bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of interaction between Kalmia angustifolia cover and Picea mariana seedlings
Authors: Wallstedt Anna , Coughlan Andrew , Munson Alison D , Nilsson Marie-Charlotte , Margolis Hank A
Published: November 2002

Sites dominated by Kalmia angustifolia L. are often associated with slow decomposition of organic matter, decreased nitrogen (N) mineralization rates, and low black spruce (Picea mariana (Mill.) BSP) productivity. The objective of this study was to separate the effects of belowground competition by Kalmia from the effects of water-soluble soil phenols on black spruce seedlings growing under different levels of Kalmia cover. A factorial greenhouse bioassay was established in which black spruce seedlings were grown for 6 months in intact blocks of soil with three different levels of Kalmia cover. The soil was treated with charcoal to reduce the amounts of water-soluble phenols, and (or) tubes were inserted to exclude Kalmia roots. At low Kalmia cover, reducing the level of belowground competition increased seedling biomass by 134%. However, reducing belowground competition did not increase seedling biomass at the two higher levels of Kalmia cover. It is possible that seedling biomass remained low because of an increased immobilization of N in the organic layer. Furthermore, the proportion of ectomycorrhiza morphotypes differed among seedlings growing under different levels of Kalmia cover. The effect of water-soluble phenols on seedling growth remains uncertain, since we observed a confounding effect of the charcoal treatment on soil microbial biomass and seedling response.
Predicting survival and growth rates for individual loblolly pine trees from light capture estimates
Authors: MacFarlane David W , Green Edwin J , Brunner Andreas , Burkhart Harold E
Published: November 2002

Light capture estimates from models can be related to survival and growth rates and may provide new ways to model forest dynamics. However, relationships between light capture, growth, and survival should vary widely with tree age, site conditions, and stand density, so predictions from light capture models need to be tested over a range of stand conditions. We used the tRAYci stand light model (A. Brunner. 1998. For. Ecol. Manage. 107: 1946) to estimate weighted leaf area (WLA), an estimate of annual light capture, for every tree, in 36 even-aged loblolly pine (Pinus taeda L.) stands, representing different combinations of site index and planting density, over an 8-year period. We also developed regression equations relating light capture estimates to height growth, basal area growth, stem volume growth, and survival probability for individual trees at different ages, sites, and planting densities. Our results suggest a significant correlation between estimates of WLA and tree growth and survival rates, and that the tRAYci model is robust across a range of stand conditions. An important finding was that WLA was a better predictor of survival probability than measured basal area increment. Effects of site index, age, and planting density on light capture  growth relationships are also discussed.
Short-term population dynamics of Glaucomys sabrinus and Tamiasciurus douglasii in commercially thinned and unthinned stands of coastal coniferous forest
Authors: Ransome Douglas B , Sullivan Thomas P
Published: November 2002

Population dynamics of Glaucomys sabrinus (Shaw) and Tamiasciurus douglasii (Audubon and Bachman) were examined in commercially thinned and unthinned stands in British Columbia, Canada. We tested the hypothesis that commercial thinning would have negative short-term effects on the population dynamics of these species. Populations were monitored using markrecapture techniques in two commercially thinned and two unthinned stands dominated by 60- to 70-year-old western hemlock (Tsuga heterophylla (Raf.) Sarg.) and western redcedar (Thuja plicata Donn. ex D. Don). Populations were sampled intensively from August 1995 to May 1999 at Chehalis Lake and from May 1997 to March 2000 in the Malcolm Knapp Research Forest (MKRF). There were no differences among stands thinned and unthinned in movement, abundance, recruitment, survival, duration individuals remained in stands, percentage of males breeding, and mass of males for G. sabrinus or T. douglasii. Mean density of G. sabrinus in thinned and unthinned stands were 0.65 and 0.89 individuals/ha, respectively, at Chehalis and 0.09 and 0.51 individuals/ha, respectively, at MKRF. Mean density of T. douglasii in thinned and unthinned stands were 1.18 and 0.87 individuals/ha, respectively, at Chehalis and 1.08 and 1.00 individuals/ha, respectively, at MKRF. We concluded that commercial thinning had no negative short-term effects on the population dynamics of these species.
Developing a system of annual tree growth equations for the loblolly pine  shortleaf pine type in Louisiana
Authors: Cao Quang V , Li Shiansong , McDill Marc E
Published: November 2002

