Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

Accumulation of a soluble form of human nectin-2 is required for exerting the resistance against herpes simplex virus type 2 infection in transfected cells.

Cell entry of herpes simplex virus type 2 (HSV-2) requires the interaction of viral glycoprotein D (gD) with the receptor nectin-1 and herpesvirus entry mediator (HVEM). In addition, it is known that nectin-2 is also functional as a receptor for HSV-2, although the binding to the gD is weak. To examine an antiviral potential of a soluble form of human nectin-2 (hNectin-2Ig), transfected Vero cells expressing the entire ectodomain of nectin-2 fused to the Fc portion of human IgG were established. Specific binding of hNectin-2Ig to HSV-2 gD was confirmed by ELISA. Competitive ELISA demonstrated that accumulation of hNectin-2Ig in transfected cells increased significantly in a cell culture time dependent manner. Viral growth of several HSV-2 strains was significantly inhibited in the transfected cells that were cultured for 72 hr compared with control Vero cells, but not in cells that were cultured for 24 hr. These results indicate that accumulation of a soluble form of nectin-2 is required for exerting the resistance against HSV-2 infection.

Aflatoxins ingestion and canine mammary tumors: There is an association?

The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60).

Immunophenotypic profile and increased risk of hospital admission for infection in infants born to female kidney transplant recipients.

Children born to female kidney recipients are exposed to immunosuppressive drugs during gestation. Little is known about their immune system at birth or in the long term. Twenty-eight children born to female kidney recipients and 40 full-term children born to healthy mothers were evaluated. T, B, NK, NKT, γδT cells were assessed by flow cytometry and functional evaluation of T and dendritic cells after in vitro activation was performed at birth and at 8 months of age. At birth, infants born to female kidney recipients showed lower numbers of CD4+ T, NKT and intense reduction of B cells (median cells/mm(3) , transplant: 153.7 X control: 512.4; p < 0.001). There was also a reduced percentage of activated CD8+ T and of CD4+ regulatory T cells. Activated memory and exhausted memory B cells showed higher percentages among children exposed to immunosuppressors when compared to control group. At 8 months, most immune alterations were no longer observed, but four children still had low numbers of some lymphocyte subsets at this age. Children born to female kidney recipients had 4.351 (95% CI: 1.026-15.225; p = 0.046) higher risk of hospital admission in the first months of life-some, with severe clinical manifestations-than those born to healthy women.

A radiologia odontológica e o meio ambiente / The dental radiology and the environment

O descarte irregular de resíduos de saúde, especialmente o odontológico, está se tornando um um grande motivo de preocupação. O lixo proveniente de rejeitos no processo radiográfico não é diferente, uma vez que, além de resíduo contaminado, há rejeitos químicos, metais pesados e plásticos. Sendo eles: invólucro do filme radiográfico, soluções processadoras, lâminas de chumbo, películas dos filmes radiográficos - todos eles capazes de causar grande impacto no meio ambiente, se descartados de forma incorreta. Por esse motivo, é imprescindível conscientizar os cirurgiões-dentistas do impacto prejudicial no meio ambiente e, consequentemente, na saúde da população, atentando para a correta forma de descarte de cada rejeito do processo radiográfico

The irregular disposal of health waste, especially dental care, is becoming a great concern. The waste tailings from the radiographic process is not different, since, apart from contaminated waste, there are chemical waste, heavy metals and plastics. Namely: casing radiographic film, processing solutions, blade lead, radiographic films - all they with large capacity to cause impact on the environment if disposed incorrectly. For this reason it is essential to educate dentists in the harmful impact on the environment and consequently on the health of people, paying attention to the correct way to dispose of each reject of the radiographic process

Acetyl-L-carnitine normalizes the impaired long-term potentiation and spine density in a rat model of global ischemia.

