TPGS (1:3, weight ratio) demonstrated the best physicochemical properties together with a high DL capacity (6.43% w/v). Particularly, DOX in vitro release was higher at acidic tumour microenvironment pH value (5.5) than at physiological counterpart (7.4). The hydrodynamic diameter of the DOX/NaDC-loaded mixed micellar system was 10.7nm (PDI=0.239). The in vitro cytotoxicity of the mixed micellar formulation resulted significantly (p<0.05) higher than Doxil® against ovarian (SKOV-3) and triple-negative breast cancer cells (MDA-MB- 231). Further, the in vitro cellular uptake assays demonstrated a significant increment (p<0.05) of the DOX intracellular content for the mixed micelles versus Doxil® for both, SKOV-3 (at 2, 4 and 6h of incubation) and MDA-MB-231 (at 4h of incubation) cells. These findings suggest that T1107:TPGS (1:3) mixed micelles could be employed as a potential nanotechnological platform for drug delivery of DOX.

A glucose-targeted mixed micellar formulation outperforms Genexol in breast cancer cells.

Breast cancer represents the top cancer among women, accounting 521.000 deaths per year. Development of targeted nanomedicines to breast cancer tissues represents a milestone to reduce chemotherapy side effects. Taking advantage of the over-expression of glucose (Glu) membrane transporters in breast cancer cells, we aim to expand the potential of a paclitaxel (PTX)-loaded mixed micellar formulation based on polyvinyl caprolactam-polyvinylacetate-polyethylene glycol graft copolymer (Soluplus®) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) by its surface decoration with Glu moieties. The glycopolymer (Soluplus(Glu)) was obtained by microwave-assisted ring opening reaction of δ-gluconolactone initiated by Soluplus®. The glycosylation was confirmed by 1H NMR and by agglutination assays employing Concanavalin A. The hydrodynamic diameter of Soluplus(Glu) micelles was characterized by dynamic light scattering (100.3±3.8nm) as well as the critical micellar concentration value (0.0151% w/v). Then, a mixed micelle formulation employing Soluplus®, Soluplus(Glu) and TPGS (3:1:1wt ratio) loaded with PTX (4mg/mL) was developed as a multifunctional nanocarrier. Its in vitro anticancer performance in MCF-7 (1.6-fold) and MDA-MB-231 (14.1-fold) was significantly enhanced (p<0.05) versus the unique commercially available micellar-based PTX-nanoformulation (Genexol®). Furthermore, the in vitro PTX cellular uptake assays revealed that the drug intracellular/cell content was significantly (p<0.05) higher for the Glu-containing mixed micelles versus Genexol® after 6h of incubation with MCF-7 (30.5-fold) and MDA-MB-231 (5-fold). Overall, results confirmed the potential of our Glu-decorated mixed colloidal formulation as an intelligent nanocarrier for PTX-targeted breast cancer chemotherapy.

Polymeric mixed micelles as nanomedicines: Achievements and perspectives.

During the past few decades, polymeric micelles have raised special attention as novel nano-sized drug delivery systems for optimizing the treatment and diagnosis of numerous diseases. These nanocarriers exhibit several in vitro and in vivo advantages as well as increased stability and solubility to hydrophobic drugs. An interesting approach for optimizing these properties and overcoming some of their disadvantages is the combination of two or more polymers in order to assemble polymeric mixed micelles. This review article gives an overview on the current state of the art of several mixed micellar formulations as nanocarriers for drugs and imaging probes, evaluating their ongoing status (preclinical or clinical stage), with special emphasis on type of copolymers, physicochemical properties, in vivo progress achieved so far and toxicity profiles. Besides, the present article presents relevant research outcomes about polymeric mixed micelles as better drug delivery systems, when compared to polymeric pristine micelles. The reported data clearly illustrates the promise of these nanovehicles reaching clinical stages in the near future.

Hepato and Cardiotoxicity of Chemotherapeutic Treatment Evaluated by Means of Small Animal Imaging.

