Publications by authors named "Javier Mancilla-Ramírez"

26 Publications

  • Page 1 of 1

CD71 Erythroid Cells in Human Neonates Exhibit Immunosuppressive Properties and Compromise Immune Response Against Systemic Infection in Neonatal Mice.

Front Immunol 2020 24;11:597433. Epub 2020 Nov 24.

School of Dentistry, University of Alberta, Edmonton, AB, Canada.

Newborns are highly susceptible to infectious diseases. The underlying mechanism of neonatal infection susceptibility has generally been related to their under-developed immune system. Nevertheless, this notion has recently been challenged by the discovery of the physiological abundance of immunosuppressive erythroid precursors D71rythroid ell (CECs) in newborn mice and human cord blood. Here, as proof of concept, we show that these cells are also abundant in the peripheral blood of human newborns. Although their frequency appears to be more variable compared to their counterparts in mice, they rapidly decline by 4 weeks of age. However, their proportion remains significantly higher in infants up to six months of age compared to older infants. We found CD45 expressing CECs, as erythroid progenitors, were the prominent source of reactive oxygen species (ROS) production in both humans and mice. Interestingly, a higher proportion of CD45CECs was observed in the spleen versus bone marrow of neonatal mice, which was associated with a higher ROS production by splenic CECs compared to their siblings in the bone marrow. CECs from human newborns suppressed cytokine production by CD14 monocytes and T cells, which was partially abrogated by apocynin . Moreover, the depletion of CECs in neonatal mice increased the number of activated effector immune cells in their spleen and liver, which rendered them more resistant to infection. This was evident by a significant reduction in the bacteria load in the spleen, liver and brain of treated-mice compared to the control group, which enhanced their survival rate. Our finding highlights the immunoregulatory processes mediated by CECs in newborns. Thus, such tightly regulated immune system in newborns/infants may explain one potential mechanism for the asymptomatic or mild COVID-19 infection in this population.
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http://dx.doi.org/10.3389/fimmu.2020.597433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732591PMC
December 2020

Neurophysiological Mechanisms Related to Pain Management in Bone Tumors.

Curr Neuropharmacol 2021 ;19(3):308-319

Instituto Nacional de Rehabilitacion, "Luis Guillermo Ibarra, Ibarra", SSA, Ciudad de Mexico, Mexico.

Background: Primary and metastatic bone tumor incidence has increased in the previous years. Pain is a common symptom and is one of the most important related factors to the decrease of quality of life in patients with bone tumor. Different pain management strategies are not completely effective and many patients afflicted by cancer pain cannot be controlled properly. In this sense, we need to elucidate the neurophysiology of cancer-induced pain, contemplating other components such as inflammation, neuropathies and cognitive components regarding bone tumors, and thus pave the way for novel therapeutic approaches in this field.

Aim: This study aims to identify the neurophysiology of the mechanisms related to pain management in bone tumors.

Methods: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index to get information about the neurophysiology mechanisms related to pain management in bone tumors.

Results: The central and peripheral mechanisms that promote bone cancer pain are poorly understood. Studies have shown that bone cancer could be related to neurochemicals produced by tumor and inflammatory cells, coupled with peripheral sensitization due to nerve compression and injury caused by tumor growth. The activity of mesolimbic dopaminergic neurons, substance P, cysteine/ glutamate antiporter, and other neurochemical dynamics brings us putative strategies to suggest better and efficient treatments against pain in cancer patients.

Conclusion: Cancer-induced bone pain could include neuropathic and inflammatory pain, but with different modifications to the periphery tissue, nerves and neurochemical changes in different neurological levels. In this sense, we explore opportunity areas in pharmacological and nonpharmacological pain management, according to pain-involved mechanisms in this study.
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http://dx.doi.org/10.2174/1570159X18666201111112748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033964PMC
January 2021

Factors associated with death in children with COVID-19 in Mexico.

Gac Med Mex 2020 ;156(6):516-522

Hospital Infantil de México "Federico Gómez", Secretaría de Salud, Mexico City. Mexico.

Introduction: Most children affected by SARS-CoV-2 are reported to be asymptomatic, and COVID-19-related mortality in them is low; in Mexico, there is a lack of information on the subject in this population group.

Objective: To assess the risk factors associated with mortality in Mexican children with COVID-19.

Method: Secondary analysis of the General Directorate of Epidemiology database. Children younger than 19 years, in whom SARS-CoV-2 infection was confirmed by RT-PCR, were included.

Results: 1443 children were included. Median age was eight years; 3.3 % were admitted to the intensive care unit, 1.8 % required assisted mechanical ventilation, and mortality was 1.9 %. In multivariate models, the development of pneumonia was the main risk factor for mortality, with an odds ratio (OR) of 6.45 (95 % CI: 1.99, 20.89); patients who required intubation had an OR of 8.75 (95 % CI: 3.23, 23.7).

