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Influence of intravenous fentanyl on fetal biophysical parameters during labor.

The short-acting opioid fentanyl has been shown to be a useful analgesic during labor. The purpose of this prospective, comparative investigation was to determine whether fentanyl influenced fetal biophysical parameters during labor. Twenty-four uncomplicated pregnancies at 37-41 weeks were studied during the early active phase of labor. Those patients who requested analgesia (study group) were given a standard 50-micrograms dose of fentanyl intravenously. The study (N = 12) and control (N = 12) groups were similar in maternal age, parity, and gestational age distribution. Fetal body and breathing movements and heart rate patterns were evaluated continuously for 80 min at 10-min epochs. Unlike the control group, fetuses exposed to fentanyl had fewer body movements between contractions (P < 0.03) and spent less overall time moving (P < 0.02). Breathing was abolished at 10 min postdosing in all fetuses exposed to fentanyl but not in the control group. The FHR beat-to-beat variability was reduced between contractions for the first 30 min in 8 (66%) of study cases and none of the control cases (P < 0.01). A sine wave-like FHR pattern was observed for 30 min in two fetuses exposed to fentanyl. All infants had 1- and 5-minute Apgar scores > 6, an umbilical artery pH > 7.20, and no need for resuscitation. In conclusion, an intravenous dose of fentanyl during early active labor was associated with temporary depressant effects on many fetal biophysical parameters without apparent harm being observed at delivery.

Analgesics, Opioid↗

Serial changes in the biophysical profile in patients undergoing cervical ripening with a controlled release PGE2 vaginal pessary.

OBJECTIVE: The purpose of this study was to evaluate the effects of exogenous administration of PGE2 upon the components of the biophysical profile. METHODS: The study group included 17 nulliparas at > or = 38 weeks gestation, with a Bishop score of < or = 4, requiring induction of labor. A controlled release vaginal pessary containing 10 mg of PGE2, designed to release hormones at approximately 0.8 mg per hour in vitro, was used for 12 hours of cervical ripening. The BPP was performed by the same sonographer at three intervals: prior to pessary insertion, at 6 hours, and 12 hours. RESULTS: None of these patients had membrane rupture or went into spontaneous labor during the ripening process. All patients subsequently required amniotomy and oxytocin. The proportion of patients scoring 2 points for fetal breathing movements decreased from 59% at baseline to 0% at 12 hours, P < 0.0005, and the proportion of patients with fetal body movements decreased from 100% at baseline to 25% at 12 hours, P < 0.0005. However, the other components of the biophysical profile were not affected. The mean maternal plasma PGE2 metabolite concentrations were 235 pg/ml, 475 pg/ml, and 466 pg/ml at 0, 6 and 12 hours, respectively, P < 0.005. CONCLUSIONS: In term patients, vaginal administration of the PGE2 pessary was associated with improved Bishop score over 12 hours and significant increases in maternal plasma PGEM levels at 6 hours and 12 hours. These changes were inversely related to fetal breathing and body movements.

Administration, Intravaginal↗

Endocrinological and biophysical responses to further reduction in oxygenation following sustained hypoxemia in fetal goats.

OBJECTIVE: The purpose of this study was to determine fetal endocrinological and biophysical responses to the further reduction in oxygenation following prolonged nonacidemic hypoxemia in fetal goats. METHODS: Seven further hypoxic experiments were performed after prolonged (24-h) nonacidemic hypoxemia, caused by an infusion of nitrogen into the maternal trachea and by reducing uterine arterial blood flow in four chronically instrumented goat fetuses at 123-131 days' gestation. We measured arginine vasopressin, adrenocorticotropic hormone, cortisol, and catecholamines as endocrinological parameters. Fetal heart rate, fetal blood pressure, and fetal breathing movement were observed as biophysical parameters. RESULTS: Fetal arterial pO2 was significantly decreased from 27.0 +/- 1.2 mmHg (control) to 18.0 +/- 0.7 mmHg and 11.3 +/- 1.3 mmHg at the end of the prolonged hypoxemia and the further hypoxia, respectively. The further hypoxia induced reductions in fetal heart rate, increases in fetal blood pressure, and a series of gasping. Arginine vasopressin and catecholamines were elevated significantly by the further hypoxia. Although adrenocorticotropic hormone and cortisol were increasingly elevated, they did not reach a significant level. CONCLUSIONS: Some specific fetal responses-excessive elevations of fetal catecholamines, arginine vasopressin, accompanied with fetal gasping-were observed during further severe hypoxia.

