Induction of eosinophil apoptosis by hydrogen peroxide promotes the resolution of allergic inflammation.

Eosinophils are effector cells that have an important role in the pathogenesis of allergic disease. Defective removal of these cells likely leads to chronic inflammatory diseases such as asthma. Thus, there is great interest in understanding the mechanisms responsible for the elimination of eosinophils from inflammatory sites. Previous studies have demonstrated a role for certain mediators and molecular pathways responsible for the survival and death of leukocytes at sites of inflammation. Reactive oxygen species have been described as proinflammatory mediators but their role in the resolution phase of inflammation is poorly understood. The aim of this study was to investigate the effect of reactive oxygen species in the resolution of allergic inflammatory responses. An eosinophilic cell line (Eol-1) was treated with hydrogen peroxide and apoptosis was measured. Allergic inflammation was induced in ovalbumin sensitized and challenged mouse models and reactive oxygen species were administered at the peak of inflammatory cell infiltrate. Inflammatory cell numbers, cytokine and chemokine levels, mucus production, inflammatory cell apoptosis and peribronchiolar matrix deposition was quantified in the lungs. Resistance and elastance were measured at baseline and after aerosolized methacholine. Hydrogen peroxide accelerates resolution of airway inflammation by induction of caspase-dependent apoptosis of eosinophils and decrease remodeling, mucus deposition, inflammatory cytokine production and airway hyperreactivity. Moreover, the inhibition of reactive oxygen species production by apocynin or in gp91(phox-/-) mice prolonged the inflammatory response. Hydrogen peroxide induces Eol-1 apoptosis in vitro and enhances the resolution of inflammation and improves lung function in vivo by inducing caspase-dependent apoptosis of eosinophils.

Soluble tumour necrosis factor receptor-1 (sTNFR1) levels are positively associated with exercise intensity in athletes after strenuous off-road cycling.

AIM: Strenuous exercise can enhance plasma levels of pro- and anti-inflammatory cytokines. Increases in plasma tumor necrosis factor-alpha (TNF-α) are followed rapidly by a rise in its natural inhibitors, soluble TNF receptors (sTNFRs). These inhibitors likely prevent an over-response to the cytokine. Aims of the present study were: 1) analyze plasma sTNFR1 at different time-points in response to a strenuous off-road cycling competition; 2) evaluate whether plasma levels of sTNFR1 correlate to increased blood lactate levels on completion of the exercise. METHODS: Eight trained off-road cyclists took part in this study and the data collection occurred during an official off-road race. Blood samples were collected pre-race, immediately post-race, and 1 h, 2 h and 24 h during the recovery period, for plasma sTNFR1 and blood lactate determination. RESULTS: Increase in sTNFR1 plasma levels were observed immediately post-race, 1 h and 2 h post-race (P<0.01), returning to baseline levels at the end of the recovery period (24 h). Significant correlation between plasma levels of sTNFR1 and blood lactate concentration were observed at the end of the race (r=0.925; P<0.001). CONCLUSION: An off-road cycling race stimulated an increase in plasma sTNFR1 and this anti-inflammatory molecule was positively correlated to blood lactate concentration. This result reinforces the view that exercise intensity influences the increase in plasma anti-inflammatory molecules.

Aquagenic wrinkling of the palms and cystic fibrosis: an Italian study with controls and genotype-phenotype correlations.

AIMS: The primary aim was to determine the prevalence of aquagenic wrinkling of the palms (AWP) in patients with cystic fibrosis (CF) compared to controls, and secondarily to evaluate genotype-phenotype correlations among CF subjects found to have AWP. METHODS: Fifty-eight patients with CF underwent a hand immersion test in tap water. Twenty-three of their CF carrier relatives and 7 subjects with a negative genetic test for CF were recruited as controls. Secondary analyses explored associations with genotype, pulmonary function, and sweat electrolyte levels in all subjects with and without AWP. Additional information about atopic diathesis, hyperhidrosis of the palms and drug intake were also collected. RESULTS: Thirty-one of the patients with CF (53.4%) exhibited AWP, in contrast to only 2 carriers (8.7%) and none in the control group. No correlation was found between CF genotype and AWP score severity. Twenty-three (39.7%) CF patients reported a history of hyperhidrosis, and in 17 of them (74%) AWP had been provoked. No correlation with history of atopy and lung function was noted. The difference between CF patients with hyperhidrosis and those without was highly significant (p = 0.016). Salt concentrations were significantly higher in patients with AWP. CONCLUSIONS: AWP is linked to CF and its diagnosis should lead the patients to a genetic or sweat test for CF. We found a significant association with hyperhidrosis and sweat electrolytes which supports the 'hyperconcentrated sweat' pathogenetic theory of AWP.

