Preterm Neonates with Respiratory Distress Syndrome: Ventilator-Induced Lung Injury and Oxidative Stress.

Ventilator-induced lung injury is well recognized, and appropriate arterial saturation target is unknown, so gentle modes of ventilation and minimizing oxidative stress have been well studied. Our objective was to analyze any association between the oxygen levels at blood sampling and plasma levels of the interleukins IL-6, IL-1ß, IL-10, and IL-8 and TNF-α in preterm newborns under mechanical ventilation (MV) in their first two days. Methods. Prospective cohort including neonates with severe respiratory distress. Blood samples were collected right before and 2 hours after invasive MV. For analysis purposes, newborns were separated according to oxygen requirement: low oxygen (≤30%) and high oxygen (>30%) groups. Interleukins were measured using a commercially available kit. Results. 20 neonates (gestational age 32.2 ± 3 weeks) were evaluated. Median O2 saturation levels pre-MV were not different in both oxygen groups. In the high oxygen group, IL-6, IL-8, and TNF-α plasma levels increased significantly after two hours under MV. Conclusions. Despite the small sample studied, data showed that there is a relationship between VILI, proinflammatory cytokines, and oxygen-induced lung injury, but a study considering oxidative marker measurements is needed. It seems that less oxygen may keep safer saturation targets playing a less harmful role.

Investigation of newborns with abnormal results in a newborn screening program for four lysosomal storage diseases in Brazil.

Lysosomal storage diseases (LSDs) are genetic disorders, clinically heterogeneous, mainly caused by defects in genes encoding lysosomal enzymes that degrade macromolecules. Several LSDs already have specific therapies that may improve clinical outcomes, especially if introduced early in life. With this aim, screening methods have been established and newborn screening (NBS) for some LSDs has been developed. Such programs should include additional procedures for the confirmation (or not) of the cases that had an abnormal result in the initial screening. We present here the methods and results of the additional investigation performed in four babies with positive initial screening results in a program of NBS for LSDs performed by a private laboratory in over 10,000 newborns in Brazil. The suspicion in these cases was of Mucopolysaccharidosis I - MPS I (in two babies), Pompe disease and Gaucher disease (one baby each). One case of pseudodeficiency for MPS I, 1 carrier for MPS I, 1 case of pseudodeficiency for Pompe disease and 1 carrier for Gaucher disease were identified. This report illustrates the challenges that may be encountered by NBS programs for LSDs, and the need of a comprehensive protocol for the rapid and precise investigation of the babies who have an abnormal screening result.

Osteopontin: a potential biomarker of Gaucher disease.

Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and the disorder that has the greatest immune system involvement. Pathologic lipid accumulation in macrophages accounts for a small amount of the additional tissue mass in the liver and spleen. The additional increase may be related to an inflammatory response because Gaucher cells secrete inflammatory mediators. Osteopontin (OPN) is a protein identified in cancer cells and in bone cells that is produced by several types of immune cells including T-cells and macrophages. We report here elevated OPN levels in the plasma of type 1 GD patients and its sensitive response to enzyme replacement therapy. The mean OPN value of GD patients receiving ERT was similar to the values of controls and patients with other lysosomal disorders. When comparing untreated and treated GD patients, the p value was <0.001. In GD, OPN appears to be more sensitive to ERT than chitotriosidase and can be used during the follow-up of patients who are chitotriosidase deficient. Additional extended studies are required to relate variations in the OPN levels to clinical findings and response to therapy in GD patients.

Plasma cytokine levels fall in preterm newborn infants on nasal CPAP with early respiratory distress.

INTRODUCTION: Early nCPAP seems to prevent ventilator-induced lung injury in humans, although the pathophysiological mechanisms underlying this beneficial effect have not been clarified yet. OBJECTIVE: To evaluate plasma levels IL-1ß, IL-6, IL-8, IL-10, and TNF-α immediately before the start of nCPAP and 2 hours later in preterm infants. METHODS: Prospective cohort including preterm infants with 28 to 35 weeks gestational age with moderate respiratory distress requiring nCPAP. Extreme preemies, newborns with malformations, congenital infections, sepsis, surfactant treatment, and receiving ventilatory support in the delivery room were excluded. Blood samples were collected right before and 2 hours after the start of nCPAP. RESULTS: 23 preterm infants (birth weight 1851±403 grams; GA 32.3±1.7 weeks) were treated with nCPAP. IL-1ß, IL-10, TNF-α levels were similar, IL-8 levels were reduced in 18/23 preterm infants and a significant decrease in IL-6 levels was observed after 2 hours of nCPAP. All newborns whose mothers received antenatal steroids had lower cytokine levels at the onset of nCPAP than those whose mothers didn't receive it; this effect was not sustained after 2 hours of nCPAP. CONCLUSION: Early use nCPAP is not associated with rising of plasma pro-inflammatory cytokines and it seems to be a less harmful respiratory strategy for preterm with moderate respiratory distress.