An individual tree growth modeling system was developed for the loblolly pine (Pinus taeda L.)  shortleaf pine (Pinus echinata Mill.) forest type in Louisiana using USDA Forest Service Forest Inventory and Analysis (FIA) data. In this study, the loblolly pine  shortleaf pine forest type was divided into three species groups: loblolly pine, other pines, and hardwoods. The growth system includes models for individual tree survival, diameter growth, height growth, and change in crown ratio for each of the three species groups. A multivariate extension of a two-step, model-based interpolation method is proposed to estimate parameters of annual tree growth equations based on measurements from 7-year growth periods. Results based on evaluation statistics such as mean difference, mean absolute difference, and fit index show that the two-step interpolation method is clearly superior to the averaging method, which is a typical linear interpolation method. The two-step method produced growth equations that project tree and plot attributes more accurately than the averaging method. Additionally, a Monte Carlo simulation analysis reveals that parameter estimates obtained from the two-step method are closer to the true parameter values than those from the averaging method. The approach described here should be useful for estimating parameters of other systems of annual tree growth equations from periodic measurements. Models such as the one presented here may be useful for projecting the characteristics of undisturbed forest inventory plots, e.g., FIA plots, and providing more up-to-date inventory estimates.
Dynamics of an old-growth, fire-initiated, subalpine forest in southern interior British Columbia: tree-ring reconstruction of 2 year cycle spruce budworm outbreaks
Authors: Parish Roberta , Antos Joseph A
Published: November 2002

Tree-ring width chronologies of three species from a 330-year-old subalpine forest were used to reconstruct outbreaks of 2 year cycle spruce budworm (Choristoneura biennis Freeman). The growth of host species, Engelmann spruce (Picea engelmannii Parry ex Engelm.) and subalpine fir (Abies lasiocarpa (Hook.) Nutt.), was compared with that of the nonhost, lodgepole pine (Pinus contorta Dougl. ex Loud.) with and without the removal of the effects of climate on growth. Seven periods, 19891991, 19431957, 19111927, 18691875, 18391861, 18231829, 17851801, were identified in which the growth of both host species was reduced relative to the non-host; this includes the single known outbreak from 1944 to 1956. Spectral analysis indicated a periodicity for growth reduction of the host relative to non-host species of ca. 45 years for both spruce and fir. For three periods, the known outbreak in the 19401950s, and two inferred outbreaks in the 19101920s and 18401850s, we calculated the four measures of radial growth first proposed by Brubaker and Greene (L.B. Brubaker and S.K. Greene. 1979. Can. J. For. Res. 9: 95105): the maximum rate of growth loss, 1-year and 5-year losses, and the rate and time to recovery. Growth losses were greater for fir than for spruce during all three periods. During the 19401950s, growth losses were severe, but losses were less in the 19101920s. The impact of C. biennis has varied among outbreak periods but, overall, has made a pronounced contribution to present stand conditions. Our work suggests that budworms have been a frequent agent of disturbance with major effects on forest dynamics in southern British Columbia, especially in sprucefir forests when long periods occur between fires.
Combining environmentally dependent and independent analyses of witness tree data in east-central Alabama
Authors: Black Bryan A , Foster H Thomas , Abrams Marc D
Published: November 2002

We reconstructed pre-European settlement forest composition across 13 000 km2 of east-central Alabama using 43 610 witness trees recorded in the original Public Land Surveys. First, we interpolated the witness tree data to estimate broad-scale vegetation patterns. Next, we conducted speciessite analysis on landforms, an approach that was dependent on underlying environmental variables yet better resolved fine-scale vegetation patterns. East-central Alabama was dominated by three community types: oakhickory across the Piedmont physiographic province and valleys of the Ridge and Valley province, pine  blackjack oak on the Coastal Plain province and ridges of the Ridge and Valley province, and white oak  mixed mesophytic in stream valleys and floodplains. Witness tree concentration (trees/km2) was highly uniform across much of the study area. However, there was an unusually low concentration of witness trees in the southwestern corner of the study area, and an unusually high concentration in stream valleys. Another irregularity was the inability of surveyors to distinguish black oak and red oak. Overall, the interpolations provided an unbiased, yet broad-scale estimate of forest composition, while the specieslandform analysis greatly increased resolution of forest cover despite the subjectivity of defining environmental variables a priori.
DIMENSIONAL REDUCTION AND THE VACUUM STATE IN THE SUPERSTRING THEORY
Authors: POLLOCK M. D.
Published: November 2002

The ten-dimensional effective action of the heterotic superstring theory contains a quadratic higher-derivative term in the form of the Euler-number density [Formula: see text]. We discuss the role of this term in determining the dimensionality [Formula: see text] of the physical space–time, obtained by dimensional reduction, applying the Feynman propagator and the zero-action hypothesis.
SOLVING OPERATOR DIFFERENTIAL EQUATIONS IN TERMS OF THE WEYL-ORDERED POLYNOMIALS
Authors: CHEN ZENG-BING , LU HUAI-XIN , LI JUN
Published: November 2002

A systematic approach to integrate the Heisenberg equations of motion is proposed by using the Weyl-ordered polynomials. The solutions of the Heisenberg equations of motion, i.e. P(t) and Q(t), are expanded as a sum over the Weyl-ordered polynomials Tm,n(P(t),Q(t)) at time t = 0. The coefficients of the expansions satisfy two sets of first-order ordinary differential equations resulting from the Heisenberg equations of motion for time-independent systems. This general approach for time-independent systems is also tractable in obtaining the adiabatic invariants of the time-dependent systems. In this paper, interest is mainly focused on the formal aspect of the approach.
GRAVITATIONAL CONSTANT AND TORSION
Authors: MAHATO PRASANTA
Published: November 2002

