Biomedical subjects

Andreas Trotter

Publications and source records attributed to Andreas Trotter.

8 recordsLinked to original sources

PubMed2006

Amiloride-sensitive nasal potential difference is not changed by estradiol and progesterone replacement but relates to BPD or death in a randomized trial on preterm infants.

Postnatal replacement of placental estradiol (E2) and progesterone (P) in preterm infants may improve lung function, possibly mediated through enhanced epithelial Na(+) transport and alveolar fluid clearance. Preterm infants of <29 wk gestational age and <1000 g birth weight requiring mechanical ventilation within 12 h of birth were randomized to receive either 2.5 mg/kg E2 and 22.5 mg/kg P per day (E2/P), or vehicle placebo. Epithelial Na(+) transport was assessed in 29 infants by measuring total nasal potential difference (NPD) and amiloride-sensitive NPD (ASNPD) on postnatal days of life 1, 3, 5, and 7, and mean values of all four measurements were calculated. Bronchopulmonary dysplasia (BPD) was defined as need for supplemental oxygen (goal Sa(O2) 90%) or mechanical ventilation at 36 wk corrected postmenstrual age. Mean ASNPD was -6.5 +/- 2.8 mV in infants receiving E2/P and -6.1 +/- 2.6 mV in infants receiving placebo (not significant). NPD was -10.6 +/- 3.8 mV and -10.7 +/- 3.6 mV, respectively. The ASNPD was significantly higher in infants surviving without BPD (-7.1 +/- 2.5 mV) than in infants developing BPD or not surviving (-5.2 +/- 2.4 mV). In conclusion, ASNPD is not changed by postnatal replacement of E2 and P. Infants at high risk of developing BPD had lower ASNPD values in the immediate postnatal period.

Amiloride↗

PubMed2006

Impact of 17beta-estradiol on cytokine-mediated apoptotic effects in primary hippocampal and neocortical cell cultures.

Estrogens are developmental regulators of mitochondrial apoptotic pathway in the central nervous system, but little is known about their involvement in cytokine-induced apoptosis. In the present study, we evaluated effects of 17beta-estradiol on pro-inflammatory cytokine- and staurosporine-mediated activation of caspase-3 and LDH-release in primary neuronal/glial cell cultures of mouse hippocampal and neocortical cells at different stages of their development in vitro. Enzyme activities were determined with colorimetric methods 6 h, 14 h, 24 h, and 48 h after exposure to the apoptotic agents. Biochemical data were supported at the cellular level by Hoechst 33342 and MAP-2 stainings, which were carried out 48 h after the treatment. Cytokines (co-treatment with Il-1beta and TNFalpha; 1 ng/ml) increased caspase-3 activity in the hippocampal and neocortical cells up to over 200% of control values, and these effects were mostly observed on 2 and 7 days in vitro (DIV). Moderate, but significant cytokine-mediated increase in LDH-release was demonstrated in both tissues, especially on 7 and 12 DIV. Estradiol (100 nM) inhibited the activation of caspase-3 at early stage of development (2 DIV) in the hippocampal, but not in the neocortical cultures. The cytokine-induced activation of caspase-3 and LDH-release was inhibited by estradiol in estrogen receptor-independent way. These data point to a possible role of estrogens as non-estrogen receptor-related inhibitors of cytokine-activated apoptotic pathway in the developing central nervous system.

Animals↗

PubMed2006

Prenatal estrogen and progesterone deprivation impairs alveolar formation and fluid clearance in newborn piglets.

