Human airway trypsin-like protease, a serine protease involved in respiratory diseases.

More than 2% of all human genes are coding for a complex system of more than 700 proteases and protease inhibitors. Among them, serine proteases play extraordinary, diverse functions in different physiological and pathological processes. The human airway trypsin-like protease (HAT), also referred to as TMPRSS11D and serine 11D, belongs to the emerging family of cell surface proteolytic enzymes, the type II transmembrane serine proteases (TTSPs). Through the cleavage of its four major identified substrates, HAT triggers specific responses, notably in epithelial cells, within the pericellular and extracellular environment, including notably inflammatory cytokine production, inflammatory cell recruitment, or anticoagulant processes. This review summarizes the potential role of this recently described protease in mediating cell surface proteolytic events, to highlight the structural features, proteolytic activity, and regulation, including the expression profile of HAT, and discuss its possible roles in respiratory physiology and disease.

Metría del estrés: reto de la posmodernidad / Metrics of stress: a challenge of post-modernity

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Three-dimensional ultrasound fetal lung volumes and infant respiratory outcome: a prospective observational study.

OBJECTIVE: To determine if fetal lung volumes (FLVs), determined by three-dimensional rotational ultrasound and virtual organ computer-aided analysis software (vocal), correlated with neonatal respiratory outcomes in surviving infants who had a high risk [fetuses with congenital diaphragmatic hernia (CDH)], lower risk [fetuses with anterior wall defects (AWDs)] and no risk (controls) of abnormal antenatal lung growth. DESIGN: Prospective observational study. SETTING: Tertiary fetal medicine and neonatal intensive care units. POPULATION: Sixty fetuses (25 with CDH, 25 with AWDs and ten controls). METHODS: FLVs were measured and expressed as the percentage of the observed compared with the expected for gestational age. MAIN OUTCOME MEASURES: Neonatal respiratory outcome was determined by the duration of supplemental oxygen, mechanical ventilation and dependencies, and assessment of lung volume using a gas dilution technique to measure functional residual capacity (FRC). RESULTS: The infants with CDH had lower FLV results than both the infants with AWDs (P=0.05) and the controls (P<0.05). The infants with CDH had longer durations of mechanical ventilation (P<0.001) and supplementary oxygen (P<0.001) dependence, compared with infants with AWDs. The infants with CDH had a lower median FRC than both the infants with AWDs (P<0.001) and the controls (P<0.001). FLV results correlated significantly with the durations of dependency on ventilation (r= -0.744, P<0.01) and oxygen (r= -0.788, P<0.001), and with FRC results (r=0.429, P=0.001). CONCLUSIONS: These results suggest that FLVs obtained using three-dimensional rotational ultrasound might be useful in predicting neonatal respiratory outcome in surviving infants who had varying risks of abnormal lung growth. Larger and more comprehensive studies are needed to clarify the role that lung volume measurements have in assessing lung function and growth.

Respiratory outcomes in early childhood following antenatal vitamin C and E supplementation.

BACKGROUND: Prenatal antioxidant supplementation might influence fetal lung growth and development and reduce infant respiratory morbidity. The aim of this study was to test the hypothesis that infants of mothers at risk of pre-eclampsia who were randomised to receive high-dose vitamins C and E (1000 mg vitamin C and 400 IU RRR α-tocopherol daily) during pregnancy would have better respiratory outcomes than infants whose mothers were randomised to receive placebo. METHODS: Respiratory outcomes to 2 years of age were documented using questionnaires and, in a subset, by recording their healthcare utilisation and calculating the cost of care data. RESULTS: 330 women who had taken vitamin supplementation and 313 who had taken placebo completed the respiratory questionnaire (386 and 366 infants, respectively). There were no significant differences between the two groups in the proportions diagnosed with asthma. 54 women who had taken vitamin supplementation and 45 who had taken placebo took part in the healthcare utilisation study (65 and 53 infants, respectively). On average, infants of mothers receiving vitamin supplementation had 2.6 (99% CI 0.8 to 5.1) times more A&E/outpatient visits and 3.2 (99% CI 0.2 to 6.9) times more GP visits than infants of mothers receiving placebo, and their costs of care were £226 (99% CI £27 to £488) more for outpatient admissions, £57 (99% CI £3 to £123) more for GP visits and £22 (99% CI £3 to £50) more for medications. CONCLUSIONS: High-dose antenatal vitamin C and E supplementation does not improve infant respiratory outcome and is associated with increased healthcare utilisation and cost of care.