Conclusions: Children with COVID-19 exhibit high mortality in Mexico, and avoiding pneumonia should therefore be tried in them, especially in children younger than four years, with cardiovascular risk or immunosuppression.

IntroducciÓn: Se informa que la mayoría de los niños afectados por SARS-CoV-2 cursan asintomáticos y que en ellos la mortalidad por COVID-19 es baja; en México se desconoce la información al respecto en este grupo de la población. ­.

Objetivo: Evaluar los factores de riesgo asociados a mortalidad en niños mexicanos con COVID-19.

MÉtodo: Análisis secundario de la base de datos de la Dirección General de Epidemiología. Se incluyeron niños menores de 19 años, en quienes se confirmó SARS-CoV-2 mediante RT-PCR.

Resultados: Se incluyeron 1443 niños. La mediana de edad fue de ocho años; 3.3 % ingresó a la unidad de cuidados intensivos, 1.8 % requirió ventilación mecánica asistida y la mortalidad fue de 1.9 %. En los modelos multivariados, el desarrollo de neumonía constituyó el principal factor de riesgo de mortalidad, con razón de momios (RM) de 6.45 (IC 95 % 1.99, 20.89); los pacientes que requirieron intubación tuvieron RM de 8.75 (IC 95 % 3.23, 23.7).

Conclusiones: Los niños con COVID 19 tienen alta mortalidad en México, por lo que en ellos se debe procurar evitar la neumonía, especialmente en los menores de cuatro años, con riesgo cardiovascular o inmunosupresión.
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http://dx.doi.org/10.24875/GMM.M21000478DOI Listing
April 2021

Multiparameter flow cytometry analysis of leukocyte markers for diagnosis in preterm neonatal sepsis.

J Matern Fetal Neonatal Med 2019 Sep 19:1-11. Epub 2019 Sep 19.

Faculty of Medicine, Combined Studies Plan in Medicine, National Autonomous University of Mexico , Mexico City , Mexico.

Neonatal sepsis is an important public health concern worldwide due to its immediate lethality and long-term morbidity rates, Clinical evaluation and laboratory analyses are indispensable for diagnosis of neonatal sepsis. However, assessing multiple biomarkers in neonates is difficult due to limited blood availability. The aim is to investigate if the neonatal sepsis in preterm could be identified by multiparameter analysis with flow cytometry. The expression of activation-related molecules was evaluated by flow cytometry in newborn with or without risk factors for sepsis. Our analysis revealed that several markers could be useful for sepsis diagnosis, such as CD45RA, CD45RO, or CD71 on T cells; HLA-DR on NKT or classic monocytes, and TREM-1 on non-classic monocytes or neutrophils. However, ROC analysis shows that the expression of CD45RO on T lymphocytes is the only useful biomarker for diagnosis of neonatal late-onset sepsis. Also, decision tree analyses showed that CD45RO plus CD27 could help differentiate the preterm septic neonates from those with risk factors. Our study shows a complementary and practical strategy for biomarker assessment in neonatal sepsis.
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http://dx.doi.org/10.1080/14767058.2019.1666100DOI Listing
September 2019

Medical Outcomes in Women Who Became Pregnant after Vaccination with a Virus-Like Particle Experimental Vaccine against Influenza A (H1N1) 2009 Virus Tested during 2009 Pandemic Outbreak.

Viruses 2019 09 17;11(9). Epub 2019 Sep 17.

Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City CP 06720, Mexico.

The clinical effects and immunological response to the influenza vaccine in women who later become pregnant remain to be thoroughly studied. Here, we report the medical outcomes of 40 women volunteers who became pregnant after vaccination with an experimental virus-like particle (VLP) vaccine against pandemic influenza A(H1N1)2009 (influenza A(H1N1)pdm09) and their infants. When included in the VLP vaccine trial, none of the women were pregnant and were randomly assigned to one of the following groups: (1) placebo, (2) 15 μg dose of VLP vaccine, or (3) 45 μg dose of VLP vaccine. These 40 women reported becoming pregnant during the follow-up phase after receiving the placebo or VLP vaccine. Women were monitored throughout pregnancy and their infants were monitored until one year after birth. Antibody titers against VLP were measured in the mothers and infants at delivery and at six months and one year after birth. The incidence of preeclampsia, fetal death, preterm delivery, and premature rupture of membranes was similar among groups. All vaccinated women and their infants elicited antibody titers (≥1:40). Women vaccinated prior to pregnancy had no adverse events that were different from the nonvaccinated population. Even though this study is limited by the sample size, the results suggest that the anti-influenza A(H1N1)pdm09 VLP experimental vaccine applied before pregnancy is safe for both mothers and their infants.
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http://dx.doi.org/10.3390/v11090868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783846PMC
September 2019

The role of complement in preterm birth and prematurity.