As a consequence of an ischemic episode, energy production is disturbed, leading to neuronal cell death. Despite intensive research, the quest for promising neuroprotective drugs has largely failed, not only because of ineffectiveness, but also because of serious side-effects and dosing difficulties. Acetyl-l-carnitine (ALC) is an essential nutrient which plays a key role in energy metabolism by transporting fatty acids into mitochondria for ß-oxidation. It is an endogenous compound and can be used at high dose without toxicity in research into ischemia. Its neuroprotective properties have been reported in many studies, but its potential action on long-term potentiation (LTP) and dendritic spine density has not been described to date. The aim of the present study was an evaluation of the possible protective effect of ALC after ischemic insults inflicted on hippocampal synaptic plasticity in a 2-vessel occlusion (2VO) model in rats. For electrophysiological measurements, LTP was tested on hippocampal slices. The Golgi-Cox staining technique was used to determine spine density. 2VO resulted in a decreased, unstable LTP and a significant loss of dendritic spines. ALC administered after 2VO was not protective, but as pretreatment prior to 2VO it restored LTP nearly to the control level. This finding paralleled the histological analysis: ALC pretreatment resulted in the reappearance of dendritic spines on the CA1 pyramidal cells. Our data demonstrate that ALC administration can restore hippocampal function and spine density. ALC probably acts by enhancing the aerobic metabolic pathway, which is inhibited during and following ischemic attacks.

Obesity and aspirin intolerance are risk factors for difficult-to-treat asthma in Japanese non-atopic women.

BACKGROUND: Asthma is a clinical syndrome characterized by variabilities in disease expression and severity. The pathophysiological mechanism underlying anti-asthma treatment resistance is also assumed to be different between disease phenotypes. OBJECTIVE: To elucidate the effect of gender and atopic phenotype on the relationship between clinical factors and the risk of treatment resistance. METHODS: We compared outpatients with difficult-to-treat asthma (DTA; n = 486) in a tertiary hospital for allergic diseases in central Japan with those with controlled severe asthma (n = 621) with respect to clinical factors including body mass index (BMI) and aspirin intolerance using multivariate logistic regression analysis stratified by gender and atopic phenotype. RESULTS: When analysis was performed on the entire study populations, obesity (BMI ≥ 30 kg/m(2); adjusted odds ratio (OR) 1.92; 95% confidence interval (95% CI: 1.07-3.43) and aspirin intolerance (OR: 2.56, 95% CI: 1.44-4.57) were found to be the significant risk factors for DTA. However, after the stratification by gender and atopic phenotype, the association between obesity and DTA was significant only in women (OR: 2.76, 95% CI: 1.31-5.78), but not in men (OR: 1.03, 95% CI: 0.38-2.81), and only in non-atopics (OR: 4.03, 95% CI: 1.15-14.08), but not in atopics (OR: 1.54, 95% CI: 0.79-3.02). The similar gender and phenotypic differences were also observed in the association between aspirin intolerance and DTA: namely, the association was significant only in women (OR: 3.96, 95% CI: 1.84-8.50), but not in men (OR: 1.19, 95% CI: 0.46-3.05); and only in non-atopics (OR: 5.49, 95% CI: 1.98-15.19), but not in atopics (OR: 1.39, 95% CI: 0.65-2.98). CONCLUSIONS AND CLINICAL RELEVANCE: Significant associations of obesity and aspirin intolerance with DTA were observed only in women and in non-atopics. These findings suggest that a phenotype-specific approach is needed to treat patients with DTA.

Urinary concentrations of 15-epimer of lipoxin A(4) are lower in patients with aspirin-intolerant compared with aspirin-tolerant asthma.

BACKGROUND: Although an abnormality in arachidonic acid metabolism may be responsible for aspirin-intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A(4) (LXA(4)) and the 15-epimer of LXA(4) (15-epi-LXA(4)) in relation to asthma severity in AIA subjects. OBJECTIVE: The purpose of this study is to estimate urinary LXA(4) and the 15-epimer concentrations to investigate lipoxins in AIA. METHODS: In this study, we examined AIA, aspirin-tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non-severe asthma subgroups. Urinary LXA(4), 15-epi-LXA(4) and leukotriene E(4) (LTE(4) ) were quantified using enzyme immunoassay after separating these compounds using high-performance liquid chromatography. RESULTS: The urinary LXA(4) concentration was significantly lower than the 15-epi-LXA(4) concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA(4) (P < 0.01) and higher urinary LTE(4) concentrations (P < 0.05) than the ATA group. Comparison of 15-epi-LXA(4) concentrations between the severe asthmatic and non-severe asthmatic subjects in the AIA and ATA groups revealed that the decreased 15-epi-LXA(4) concentration may be related to aspirin intolerance, but not asthma severity. Receiver operator characteristic curves demonstrated that the concentration ratio of LTE(4) to 15-epi-LXA(4) was superior to 15-epi-LXA(4) concentration and LTE(4) concentration as a predictive factor for aspirin intolerance. CONCLUSIONS AND CLINICAL RELEVANCE: We have demonstrated for the first time that urinary 15-epi-LXA(4) concentration is significantly higher than LXA(4) concentration in both the AIA and ATA groups. 15-Epi-LXA(4) concentration was significantly lower in the AIA group with an increased urinary LTE(4) concentration than in the ATA group. An imbalance between proinflammatory cysteinyl-leukotrienes and anti-inflammatory 15-epi-LXA(4) may be involved in AIA pathogenesis.