Adrenocorticotropic Hormone↗

Acute oligohydramnios and deteriorating fetal biophysical profile associated with severe preeclampsia.

Acute changes in fetal biophysical profile (BPP) status usually include rapid cessation of all nonessential acute biophysical activities, yet not necessarily an acute decrease in the amniotic fluid volume, or oligohydramnios. A 36-year-old para 3 with early third-trimester severe preeclampsia, mild placental abruption, and fetal growth restriction, with a reassuring BPP of 8/8, was managed expectantly with intravenous magnesium sulfate, hydralazine, and intramuscular corticosteroids. Within 20 h of admission a marked change in the BPP was noted, with a score of 0/8. Amniotic fluid index (AFI), which on admission had been 20.1, progressively became 0, despite a stable normovolemic maternal status. At immediate cesarean, a mildly acidotic and hypoxic fetus was delivered which subsequently did well. This case supports the concept that acute oligohydramnios may develop rapidly in the presence of acute fetal hypoxemia.

Adult↗

Effect of gamma-irradiation on the biophysical and morphological properties of corn.

The effects of gamma-irradiation on the biophysical and morphological properties of corn plants were investigated. The irradiation doses were 0, 1, 1.5, 2.5, 5, and 10 krad. Corn grains exposed to 1.5 and 2.5 krad showed highly significant changes in all growth parameters. Fluorescence and light absorption spectra of chlorophyll attributed to different doses treatments of corn grains clearly confirmed the superiority of 1.5 krad irradiation dose in stimulating corn plants. Furthermore, the frequency dependence of the relative permittivity and the electric conductivity of the treated samples have been performed and discussed. The obtained results give another support via the biophysical properties for the 1.5 krad irradiation dose to be the most favorable one to improve the plant growth characteristics.

Chlorophyll↗

Acceleration of experimental endochondral ossification by biophysical stimulation of the progenitor cell pool.

Endochondral ossification can be modulated by a number of biochemical and biophysical stimuli. This study uses the experimental model of decalcified bone matrix-induced endochondral ossification to examine the effect of one biophysical stimulus, an electromagnetic field, on chondrogenesis, calcification, and osteogenesis. A temporal acceleration and quantitative increase in sulfate incorporation, glycosaminoglycan content, and calcification suggests that the stimulation of endochondral ossification is due to an increase in extracellular matrix synthesis. The locus of that stimulation is identified in the mesenchymal stage of endochondral bone development, and stimulation at this stage is essential for accelerated bone formation. The data suggest that enhanced differentiation of mesenchymal stem cells present at this stage is most likely responsible for the increase in extracellular matrix synthesis and bone maturation.

Animals↗

Ionic channels: I. The biophysical basis for ion passage and channel gating.

This article reviews the biophysics of ion passage through membrane pores, as well as the physical factors that control the ion selectivity, gating, and conductance of an ionic channel. Different voltage clamp techniques are discussed in detail. The biophysical properties of sodium channels are reviewed.

Action Potentials↗

A novel method for the study of the biophysical interface in soils using nano-scale secondary ion mass spectrometry.

