Personalised iron supply for prophylaxis and treatment of pregnant women as a way to ensure normal iron levels in their breast milk.

RATIONALE: Because the characteristics of all body fluids depends on patient's health status, is it possible that disadvantaged and socially vulnerable mothers may have lower amounts of iron in their breast milk, and that their babies receive lower content of the mineral for their normal growth and development. Assuring a preventive treatment of the mother might solve this problem. OBJECTIVE: To demonstrate breast milk iron content from disadvantaged mothers and impact of personalized iron supplementation program. MATERIALS AND METHODS: cross-sectional study. Breast milk samples were obtained for ferritin analysis. Health's services usually provides free folic acid and iron treatment however, treatment compliance is low. Patients were random in two groups: "A: Controls" that had free iron tablets available from Health Centre; and "B: Intervention" group where patients accepted to be periodically contacted at home by health's team for personalized iron dispensation. RESULTS: 360 patients were included. Profilaxis and treatment compliance were 100% and 97,6% for B group while for "Control" one was 63% and 34%(p0.0001). Higher breast milk iron levels were detected in Intervention's mothers compared with control's patients (p0.007). CONCLUSION: Personalized iron prophylaxis and treatment increased breast milk iron levels. Public health policy must ensure iron dispensation for each underserved mother in order to reduce children problems associate to iron deficiency during the first year of their life.

Outstanding survival and regeneration process by the use of intelligent acellular dermal matrices and mesenchymal stem cells in a burn pig model.

A pig model with a deep large burn was used to study the regeneration process induced by mesenchymal stem cells (MSCs) and acellular pig dermal matrices, made intelligent by the combination with biodegradable nanofibers loaded with growth factors (granulocyte-macrophage colony-stimulating factor and epidermal growth factor) and coated with the anti-CD44 monoclonal antibody (intelligent acellular dermal matrices, IADMs). These IADMs are specially designed to integrate in the wound bed as new biological scaffolds as well as to specifically recruit and attach circulating and/or externally applied MSCs through the anti-CD44 antibody while delivering precise amounts of growth factors. In this way, the reparative process as well as the aesthetic and functional results were enhanced in our burn model. The animal survived, the wound was completely closed, and total regeneration of the skin was obtained without much scarring. Surprisingly, hair follicles and other skin appendages developed despite the severity and deepness of the burn. Even burned muscles and ribs seemed to have undergone a regenerative process by the end of the study. Based on these findings, we have proposed the use of IADMs and autologous, allogeneic or xenogeneic MSCs, as a new paradigm for the future treatment of large burns and probably other dermatological and cosmetic human conditions.

The next generation of burns treatment: intelligent films and matrix, controlled enzymatic debridement, and adult stem cells.

We describe a novel technology based on nanoengineered multifunctional acellular biologic scaffolds combined with wound dressings and films of the same kind. This method allows selective delivery and release of shielded biomaterials and bioactive substances to a desired wound or damaged tissue while stimulating the selective anchoring and adhesion of endogenous circulating repairing cells, such as mesenchymal stem cells, to obtain a faster and more physiologic healing process. We also present a new controlled enzymatic debridement process for more effective burned tissue scarolysis. In light of our preliminary in vitro and in vivo data, we are convinced that these approaches can include the use of other kinds of adult stem cells, such as endometrial regenerative cells, to improve the vascularization of the constructs, with great potential in the entire tissue and organ regeneration field but especially for the treatment of severely burned patients, changing the way these lesions may be treated in the future.

Matrix superhighways configurations: new concepts for complex organ regeneration.

New ideas and experimental models for tissue and organ regeneration are urgently needed. There are several exciting challenges in the field of organogenesis that need to be defined. The integrated signals and molecular repertoires that shape the particular architecture of specific organs like the kidney or the liver are not completely understood yet. To develop a new scientific platform to be able to build up complex organs we have established a research program using basically Acellular Xenogeneic Isomorphic Matrices (AXIMs) and mesenchymal stem cells (MSCs) generating the necessary concepts for the definition, production, and application of the specific configurations of these matrices for organ regeneration. New and interesting pathways for MSC differentiation were identified. We believe that all extracellular matrices were created fundamentally equal or at least very similar in nature. We also believe that there are true "matrix superhighway configurations" with different three-dimensional geometrical architectures as well as biochemical, electrical, and molecular properties that are tissue and organ specific that influence cell differentiation and organogenesis and will be fundamental for the in vitro regeneration of complex organs for transplantation.

[Interdisciplinary health project: a model based in home care makes the difference]. / Proyecto de acción interdisciplinaria en salud (PAIS): un modelo de atención centrado en el hogar hace la diferencia.

