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Biomedical subjects

B Robertson

Publications and source records attributed to B Robertson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Direct and phagocyte-mediated lipid peroxidation of lung surfactant by group B streptococci.

In newborn infants, group B streptococci (GBS) often cause pneumonia, with polymorphonuclear leukocytes (PMN) migrating into the lungs. Because surfactant therapy may be needed in such patients, we evaluated the interaction between GBS or GBS-stimulated PMN and a surfactant preparation (Curosurf) in vitro. The superoxide production of GBS strains or GBS-activated PMN was measured, using the nitroblue tetrazolium (NBT) test and the subsequent lipid peroxidation (LPO) as the content of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE). The growth of GBS in surfactant was determined and related to the LPO. Finally, the effect of LPO on surfactant activity, caused by GBS-stimulated PMN, was assessed by measuring dynamic surface tension in a pulsating bubble surfactometer. Curosurf diminished the NBT reduction by both live GBS and GBS-stimulated PMN. Surfactant was peroxidized by reactive oxygen species (ROS) from both GBS and GBS-stimulated PMN in a time-dependent manner. Vitamin E significantly reduced the peroxidation level of surfactant in both cases. Surfactant peroxidation was associated with a reduction in the number of live bacteria. The biophysical activity of Curosurf was impaired by GBS-stimulated PMN, as reflected by increased minimum surface tension during cyclic compression. These findings indicate that Curosurf undergoes LPO by ROS produced by GBS and/or PMN. We speculate that exogenous surfactant preparations should be supplemented with vitamin E or another antioxidant, when given to infants with GBS pneumonia.

Adult↗
PubMed2000

Measurement of proton release and uptake by analogs of bacteriorhodopsin.

Proton release and subsequent uptake by several forms of bacteriorhodopsin (bR), including 4-keto analogs of wild-type (WT) and D96N and D85N mutants as well as the 9-demethylretinal analog of WT and D96N mutants, have been measured using a highly sensitive electrochemical technique. Release and uptake of protons by bR in membrane patches on a tin oxide electrode produce a current transient whose amplitude is proportional to the rate of pH change at the electrode surface. Profiles of proton release by the analogs vs. pH are substantially different from the profiles of the native proteins.

Bacteriorhodopsins↗
PubMed2000

Synthetic surfactants to treat neonatal lung disease.

Pulmonary surfactant is a complex of surface-active lipids mixed with specific proteins. Two of these, SP-B and SP-C, are essential for adsorption of surfactant lipids to the air-liquid interfaces of the lungs and, hence, are also essential for alveolar stability and effective gas exchange. Surfactant substitutes must contain at least one of these proteins (or analogues of them) to be optimally effective when administered into the airways of babies with surfactant deficiency or dysfunction. This review describes how an increased understanding of the properties of surfactant proteins has led to the development of improved synthetic surfactants with the potential to treat a wide range of respiratory disorders.

Amino Acid Sequence↗
PubMed2000

Aerosolized surfactant in lung-lavaged adult rats: factors influencing the therapeutic response.

OBJECTIVE: To evaluate the effect of aerosolized modified natural surfactant in adult rats with respiratory failure. METHODS: Lung-lavaged adult rats were treated with aerosolized surfactant, aerosolized saline or a bolus of surfactant. Surfactant was labelled with dimyristoylphosphatidylcholine (DMPC) and human serum albumin was given intravenously for evaluation of lung protein leakage. Blood gases and dynamic compliance were measured intermittently. At the end of ventilation, the lungs were either fixed by vascular perfusion for histological examination or washed for determination of total phospholipids, DMPC and human albumin in the lavage fluid. RESULTS: Treatment with bolus surfactant led to a quick and sustained restoration of pre-lavage blood gas values in most animals. The response to aerosolized surfactant varied considerably, with an overall moderate improvement of gas exchange. The saline-treated group failed to show any significant recovery of lung function. No histopathological differences were found between any of the groups. On average 0.46% of total administered aerosolized surfactant could be recovered. Vascular-to-alveolar leakage of human albumin averaged 11%, with no significant differences between the groups. Final values for PaO2 were significantly correlated with total phospholipids in the lavage fluid, and inversely related to the vascular-to-alveolar leakage of albumin. CONCLUSION: Neither bolus nor aerosolized surfactant influenced lung morphology. Nebulized surfactant improved lung function but the effect was inferior to that obtained with bolus surfactant, and the outcome depended on the balance between the combined pool size of exogenous and endogenous surfactant and the vascular-to-alveolar leakage of serum protein.