The spatial location of microorganisms and their activity within the soil matrix have major impacts on biological processes such as nutrient cycling. However, characterizing the biophysical interface in soils is hampered by a lack of techniques at relevant scales. A novel method for studying the distribution of microorganisms that have incorporated isotopically labelled substrate ('active' microorganisms) in relation to the soil microbial habitat is provided by nano-scale secondary ion mass spectrometry (NanoSIMS). Pseudomonas fluorescens are ubiquitous in soil and were therefore used as a model for 'active' microorganisms in soil. Batch cultures (NCTC 10038) were grown in a minimal salt medium containing 15N-ammonium sulphate (15/14N ratio of 1.174), added to quartz-based white sand or soil (coarse textured sand), embedded in Araldite 502 resin and sectioned for NanoSIMS analysis. The 15N-enriched P. fluorescens could be identified within the soil structure, demonstrating that the NanoSIMS technique enables the study of spatial location of microbial activity in relation to the heterogeneous soil matrix. This technique is complementary to the existing techniques of digital imaging analysis of soil thin sections and scanning electron microscopy. Together with advanced computer-aided tomography of soils and mathematical modelling of soil heterogeneity, NanoSIMS may be a powerful tool for studying physical and biological interactions, thereby furthering our understanding of the biophysical interface in soils.

Electron Probe Microanalysis↗

Biochemical and biophysical characterization of pulmonary surfactant in rats exposed chronically to cigarette smoke.

The pulmonary surfactant plays an important role in the gas exchange functions of the lungs. Although previous studies suggest that cigarette smoking alters the pulmonary surfactant system in human smokers, the nature of such changes is poorly understood. The aim of the present study was to determine if biochemical and biophysical properties of pulmonary surfactant are affected in rats following chronic exposure to cigarette smoke. Female Sprague-Dawley rats were exposed daily to smoke from the University of Kentucky high tar/high nicotine reference cigarettes, twice a day, for 60 weeks in a nose-only exposure system. Blood carboxyhemoglobin, plasma cotinine, and pulmonary aryl hydrocarbon hydroxylase activity measurements showed that animals effectively inhaled smoke during exposures. At termination, the bronchoalveolar lavage fluids (BALF) and the lung tissues were collected for biochemical and biophysical analyses of surfactant. The total phospholipid content of the BALF and the lung tissues from room control (RC), sham-treated (SH), and smoke-exposed (SM) animals were the same among the different groups. However, disaturated phosphatidylcholine (DSPC) levels in the BALF were significantly decreased in SM rats compared to RC or SH groups. In contrast, the lung tissue DSPC content in SM rats was not significantly different from that of control groups. Phospholipid profile analysis of the BALF also did not reveal any significant differences among other major constituents of surfactant from control and SM animals. The organic extracts of BALF obtained from different animal groups were assessed for surface activity using a Wilhelmy balance. The results showed an increase in surface compressibility and a reduction in respreadability index in SM group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Two hydrophobic protein fractions of ovine pulmonary surfactant: isolation, characterization, and biophysical activity.

Pulmonary surfactant contains two extremely hydrophobic proteins, SP-B and SP-C. We present a novel HPLC method for the preparation of these hydrophobic proteins. It is based on size-exclusion chromatography using the apolar stationary-phase butyl silica gel and isocratic elution with acidified chloroform/methanol. Samples for HPLC were prepared from sheep lung lavage fluid by centrifugation and extraction with chloroform/methanol. Amino acid analyses of the two protein fractions revealed sequences that are consistent with SP-B and SP-C, respectively. MALDI-TOF-MS analyses of the SP-B fraction showed one major peak of dimeric SP-B with m/z 17,361, and additional peaks of monomeric and oligomeric forms, which are predominantly even numbered. The SP-C fraction showed a peak at m/z 4200, consistent with the theoretical mass of the dipalmitoylated form of this protein. The biophysical activity of pure sheep SP-B and SP-C was evaluated by measuring the surface tension using axisymmetric drop shape analysis for captive bubbles. We found distinct surface pressure versus surface area isotherms of SP-B and SP-C indicating different biophysical activities for these surfactant proteins. The new preparative HPLC method is able to replace the established, time-consuming low-pressure liquid chromatography method for the isolation of SP-B and SP-C from lipids.

Animals↗

Biophysical studies of signal peptides: implications for signal sequence functions and the involvement of lipid in protein export.