OBJECTIVE: To propose an interdisciplinary approach in Community Health through a model based on Home Health Care. DESIGN: A prospective study programmed in two periods: a cross sectional study for data collection followed by home assistance for the health problems detected. METHODS: 100 families (570 inhabitants) were randomly submitted to a clinical, nutritional and laboratory examination in order to detect major health problems. Afterwards the same professional team took care of 10 families in health promotion counseling and illness treatment. RESULTS: This study shows that 84% of the patients in whom a health abnormality was detected were not aware of their illness. The population was mainly affected by hypertension, hypercholesterolemia, hypertrigliceridemia, and anemia. None of these problems were listed as the main causes of consultation in a local center belonging to the traditional health services. Almost 70% of the inhabitants consumed a daily diet with less nutrients and calories than recommended. The project included health care for all family members and free drugs provision for all illnesses detected. Ninety-eight percent of patients had a proper and continuous follow up of their illness for a 3 year period, compared with a 31% follow up provided by the traditional health care organization. CONCLUSIONS: This work shows an integrated effort by the University, health centers, and all health care disciplines to propose an alternative program that personalizes attention and moves health care from Institutions to people's own homes. This model improved community health conditions, had a high impact on illness follow up and increased health care accessibility.

Bloodstream cells phenotypically identical to human mesenchymal bone marrow stem cells circulate in large amounts under the influence of acute large skin damage: new evidence for their use in regenerative medicine.

OBJECTIVES: Recent work has shown that human bone marrow contains mesenchymal stem cells (MSCs). However, little is known about their presence in peripheral blood. Since these cells are potentially responsible for tissue repair after injury, their number should be increased during these situations. To demonstrate their number during these situations, we measured MSCs in the peripheral blood of healthy donors and burn patients. MATERIALS AND METHODS: Blood samples were obtained from 15 acute burn patients and 15 healthy donors. We performed flow cytometric analysis, using a large monoclonal antibody panel: CD44, CD45, CD14, DR, CD34, CD19, CD13, CD29, CD105, CD1a, CD90, CD38, CD25. MSC phenotype was considered positive for CD44, CD13, CD29, CD90, and CD105, and negative for the other monoclonals. The testing was performed on day 3 after injury. We correlated the results with the age, sex, and size and type of burns. RESULTS: Cells expressing the MSC phenotype were detected in the peripheral blood of both groups. Noteworthy, compared with samples from healthy donors (0.0078 +/- 0.0044), blood obtained from burn patients showed a higher MSC percentage (0.1643 +/- 0.115; P < .001). The percentage of MSCs correlated with the size and severity of the burn. Increased values were also observed among younger patients. CONCLUSIONS: MSCs have an important role in regenerative processes of human tissues. We found cells phenotypically identical to MSCs circulating in physiological number in normal subjects, but in significantly higher amounts during acute large burns. Therefore, they may represent a previously unrecognized circulatory component to the process of skin regeneration.

Human mesenchymal stem cells are tolerized by mice and improve skin and spinal cord injuries.

INTRODUCTION: We sought to use human mesenchymal stem cells (HMSC) for skin and spinal cord repair in mice. MATERIALS AND METHODS: Human bone marrow obtained from a young healthy donor was used to separate and culture human mesenchymal stem cells (HMSC). Ten mice were included in each of four groups. A full-thickness skin defect was surgically performed on all mice in groups 1 and 2. A transverse complete medullar section was performed in groups 3 and 4. Groups 1 and 3 received HMSC IV infusion and local HMSC polymer implant. Groups 2 and 4 received only the IV HMSC infusion. Five control animals from each group went through the same lesions but they didn't receive treatment. RESULTS: After local administration of HMSC into the fibrin polymer combined with the IV infusion of HMSC, there was no immune rejection; all skin defects healed without scar or retraction at a median time of 14 days. Sixty percent of the animals treated with IV infusion and polymer with HMSC simultaneously had improved neurological activities, while all control mice with spinal cord injury experiments died or perpetuated their paralysis with worsening muscular atrophy and increasing propensity to skin damage. CONCLUSIONS: HMSC are not immunologically reactive and can trespass species defense barriers. Animals treated with these cells repaired injuries better than controls. In this way we propose that universal HMSC from donors can be cultured, expanded, and cryopreserved to be used in human organ or tissue regeneration.

[Prevalence of anaemia in pregnancy and analysis of the underlying factors]. / Prevalencia de anemia del embarazo y análisis de sus factores condicionantes.