Aerosols↗
PubMed2000

Treatment of experimental Cryptococcus neoformans infection in newborn rabbits by airway instillation of specific antibody and surfactant.

Cryptococcosis in AIDS patients has a slow response to antifungal chemotherapy, and passive antibody treatment has thus been considered as an adjunct. Polyclonal anticryptococcal IgG dissolved in a suspension of modified natural surfactant was given intratracheally to near-term rabbits. Killing of Cryptococcus neoformans within the lungs was determined by counting the colony forming units (cfu). After 5 h a significant decrease in cfu was observed in rabbits treated with the IgG-surfactant mixture compared with control animals receiving saline. In conjunction with conventional therapy, the combined treatment of IgG-surfactant given by bronchoscopy might be used in high-risk patients to enhance killing of the yeast within the lungs.

Animals↗
PubMed2000

Dextran reduces surfactant inhibition by meconium.

We have previously shown that an addition of dextran to surfactant increases resistance to inactivation by albumin. The present study was designed to investigate whether dextran has a protective effect against inactivation of surfactant by meconium. The dynamic surface properties of various mixtures of modified natural surfactant (Curosurf), meconium and dextran were evaluated with the pulsating bubble technique. In the absence of meconium, an addition of dextran at 10 mg ml(-1) significantly shortened the surface adsorption time of Curosurf suspended in normal saline at a concentration of 5 mg ml(-1) from 1.6+/-1.3 (mean +/- SD) sec to 0.4+/-0.4 sec (p < 0.05). Meconium at 5 mg ml(-1) increased the mean minimum surface tension (gammamin) after 3 min of pulsation from 2.1 mN m(-1) to 24 mN m(-1) (p < 0.05). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture significantly reduced the gammamin to 6.4+/-4.5 mN m(-1) and 2.6+/-5.6 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). Meconium also increased the maximum surface tension (gammamax) of Curosurf from about 33 mN m(-1) to 53 mN m(-1). An addition of dextran at 5 and 10 mg ml(-1) to the meconium-surfactant mixture reduced the gammamax to 41 and 39 mN m(-1), respectively (p < 0.05 vs dextran 0 mg ml(-1)). There were significant negative correlations between dextran concentration and both gammamin and gammamax. We conclude that dextran reduces surfactant inhibition by meconium in a dose-dependent manner.

Adsorption↗
PubMed2000

Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome.

Thirty-four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial-to-alveolar oxygen tension ratio (a/A PO2) of 0.15-0.22 were randomized to treatment with nebulized surfactant (Curosurf) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid-base status and a/A PO2 were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO2 when entering the study. There were no significant differences between the groups in a/A PO2 1-12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice.

Aerosols↗
PubMed2000

How well does a telephone questionnaire measure drinking water intake?

BACKGROUND: Few studies have assessed the validity or reliability of drinking water intake estimations. In studies investigating potential waterborne disease, this is very important. METHODS: We carried out a validity and reliability study to evaluate water intake estimations. The validity part of the study compared a telephone questionnaire to a diary. The reliability part of the study compared two telephone questionnaires. RESULTS: 253 participants were recruited. The most commonly consumed water intake categories were plain and boiled tap water. For persons aged less than 12 years, the median volume of plain water consumption was 2.9 glasses/day according to the diary. For persons aged 12 years and over, the median volume of plain water consumption was 3.0 glasses/day and for boiled water 3.0 glasses/day according to the diary. There was negligible systematic over or under reporting by participants for the telephone questionnaire in comparison to the diary and for the comparison of both telephone questionnaires. Water intake estimates were converted to categorical variables and the per cent agreement and weighted kappa statistics were calculated. For both the validity and reliability parts of the study the per cent agreement was 57-78% and the weighted kappa was 0.57-0.81. CONCLUSION: Water intake estimates show only moderate levels of validity and reliability when using a telephone questionnaire in comparison to a diary. IMPLICATIONS: Investigators of potential waterborne disease or nutritional research should exercise some caution in drawing conclusions from minor differences in drinking water intake that are obtained from a telephone questionnaire.

Adolescent↗
PubMed2000

Influence of modified natural or synthetic surfactant preparations on growth of bacteria causing infections in the neonatal period.