BACKGROUND: Chemotherapy is one of the most common approaches for cancer treatment. Particularly Doxorubicin has been proven to be effective in the treatment of many soft and solid tumors for locally advanced and metastatic cancer. It is not easy to clinically evaluate the chemotoxic or chemoprotective effect of some drugs, even more when there is a subclinical toxicity. OBJECTIVE: To determine the usefulness of the hepatobiliary, colloid and cardiac scintigraphies, employing99mTcdisida, 99mTc-phytate and 99mTc-sestamibi respectively, in the evaluation of the hepato and cardiotoxicity of two chemotherapeutic treatments assessed in rats. METHOD: Two groups were submitted to doxorubicin (DOX) treatment and one was co-administered with histamine (DOX+HIS). Static 99mTc-phytate and 99mTc-sestamibi scintigraphies as well as a dynamic 99mTc-disida study were performed in a small field of view gamma camera at: 0 weeks (control), 1 week and 2 weeks of treatment. Imagenological parameters were calculated: Liver/Bone Marrow ratio (L/BM), Heart/Background ratio (H/B) and time to the maximum (Tmax) for 99mTc-phytate, 99mTc-sestamibi and 99mTc-disida extraction, respectively. RESULTS: Control (L/BM= 98±3; H/B=2.3±0.4; Tmax=8±3), DOX (L/BM: 85±3, 80±3; H/B, 3.5±0.5, 3.3±0.5 and Tmax 6±1, 4±1) for 1 and 2 weeks respectively and DOX+HIS (L/BM: 99±0.3, 98±1; H/B 2.9±0.5, 2.9±0.5 and Tmax, 8±2, 9±2) for 1 and 2 weeks, respectively. Histological analysis showed cardio and hepatotoxicity induced by doxorubicin. CONCLUSION: Imagenological parameters showed differences among treated and control groups and between both chemotherapy treatments. Thus, these radiopharmaceutical functional approaches were able to reflect heart and liver toxicity produced by doxorubicin.

Dietary and anthropometric indicators of nutritional status in relation to Helicobacter pylori infection in a paediatric population.

It has been postulated that Helicobacter pylori infection could affect growth and appetite, consequently influencing body weight. Therefore, the association between H. pylori infection and the dietary and anthropometric indicators of nutritional status of a paediatric population were investigated. A total of 525 children (aged 4-16 years) who were referred to the gastroenterology unit of the Sor Maria Ludovica Children's Hospital from Buenos Aires, Argentina, were enrolled and completed an epidemiological questionnaire. H. pylori infection was diagnosed using the ¹³C-urea breath test (¹³C-UBT). Height and weight were assessed for calculation of anthropometric indicators. Energy and macronutrient intakes were estimated by 24 h dietary recall. Data analysis was performed using a χ² test, a Student's t test, a Mann-Whitney U test and linear and logistic regressions. The prevalence of H. pylori infection was 25·1 % (with a mean age of 10·1 (SD 3·1) years). A tendency towards lower energy, carbohydrate, protein and fat intakes was observed in infected patients; however, it was not associated with H. pylori infection in any of the evaluated age groups (4-8, 9-13 and 14-16 years). Underweight, stunting, overweight and obesity were also not associated with the infection. Although height-for-age and BMI-for-age Z scores tended to be lower in infected patients, the differences between H. pylori-positive and H. pylori-negative children were not statistically significant. In conclusion, H. pylori infection was not associated with dietary intake or with anthropometric indicators in the present population of children with gastrointestinal symptoms; however, an increased sample size would be needed to confirm the observed tendency towards lower dietary intake and lower anthropometric indicators of nutritional status in H. pylori-infected children.

Radioactivity decontamination of materials commonly used as surfaces in general-purpose radioisotope laboratories.