Perulernaea gamitanae (Copepoda: Lernaeidae) parasitizing tambaqui (Colossoma macropomum) (Characidae) and the hybrids tambacu and tambatinga, cultured in northern Brazil / Perulernaea gamitanae (Copepoda: Lernaeidae) parasitando tambaqui (Colossoma macropomum) (Characidae) e seus híbridos tambacu e tambatinga cultivados no norte do Brasil

The infestation rate in Colossoma macropomum, hybrid tambacu (C. macropomum x Piaractus mesopotamicus) and hybrid tambatinga (C. macropomum x Piaractus brachypomum) with Perulernaea gamitanae Thatcher and Paredes, 1985 from two fish farms in Amapá State, Brazil was studied. Lernaeid parasites (n=2887) were collected mainly on the tongue and the mouth cavity and also on cartilage of gill arches and filaments. Inflammation and fibrous nodules were observed on the attachment sites of the parasites. The infestation rate varied according to the fish farm and host. The prevalence of P. gamitanae was of 100 percent in hosts from one fish farm and was lower in the other fish farm. Higher intensity of P. gamitanae occurred in hybrids tambacu and tambatinga, but despite the high prevalence its intensity was moderate. This is the first report on epidemiology of P. gamitanae in cultured fishes from Brazilian Amazonia, and the occurrence of this crustacean parasite in two new hosts, the hybrids tambacu and tambatinga.

Estudou-se as taxas de infestação pelo crustáceo Perulernaea gamitanae Thatcher & Paredes, 1985 em tambaqui (Colossoma macropomum) e seus híbridos tambacu (C. macropomum x Piaractus mesopotamicus) e tambatinga (C. macropomum x Piaractus brachypomum) de duas pisciculturas no estado do Amapá, Brasil. Os lerneídeos parasitos (n=2.887) foram coletados principalmente na língua e na boca das espécies estudadas. Os crustáceos foram encontrados também nos filamentos e cartilagem dos arcos branquiais. Nos locais parasitados foram observados inflamação e nódulos fibrosos. As taxas de infestações variaram entre espécies e entre pisciculturas. Na piscicultura um a prevalência de P. gamitanae foi 100 por cento, e na piscicultura dois, foi menor. A maior intensidade de infestação por P. gamitanae ocorreu nos híbridos tambacu e tambatinga. Apesar da elevada prevalência de P. gamitanae a intensidade de infestação foi moderada. Este é o primeiro relato sobre níveis epidemiológicos de P. gamitanae em peixes de cultivo da Amazônia brasileira, e amplia a ocorrência deste parasito crustáceo para dois novos hospedeiros, os híbridos tambacu e tambatinga.

Immunoassay based on monoclonal antibodies versus LC-MS: deoxynivalenol in wheat and flour in Southern Brazil.

An indirect competitive enzyme-linked immunosorbent assay (ELISA) method using a monoclonal antibody for deoxynivalenol (DON) detection in wheat and flour was standardised and validated (detection limit = 177.1 µg kg(-1)) and its performance was compared with LC-MS, quantification limit =140 µg kg(-1)). DON recovery ranged from 88.7% to 122.6% for wheat grain and from 70.6% to 139.3% for flour. Among the 38 wheat samples evaluated, DON was detected in 29 samples (76.3%) by ic-ELISA (281.6-12 291.4 µg kg(-1)) and in 22 samples (57.9%) by LC-MS (155.3-9906.9 µg kg(-1)). The 0.93 correlation coefficient between ic-ELISA and LC-MS data in 19 positive DON wheat samples demonstrated the reliability and efficiency of ic-ELISA. Results indicated that standardised ic-ELISA was suitable for DON screening in wheat samples and the need for continuous monitoring of mycotoxin levels in foodstuffs.