OBJECTIVE: To determine the prevalence of anaemia and to evaluate the factors that condition its occurrence.Setting. Out-patient clinics in the La Plata area, Buenos Aires, Argentina. DESIGN: Observational and prospective study. PARTICIPANTS: All the pregnant women consulting for the first time, excluding those with prior pathology or regular use of medical drugs. MEASUREMENTS: Anaemia was defined at values of Hb < 11 g/dl. Questionnaires were administered for general data and the type of nutrition, and a complete haematological report was compiled. RESULTS: 1218 pregnant women started the study. Anaemia was detected in 196 of them (16%), with average Hb 9.88 g/dl. Between normal and anaemic pregnant women, the following differences were found between the first and second consultations: weight (64.44 vs 59.50, p < 0.00001), family income (US$744.36 vs 568.28, p < 0.0001), kilocalories ingested (2,488.44 vs 2,204.28, p = 0.01), percentage of proteins in diet (15.73 vs 13.69, p = 0.002), and weekly iron consumption (15.24 mg vs 13.04, p < 0.0001). CONCLUSIONS: Pregnant women run a greater risk of suffering anaemia if they have diets of < 1800 kcal, < 13% proteins, less than 7 mg of iron per week, and haemic iron < 10%; and family income below US$400. Ensuring a proper diet and improving the social and economic conditions of this population group will reduce the risk of anaemia during pregnancy and its perinatal consequences.

Graft versus host disease in autologous stem cell transplantation.

Relapse remains the major cause of mortality in haematological malignancies treated with autologous stem cell transplantation (ASCT). Graft versus tumour reaction (GVT) associated to autologous graft versus host disease (GVDH) may contribute to eliminate minimal residual disease (MRD) after ASCT. Eighty patients with several diagnostics were submitted to ASCT. After stem cell infusion, patients randomised in 4 groups. Groups were treated as follows: Group A received either a IFN (alpha Interferon--1,000,000 U/d), Cyclosporine A (CSA--1 mg/-kg/d intravencus) for 28 days, and granulocyte-macrophage colony stimulating factor (GM-CSF-250/m2/d) until engraftment; B: CSA (same dose and way) and GM-CSF; C: CSA (1 mg/kg/d orally) and GM-CSF and D: only GM-CSF. Patients were inspected daily and if skin rash was detected, a skin biopsy was obtained at that moment, otherwise biopsies were obtained at day 21 after ASCT. GVHD was positive in 23 patients (13 from group A and 10 from group B). All cases were grades I and II. A majority of CD4+ T lymphocytes was seen in skin infiltrates. No significant differences were seen in WBC and platelets engraftment times, antibiotic administration or hospitalisation days required among the four groups. With a median follow up of 18 months, there were no differences in disease free survival (DFS) or overall survival (OS) between the patients who developed GVHD and the others. However, considering that myeloma cells do not express antigen MCH II, which is necessary for GVT effect, we excluded patients with multiple myeloma (MM) from survival analysis, thus obtaining a significant difference in OS results between patients who developed GVHD and those in whom this reaction was not observed (81% vs 58% p:0.05). We conclude that pharmacological induction of GVHD in ASCT is possible with CSA administration (1 mg/kg/d i.v.). Development of GVHD showed a better outcome for patients in our study except for those patients with MM. This results must be confirmed by a longer follow up of our patients and further studies.

[Megaloblastic anemia: rapid and economical study]. / Anemia megaloblástica: su estudio en forma rápida y económica.

The diagnosis of megaloblastic anaemias caused by cobalamine or folate deficiency are still difficult. The dosage of these two substances help to differenciate between both carencies, but it is not determinant of any of them and is an expensive method. Homocisteinuria (HC), methylmalonuria (MMA) and formiminoglutamic acid (FIGLU) are cheap tests which could help in the differential diagnosis, if they are used properly. We report 62 patients to whom we made these test simultaneously. All of the patients received 10 micrograms of vit B12 and after 72 hours, 1 mg/day of folic acid (for 3 days). In both cases waiting for the increase of reticulocytyes up to 150 x 10(9)/L as a form of therapeutic test of diagnosis. By this simple way we have detected 97.9% of specificity for cobalamin deficiency of the MMA test, and only 4.2% for HC. This last test had increased its specificity up to 91.6% in association with the negative FIGLU test. We have also found a high specificity (92.3%) for FIGLU due to the detection of folate deficiency, in opposition with other authors who had described it as low as 50%. We have also compared the costs of the 3 tests with the dosage of cobalamine and folate, and we have found that the formers are 11 times less expensive than the last ones.