Connatal bacterial pneumonia is common in neonates. Animal studies and initial clinical reports indicate that surfactant dysfunction is involved in the pathophysiology of severe neonatal pneumonia. Since respiratory distress syndrome and connatal pneumonia may be difficult to differentiate in the first hours of life, neonates with respiratory failure due to bacterial infections might receive surfactant. Under such conditions surfactant components might be catabolized by bacteria and promote bacterial growth. We therefore investigated the influence of three modified natural (Curosurf, Alveofact, and Survanta) and two synthetic (Exosurf and Pumactant) surfactant preparations on the growth of bacteria frequently cultured from blood or tracheal aspirate fluid in the first days of life. Group B streptococci (GBS), Staphyloccocus aureus, and Escherichia coli were incubated in a nutrient-free medium (normal saline) for 5 h at 37 degrees C, together with different surfactants at concentrations of 0, 1, 10, and 20 mg/ml. With the exception of E. coli, incubation in saline alone led to a variable decrease in CFU. In the presence of Alveofact, Exosurf, and Pumactant the decline in bacterial numbers was less marked than in saline alone. Curosurf was bactericidal in a dose-dependent fashion for GBS and had a strong negative impact on the growth of a GBS subtype that lacked the polysaccharide capsule. In contrast, Survanta (10 and 20 mg/ml) significantly promoted the growth of E. coli, indicating that surfactant components may actually serve as nutrients. We conclude that bacterial growth in different surfactant preparations is influenced by microbial species and the composition and dose of the surfactant. Further studies are necessary to elucidate the mechanisms behind our findings and to evaluate the effects of surfactant on bacterial growth in vivo.

Biological Products↗
PubMed2000

Polymer-surfactant treatment of meconium-induced acute lung injury.

Substances (for example, serum proteins or meconium) that interfere with the activity of pulmonary surfactant in vitro may also be important in the pathogenesis or progression of acute lung injury. Addition of polymers such as dextran or polyethylene glycol (PEG) to surfactants prevents and reverses surfactant inactivation. The purpose of this study was to find out whether surfactant/polymer mixtures are more effective for treating one form of acute lung injury than is surfactant alone. Acute lung injury in adult rats was created by tracheal instillation of human meconium. Injured animals, which were anesthetized, paralyzed, and ventilated with 100% oxygen and not treated with surfactant mixtures, remained hypoxic and required high ventilator pressures to maintain Pa(CO(2)) in the normal range over the 3 h of the experiment. Uninjured animals maintained normal values for oxygen and compliance of the respiratory system. The greatest improvement in both oxygenation (178%) and compliance (42%) occurred in animals with lung injury that were treated with Survanta and PEG (versus untreated control animals; p < 0.01), whereas little improvement was found after treatment with Survanta alone. Similar results were found when postmortem pulmonary pressure-volume curves and histology were examined. We conclude that adding PEG to Survanta improves gas exchange, pulmonary mechanics, and histologic appearance of the lungs in a rat model of acute lung injury caused by meconium.

Animals↗
PubMed2000

Reversal of meconium inhibition of pulmonary surfactant by ferric chloride, copper chloride, and acetic acid.

Meconium inhibits pulmonary surfactant function. We investigated the in vitro effect of meconium on three different commercial surfactants. The dynamic surface properties of these surfactants were evaluated at the concentration of 5 mg/ml with a pulsating bubble system. The inhibitory effect of 2.75 mg/ml meconium was significantly less on Alveofact than on Curosurf and Survanta. Ferric chloride and copper chloride completely reversed the inhibitory effect of meconium. Meconium also prevented effective spreading of surfactant in a Wilhelmy balance system, and this inhibitory effect was counteracted by addition of ferric chloride. Image analysis of Curosurf demonstrated that meconium reduced the total number of microbubbles in 15 light-microscopic fields (4.35 mm(2)) from 1,748 +/- 481 to 180 +/- 166. Ferric chloride restored the number of microbubbles. Addition of ferric chloride or copper chloride to surfactant/meconium lowers pH, and pH adjustment by acetic acid also reversed the inhibitory effect of meconium. Together with the fact that the iron-chelator deferoxamine did not attenuate the effect of ferric chloride this suggests that the observed contrainhibition is caused by lowering of pH, and that meconium inhibition of surfactant is pH-dependent. Lowering pH from 6.2 to 5-5.5 abolished the inhibitory effects of meconium on surfactant. Inhibition of 2.5 mg/ml of Curosurf with plasma could also be reversed by increasing amounts of ferric chloride. We conclude that the inhibitory effect of meconium on surfactant in vitro can be abolished by addition of ferric chloride, copper chloride, or acetic acid.

Acetic Acid↗
PubMed2000

Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Members of the Collaborative European Multicenter Study Group.