J Perinat Med 2019 Oct;47(8):793-803

Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City 11340, Mexico.

Complications of preterm birth (PTB) are the global leading cause of death in children younger than 5 years of age. Almost 15 million children are born prematurely in the world each year. Increasing evidence suggests that labor and delivery have many hallmarks of an inflammatory reaction, where complement activation has an active participation. As one of the most important components of inflammation, the role of complement during labor and PTB is becoming an attractive research target. The complement components C1q and C5b-9 are deposited on fetal membranes and release inflammatory mediators that contribute to uterine contractions, cervical ripening, cell chemotaxis, metalloproteinases production, membrane awaking and rupture, and it participates as a co-adjuvant in the onset and progress of labor. This article reviews a basic description of the complement system, its role in preterm birth and current concepts regarding its contribution in novel therapy strategies and new biomarkers.
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http://dx.doi.org/10.1515/jpm-2019-0175DOI Listing
October 2019

Morbidity Trends and Risk of Tuberculosis: Mexico 2007-2017.

Can Respir J 2019 17;2019:8295261. Epub 2019 Apr 17.

Hospital de la Mujer, SSA, Salvador Díaz Mirón 374, Col. Santo Tomas, 11340 Mexico City, Mexico.

Background: To know the current status of the epidemiological and geographic distribution of tuberculosis and its complication meningeal tuberculosis in Mexico, this work analyzes national surveillance data (ten years) issued by the General Directorate of Epidemiology (GDE).

Methods: An observational and retrospective analysis of monthly and annual reports of pulmonary and meningeal tuberculosis cases from January 2007 to December 2017 was performed on the annual reports issued by the GDE in Mexico. The number of cases and incidence were classified by year, state, age group, gender, and seasons.

Results: A national case distribution map of pulmonary and meningeal tuberculosis incidence was generated. During this period, a total of 184,003 and 3,388 cases were reported with a median of 16,727.5 and 308 cases per year for pulmonary and meningeal tuberculosis diseases, respectively. The number of cases and incidence of pulmonary and meningeal tuberculosis per year showed that male gender presented a continuous increase in both parameters. The geographic analysis of the distribution of cases of tuberculosis showed that states like Guerrero, Tabasco, and Veracruz presented higher means of tuberculosis cases during this period. Northern states had the highest number of cases in the country compared to other states. In Mexico, pulmonary tuberculosis and meningeal tuberculosis are seasonal. Interestingly, cases of meningeal tuberculosis show an increase during October and November (autumn).

Conclusions: In Mexico, during the years 2007-2017, there has been an increase in the proportion of male TB patients. It remains necessary to implement strategies to detect TB in the adult population, especially among men, because tuberculosis could be difficult to recognize in an early stage in the population, and the appearance of resistant strains can cause an increase in the incidence of the disease.
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http://dx.doi.org/10.1155/2019/8295261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501252PMC
May 2020

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

Ann Nutr Metab 2016 2;69(2):150-160. Epub 2016 Nov 2.

Unit of Medical Research in Nutrition, Hospital de Pediatria, Mexico City, Mexico.

Background: Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery.

Methods: A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed.

Results: Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 μg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (β = -27 μg/kg, p = 0.028; R2 model = 0.90) for shorter duration (β = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected.

Conclusions: Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects.
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http://dx.doi.org/10.1159/000452227DOI Listing
December 2017

Beneficial Effects of Enteral Docosahexaenoic Acid on the Markers of Inflammation and Clinical Outcomes of Neonates Undergoing Cardiovascular Surgery: An Intervention Study.

Ann Nutr Metab 2016 9;69(1):15-23. Epub 2016 Jul 9.

Medical Research Unit in Nutrition, Hospital de la Mujer, Mexico City, Mexico.

Background: Neonates undergoing surgery are at risk for uncontrolled inflammatory response and adverse clinical outcomes. Docosahexaenoic acid (DHA) ameliorates inflammation, improving clinical outcomes. However, its effect has not been evaluated in neonates undergoing surgery. We evaluated the effect of DHA on markers of inflammation and clinical outcomes in neonates undergoing surgery.

Methods: A double-blind clinical trial evaluated the effect of enteral DHA (DHA group) versus sunflower oil (SO group) perioperatively administered in neonates scheduled for cardiovascular surgery. Inflammation was evaluated by percentage of cells+ for cytokines and CD69 in mononuclear cells at baseline, 24 h and 7 days post surgery. Clinical outcomes measured were sepsis, organ dysfunctions (ODs), length of stay in intensive care and bleeding. Repeated measures analysis of variance and logistic regression were applied.