This review discusses efforts to understand the mode of action of signal sequences by biophysical study of synthetic peptides corresponding to these protein localization signals. On the basis of reports from several laboratories, it is now clear that signal peptides may adopt a variety of conformations, depending on their local environment. In membrane-mimetic systems like detergent micelles or lipid vesicles, they have a high tendency to form alpha helices. Ability to take up a helical conformation appears to be required at some point in the function of a signal sequence, since some peptides corresponding to export-defective signal sequences display reduced helical potential. By contrast, functional signal sequences share a high capacity to adopt alpha helices. High affinity for organized lipid assemblies, like monolayers or vesicles, is also a property of functional signal sequences. This correlation suggests a role for direct interaction of signal sequences with the lipids of the cytoplasmic membrane in vivo. Supporting this role are studies of the influence of signal peptides on lipid structure, which reveal an ability of these peptides to perturb lipid packing and to alter the phase state of the lipids. Insertion of the signal sequence in vivo could substantially reduce the barrier for translocation of the mature chain. Lastly, synthetic signal peptides have been added to native membranes and found to inhibit translocation of precursor proteins. This approach bridges the biophysical and the biochemical aspects of protein export and promises to shed light on the functional correlates of the properties and interactions observed in model systems.

Amino Acid Sequence↗

Functional properties of Na,K-ATPase, and their structural implications, as detected with biophysical techniques.

A full understanding of the molecular mechanism of ion transport and energetics of the Na,K-ATPase will require both structural and functional data. During recent years biophysical methods have provided a number of important pieces of information on ion binding and release and the charge transfer process. This allows the formulation of kinetic models of the transport process. Although a breakthrough has not been obtained due to the lack of detailed knowledge on the three-dimensional structure with a resolution high enough to identify the ion-binding sites and the transport pathway, the functional information has structural implications that create constraints on possible mechanisms of active transport. Here we describe briefly contributions of some biophysical methods to our conceptual understanding of the ion transport process.

Protein Conformation↗

Biophysical characteristics of swelling-activated Cl- channels in human tracheal 9HTEo-cells.

The question of whether a single molecule can account for every observed swelling-activated Cl- current deserves to be addressed and biophysical description seems to be an adequate criterion to classify these channels. We studied the biophysical properties of swelling-activated Cl- currents in 9HTEo-cells using whole-cell and outside-out patch clamp recordings. Hypotonic shock activated outwardly rectifying currents that inactivated at potentials higher than 20 mV. The decay phase of the current was well fitted by two exponential functions and both time constants were voltage-dependent. Two voltage-dependent time constants were also necessary to describe reactivation. The midpoint of current inactivation was 54 mV. The voltage dependence of kinetics did not significantly change by modifying the extracellular NaCl concentration while the inactivation midpoint slightly shifted. In conclusion, our results indicate that the voltage-dependent properties of the swelling-activated Cl- currents in 9HTEo- cells are largely independent from the extracellular ionic strength and the extracellular Cl- concentration. Excised patches from cells exposed to hypotonic shock showed single channel currents that inactivated at positive membrane potentials and displayed chord conductance of approximately 60 pS at 100 mV and of approximately 20 pS at -80 mV. The permeability sequence for the single channel was I- > Br- > Cl- > gluconate and currents were blocked by Reactive blue 2. These properties indicate that intermediate conductance outwardly rectifying channels are responsible for the macroscopic swelling-activated current.

Cell Line, Transformed↗

Converging evidence for a simplified biophysical model of synaptic plasticity.

Different mechanisms that could form the molecular basis for bi-directional synaptic plasticity have been identified experimentally and corresponding biophysical models can be constructed. However, such models are complex and therefore it is hard to deduce their consequences to compare them to existing abstract models of synaptic plasticity. In this paper we examine two such models: a phenomenological one inspired by the phenomena of AMPA receptor insertion, and a more complex biophysical model based on the phenomena of AMPA receptor phosphorylation. We show that under certain approximations both these models can be mapped on to an equivalent, calcium-dependent, differential equation. Intracellular calcium concentration varies locally in each postsynaptic compartment, thus the plasticity rule we extract is a single-synapse rule. We convert this single synapse plasticity equation to a multi-synapse rule by incorporating a model of the NMDA receptor. Finally we suggest a mathematical embodiment of metaplasticity, which is consistent with observations on NMDA receptor properties and dependence on cellular activity. These results, in combination with some of our previous results, produce converging evidence for the calcium control hypothesis including a dependence of synaptic plasticity on the level of intercellular calcium as well as on the temporal pattern of calcium transients.