Exposure to high levels of estradiol (E2) and progesterone (P) derived from the fetoplacentomaternal unit during the last trimester of pregnancy may play a crucial role in prenatal lung development and immediate postnatal alveolar fluid clearance (AFC). To measure prenatal alveolar formation and postnatal amiloride-sensitive AFC after pharmacological deprivation of E2 and P in utero, fetuses from five sows received an intramuscular depot injection of the E2 receptor blocker ICI 182.780 (ICI) and the P receptor blocker RTI 3021-022 (RTI) and fetuses of five other sows received a placebo injection (control group) during a laparotomy at 90 d of gestation (term gestation, 115 d). Piglets were delivered by cesarean section on d 114 of gestation. Of 95 live-born piglets, 35 were mechanically ventilated. The airways of the right lower lobe were isolated by a balloon catheter wedged in the bronchus and 5% albumin in 0.9% NaCl with or without 1 mmol/L amiloride was instilled. Amiloride-sensitive AFC was calculated from the protein concentration changes in fluid recovered after 120 min as the percentage of absorbed fluid. Lungs were removed under standardized conditions to perform alveolar counts. Prenatal treatment with ICI and RTI resulted in a significantly lower amiloride-sensitive AFC (median, 31%; min-max, -4-58) than placebo (74%, 18-231). Median alveolar counts per visual field were significantly lower in piglets that were exposed to ICI and RTI (38, 21-78) compared with placebo (56, 32-113). We conclude that prenatal E2 and P deprivation significantly impaired alveolar formation and amiloride-sensitive AFC.

Amiloride↗

PubMed2006

Effects of a recombinant surfactant protein-C-based surfactant on lung function and the pulmonary surfactant system in a model of meconium aspiration syndrome.

OBJECTIVE: Meconium aspiration syndrome (MAS) remains a relevant cause of neonatal respiratory failure and is characterized by severe impairment of pulmonary gas exchange, surfactant inactivation, and pronounced inflammatory changes. Surfactant administration has been shown as an effective treatment strategy in MAS. The present study aimed at investigating the impact of a recombinant surfactant protein (SP)-C-based surfactant on pulmonary gas exchange and lung function in this model of neonatal lung injury. Furthermore, SP-B and -C were determined on the transcriptional and protein level. DESIGN: Laboratory experiment. SETTING: University laboratory. SUBJECTS: Twenty three newborn piglets (median age 6 days, weight 1900-2500 g). INTERVENTIONS: Piglets were intubated and mechanically ventilated and then received 20% sterile meconium (5 mL/kg) for induction of lung injury. After 30 mins, animals were randomized for control (n = 7, MAS controls), recombinant SP-C surfactant (n = 8), or natural surfactant (n = 8). Surfactant preparations were administered as an intratracheal bolus (75 mg/kg), and animals were ventilated for another 330 mins. Nonventilated newborn piglets at term (n = 28; median weight 1484 g, range 720-1990 g) served as a healthy reference group (healthy controls). MEASUREMENTS AND MAIN RESULTS: Lung function variables, arterial blood gas samples, and lung tissues were obtained. Expression of SP-B and -C messenger RNA was quantified in left lung lobe tissue using real-time polymerase chain reaction. Protein concentrations were determined by enzyme-linked immunosorbent assay. Scanning electron microscopy and transmission electron microscopy were performed in tissue samples of the right lung lobe. Compared with healthy controls, SP-B messenger RNA expression was significantly increased in MAS (p < .02), whereas SP-C messenger RNA expression was found to be significantly reduced (p < .001). SP concentrations, however, were not significantly different. Although a significant improvement of gas exchange and lung function was observed after surfactant administration in both groups, surfactant messenger RNA expression and protein concentrations were not significantly altered. Scanning and transmission electron microscopy showed severe pulmonary ultrastructural changes after meconium aspiration improving after surfactant treatment. CONCLUSIONS: Impairment of lung function in MAS, associated with marked changes in SP messenger RNA expression, can be sufficiently treated using recombinant SP-C-based or natural surfactant. Despite improved lung function and gas exchange as well as pulmonary ultrastructure after treatment, pulmonary SP messenger RNA expression and concentrations remained significantly affected, giving important insight into the time course following surfactant treatment in MAS.

Animals↗

PubMed2005

Effect of NMDA on staurosporine-induced activation of caspase-3 and LDH release in mouse neocortical and hippocampal cells.