Vaccine antibodies and T- and B-cell interaction in juvenile systemic lupus erythematosus.

Both systemic lupus erythematosus (SLE) and its treatment can cause immunosuppression and a decreased response to vaccination. We evaluated 30 children and adolescents with SLE, and 14 age-matched healthy subjects (control group) regarding immunophenotyping and lymphocyte apoptosis by flow cytometry, while measles and tetanus antibodies were measured by enzyme-linked immunosorbent assay (ELISA). The SLE group was divided according to disease activity into inactive SLE and active SLE. Individuals with active SLE had lower CD4+ T and natural killer (NK) cells/mm(3) than the control group. Active and inactive SLE individuals had more CD38 molecules/CD8+ T cells and more CD4+ T, CD8+ T and B cells in apoptosis (as assessed by caspase-3 expression) than the control group. Patients with active SLE had a diminished CD28 expression on both CD4+ T and on CD8+ T cells and a higher CD86 expression on B cells than the control group. Measles antibody levels in the SLE groups were similar to the control group. In contrast, tetanus antibody levels were lower in the SLE groups than in the control group. The latter also directly correlated with the CD4+ T-cell and NK-cell counts from SLE patients (regression coefficient, 2.686 and 1.782; p = 0.010 and p = 0.039, respectively). We concluded that despite being up-to-date for tetanus vaccine, SLE patients presented with a poor immune response to tetanus vaccine.

The use of frequency scale for the symptoms of GERD in assessment of gastro-oesophageal reflex symptoms in asthma

In adult asthmatics the incidence of gastro-oesophageal reflux disease (GERD) reportedly ranges from 34% to 89%. Oesophageal pH monitoring and endoscopy are not required in the patient with typical GERD symptoms before the initiation of a therapeutic trial. Diagnosis of GERD on the basis of history is the simplest and quickest method, placing no demand on patients. Recently, a new questionnaire (FSSG; Frequency Scale for the Symptoms of GERD) was produced to evaluate the severity and the therapeutic response of GERD. The FSSG (F-scale) was used to assess the GERD in subjects with persistent moderate to severe asthma treated with anti-inflammatory asthma medication. In the present study, 27.4% of the patients with asthma had symptoms suggestive of GERD. There is significant correlation between GERD symptom (F-scale score) and severity of cough and sputum. The observations suggested that reflux symptoms, not gastric dysmotility symptoms, significantly associated with severity of cough, not of sputum. It is the first such study to use a FSSG as incidence of GERD symptoms in asthmatics and examine the relationship between F-scale score and asthmatic symptoms

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The use of frequency scale for the symptoms of GERD in assessment of gastro-oesophageal reflex symptoms in asthma.

In adult asthmatics the incidence of gastro-oesophageal reflux disease (GERD) reportedly ranges from 34% to 89%. Oesophageal pH monitoring and endoscopy are not required in the patient with typical GERD symptoms before the initiation of a therapeutic trial. Diagnosis of GERD on the basis of history is the simplest and quickest method, placing no demand on patients. Recently, a new questionnaire (FSSG; Frequency Scale for the Symptoms of GERD) was produced to evaluate the severity and the therapeutic response of GERD. The FSSG (F-scale) was used to assess the GERD in subjects with persistent moderate to severe asthma treated with anti-inflammatory asthma medication. In the present study, 27.4% of the patients with asthma had symptoms suggestive of GERD. There is significant correlation between GERD symptom (F-scale score) and severity of cough and sputum. The observations suggested that reflux symptoms, not gastric dysmotility symptoms, significantly associated with severity of cough, not of sputum. It is the first such study to use a FSSG as incidence of GERD symptoms in asthmatics and examine the relationship between F-scale score and asthmatic symptoms.

Concentration of 14,15-leukotriene C4 (eoxin C4) in bronchoalveolar lavage fluid.