Animals↗

Biophysical limitation of leaf cell elongation in source-reduced barley.

The biophysical basis of reduced leaf elongation rate in source-reduced barley ( Hordeum vulgare L. cv Golf) was studied. Reduction in source strength was achieved by removing the blade of leaves 1 and 2 at the time leaf 3 had emerged 3.0-6.7 cm from the encircling sheath. Third leaves of source-reduced plants elongated at 10-36% lower velocities than those of control plants. Removal of source leaves had no significant effect on maximum relative elemental growth rates (REGRs) and the length of the elongation zone (42-46 mm) but caused a shift of high REGR towards the basal portion of the elongation zone. Cell turgor was similar between treatments in the zone of maximal REGR (16-24 mm from base), but was significantly lower in source-reduced plants in the distal part of the elongation zone, where REGR was also lower. Throughout the elongation zone, osmolality and growth-associated water potential gradients were significantly smaller in source-reduced plants; bulk concentrations of sugars (hexoses, sucrose) were also lower. However, even in control plants, sugars contributed little to bulk osmotic pressure (6-11%). The most likely biophysical limitation to leaf (cell) elongation in source-reduced barley was a reduction in turgor in the distal half of the elongation zone. It is proposed that in the proximal half, increase in average tissue hydraulic conductance enabled source-reduced plants to maintain turgor and REGR at control level, while spending less energy on solute transport.

Algorithms↗

Evaluation of ablation patterns using a biophysical model of atrial fibrillation.

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia. Surgical/Radiofrequency (RF) ablation is a therapeutic procedure that consists of creating lines of conduction block to interrupt AF. The present study evaluated 13 different ablation patterns by means of a biophysical model of the human atria. In this model, ablation lines were abruptly applied transmurally during simulated sustained AF, and success rate, time to AF termination and average beat-to-beat interval were documented. The gold standard Cox's Maze III procedure was taken as reference. The effectiveness of twelve less invasive patterns was compared to it. In some of these incomplete lines (entailing a gap) were simulated. Finally, the computer simulations were compared to clinical data. The results show that the model reproduces observations made in vivo: (1) the Maze III is the most efficient ablation procedure; (2) less invasive patterns should include lines in both right and left atrium; (3) incomplete ablation lines between the pulmonary veins and the mitral valve annulus lead to uncommon flutter; (4) computer simulations of incomplete lines are consistent with clinical results of non-transumural RF ablation. Biophysical modeling may therefore be considered as a useful tool for understanding the mechanisms underlying AF therapies.

Atrial Fibrillation↗

Fetal biophysical profile scoring: a prospective study in 1,184 high-risk patients.

The results of a prospective clinical management based on fetal biophysical profile scoring method was evaluated in 1,184 referred high-risk patients. Six perinatal deaths occurred in the study group (perinatal mortality of 5.06 per 1,000); only one fetus suffered unpredictable and unpreventable death (true false negative rate 0.8 per 1,000). In addition, 13 fetuses with major congenital anomalies were detected as a result of ultrasound scanning for fetal biophysical activities. These data suggest that this method can be used effectively to screen and manage a high-risk population.

Congenital Abnormalities↗

Antepartum fetal assessment using a fetal biophysical profile score.

The application of the fetal biophysical profile score in the management of 2,400 high-risk pregnancies was assessed. The negative predictive value for normal perinatal outcome was not improved compared to single variable tests. The positive predictive value for abnormal perinatal outcome was improved. The overall perinatal mortality in 2,485 fetuses was 9.2 per 1,000. In the 1,980 fetuses with a normal biophysical profile score within 7 days of delivery, excluding lethal anomalies, the perinatal mortality was 1 per 1,000. Fetal movement counting is supported as the most valid and appropriate test for universal fetal screening.

Amniotic Fluid↗