OBJECTIVE: Connatal pneumonia caused by group B streptococcal (GBS) infection may be associated with surfactant dysfunction. We investigated the effects of surfactant treatment in term and preterm neonates with GBS infection and respiratory failure, in comparison with corresponding data from a control population of noninfected infants treated with surfactant for respiratory distress syndrome (RDS). DESIGN/METHODS: The study comprised 118 infants with respiratory failure, clinical and/or laboratory signs of acute inflammatory disease, and GBS infection proven by culture results. They were recruited retrospectively from a database of patients treated with surfactant at 28 neonatology units participating in European multicenter trials (1987-1993) and prospectively from the same units in the following years. A nonrandomized control group of 236 noninfected infants was selected from the same database. The primary parameters evaluated were oxygen requirement, ventilator settings, and incidence of complications. RESULTS: Median birth weight in the GBS study group was 1468 g (25th-75th percentiles: 1015-2170), and median gestational age was 30 (27-33) weeks. Thirty-one percent of the infants weighed >2000 g. Median age at surfactant treatment was 6 hours. The mean initial surfactant dose was 142 mg/kg (standard deviation: 53). Ninety of the infants were treated with Curosurf (Chiesi Farmaceutici, Parma, Italy), 13 with Survanta (Abboth GmbH, Wiesbaden, Germany), 12 with Alveofact (Dr Karl Thomae GmbH, Biberach, Germany), and 3 with Exosurf (Wellcome GmbH, Burgwedel, Germany). Within 1 hour of surfactant treatment, median fraction of inspiratory oxygen was reduced from .84 (25th-75th percentiles:.63-1.0) to.50 (.35-.80). The incidence of complications in the study group (mortality: 30%; pneumothorax: 16%; intracranial hemorrhage: 42%) was high, compared with infants with RDS. CONCLUSIONS: Surfactant therapy improves gas exchange in the majority of patients with GBS pneumonia. The response to surfactant is slower than in infants with RDS, and repeated surfactant doses are often needed. The mortality and morbidity are substantial, considering the relatively high mean birth weight of the treated infants.

Drug Administration Schedule↗
PubMed2000

Prospects for a new synthetic surfactant.

Physiologically active artificial surfactants can be made from lipids and analogs of SP-C and SP-B, the latter serving as cross-linking peptides promoting the formation of a surface-associated surfactant reservoir. Artificial surfactants can probably be tailored to maximize resistance to inactivation by meconium and plasma proteins by modifying the amino acid sequence of the protein analogs or adding non-ionic polymers to the final product. Comparative clinical trials are required to evaluate the efficacy of these new artificial surfactants in various forms of neonatal lung disease.

Animals↗
PubMed1999

A functional spliced-variant of beta 2 subunit of Kv1 channels in C6 glioma cells and reactive astrocytes from rat lesioned cerebellum.

Voltage-gated K(+) channels (Kv1) are important in glia, being required for cell proliferation. Herein, reactive astrocytes from a rat cerebellar lesion were shown to contain Kv1.1, -1.2, -1.3, -1.4, and -1.6 alpha plus beta1.1 subunits, as well as an unusual beta2.1 constituent; the latter was also found in a glioblastoma C6 cell line, together with Kv1.1, -1.3, and -1.6 and beta1.1 subunits. Reverse transcriptase-polymerase chain reaction revealed a novel product of the beta2 gene in C6 cells and reactive astrocytes, but not in cultured astrocytes or rat normal brain. Its cloning identified a variant, Kvbeta2.1A, alternatively spliced between I24 and Y39. Despite this 14 residue deletion, Kvbeta2.1A assembled cotranslationally with Kv1.1 or -1.2 and, when coexpressed with Kv1. 4 in oocytes, increased the inactivation rate of this K(+) current. Whereas the full-length beta2.1 gave a large increase in the amplitude of the Kv1.1 current in oocytes, the effect of beta2.1A varied from a modest elevation of the current to a slight suppression in some cases. In summary, this is the first report of the existence of an alternatively spliced product of the Kvbeta2.1 gene in C6 cells and reactive astrocytes, and supports the involvement of its core region (residues 39 onward) in assembly with alpha subunits while excluding a contribution of the adjacent 14 residues to accelerating the inactivation of Kv1.4.

Alternative Splicing↗
PubMed1999

Light-dependent regulation and postnatal development of the interferon-gamma receptor in the rat suprachiasmatic nuclei.

The interferon-gamma receptor gene was detected in the rat hypothalamic suprachiasmatic nuclei (SCN), the main pacemaker for circadian rhythms, and the molecular identity of the transcript was confirmed by sequencing. The expression of the receptor protein showed a daily rhythm that was dependent on light. It reached its adult pattern in the SCN between postnatal day 11 and 20, i.e., at a time when capacity for photic entrainment of the pacemaker is established.

Aging↗