BACKGROUND: There has been no information about the concentration of 14,15-leukotriene C4, which is generated by 15- and 12-lipoxygenase and has been recently named eoxin C4, in biological fluids. OBJECTIVE: To determine the clinical concentrations of eoxin C4 in various respiratory inflammatory diseases, we quantified eoxin C4 in relation to the concentrations of cysteinyl-leukotrienes (CysLTs) and 15-hydroxyeicosatetraenoic acid (15-HETE) in bronchoalveolar lavage fluid (BALF). METHODS: BALF fluid was obtained from patients with a number of inflammatory lung diseases. Eoxin C4 and CysLTs were quantified by enzyme immunoassay in combination with high-performance liquid chromatography. Eoxin C4 immunoassay does not detect eoxin D4 or eoxin E4. 15-HETE was quantified by gas chromatography-mass spectrometry using (18)O-labeled compounds as an internal standard. RESULTS: The concentration of eoxin C4 (median 1.4, range <1.12-6.7 pg/mL) was significantly lower than that of eoxin C4 or CysLTs (P<0.0001). The concentration of 15-HETE significantly correlated with those of LTC4 and CysLTs or the number and the percentage of eosinophils in BALF. On the other hand, eoxin C4 concentration did not correlate with eosinophil number or CysLTs concentration in BALF. CONCLUSIONS: This is the first study demonstrating the presence of eoxin C4 in human biological fluids. Further studies are necessary to elucidate the pathophysiological role of eoxin C4 in some respiratory inflammatory diseases.

Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxis.

BACKGROUND: Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. However, pathological evidence of the association between inflammatory mediators and human anaphylaxis is insufficient. OBJECTIVE: The aim of this study was to better understand the relationship between in vivo production of inflammatory mediators and the pathogenesis of anaphylaxis. We also sought to evaluate mast cell activation in anaphylaxis. METHODS: We measured the concentrations of various inflammatory mediators in urine samples, which were collected from 32 anaphylactic patients during the onset of anaphylaxis and during clinical remission, 21 patients with asthma on acute exacerbation and 15 healthy control subjects. Blood and urine specimens were collected from the patients after provocation test. Urinary leukotriene E4 (LTE4), 9alpha, 11beta-prostaglandin F2 (9alpha, 11beta-PGF2), eosinophil-derived neurotoxin (EDN) and leukotriene B4 glucuronide (LTBG) concentrations were determined by enzyme immunoassay, and the activity of plasma platelet-activating factor acetylhydrolase and serum tryptase concentration were measured using commercially available kits. RESULTS: Significantly higher concentrations of urinary LTE4 and 9alpha, 11beta-PGF2, which immediately decreased during clinical remission, were observed in the anaphylactic patients than in asthmatic patients on acute exacerbation and healthy control subjects. Concentrations of EDN and LTBG were not significantly different among the anaphylactic patients, asthmatic patients on acute exacerbation and healthy subjects. There was a significant correlation between urinary LTE4 and 9alpha, 11beta-PGF2 concentrations in the anaphylactic patients (r=0.672, P=0.005, n=32). In addition, LTE4 concentration in patients with anaphylactic shock is significantly elevated compared with that in patients without anaphylactic shock. CONCLUSIONS: This is a report on the significant increase in urinary LTE4 and 9alpha, 11beta-PGF2 concentrations during anaphylaxis. Urinary LTE4 and 9alpha, 11beta-PGF2 concentrations may be a reliable marker of endogenous production of inflammatory mediators associated with anaphylaxis.

Comparison of cysteinyl leukotriene concentrations between exhaled breath condensate and bronchoalveolar lavage fluid.