Results: Sixteen neonates received DHA and 18 received SO. Cells+ from neonates in the DHA group showed an early increase in receptor antagonist of interleukin (IL)-1+ (IL-1ra+) and IL-10+ and a late decrease in IL-6+. IL-1β+ and IL-10+ changes were different between groups. After adjusting for confounders, less cells from DHA group were IL-1β+, IL-6+, IL-1ra+ and IL-10+. DHA group presented less sepsis, ODs and shorter stay, but no difference in CD69+CD4+ cells or bleeding between groups.

Conclusions: Administration of enteral DHA ameliorates markers of inflammation and improves clinical outcomes in surgical neonates.
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http://dx.doi.org/10.1159/000447498DOI Listing
January 2018

Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis.

Mediators Inflamm 2016 16;2016:6740827. Epub 2016 May 16.

Departamento de Infectología e Inmunología, Instituto Nacional de Perinatología, SSa, Montes Urales 800, Colonia Lomas de Virreyes, 11000 Mexico City, Mexico.

The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.
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http://dx.doi.org/10.1155/2016/6740827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4884838PMC
January 2017

Complement activation in both normal and complicated pregnancies.

J Reprod Immunol 2015 Nov 28;112:120. Epub 2015 Aug 28.

Instituto Nacional de Perinatología, Departamento de Epidemiología Hospitalaria, México City, Mexico. Electronic address:

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http://dx.doi.org/10.1016/j.jri.2015.08.003DOI Listing
November 2015

Blood SC5b-9 complement levels increase at parturition during term and preterm labor.

J Reprod Immunol 2015 Jun 2;109:24-30. Epub 2015 Apr 2.

Departamento de Infectología e Inmunología Perinatal, Instituto Nacional de Perinatologia (INPer), Mexico. Electronic address:

We explored the hypothesis that complement, an innate and adaptive immune effector, is active in the plasma of parturient women and is deposited on fetal membranes collected after delivery. A cross-sectional study was designed to evaluate complement activity at parturition. Pregnant women (n = 97) between 15 and 41 years of age were enrolled in a hospital protocol during the perinatal period to assess both SC5b-9 complement activity in blood and complement deposition on fetal membranes during parturition. Soluble SC5b-9 complement activity in plasma fractions was measured using a standard enzyme-linked immunosorbent assay (ELISA) that included specific anti-complement antibodies. Complement deposition on membranes was analyzed using immuno-dot blots and immunohistochemistry. Soluble SC5b-9 complement complex levels were increased in the plasma of women during term labor (TL; median 3361; range 1726-5670 ng/mL), preterm labor (PL; median 2958; range 1552-7092 ng/mL), and preterm premature rupture of membranes (PPROM; median 2272; range 167-6540 ng/mL) compared with pregnant women who were not in labor (P; median 1384; range 174-4570 ng/mL; P < 0.001, Kruskal-Wallis test). Active complement, as assessed by the C9 neo-antigen in C5b-9 complexes, was deposited on fetal membranes, with no difference between term and preterm delivery. The deposition of active complement on fetal membranes was confirmed by immunohistochemistry. Women who underwent non-labor-indicated Cesarean sections did not exhibit complement deposition. Soluble SC5b-9 complement complex levels increased in the plasma of women during parturition, and complement C5b-9 complexes were deposited on fetal membranes.
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http://dx.doi.org/10.1016/j.jri.2015.02.008DOI Listing
June 2015

Pregnant women infected with pandemic H1N1pdm2009 influenza virus displayed overproduction of peripheral blood CD69+ lymphocytes and increased levels of serum cytokines.

PLoS One 2014 25;9(9):e107900. Epub 2014 Sep 25.

Infectology and Immunology Department, National Institute of Perinatology (INPer), Mexico City, Mexico.

The first pandemic of the 21st century occurred in 2009 and was caused by the H1N1pdm influenza A virus. Severe cases of H1N1pdm infection in adults are characterized by sustained immune activation, whereas pregnant women are prone to more severe forms of influenza, with increased morbi-mortality. During the H1N1pdm09 pandemic, few studies assessed the immune status of infected pregnant women. The objective of this study was to evaluate the behavior of several immune markers in 13 H1N1pdm2009 virus-infected pregnant (PH1N1) women, in comparison to pregnant women with an influenza-like illness (ILI), healthy pregnant women (HP) and healthy non-pregnant women (HW). The blood leukocyte phenotypes and the serological cytokine and chemokine concentrations of the blood leukocytes, as measured by flow cytometry, showed that the CD69+ cell counts in the T and B-lymphocytes were significantly higher in the PH1N1 group. We found that pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines and some chemokines (CXCL8, CXCL10), which are typically at lower levels during pregnancy, were substantially increased in the women in the ILI group. Our findings suggest that CD69 overexpression in blood lymphocytes and elevated levels of serum cytokines might be potential markers for the discrimination of H1N1 disease from other influenza-like illnesses in pregnant women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0107900PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177855PMC
June 2015

Safety of a dual potential prebiotic system from Mexican agave "Metlin® and Metlos®", incorporated to an infant formula for term newborn babies: a randomized controlled trial.