UNLABELLED: In accord with as-low-as-reasonably-achievable and good-manufacturing-practice concepts, the present study evaluated the efficiency of radioactivity decontamination of materials commonly used in laboratory surfaces and whether solvent spills on these materials affect the findings. METHODS: Four materials were evaluated: stainless steel, a surface comprising one-third acrylic resin and two-thirds natural minerals, an epoxy cover, and vinyl-based multipurpose flooring. Radioactive material was eluted from a (99)Mo/(99m)Tc generator, and samples of the surfaces were control-contaminated with 37 MBq (100 µL) of this eluate. The same procedure was repeated with samples of surfaces previously treated with 4 solvents: methanol, methyl ethyl ketone, acetone, and ethanol. The wet radioactive contamination was allowed to dry and then was removed with cotton swabs soaked in soapy water. The effectiveness of decontamination was defined as the percentage of activity removed per cotton swab, and the efficacy of decontamination was defined as the total percentage of activity removed, which was obtained by summing the percentages of activity in all the swabs required to complete the decontamination. RESULTS: Decontamination using our protocol was most effective and most efficacious for stainless steel and multipurpose flooring. Moreover, treatment with common organic solvents seemed not to affect the decontamination of these surfaces. Decontamination of the other two materials was less efficient and was interfered with by the organic solvents; there was also great variability in the overall results obtained for these other two materials. CONCLUSION: In expanding our laboratory, it is possible for us to select those surface materials on which our decontamination protocol works best.

Validation of a paper chromatographic methodology as an alternative for determination of the radiochemical purity of Na18F.

UNLABELLED: The aim of the present work was to validate a paper chromatography system as an alternative way to determine the radiochemical purity of Na(18)F. METHODS: The evaluated parameters were specificity, limit of quantification, measurement interval, linearity, precision, accuracy, and robustness. RESULTS: The proposed method proved to be linear (P > 0.05; r(2) = 1.000), precise (relative SD, 8.6%), accurate (mean recovery, 95.9%; relative SD, 1.5%-1.8%), and robust under different conditions since no influence of the operative variables on the chromatographic performance was observed. CONCLUSION: This system can be used as a reliable alternative method to determine the radiochemical purity of Na(18)F samples that can be easily performed in PET radiopharmacies at low cost.

Diagnóstico y seguimiento de cáncer de piel no-melanoma utilizando 99mTc-MIBI: estudios en un modelo animal / Usefulness of 99mTc-MIBI for the diagnosis and follow up of non-melanoma skin cancer: study in an animal model

El objetivo consistió en evaluar la utilidad del 99mTc-MIBI como marcador para diagnóstico y seguimiento de la progresión tumoral del NMSC en un modelo de carcinogénesis completa en ratones. Los animales en estudio fueron inyectados con 99mTc-MIBI a diferentes tiempos y eutanasiados. Se disecaron muestras de tumor y piel sana para evaluar la captación del radiofármaco y realizar el diagnóstico histológico. En animales con 22 semanas de progresión tumoral se observó una diferencia significativa en la captación del 99mTc-MIBI entre piel sana y NMSC. El protocolo que mejor se adapta al uso del 99mTc-MIBI como marcador para el diagnóstico y seguimiento de la progresión tumoral en ratones portadores de NMSC inducidos es la administración i.v de 1 mCi de 99mTc-MIBI con adquisición de datos a los 30 minutos post inyección. Se observó que a medida que los tumores progresan, la captación de 99mTc-MIBI disminuye respecto a la piel normal.

The aim of the work was to evaluate the usefulness of 99mTc-MIBI as a tracer for the tumor diagnosis and progression of NMSC in a chemically induced model in mice. After administration of 99mTc-MIBI animals were sacrificed at different times. Samples of tumor and healthy skin were dissected in order to perform histological analysis and to evaluate 99mTc-MIBI uptake. Animals under 22 weeks of tumor evolution showed a statistically difference in 99mTc-MIBI uptake between healthy skin and NMSC. Our results showed that the better protocol for the study of the tumor diagnosis and progression of NMSC in mice is the administration of 1 mCi of 99mTc-MIBI and acquisition of images 30 minutes post injection. Results showed that, as tumor progresses, the uptake of 99mTc-MIBI is significantly lower than healthy skin.