BACKGROUND: Collection of exhaled breath condensate (EBC) is a simple, non-invasive method of obtaining samples from the airways and it can be repeated in short intervals without side effects; therefore, it provides an opportunity to monitor the changes in concentration of inflammatory mediators in the airways. However, EBC analysis still has several unresolved issues. OBJECTIVE: To better understand the characteristics of EBC, we compared cysteinyl leukotriene (CysLT) concentrations between bronchoalveolar lavage fluid (BALF) and EBC. We also attempted to correct CysLT concentrations in BALF and EBC diluted with saline and water vapour using biological markers. METHODS: EBC was collected from 14 patients with idiopathic pulmonary fibrosis before bronchoscopy. We measured CysLT concentrations and also quantified tyrosine, urea and total protein as possible biomarkers for correcting dilution. RESULTS: (1) We have validated the quantification of CysLTs in EBC. (2) Although a significant correlation was observed among tyrosine and urea concentrations in BALF, urea and total protein concentrations were below the detection limit in EBC. (3) CysLT concentrations were higher in BALF than in EBC (median, 15.96 pg/mL vs. 5.5 pg/mL; P=0.001) and there was no correlation of CysLT concentrations in BALF with those in EBC. A significant correlation of the ratio of total CysLT concentration to tyrosine concentration (CysLT/Y) in EBC with that in BALF was observed (r=0.547, P=0.043). (4) CysLT/Y in EBC correlated with serum KL-6 concentration and total cell count in BALF, and CysLT/Y in BALF also correlated with exhaled NO concentration and %VC. CONCLUSIONS: CysLT/Y in EBC significantly correlated with that in BALF and some clinical parameters correlated with CysLT/Y. Tyrosine concentration may be used to correct the dilution error for CysLT concentrations, and CysLT/Y in EBC can be a surrogate marker for CysLT concentrations in BALF.

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART.

The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8 percent. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1 percent, P < 0.001; CD8+, 70.9 vs 79.6 percent, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7 percent, P < 0.001; CD8+, 8.6 vs 4.8 percent, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.

Effect of the time interval from harvesting to the pre-drying step on natural fumonisin contamination in freshly harvested corn from the State of Parana, Brazil.

Natural mycoflora and fumonisins were analysed in 490 samples of freshly harvested corn (Zea mays L.) (2003 and 2004 crops) collected at three points in the producing chain from the Northern region of Parana State, Brazil, and correlated to the time interval between the harvesting and the pre-drying step. The two crops showed a similar profile concerning the fungal frequency, and Fusarium sp. was the prevalent genera (100%) for the sampling sites from both crops. Fumonisins were detected in all samples from the three points of the producing chain (2003 and 2004 crops). The levels ranged from 0.11 to 15.32 microg g(-1)in field samples, from 0.16 to 15.90 microg g(-1)in reception samples, and from 0.02 to 18.78 microg g(-1)in pre-drying samples (2003 crop). Samples from the 2004 crop showed lower contamination and fumonisin levels ranged from 0.07 to 4.78 microg g(-1)in field samples, from 0.03 to 4.09 microg g(-1)in reception samples, and from 0.11 to 11.21 microg g(-1)in pre-drying samples. The mean fumonisin level increased gradually from < or = 5.0 to 19.0 microg g(-1)as the time interval between the harvesting and the pre-drying step increased from 3.22 to 8.89 h (2003 crop). The same profile was observed for samples from the 2004 crop. Fumonisin levels and the time interval (rho = 0.96) showed positive correlation (p < or = 0.05), indicating that delay in the drying process can increase fumonisin levels.

Increased urinary leukotriene E4 concentration in patients with eosinophilic pneumonia.

Although eosinophils produce cysteinyl leukotrienes (CysLTs) in large quantities, information on the relationship between CysLTs and eosinophilic pneumonia (EP) is lacking. Inflammatory mediator concentrations in urine were quantified to clarify the relationship between CysLT concentrations and EP severity. Leukotriene (LT)E(4), eosinophil-derived neurotoxin (EDN), 9alpha,11beta-prostaglandin F2 and LTB(4) glucuronide concentrations were quantified in the urine of: EP patients during acute exacerbation and clinical remission; asthmatic patients during acute exacerbation and under stable conditions; and healthy control subjects. The urinary LTE(4) and EDN concentrations of EP patients during acute exacerbation were significantly higher than those of asthmatic patients and healthy subjects, and decreased immediately during clinical remission. The urinary LTE(4) concentration was associated with the urinary EDN concentration of EP patients during acute exacerbation. The urinary LTE(4) concentration significantly correlated with the diffusing capacity of the lung for carbon monoxide in EP patients during acute exacerbation. The increased urinary concentrations of leukotriene and eosinophil-derived neurotoxin were associated with acute exacerbation in eosinophilic pneumonia patients. The increased leukotriene concentration significantly correlated with diffusing capacity of the lung for carbon monoxide, suggesting that the monitoring of leukotriene concentration may aid in the management of eosinophilic pneumonia patients.