Rev Invest Clin 2013 Nov-Dec;65(6):483-90

Rationale: Infant formulae are being supplemented with probiotics, prebiotics, or symbiotic despite uncertainties regarding their efficacy. Mexican agave is an interesting source of fructans with particular features and with potential prebiotic effects.

Material And Methods: RCT in 600 healthy term babies (20 ± 7 days), allocated to receive standard infant formula (control) or infant formula added with a dual prebiotic system "Metlin® and Metlos®", from Mexican agave. Primary outcomes include stools frequency, stools consistency, gastrointestinal intolerance (frequency of abdominal distension, flatulency, regurgitations, vomiting). Secondary outcomes include changes on weight and height along the study and frequency of dermatologic problems (eczema).

Results: In 66,120 days of total follow-up, there were no differences on the frequency of stools passage (Human Milk: 3.8 ± 2.4 evacuations per day; Pro + Metlin + Metlos 3.6 ± 2.0; Pro + Metlin 3.6 ± 2; only Pro 3.4 ± 2.3¸ only formula 3.4 ± 2.0; p NS). Consistency of stools was similar between human milk and prebiotics supplemented groups. Also the frequency of gastrointestinal symptoms was significantly low between these groups.

Conclusions: Fructans derivate from agave and added to infant formula are safe and well tolerated by Mexican healthy term babies.
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May 2014

Diarrhea in preschool children and Lactobacillus reuteri: a randomized controlled trial.

Pediatrics 2014 Apr 17;133(4):e904-9. Epub 2014 Mar 17.

National Perinatology Institute, Mexico City, Mexico.

Objectives: To evaluate whether daily administration of Lactobacillus reuteri DSM 17938 reduces the frequency and duration of diarrheal episodes and other health outcomes in day school children in Mexico.

Methods: Healthy children (born at term, aged 6-36 months) attending day care centers were enrolled in this randomized, double-blind, placebo-controlled trial. They received L reuteri DSM 17938 (dose 10(8) colony-forming unit; n = 168) or identical placebo (n = 168) by mouth, daily for 3 months, after which they were followed-up after a further 3 months without supplementation.

Results: Data from all children were included in the final analysis. L reuteri DSM 17938 significantly reduced the frequency and duration of episodes of diarrhea and respiratory tract infection at both 3 and 6 months (P < .05). Additionally, the number of doctor visits, antibiotic use, absenteeism from day school and parental absenteeism from work were significantly reduced in the L reuteri group (P < .05). A cost-benefit analysis revealed significant reductions in costs in the L reuteri-treated children. No adverse events related to the study product were reported.

Conclusions: In healthy children attending day care centers, daily administration of L reuteri DSM 17938 had a significant effect in reducing episodes and duration of diarrhea and respiratory tract infection, with consequent cost savings for the community.
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http://dx.doi.org/10.1542/peds.2013-0652DOI Listing
April 2014

Transplacental transmission of cutaneous Leishmania mexicana strain in BALB/c mice.

Am J Trop Med Hyg 2013 Aug 24;89(2):354-8. Epub 2013 Jun 24.

Departamento de Infectologia e Inmunologia Perinatal, Instituto Nacional de Perinatologia, Mexico City, Mexico.

The vertical transmission of leishmaniasis has been reported in species that cause visceral leishmaniasis. However, this condition has scarcely been documented in species that cause cutaneous leishmaniasis. The aim of this study was to determine experimentally whether L. mexicana is transmitted vertically. A control group of BALB/c mice and a group infected with L. mexicana were mated, the gestation was monitored, and females were killed before delivery. Four resorptions (P = 0.023) and eight fetal deaths (P = 0.010) were observed in the infected female group; furthermore, the offspring body weight of the infected group was lower than the body weight of the healthy group (P = 0.009). DNA amplification by polymerase chain reaction (PCR) revealed that all placentas and maternal spleens as well as 39 of 110 fetal spleens obtained from the offspring of infected mothers tested positive for Leishmania. In conclusion, L. mexicana is transmitted transplacentally and causes fetal death, resorption, and reduction in offspring body weight.
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http://dx.doi.org/10.4269/ajtmh.12-0716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741259PMC
August 2013

Interleukin-1 receptor antagonist gene polymorphism increases susceptibility to septic shock in children with acute lymphoblastic leukemia.