Brain-derived neurotrophic factor expression increases after enzyme replacement therapy in Gaucher disease.

Mutations in the GBA gene are related to an increased risk of developing neurodegenerative diseases. The exact molecular mechanisms involved in the interaction between GBA and α-synuclein, a protein that has been associated with several neurological diseases, remain unsolved. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is important for the normal development of the peripheral and central nervous system, and it plays a key role in neuronal survival and synaptic plasticity in the adult brain. A reduction in BDNF expression has been reported in patients with Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies. We analyzed BDNF levels in the plasma of Gaucher Disease (GD) patients who were not being treated with enzyme replacement therapy (ERT) and then subsequently following ERT; we compared the levels to those of healthy controls. We demonstrated that BDNF levels were remarkably diminished in GD patients who were under no specific treatment and these levels increased following ERT. This is the first study that demonstrates a variation in the plasma levels of a neurotrophic factor in GD type 1 patients. Further studies are required to correlate BDNF level variations with the clinical findings and the response to therapy in GD patients. Low levels of BDNF are associated with neurodegenerative diseases; therefore, BDNF could provide a new therapeutic target for GD patients with neurological symptoms.

Association of adipokines and adhesion molecules with indicators of obesity in women undergoing mammography screening.

BACKGROUND: The soluble cell adhesion molecules and adipokines are elevated in patients with obesity, hypertension, type 2 diabetes mellitus, breast cancer and atherosclerosis. OBJECTIVE: To investigate the relationship between anthropometric profile, dietary intake, lipid profile and fasting glycemia with serum levels of adipokines (adiponectin and PAI-1) and adhesion molecules (ICAM-1 and VCAM-1) in women without breast cancer undergoing routine mammographic screening. DESIGN: Transversal study. SUBJECTS: One hundred and forty-five women over 40-years old participated in this study. RESULTS: In 39.3% of cases the BMI was above 30 kg/m2; 46.9% had hypertension, 14.5% had type 2 Diabetes Mellitus, 31.7% had dyslipidemia and 88.3% presented a waist-to-hip ratio ≥ 0.8. A linear correlation was found between serum levels of PAI-1 and triglycerides, between serum levels of PAI-1 and WHR and between serum levels of VCAM-1 and BMI. CONCLUSION: We found a high prevalence of obesity and metabolic syndrome. PAI-1 and VCAM-1 levels were correlated with clinical indicators of obesity and overweight.

Estimativa da distribuição regional da toxoplasmose congênita no Brasil a partir dos resultados de triagem neonatal / Estimation of the regional distribution of congenital toxoplasmosisin Brazil from the results of neonatal screening

Aims: To determine the prevalence of congenital toxoplasmosis in Brazil from samples of dried blood on filter paper from neonates attended by a private program of neonatal screening. Methods: Blood samples collected from neonates by puncturing the heel and dried on filter paper, received from all Brazilian states from September 1995 to July 2009, were tested for Toxoplasma gondii-specific IgM antibodies. For each positive screening test, confirmatory tests were performed in sera of mothers and newborns, obtained by venipuncture. The infants were monitored and classified as infected according to one of the following criteria: presence of Toxoplasma gondii-specific IgM and IgG in the newborn and the mother; Toxoplasma gondii-specific IgM and IgG in the newborn only; Toxoplasma gondii-specific IgM and IgG in the mother only; or increasing amount of Toxoplasma gondii-specific IgG in the infant. Results: A total of 800,164 blood samples were tested. The overall prevalence of congenital toxoplasmosis was found to be 1/1,613 (6/10,000) in the country, ranging from 1/5,447 to 1/495 (2/10,000 to 20/10,000) in different states. Conclusions: Neonatal screening on a large scale is an important tool for determining the prevalence of congenital toxoplasmosis. The high prevalence of the infection in Brazil and the wide variability of its epidemiology among the states support the need to develop policies on health and education to prevent and control congenital toxoplasmosis across the country, respecting the peculiarities of each state.