Reliability of the bright liver echo pattern in diagnosing steatosis in patients with cryptogenic and HCV-related hypertransaminasaemia.

AIM: To evaluate the reliability of the bright liver (BL) echo pattern on ultrasound to detect histological steatosis in chronic cryptogenic hypertransaminasaemia (CCH) and hepatitis C virus (HCV)-related forms of hypertransaminasaemia. MATERIALS AND METHODS: One hundred and fifty patients, 54 with CCH and 96 with HCV hypertransaminasaemia (76 genotype 1/2 and 20 genotype 3), were enrolled. Histological steatosis was measured as the percentage of hepatocytes involved. The reliability of the BL sign was estimated using the sensitivity, specificity, positive and negative predictive values. RESULTS: Histological steatosis was present in 102/150 patients (68%) divided into 59/96 (62%) in the HCV group and 43/54 (79.6%) in the CCH group (chi(2)=4.4; p=0.035). In a multivariate analysis, the variable associated with the BL echo pattern was steatosis percentage (p=0.0018). Steatosis percentage was higher in CCH group than in the HCV genotype 1/2 and 3 groups (p=0.02). The sensitivity of the BL echo pattern was 88% in the CCH group [confidence interval (CI) 95% 74-95] versus 61% (CI 95% 44-73) in the HCV genotype 1/2 group. The CI indicates that ultrasound can provide evidence for steatosis in a statistically significant way in the CCH versus HCV genotype 1/2 patients. In the genotype 3 group, the sensitivity was high (90%), but the limited number of cases limited the statistical significance due to the high CI. CONCLUSION: In CCH the BL echo pattern has excellent reliability in diagnosing steatosis, better than in HCV hypertransaminasaemia because of the higher prevalence and extent of steatosis.

Noninvasive ventilation with positive airway pressure in paediatric intensive care.

AIM: The aim of the present study is to retrospectively evaluate the effectiveness of noninvasive pressure ventilation in the 24-bed Pediatric Intensive Care Unit (PICU) of the G. Gaslini Institute during a 24-month period. METHODS: A retrospective analysis of the characteristics (pH, CO2, SpO2, respiratory rate, oxygen requirement) of patients treated with noninvasive mechanical ventilation for different acute pathologies has been performed. RESULTS: Twenty patients (mean age 7.4+/-0.28 years) with acute respiratory failure due to different pathologies were treated with noninvasive mechanical ventilation. They were divided into 2 groups: the hypoxic group, suffering from pulmonary diseases, and the hypercapnic group, presenting a failure of the mechanical strength or increased dead space. Modalities of ventilation were pressure assisted/controlled or pressure support, delivered through nasal or facial masks. Fifteen out of 20 patients presented a marked improvement of oxygenation and ventilation. Mean times of treatment were 69 and 200 h in the hypoxic and hypercapnic groups, respectively. Five patients required intubation. Two patients presented reversible skin lesions over the nasal bridge. CONCLUSIONS: Noninvasive ventilation can be used in PICU. Major advantages regard immunocompromised children and patients with exacerbations from chronic respiratory diseases, whereas the exact role of noninvasive positive pressure ventilation in patients affected by acute respiratory distress syndrome is still controversial.

Liver disease as risk factor for cystic fibrosis-related diabetes development.

AIM: To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. METHODS: Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. RESULTS: Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43-93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1 = 58.4 +/- 27% predicted versus 67.4 +/- 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. CONCLUSION: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance.

A review on techniques for tremor recording and quantification.

Tremor is the most common movement disorder and differs from other disorders by its repetitive, stereotyped movements, with regular frequency and amplitude. The three most frequent pathological forms of it are the essential tremor (ET), the Parkinson's disease (PD) tremor, and the enhanced physiological tremor. The ET and PD tremor affect the older population mostly. Although there are cases of tremor reported since ancient times, there is currently no consensus about its causes or about its main differential characteristics. In this article, we present a review of the methods more frequently used in measurement and analysis of tremor and the difficulties encountered in the research for the identification of methodologies that allow a significant advance in the study of tremor.

Impact of liver steatosis on the antiviral response in the hepatitis C virus-associated chronic hepatitis.