To achieve a better understanding of developmentally regulated NMDA- and staurosporine-induced apoptotic processes, we investigated the concerted action of these agents on caspase-3 activity and LDH release in neocortical and hippocampal cell cultures at different stages in vitro (DIV). Hoechst 33342 and MAP-2 stainings were additionally employed to visualize apoptotic changes and cell damage. The vulnerability of neocortical cells to NMDA was more prominent at later culture stages, whereas hippocampal neurons were more susceptible to NMDA treatment at earlier stages. A persistent activation of caspase-3 by staurosporine was found at all experimental stages. Despite of certain differences in susceptibility to NMDA and staurosporine, both tissues responded to regulatory action of NMDA towards staurosporine-activated caspase-3 in a similar way. Combined treatment with NMDA and staurosporine resulted in a substantial increase in caspase-3 activity in neocortical and hippocampal neurons on 2 DIV. Additive effects were also observed in neocortical cultures on 12 DIV. In contrast, NMDA substantially inhibited staurosporine-induced caspase-3 activity on 7 DIV in neocortical and hippocampal cultures. Additionally, pro-apoptotic effects of 17beta-estradiol were attenuated by NMDA on 7 DIV. Changes in vulnerability to NMDA- and staurosporine-mediated activation of caspase-3 were not strictly related to LDH release. Our data revealed that NMDA can both enhance and inhibit the staurosporine-induced neuronal cell apoptosis. The pro-apoptotic effect of NMDA was exhibited at early and late culture stages, whereas the anti-apoptotic effect was transient occurring on 7 DIV only.

Animals↗

PubMed2003

Ontogenetic expression of estrogen and progesterone receptors in the mouse lung.

In the mammalian lung, estrogen and progesterone seem to be import for the morphological and functional maturation. Despite this, only sparse information is available on the onset and ontogenic expression of estrogen receptors (ER) and progesterone receptors (PR) in the perinatal lung. The expression patterns of the two known nuclear isoforms ER-alpha and ER-beta and the PR were analyzed in the pre- and postnatal lungs of BALB/c mice. Steroid receptor mRNA expression of all three receptors were highest in the prenatal lung and declined thereafter to significantly lower levels in the postnatal and adult lung. The ontogenetic pattern of ER and PR expression supports the view that both gonadal steroids are pivotal for prenatal lung maturation and development.

Aging↗

PubMed2002

Calcium and phosphorus balance of extremely preterm infants with estradiol and progesterone replacement.

Infants born extremely prematurely are deprived of the placental supply of estradiol (E2) and progesterone (Prog) at an earlier developmental stage compared to an infant born at term. We hypothesized that the retention of Ca (calcium) and P (phosphorus) would be improved by an E2 and Prog replacement. Twenty female infants with a mean gestational age of 26.6 weeks (+/-1.5 SD) and a mean birth weight of 744 g (+/-156) were enrolled in a randomized controlled pilot study. One group received an E2 and Prog replacement to maintain intrauterine plasma concentrations of E2 and Prog and the other group served as control. When intake of formula was at least 100 mL/kg/d, a 3-day Ca and P balance study was performed. Ca and P intake was increased individually until both elements were excreted in the urine. The mean Ca and P retention was 4.21 (+/-1.75) mMol/kg/d (58% of intake) and 2.66 (+/-1.01) mMol/kg/d (80%) in the replaced group and 3.39 (+/-1.69) mMol/kg/d (56%) and 2.03 (+/-0.79) mMol/kg/d (71%) in the control group, respectively. In this pilot study the retention of Ca and P was not improved by an E2 and Prog replacement.

Calcium↗

PubMed2002

Growth of the uterus and mammary glands and vaginal cytologic features in extremely premature infants with postnatal replacement of estradiol and progesterone.

OBJECTIVE: Growth of the uterus and the mammary glands and changes in vaginal cytologic features are known to be estrogen dependent and were evaluated to proof the biologic effectiveness of a postnatal replacement of estradiol and progesterone in extremely premature infants. STUDY DESIGN: Thirty female infants with a mean gestational age of 26.4 weeks (24.1-28.7 weeks) and a mean birth weight of 708 g (370-990 g) were investigated. Fifteen infants received postnatal replacement of estradiol and progesterone for 6 weeks to maintain intrauterine plasma levels of estradiol and progesterone. Uterine size and the diameter of mammary glands were assessed repeatedly by ultrasound scans and palpation. Vaginal smears were also obtained. RESULTS: The uterus and mammary glands showed significant growth during the hormone replacement, but growth was not observed in nontreated infants. Vaginal smears showed high karyopyknotic and eosinophilic indices in both groups at birth; the indices remained significantly higher at 3 and 6 weeks in the hormone-treated infants. CONCLUSION: The biologic effectiveness of postnatal estradiol and progesterone replacement in extremely premature infants was proved.

Breast↗