Decreasing trend of Helicobacter pylori infection in children with gastrointestinal symptoms from Buenos Aires, Argentina.

BACKGROUND: Helicobacter pylori infection is declining in developed and developing countries. The aim of this study was to retrospectively evaluate over an 8-year period the rate of H. pylori infection in children with gastrointestinal symptoms from Buenos Aires, Argentina. MATERIALS AND METHODS: We reviewed the records of children referred from 2002 to 2009 to the gastroenterology unit of the Children Hospital "Superiora Sor Maria Ludovica" for evaluation of upper gastrointestinal signs and symptoms in which the (13) C-urea breath test was performed to diagnose H. pylori infection and a sociodemographic questionnaire was obtained. RESULTS: Records of a total of 1030 children and adolescents with a mean age of 9.99 years were included in the analysis. We found an H. pylori prevalence of 41.2% (95% CI, 36.9-46.0%) for the triennium 2002-2004, dropping to 26.0% (95% CI, 20.7-31.8%) in the triennium 2007-2009. CONCLUSION: Our results showed a significant decrease in H. pylori infection rates from children referred for upper gastrointestinal symptoms evaluation from 2002 to 2009, following the H. pylori epidemiologic trend reported in other countries.

Novel gastric helicobacters and oral campylobacters are present in captive and wild cetaceans.

The mammalian gastric and oral mucosa may be colonized by mixed Helicobacter and Campylobacter species, respectively, in individual animals. To better characterize the presence and distribution of Helicobacter and Campylobacter among marine mammals, we used PCR and 16S rDNA sequence analysis to examine gastric and oral samples from ten dolphins (Tursiops gephyreus), one killer whale (Orcinus orca), one false killer whale (Pseudorca crassidens), and three wild La Plata river dolphins (Pontoporia blainvillei). Helicobacter spp. DNA was widely distributed in gastric and oral samples from both captive and wild cetaceans. Phylogenetic analysis demonstrated two Helicobacter sequence clusters, one closely related to H. cetorum, a species isolated from dolphins and whales in North America. The second related cluster was to sequences obtained from dolphins in Australia and to gastric non-H. pylori helicobacters, and may represent a novel taxonomic group. Dental plaque sequences from four dolphins formed a third cluster within the Campylobacter genus that likely represents a novel species isolated from marine mammals. Identification of identical Helicobacter spp. DNA sequences from dental plaque, saliva and gastric fluids from the same hosts, suggests that the oral cavity may be involved in transmission. These results demonstrate that Helicobacter and Campylobacter species are commonly distributed in marine mammals, and identify taxonomic clusters that may represent novel species.

Iron, zinc, and copper nutritional status in children infected with Helicobacter pylori.

OBJECTIVE: : Helicobacter pylori colonizes the gastric mucosa of about half of the world's population and it has been related to extragastrointestinal diseases. The present study sought to evaluate the association between H pylori infection and iron, zinc, and copper nutritional status in symptomatic children. PATIENTS AND METHODS: : A cross-sectional study was carried out in 395 children (4-16 years) with upper gastrointestinal symptoms, who were tested for H pylori infection by the C-urea breath test. Iron status was determined by hemoglobin, serum ferritin, and serum transferrin receptors. Copper and zinc serum concentrations were also evaluated. Epidemiological data, dietary assessment, and anthropometric indicators were analyzed as potential confounding factors. RESULTS: : Prevalence of H pylori infection was 24.3%. Anemia and iron deficiency (ID) were found in 12.0% and 14.3% of the H pylori-positive and 8.9% and 11.0% of the H pylori-negative children, respectively. There was no association between H pylori infection and anemia (odds ratio = 1.54 [95% confidence interval [CI] 0.73%-3.24%]) or ID (odds ratio = 1.35 [95% CI 0.67-2.70]). Crude beta coefficients showed that H pylori has no significant effect on hemoglobin, serum ferritin, serum transferrin receptors, copper, and zinc concentrations. However, adjusted results suggested that H pylori-infected children had an increase of 9.74 microg/dL (95% CI 2.12-17.37 microg/dL) in copper concentrations. CONCLUSIONS: : This study revealed that H pylori infection was not associated with iron deficiency, anemia, or zinc concentrations; however, a positive relation with copper status was found after adjusting for confounding factors. The contribution of H pylori infection to higher copper concentrations needs to be confirmed by additional studies.