Fetal poisoning after maternal paraquat ingestion during third trimester of pregnancy: case report and literature review.

INTRODUCTION: Paraquat remains one of the common substances involved in intentional ingestions in Thailand. However, data on outcomes of paraquat ingestion during pregnancy is rarely available and the management is controversial. CASE REPORT: A 17-year-old female in 36 weeks of gestation attempted suicide by ingesting 1/2 a glass of Gramozonetrade mark (paraquat 27.6 % w/v) 5 hours prior to arrival to the hospital. Gastric aspiration and lavage was performed and she was given 50 g of activated charcoal and 150 g of Fuller's Earth suspension. A male infant, weighing 2,390 g with an Apgar score of 71 1010, was delivered via emergency caesarean section 7 hours after ingestion. Due to presence of paraquat in the gastric lavage fluid, the mother was placed on dexamethasone/cyclophosphamide therapy. She developed mild renal insufficiency 63 hours after the ingestion. The infant developed tachypnea immediately after birth that self-resolved. The infant developed tachypnea again on day 6 of life. A chest x-ray revealed right lower lobe infiltration that progressed to diffuse interstitial pattern; subsequent chest x-rays showed evidence of fibrosis. Both mother and infant survived and the infant was discharged and sent home with oxygen 0.5 LPM. Upon follow up at 10 months of age, he still had evidence of chronic lung disease clinically and on chest x-ray. CONCLUSION: Paraquat ingestion during the third trimester of pregnancy usually carries a very poor prognosis. Review of reported literature suggests that this case report represents only the second survival of mother and child.

Cardiorespiratory fitness and metabolic syndrome: US National Health and Nutrition Examination Survey 1999-2002.

Increasing physical activity is recommended as a therapeutic lifestyle change in the treatment of metabolic syndrome (MetS); however, little evidence exists for a relationship between cardiorespiratory fitness (CRF) and MetS in representative samples. Using data from the US National Health and Nutrition Examination Survey, 1999-2002, the relationship between CRF and MetS was examined in 692 men and 608 women between the ages of 18 and 49 y who were free of major disease and disability. In men, the odds of MetS were significantly lower in moderate and high CRF categories versus the low CRF category, whereas in women there were no significant relationships between CRF and MetS.

Maternal food consumption during pregnancy and asthma, respiratory and atopic symptoms in 5-year-old children.

BACKGROUND: Associations between maternal vitamin E, vitamin D and zinc intakes during pregnancy and asthma, wheeze and eczema in 5-year-old children have previously been reported. A study was undertaken to investigate whether maternal intake of specific foods during pregnancy is associated with asthma and allergic outcomes in the same children. METHODS: A longitudinal birth cohort study was conducted in 1,924 children born to women recruited during pregnancy. Maternal diet during pregnancy was assessed by food frequency questionnaire (FFQ). Cohort children were followed up at 5 years by symptom questionnaire and FFQ. Food groups of interest were fruit, vegetables, fruit juice, whole grain products, fish, dairy products and fat spreads. Trends across outcome groups defined by level of food intake are presented. RESULTS: 1,253 children participated at 5 years and maternal FFQ data were available for 1,212. No consistent associations were found between childhood outcomes and maternal intake of the analysed foods except for apples and fish. Maternal apple intake was beneficially associated with ever wheeze (OR highest vs lowest tertile 0.63, 95% CI 0.42 to 0.95), ever asthma (OR 0.54, 95% CI 0.32 to 0.92) and doctor-confirmed asthma (OR 0.47, 95% CI 0.27 to 0.82) in the children. Maternal fish consumption was beneficially associated with doctor-confirmed eczema (OR >or=1/week vs never 0.57, 95% CI 0.35 to 0.92). CONCLUSION: There was no evidence for associations between maternal intake of most foods during pregnancy and asthma, respiratory and allergic outcomes in 5-year-old children, except for apples and fish. Consumption of apples and fish during pregnancy may have a protective effect against the development of childhood asthma and allergic disease.

Application of ES cells for generation of respiration-deficient mice carrying mtDNA with a large-scale deletion.