Pediatr Infect Dis J 2013 Feb;32(2):136-9

Division of Pediatric Oncology, Hospital Infantil de Mexico Federico Gomez, Mexico City, Mexico.

Background: Interleukin-1 receptor antagonist polymorphism (ILRN) 2 (ILRN*2) has been associated with a poor outcome in septic patients because of an elevated production of anti-inflammatory cytokines. In >70% of patients, morbidity and mortality in childhood acute lymphoblastic leukemia is caused by infections. The aim of this study was to determine the association between this polymorphism and the frequency of septic shock from the time of diagnosis until completion of treatment.

Methods: This cohort study was conducted in 57 consecutive children with acute lymphoblastic leukemia. At the end of follow-up, children were stratified according to their IL1RN polymorphism (ILRN*1/ILRN*2), evaluating the impact of genotype on the severity of febrile neutropenic events during their treatment.

Results: Overall survival was 80% at 55 months after treatment. The average number of febrile neutropenic events in this cohort was 2.82 per patient. Genotype distribution was 50.9% for homozygote IL-1RN*1, 38.6% for heterozygote ILRN*1/ILRN*2 and 10.5% for homozygote IL-1RN*2. The risk of presenting septic shock for homozygote IL1RN*2/IL1RN*2 and heterozygote ILRN*1/ILRN*2 patients was significantly greater (odds ratio, 45; P = 0.001) adjusted for age, gender, risk of leukemia and presence of pathogenic bacteria. Genotype IL-1RN*2 is associated with the risk of development of septic shock in children with acute lymphoblastic leukemia. Further research in larger population-based studies is needed to replicate these findings.

Conclusions: This information would allow us to identify more predictive factors in this group of acute lymphoblastic leukemia patients in whom this information is lacking to establish an earlier and more aggressive approach.
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http://dx.doi.org/10.1097/INF.0b013e31827566ddDOI Listing
February 2013

Evaluation of conventional Doppler fetal cardiac function parameters: E/A ratios, outflow tracts, and myocardial performance index.

Fetal Diagn Ther 2012 1;32(1-2):22-9. Epub 2012 Jun 1.

Direction of Clinical Research, National Institute of Perinatology, Mexico City, Mexico.

Structural evaluation of the fetal heart is well established. Functional evaluation using pulsed-wave Doppler may also be performed. E/A ratios express the relationship between the maximal velocities of the E and A waveforms of ventricular filling. In normal fetuses, E/A ratios are usually <1 but show a constant increment during gestation, mainly related to the increment of the E wave. In intrauterine growth restriction (IUGR) fetuses, E/A ratios are lower compared to values in normally grown fetuses at the same gestational age. Cardiac outflows provide information on the time-velocity integral that, combined with the vessel area, allows calculation of the left and right cardiac outputs. In normal fetuses there is a predominance of the right ventricle (55-60%) in contributing to the combined cardiac output. In IUGR fetuses this predominance shifts to the left ventricle in order to increase the flow to the upper part of the fetal body and brain. The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function. The MPI is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome.
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http://dx.doi.org/10.1159/000330792DOI Listing
January 2013

Effect of ambient temperature on the clinical manifestations of experimental diffuse cutaneous leishmaniasis in a rodent model.

Vector Borne Zoonotic Dis 2012 Oct 31;12(10):851-60. Epub 2012 May 31.

Centro de Investigación, División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco, México.

Dermal species of Leishmania have a relatively broad temperature range for optimal growth in vitro, with temperature differences accompanied by a form change. This suggests that when the host is living in moderate temperatures (22°C), infection may proceed at temperatures lower than those that occur in tropical regions (32°C), and a different clinical expression of the disease due to a different parasitic form may result. The aim of this study was to investigate the effect of environmental temperature on the clinical expression of the disease. BALB/C mice infected with Leishmania mexicana were housed at 32°±2°C or 22°±1°C, and assessed for the development of inflammation and the presence of parasites in organs using PCR and immunohistology. The clinical expression of leishmaniasis at 32°C included inflammation at the site of inoculation with swelling of the nose and tail, whereas at 22°C, up to 50% of the infected mice developed dry exfoliative dermatitis with alopecia on the dorsum. In both cases, parasite colonization was confirmed in the skin, with parasites at more external locations at 22°C. Parasite visceralization was confirmed in all internal organs and glands in both cases based on PCR and immunohistology. In conclusion, the clinical expression of diffuse leishmaniasis by Leishmania mexicana in laboratory mice is modified by temperature, from nodular inflammation at 32°C, to dry exfoliative dermatitis and alopecia at 22°C, with parasite visceralization in both cases.
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http://dx.doi.org/10.1089/vbz.2011.0844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466070PMC
October 2012

Tumor necrosis factor -308 and lymphotoxin +252 polymorphisms in Mexican children with Kawasaki disease and coronary aneurysms.