Radioactive treatment of a murine melanoma using a (32)P-patch.

OBJECTIVE: To evaluate the therapeutic effects of a (32)P-patch in the treatment of a murine melanoma. MATERIALS AND METHODS: Thirty male C57BL6 mice were divided into two groups: treated and control. Superficial tumors were induced in both groups by injecting B16F1 melanoma at about 10 cells/mouse subcutaneously. Tumors developed 10-15 days after transplantation and the (32)P-patch was applied on palpable tumors of the treated group. Tumor growth was followed up in both groups by measuring tumor size with a caliper. After the follow-up period, the animals were killed and tumor samples of the treated and control groups were collected for histological study by preparing paraffin sections stained with hematoxylin-eosin. RESULTS: The (32)P-patch showed the absence of radioactivity leakage in vitro and the homogeneous distribution of the radionuclide. The skin surface at the application site of the (32)P-patch appeared hairless, and erythema developed, but reversed to normal after a few days in the treated group. Control of tumor growth was achieved in the treated group compared with the control group, although complete remission did not occur. CONCLUSION: The (32)P-patch tested for the treatment of a murine melanoma model showed its efficacy, as tumor growth was retarded after application of the patch Nevertheless, adjustment of some therapeutic parameters and/or combining the patch with other treatment modalities may be necessary to achieve complete regression. The P-patch represents a powerful tool to individualize the treatment of melanoma.

Bioevaluation of 32P patch designed for the treatment of skin diseases.

OBJECTIVE: The objective of this study was to design and evaluate a 32P patch for the treatment of skin diseases. MATERIALS AND METHODS: The patch was prepared from chromic phosphate 32P and silicone. Bioelimination and biodistribution in healthy and treated animals, and the therapeutic efficacy of two treatment schemes (single dose and fractionated dose) in an animal model of skin cancer were studied. RESULTS: Based on the bioelimination and biodistribution studies, no leakage of 32P from the patch was observed. The treated tumors reduced their mean diameter compared to controls. The single-dose therapeutic scheme showed a higher number of complete and partial remissions compared to the fractionated scheme. These results were confirmed by histopathological analysis of the samples. CONCLUSION: The 32P patch was designed and produced according to specifications for the treatment of superficial lesions of the skin. Although the 32P patch is an open source, it behaves like a sealed one for use in brachytherapy treatments.

Modificación de la biodistribución de los glóbulos rojos marcados con 99mtc en la anemia ferropénica / Alteration in the biodistribution of 99mTc-RBC in an animal model of ferropenic anemia

Objetivo: Evaluar la biodistribución de 99mTc-GR en un modelo animal de anemia ferropénica. Materiales y métodos: Se utilizaron ratas alimentadas con dietas con diferente contenido de Fe: grupo A (anemia severa, 6.5 ppm), grupo B (anemia moderada, 18 ppm) y grupo C (control, 100 ppm). Se realizó la marcación in vivo de los 99mTc-GR y se evaluó la EBM y su biodistribución a los 30 minutos y a las 24 horas en sangre, hígado, bazo, tracto gastrointestinal, riñones, corazón y pulmones. Los resultados se expresaron como concentración de actividad porcentual (CA por ciento). Resultados: En todos los grupos la EBM fue superior al 98 por ciento. Se observó un aumento de CA por ciento en bazo a las 24 horas en el grupo A, acompañado de una disminución de la CA por ciento del pool sanguíneo posiblemente por aumento del secuestro esplénico de los GR. En los tres grupos hubo un aumento de la CA por ciento en riñón a las 24 horas. Conclusión: La biodistribución de 99mTc-GR se ve modificada en la anemia ferropénica.