In a previous study, we used mouse zygotes as recipients of mtDNA with a large-scale deletion mutation (DeltamtDNA) and generated respiration-deficient mice (mito-mice) carrying DeltamtDNA. In this study, we used mouse ES cells as recipients of DeltamtDNA, and generated mito-mice with DeltamtDNA only when the ES cells carried 17% DeltamtDNA. No chimera mice or their F(1) progenies were obtained from ES cells carrying more than 61% DeltamtDNA. These observations suggest that respiratory defects of ES cells inhibit their normal differentiation into chimera mice and mito-mice, and that ES cells are more effective than zygotes for generation of mito-mice carrying mtDNAs without significant pathogenic mutations.

Reliability of the lung-to-head ratio in predicting outcome and neonatal ventilation parameters in fetuses with congenital diaphragmatic hernia.

OBJECTIVES: The ratio of the lung area (on the contralateral side of the hernia) to the head circumference, the lung-to-head ratio (LHR), has been proposed as a reliable tool in the assessment of the prognosis of congenital diaphragmatic hernia (CDH). An LHR < 0.6 has been associated with poor outcome whereas one > 1.4 has been associated with survival. We aimed to analyze the role of LHR in predicting fetal outcome and ventilation parameters in cases of isolated CDH in our center. METHODS: During the 40-month study period, 22 fetuses with an isolated CDH were delivered alive under optimized conditions at our perinatal center. LHR was measured at the time of diagnosis (median, 27 weeks' gestation). In addition to survival, postnatal ventilation parameters including pCO2, pO2, inspiratory O2 partial pressure, inspiratory pressure and oxygenation index were determined, as was the occurrence of pulmonary hypertension. RESULTS: The overall survival rate was 59%. The LHR was not able to predict fetal outcome reliably. There was no correlation between the liver herniation, LHR and fetal outcome. The prenatally determined lung size reflected in the LHR did not show any significant association with individual ventilation parameters. Eleven of 17 infants examined had signs of pulmonary hypertension and the LHR did not predict this condition. CONCLUSION: Our study cannot support the optimistic results reported by other groups on the use of LHR as a reliable predictor of outcome in fetuses with CDH. The LHR, as a reflection of lung size, correlates neither with survival patterns nor with various postnatal ventilation parameters.

Perceived health of adults after prenatal exposure to the Dutch famine.

People who were undernourished in early gestation are more obese, have a more atherogenic lipid profile, and altered blood coagulation and seem to have an increased risk of coronary heart disease. We now report on whether they also feel less healthy. We therefore assessed the perceived health of 50-year-old-men and women born alive as singletons around the time of the Dutch famine in the Wilhelmina Gasthuis in Amsterdam. People who had been exposed to famine in early gestation, but not those exposed in mid- or late gestation, more often rated their health as poor (10.3% vs. to 4.9% in the unexposed, odds ratio (OR) 2.2 [1.0, 4.8]). The effect of exposure to famine in early gestation on perceived health could only partly be explained by an increased prevalence of coronary heart disease, respiratory diseases, hypertension, type 2 diabetes, hypercholesterolaemia or cancer (adjusted OR 2.2 [0.9, 5.2]). Adjustment for adult risk factors (BMI, LDL/HDL cholesterol ratio, blood pressure, smoking, lung function) also attenuated the results to some extent (adjusted OR 1.9 [0.6, 5.5]). People who were exposed to famine in early gestation were not only less healthy in terms of objective measures of health but they also felt less healthy. Because poor perceived health is a strong predictor of mortality, we may expect increased mortality in people who were exposed to famine in early gestation in the future.

[Analysis of selected parameters of maternal and fetal status during stimulation of fetal lung maturation]. / Analiza wybranych parametrów stanu ciezarnej i plodu w trakcie stymulacji dojrzewania ukladu oddechowego.

At patients threatened with premature childbirth the influence of glicocorticoids on short and tong-term fetal heart rate variability and the occurrence of respiratory arrhythmia was evaluated. It has been ascertained statistical significant lowering of the incidence of fetal respiratory arrhythmia and short-term variability. Described changes had a temporary character and surrendered of normalization in the course 72 of hours after last use of glicocorticoids. The influence of glicocorticoids on select biochemical and biophysical parameters of state pregnant women was also studied. One specified occurrence of incidental symptoms in road drove of therapy. Pregnant women in road of treatment glicocorticoids have also observed a temporary weakness of feeling of fetal movements.

In utero diagnosis and management of fetal tachypnea. A case report.

Fetal tachypnea, defined as more than 60 fetal breaths per minute, has been reported to occur almost always in diabetic pregnancies. We treated a patient for fetal tachypnea and tachycardia, the initial presentation of which led to the diagnosis of diabetes mellitus.