BACKGROUND/AIM: Liver steatosis (LS) has been variably associated with chronic hepatitis C (CHC) but whether it affects sustained virological response to antiviral treatment and by what mechanisms is a question still under debate, at least for some genotypes. The aim of this work was to assess the frequency of LS, its relationship with host and viral factors and to what extent it can influence the response to antiviral combination therapy with pegylated interferon (INF)+ribavirin in a group of patients with CHC from a single center. PATIENTS: One hundred and twelve patients with histologically proven CHC were treated with Peg INF-alpha 2a 180 microg a week subcutaneously for 48 weeks plus ribavirin 1000 or 1200 mg/day, according to the patient's body weight. Steatosis was graded according to Brunt et al. RESULTS: Forty-six out of 112 patients (41.1%) were sustained virological responders (SVR). Seventy-two out of 112 (64.3%) presented with LS at histology; in this group, there were 24 patients (33.3%) with SVR compared with 22 (55%) of the non-steatosis group (chi(2)=6.5, P<0.02). Variables associated with the steatosis group were: higher serum levels of AST (P<0.04), alanine aminotransferase (P<0.02), gamma-GT (P<0.004), genotype 3a (P<0.03) and severity of histology (staging P<0.05) but at multiple linear regression analysis only genotype 3a and staging were significantly associated with LS. In the SVR group, age and body mass index (BMI) were significantly lower (P<0001 and P<0.03, respectively) compared with non-responders; moreover, genotype 1 was more frequent in the NR group, while genotype 3 was more frequent in the SVR group. At histology, grading and staging were also lower in the SVR group. Multiple logistic regression showed that only the grade of steatosis and genotype 3a were the variables independently associated with SVR. CONCLUSIONS: This study showed a frequency of LS on the higher side of the range so far reported in the literature and confirmed that it negatively influences response to therapy. Genotype1 was confirmed to be the most frequent type in our area. It is more frequent in patients with mild-moderate steatosis and seems to condition therapeutic response negatively, together with BMI and age. In contrast, genotype 3a is more frequent in patients with severe steatosis, but is a favorable predictor of successful therapy.

Concentrations of CXCL8, CXCL9 and sTNFR1 in plasma of patients with pulmonary tuberculosis undergoing treatment.

BACKGROUND: Chemokines are a class of cytokines with chemotactic properties shown to be induced by M. tuberculosis or its antigens in vitro and in experimental infection in vivo. A few studies have also demonstrated the expression of chemokines in clinical samples of patients with active tuberculosis (TB). In the present work, we measured the concentration of chemokines in plasma samples of HIV-negative patients with pulmonary tuberculosis at different stages of chemotherapy. For comparison, we also evaluated the levels of sTNFR1 and TNF-alpha. METHODS: Cytokines and chemokines were measured by ELISA in healthy individuals and patients with active pulmonary TB at different stages of treatment. RESULTS: The concentrations of CXCL8, CXCL9 and sTNFR1 were elevated in patients with active pulmonary TB but returned to background levels at 4-6 months of chemotherapy. The concentration of CCL11 was elevated in patients with active pulmonary tuberculosis when compared to control and remained elevated throughout the specific therapy. There was no difference in the plasma concentration of CCL2 and CXCL10 between pulmonary TB patients and control subjects. CONCLUSION: Measurement of the CXCL8, CXCL9 and sTNFR1 may be useful to assess response to treatment in pulmonary TB patients.

Optimization-based learning with bounded error for feedforward neural networks.

An optimization-based learning algorithm for feedforward neural networks is presented, in which the network weights are determined by minimizing a sliding-window cost. The algorithm is particularly well suited for batch learning and allows one to deal with large data sets in a computationally efficient way. An analysis of its convergence and robustness properties is made. Simulation results confirm the effectiveness of the algorithm and its advantages over learning based on backpropagation and extended Kalman filter.

Sincronizaçäo da ovulaçäo em fêmeas suínas submetidas ao desmame precoce / Synchronization of ovulation in sows in early weaning system

Verificou-se a eficiência de protocolos para sincronizar a ovulaçäo em porcas desmamadas precocemente. Trinta porcas com média de 4,4ñ2,0 partos e estádio de lactaçäo de 14,8ñ0,7 dias foram distribuídas em três grupos de 10 animais: 1- nenhum tratamento hormonal; 2- 1000 UI de PMSG, via intramuscular (IM), 48h pós-desmame e 0,25mg de GnRH, IM, 72h após a aplicaçäo do PMSG; 3- 1000 UI de PMSG, IM, 48h pós-desmame e 500 UI de hCG, IM, 72h após o PMSG. O momento da ovulaçäo foi detectado por ultra-sonografia transretal. A taxa de sincronizaçäo (ovulaçäo até 48h após aplicaçäo de hCG ou GnRH) dos grupos 2 e 3 (94,7 por cento) foi maior (P<0,01) que no grupo controle (40 por cento). Com o uso dos protocolos de sincronizaçäo de ovulaçäo, as fêmeas tratadas apresentaram, em relaçäo ao grupo controle, tendência de maior taxa de prenhez (95 por cento vs. 70 por cento; P<0,10) e similares intervalo do desmame ao estro (96,5ñ3,0 vs. 130,2ñ31,4h) e número de leitöes nascidos vivos por fêmea gestante no primeiro cio pós-desmame (10,9ñ0,8 vs. 12,0ñ0,9). Dessa maneira, os protocolos de sincronizaçäo usados neste estudo foram eficientes em sincronizar a ovulaçäo, e podem viabilizar o uso da inseminaçäo artificial em horários predeterminados

Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma.