Aim: To evaluate the biodistribution of 99mTc-RBC in an animal model of ferropenic anemia. Materials and methods: We used rats which were fed with different iron contents diets: group A (severeanemia, 6.5 ppm), group B (moderate anemia, 18 ppm) and group C (control, 100 ppm). We performed the in vivo labeling of RBC and evaluated the labeling efficiency and the biodistribution at 30 minutes and 24 hours in blood, liver, spleen, gastrointestinal tract, kidneys, heart and lungs. The results were expressed as activity concentration percentage (CA percent). Results: In all groups the labeling efficiency was higher than 98 percent. We observed an increase of CA percent in spleen at 24 hours in the group A, followed by a decrease of CA percent in blood. This could be a consequence of an increase of splenic uptake of RBC. An increase in CA percent in kidney was obtained at 24 hours for all the groups. Conclusion: An alteration in the RBC biodistribution is observed in an animal model of ferropenic anemia.

Bioavailability studies of stabilized iron (II) sulfate by means of the prophylactic-preventive method.

The bioavailability of stabilized ferrous sulfate was studied by means of the prophylactic-preventive test in rats. For comparative purposes, ferrous sulfate was used as reference standard. The test was performed in male weaned rats during 3 weeks, which were randomized into three groups of ten animals each. A control group received a basal diet of low iron content while the other groups received the same diet added with iron at a dose of 15 mg/kg as FeSO4 7H2O and stabilized ferrous sulfate, respectively. Individual hemoglobin concentrations and weights were determined at the beginning and at the end of the study, and food intake was daily registered. Iron bioavailability (BioFe) of each source was calculated as the ratio between the amount of iron incorporated into hemoglobin during the treatment and the total iron intake per animal. A relative biological value was obtained as the ratio between the BioFe of stabilized ferrous sulfate and the reference standard given a value of 96%. Stabilized ferrous sulfate showed a high bioavailability, and when it is used to fortify dairy products as cheese and fluid milk in a dose of 15-20 mg of iron per kilogram, it behaved inertly in relation to the sensorial properties of the fortified food. These results suggest that this iron compound is a promising source to be use in food fortification.

Effect of a probiotic food as an adjuvant to triple therapy for eradication of Helicobacter pylori infection in children.

OBJECTIVE: Current recommendations for treatment of Helicobacter pylori infection include a proton pump inhibitor in combination with two antibiotics. We evaluated the potential activity of a probiotic food as an adjuvant to antibiotic triple therapy for eradication of H. pylori infection in children from Buenos Aires, Argentina. METHODS: Sixty-five children who tested positive for H. pylori, as diagnosed by (13)C-urea breath test and endoscopy, were included in this study. Patients were randomized to receive 1-wk triple therapy plus probiotic food (treated group) or milk placebo (control) that was administered for 3 mo. Probiotic food consisted of 250 mL of a commercial yogurt containing Bifidobacterium animalis and Lactobacillus casei (10(7) colony-forming units/mL). Post-treatment urea breath test controls were performed 1 and 3 mo after the end of triple therapy. RESULTS: We found no significant differences in H. pylori eradication rates (ERs) at 1 and 3 mo between the treated group (ER = 45.5% and 42.4%) and the control group (ER = 37.5% and 40.6%). Relative risks between groups were 0.87 (95% confidence interval 0.58-1.32, P = 0.345) in the first month and 0.97 (95% confidence interval 0.64-1.46, P = 0.542) in the third month. CONCLUSIONS: We could not demonstrate an adjuvant effect of the studied probiotic food to triple therapy in the eradication of H. pylori infection in children in Buenos Aires, Argentina. However, we found lower ERs than those reported for the same therapeutic scheme in developed countries, indicating that bacterial resistance and alternative therapeutic strategies should be studied.