Arch Med Res 2011 Oct 17;42(7):602-7. Epub 2011 Nov 17.

Servicio de Medicina Interna Pediátrica, UMAE Hospital General, Mexico City, Mexico.

Background And Aims: The Mexican population has a distinct capacity for the expression of tumor necrosis factor (TNF), a cytokine that plays a cardinal role in Kawasaki disease (KD), particularly in those who develop coronary aneurysms. It is important to identify, in Mexican pediatric patients, the association of the frequency of TNF. This study determined the association of TNF -308 and lymphotoxin-alpha (LTA) +252 polymorphisms in Mexican pediatric patients with KD and coronary aneurysms (CA).

Methods: We conducted a cross-sectional, analytical study in 48 children with KD, 22 with CA. Control samples were obtained from 61 aged-matched children. We took a peripheral blood sample and extracted genomic DNA from all children participating in the study. Using restriction factor length polymorphism-polymerase chain reaction (RFLP-PCR), we performed determination of TNF -308 and LTA +252.

Results: There was no difference in frequency between the study groups for genotype LTA +252 (OR 0.37, 95% CI, 0.06-2, p = 0.44) or between groups for KD with or without coronary aneurysms for both polymorphisms. In subjects with KD, we did not observe the heterozygous genotype of TNF -308, the difference being significant (OR 12, 95% CI, 4.8-30.4, p = 0.0001) using the χ(2) test with the continuity correction on comparison with the control group.

Conclusions: Comparative analysis by group did not show a significant difference in the frequency of the alleles and genotypes between KD with CA vs. KD without CA vs. controls, for both TNF -308 and LTA +252.
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http://dx.doi.org/10.1016/j.arcmed.2011.11.002DOI Listing
October 2011

Urban PM2.5 induces ROS generation and RBC damage in COPD patients.

Front Biosci (Elite Ed) 2011 Jun 1;3:808-17. Epub 2011 Jun 1.

Departamento de Bioquimica y Biologia Molecular, Instituto Nacional de Perinatologia, Isidro Espinosa de los Reyes (INPerIER), Mexico.

Particulate matters (PM) produce adverse effects on the respiratory system and cause COPD. These effects are thought to involve intrinsic generation of ROS which are present in ambient PM (transition metals and aromatic organic compounds). Here, we examined the chemical composition and ultra-microscopic structure of PM2.5. The effect of this PM was studied in red blood cell (RBC) membranes (ghosts) from healthy volunteers (n = 11) and COPD patients (n = 43). These effects were compared with that produced by a Fenton metal-catalytic ROS generator. Oxidative biomarkers and cell damage were singificantly increased in presence of PM2.5 or ROS generator in RBC of COPD patients as compared with those in cells from healthy volunteers. In contrast, total SH groups, band 3 phospho-tyrosine phosphatase (PTPase) and glucose-6 phosphate dehydrogenase (G6PD) activities were all diminished in cells from COPD patients. In conclusion, PM2.5 increases damage to RBCs from COPD patients, decreases the activity of PTPase and G6PD, and alters the function of the anionic exchanger (AE1) and the antioxidant response by decreasing SH groups.
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http://dx.doi.org/10.2741/e288DOI Listing
June 2011

[Laser ablation of the placental vascular anastomoses for the treatment of twin-to-twin transfusion syndrome].

Rev Invest Clin 2011 Jan-Feb;63(1):46-52

Subdirección de Investigación Clínica, Institute Nacional de Perinatología Isidro Espinosa de los Reyes, México, DF.

Aim: To report the experience of the intrauterine treatment of monochorionic biamnotic (MC/BA) twin pregnancies complicated with twin-to-twin transfusion syndrome (TTTS) applying laser ablation of the placental vascular anastomoses (LAPVA).

Material And Methods: During 18 months period 35 MC/BA twin pregnancies were treated. TTTS was diagnosed based on the discrepancies in amniotic fluid and bladder size between both twins. Severity of TTTS was classified according to the hemodynamic changes in both twins. LAPVA was performed between 16-26 weeks of gestation using a rigid straight fetoscope and a YAG (neodymium: yttrium aluminium garnet) laser equipment. Survival was considered when the neonate was home discharged.

Results: Overall survival was 62.8% (44/70 fetuses). In 77% of pregnancies (27/35) at least one twin survived, and in 48.5% (17/35) of cases both twins survived. Bleed was the most frequent complication (12/35; 34%). In 5 cases there was severe bleeding leading to late premature rupture of membranes and death of both twins. Median time stay in the neonatal intensive care unit was 20 days (range, 7-120). There were no signs of brain damage at the time of discharge.