BACKGROUND: A relationship between young age and increased risk of recurrence of pediatric differentiated thyroid carcinoma has been suggested; however, no attempts have been made to assess the prognostic factors or efficacy of treatment in very young children with this malignancy. The objectives of this study were to evaluate the association of age with outcome in pediatric differentiated thyroid carcinoma and to compare the clinical, pathologic, prognostic, and treatment variables between younger and older children with this disease. PROCEDURE: A retrospective review of all patients presenting to the British Columbia's Children's Hospital or British Columbia Cancer Agency <17 years of age at diagnosis with differentiated thyroid carcinoma between January, 1955, and December, 1996, was completed. RESULTS: Thirty-eight patients were identified, 12 of whom were 10 years. An association between young age and extrathyroidal tumor invasion was identified (P = 0.016); however, the latter factor did not independently predict outcome. There was a trend for suppressive doses of thyroid hormone to improve outcome, particularly with increasing age at diagnosis, but this was not statistically significant. CONCLUSIONS: Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma. The results suggest different tumor biology in young children requiring novel approaches to therapy to decrease recurrence rates.

Diamond-blackfan anemia and cyclosporine therapy revisited.

A girl with Diamond-Blackfan anemia diagnosed in infancy started cyclosporine A (CSA) therapy at 9 years and 8 months of age after experiencing unacceptable side effects while receiving prednisone. Since then, she has been followed-up for more than 4 years. She exhibited a dramatic response to CSA, with weaning and then cessation of steroid therapy after 5 months. She has remained transfusion-independent. Attempts to discontinue CSA therapy have been unsuccessful. Relapse of the anemia has occurred in the context of viral infections with missed CSA doses. The major clinical problem during treatment has been recurrent oral aphthous ulceration, which responds to topical therapy. She is currently maintained on CSA 100 mg twice daily with a hemoglobin of 10.2 g/dL and a reticulocyte count of 1.6%. A trial of CSA therapy should be considered in patients with Diamond-Blackfan anemia in whom steroid therapy has failed before a transfusion program is instituted or alternative donor stem cell transplantation is entertained.

Twenty-four-hour heart rate variability to assess autonomic function in Parkinson's disease.

OBJECTIVES: To evaluate the autonomic dysfunction in Parkinson's disease patients by means of a 24-h heart rate variability (HRV) method. MATERIAL AND METHODS: Thirteen patients with a diagnosis of Parkinson's disease were compared with 13 age-matched healthy persons (control group). The 13 patients had a mean age of 70.5 years, and mean disease duration of 10.9 years. The autonomic function was evaluated by HRV analysis using a continuous 24-h ECG. The parameters of SDNN (standard deviation of the normal-to-normal intervals between adjacent QRS complexes), of LF (power in low frequency) and of HF (power in high frequency) were studied during the following 3 periods: 24 h, night and day. RESULTS: The data show a statistically significant difference between groups for SDNN and LF in all the periods, while for HF parameters the difference is statistically significant only in the night period. CONCLUSION: The use of the 24-h HRV method can provide more accurate and reproducible data than other conventional cardiovascular tests.

IgA antiendomysium antibodies in human umbilical cord sections as a screening test in relatives of patients with celiac disease.

We performed the serum IgA antiendomysium antibody (EmA) assay by indirect immunofluorescence on human umbilical cord sections in 86 subjects with celiac disease, in 187 first-degree relatives of such patients, and in a control group of 68 unrelated subjects, to investigate the suitability of the method in the screening of populations at risk of gluten sensitivity. Conventional EmA assay using monkey esophagus sections was performed in parallel experiments. The results obtained showed a perfect correlation between the two methods. All the celiac patients and none of the controls were positive for EmA. EmA positivity was also observed in 11 apparently healthy relatives: intestinal biopsy performed in five of them invariably showed villous atrophy and increase of mucosal lymphocytes. Taking into account the low cost of EmA assay on human umbilical cord, especially when compared to monkey esophagus sections, the method is probably suitable and effective in identifying latent, asymptomatic gluten sensitivity in at-risk populations.