Objetivo: estimar a prevalência da toxoplasmose congênita Brasil por meio de amostras de sangue seco em papel filtro, obtidas de neonatos atendidos por um programa privado de triagem neonatal. Métodos: amostras de sangue coletadas de neonatos por punção de calcâneo e absorvidas em papel filtro, recebidas de todos os estados brasileiros entre setembro de 1995 e julho de 2009, foram testadas para anticorpos IgM anti-Toxoplasma gondii. Para cada teste positivo na triagem, foram realizados exames confirmatórios em soros das mães e dos neonatos, obtidos por punção venosa periférica. Os casos foram considerados confirmados de acordo com um dos seguintes critérios: presença de IgM e IgG anti-Toxoplasma gondii no neonato e na mãe; IgM e IgG anti-Toxoplasma gondii somente no neonato; IgM e IgG anti-Toxoplasma gondii somente na mãe; ou aumento progressivo dos anticorpos IgG anti-Toxoplasma gondii no lactente. Resultados: foram testadas 800.164 amostras. Observou-se uma prevalência geral de toxoplasmose congênita no país de 1/1.613, variando de 1/1.547 a 1/495 (2/10.000 to 20/10.000) em diferentes estados. Conclusões: a triagem neonatal em larga escala é uma ferramenta importante para a determinação da prevalência da toxoplasmose congênita. A alta prevalência dessa infecção no Brasil e a ampla variabilidade de sua epidemiologia entre os estados confirmam a necessidade de políticas de saúde e educação voltadas à prevenção e ao controle da toxoplasmose congênita em todo o país, respeitando as peculiaridades de cada estado.

Recovery of anti-Toxoplasma gondii immunoglobulin M in stored guthrie card blood spots.

Retrospective testing of neonatal Guthrie card blood spots for specific immunoglobulin M (IgM) can distinguish congenital toxoplasmosis from acquired toxoplasmosis. We determined whether storage temperature reduced IgM detection, using filter paper blood samples "spiked" with anti-Toxoplasma IgM. After 300 days, IgM detection deteriorated with storage at room temperature but not at temperatures of 4 degrees C or lower.

Newborn screening for congenital infectious diseases.

To estimate the prevalence of congenital toxoplasmosis, Chagas disease, cytomegalovirus, and rubella, blood samples on dried blood spot (DBS) from neonates (day 3-20 of life) were screened for immunoglobulin (Ig) M against Toxoplasma gondii, cytomegalovirus, rubella virus, and IgG against Trypanosoma cruzi by methods used for serum and adapted for use with DBS. Positive samples were further analyzed for IgM and IgG in serum from neonates and mothers. DBS samples from 364,130 neonates were tested for Toxoplasma gondii-specific IgM, and 15,873 neonates were also tested for IgM against cytomegalovirus and rubella virus and for Trypanosoma cruzi-specific IgG. A total of 195 were diagnosed with congenital toxoplasmosis, 16 with cytomegalovirus, and 11 with congenital rubella. One newborn had a confirmed result for Chagas disease, and 21 mothers had positive serum antibodies. These results suggest that infectious diseases should be considered for future inclusion in programs for newborn screening of metabolic diseases in disease-endemic areas.

[Neonatal screening for hemoglobinopathies: a pilot study in Porto Alegre, Rio Grande do Sul, Brazil]. / Triagem neonatal para hemoglobinopatias: um estudo piloto em Porto Alegre, Rio Grande do Sul, Brasil.

This study was conducted to establish the frequency of hemoglobinopathies among newborns undergoing screening tests for metabolic diseases at the University Hospital (Hospital de Clínicas) in Porto Alegre, Rio Grande do Sul, Brazil. Testing for abnormal hemoglobins was performed by isoelectric focusing electrophoresis on agarose gel with blood obtained by heel stick and applied to filter paper. For confirmatory testing of abnormal neonatal screening, a venopuncture blood sample was obtained from the infant and parents and then submitted to hemoglobin electrophoresis on cellulose acetate at pH 8.6 and citrate agar at pH 6.2. A total of 1,615 subjects were studied: 20 samples showed the Hb S pattern and six samples showed Hb C. Thus, frequency of the sickle cell gene was 1.2% and that of the Hb C gene was 0.4%, regardless of race or origin. These data suggest that the inclusion of universal neonatal screening for hemoglobinopathies in the ongoing projects for the detection of phenylketonuria and congenital hypothyroidism has many advantages and should be considered in health programs.