Conclusion: These results are similar to those already published. Bleeding was the most frequent complication, however as the experience improved it was less frequent. Overall success is highly associated with a good neonatal care support.
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June 2011

[Institutional strengthening and updating of the National Academy of Medicine of Mexico (results and instrumentalization 2010-2012)].

Gac Med Mex 2011 Jan-Feb;147(1):51-62

Mesa Directiva de la Academia Nacional de Medicina 2009-2010, México D.F.

In order to strengthen the academic and social management of the National Academy of Medicine of Mexico, from the draft paper presented to run for Vice President of the corporation, in 2007 I proposed to the plenary of the institution to develop a planning exercise strategy, in fact supporting the achievement of that objective. The idea behind the proposal, which was supported by most scholars, started from the consideration that although the Academy has always been an area of excellence for the advancement of medicine in the country, it was now necessary to strengthen, modernize and give a new direction to its work, on the basis of an exercise analysis and background checks, work, commitment and vision, under a inclusive, plural and agreed strategy with the academic body of the corporation, i.e. through a designed planning exercise. The result of this surely positive effort is presented in the following pages. To this end, part of the initial project description illustrates the process of technical and methodological development, the lines of action considered as priorities by academics, and details involving its realization. This planning strategy project yielded three specific conclusions: (i) the necessity for a functional reorganization proposal of the Academy's structure; (ii) the need for a self-sustainability financial project to fortify the economic capacity of the Academy; and (iii) the need for an updated project on technological communication of the Academy.
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June 2011

Activity of hydroxyurea against Leishmania mexicana.

Antimicrob Agents Chemother 2008 Oct 11;52(10):3642-7. Epub 2008 Aug 11.

Departamento de Posgrado, Escuela Superior de Medicina, Instituto Politecnico Nacional, Mexico City, Mexico.

Leishmania mexicana is a protozoan parasite that causes a disease in humans with frequent relapses after treatment. It is also highly resistant to the currently available drugs. For this reason, there is an urgent need for more effective antileishmanial drugs. Hydroxyurea, an anticancer drug, is toxic to replicating eukaryotic cells and has been proven to be effective in arresting the Leishmania major cell cycle. In this study, hydroxyurea was tested in an in vitro model of intracellular Leishmania infection in macrophages. The parasite density in infected macrophages was measured by microscopy after incubation for various times and treatment with hydroxyurea at different concentrations. Viable parasites that could be transformed into promastigotes by shifting the temperature to 26 degrees C were counted every other day after the replacement of hydroxyurea with fresh medium. Meglumine antimoniate, the standard drug treatment for Leishmania mexicana, was used as a reference drug under the same experimental conditions. Hydroxyurea completely eliminated Leishmania parasites when it was used at a dosage of 10 or 100 microg/ml. Differences in the length of treatment needed to achieve elimination were as follows: the 10-microg/ml doses required 9 days, while 3 days was sufficient when 100 microg/ml was used. Hydroxyurea had a 50% effective dose of 0.015 microg/ml in vitro, which was observed on day 6 after exposure. Hydroxyurea is highly effective in killing intracellular amastigotes in vitro.
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http://dx.doi.org/10.1128/AAC.00124-08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2565871PMC
October 2008

Linezolid diminishes inflammatory cytokine production from human peripheral blood mononuclear cells.

Arch Med Res 2006 Jan;37(1):31-5

Departamento de Inmunoquímica y Biología Celular, Hospital Infantil de México, Federico Gómez, México, D.F., México.

Background: Active peptides produced by monocytes, in response to endotoxin, initiate and maintain the acute phase of inflammatory response. Some antibiotics have been reported to have immunomodulatory effects in addition to their antimicrobial activity. We examined the effect of linezolid on cytokine synthesis.

Methods: The modulatory effects of erythromycin and linezolid were evaluated in LPS-stimulated human peripheral blood mononuclear cells (PBMCs). Blood was obtained by venipuncture from healthy donor volunteers. PBMCs were separated by Ficoll-Paque. More than 90% of the cells were monocytes as determined by esterase staining. Cells were incubated in the presence of LPS, with or without various concentrations of erythromycin and linezolid. The concentration of each cytokine was determined by ELISA with commercially available reagents.

Results: The two drugs suppressed significantly the synthesis of the cytokines tested in a concentration-dependent manner.

Conclusions: These data indicate that antibacterial agents may modify acute phase inflammatory response through their effects on cytokines synthesis by monocytes.
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http://dx.doi.org/10.1016/j.arcmed.2005.05.022DOI Listing
January 2006