Riemann–Cartan space–time U4 is considered here. It has been shown that when we link topological Nieh–Yan density with the gravitational constant, we then obtain Einstein–Hilbert Lagrangian as a consequence.
ON THE PSEUDO-HERMITICITY OF A CLASS OF PT-SYMMETRIC HAMILTONIANS IN ONE DIMENSION
Authors: MOSTAFAZADEH ALI
Published: November 2002

For a given standard Hamiltonian H = [p - A(x)]2/(2m) + V(x) with arbitrary complex scalar potential V and vector potential A, with x ∈ ℝ, we construct an invertible antilinear operator τ such that H is τ-anti-pseudo-hermitian, i.e. H† = τHτ-1. We use this result to give the explicit form of a linear hermitian invertible operator with respect to which any standard PT-symmetric Hamiltonian with a real degree of freedom is pseudo-hermitian. Our results do not make use of the assumption that H is diagonalizable or that its spectrum is discrete.
SPONTANEOUS SYMMETRY BREAKING IN THE SPACE–TIME OF AN ARBITRARY DIMENSION
Authors: GU JE-AN , HWANG W.-Y. P.
Published: November 2002

We study the spontaneous symmetry breaking (SSB) induced by a scalar field and its non-minimal interaction with gravity in the space–time of an arbitrary dimension (D > 2), where the gravitational field is treated as a dynamical field. We explore mainly the possibility of implementing SSB after introducing the non-minimal coupling with such dynamical gravitational field.
THE DIRAC EQUATION IN A PSEUDOSCALAR COULOMB POTENTIAL
Authors: McKEON D. G. C. , VAN LEEUWEN G.
Published: November 2002

We consider solutions to the Dirac equation in the presence of an external pseudoscalar potential V(r) = 1/r. It is found that no normalizable bound state solutions exist.
SLq(2) GLOBAL SYMMETRY FOR FOUR-STATE QUANTUM CHAINS
Authors: RODRÍGUEZ-ROMO SUEMI
Published: November 2002

Following the method already used to obtain quantum chains with Dipper–Donkin global symmetry,14 we obtain all possible four-state quantum chains with SL q(2,C) global symmetry when q is not a root of unity. One of these Hamiltonians is written in terms of matrix units, as an example.
INHOMOGENEOUS COSMOLOGICAL MODEL IN LYRA GEOMETRY
Authors: RAHAMAN F. , CHAKRABORTY S. , BERA J.
Published: November 2002

Exact solutions are obtained for an inhomogeneous cosmological model in normal gauge for Lyra's geometry. Some properties of the model have also been discussed.
Conus Venom Peptides: Reflections from the Biology of Clades and Species
Authors: Olivera Baldomero M.
Published: November 2002

▪ Abstract  The 500 cone snail species (Conus) use complex venoms to capture prey, defend against predators and deter competitors. Most biologically active venom components are small, highly structured peptides, each encoded by a separate gene. Every Conus species has its own distinct repertoire of 100–200 venom peptides, with each peptide presumably having a physiologically relevant target in prey or potential predators/competitors. There is a remarkable interspecific divergence observed in venom peptide genes, which can be rationalized because of biotic interactions that are species specific. The peptide families/subfamilies characteristic of clades of related Conus species are potentially useful clade markers and can be used to indicate common biological mechanisms characterizing that clade. By knowing both the distribution and the physiological function of venom peptides, a type of reverse ecology becomes possible; the peptides in a Conus venom are a molecular readout of the biotic interactions of a species or clade.
Animal Practices and the Racialization of Filipinas in Los Angeles
Authors: Lassiter Unna , Griffith Marcie , Wolch Jennifer
Published: November 2002

Many factors contribute to the racialization of minority groups in the United States. Some individual characteristics, such as skin color or phenotype, are an obvious holdover from colonial times. Cultural differences in representational practices, customs and rituals, and belief systems are now more significant in racialization. Although not typically a focus of academic scrutiny, some of these differences involve contrasts in nature-society relations, and more specifically, nonhuman animal-society relations. In order to examine the relationship between culturally based animal practices and racialization, we organized and conducted a focus group consisting of low-income inner city Filipinas living in Los Angeles, California. Analysis of focus group data reveal that Filipinos in southern California are subject to racialization by Anglos because of their culturally based animal practices, in particular the traditional Filipino practice of treating dogs as food animals. The experience of racialization appeared to engender cultural relativism and tolerance toward the animal practices of other non-Anglo groups.
Ethnic Variations in Pet Attachment among Students at an American School of Veterinary Medicine
Authors: Brown Sue-Ellen
Published: November 2002

This study explores ethnic variations in animal companion ("pet") attachment among 133 students enrolled in a school of veterinary medicine. The 57 White and 76 African American participants completed surveys that included background information, several questions about their animal companions, and a pet attachment questionnaire (PAQ).White students had significantly higher PAQ scores than did African American students (p<.001). White students also had significantly more pets (M =4.05 vs. 2.18, p<.001) and more kinds of pets (M =2.30 vs. 1.57, p<.001) and were more likely to allow pets to sleep on their beds (70% vs. 53%, p<.05). Although keeping pets is a universal cultural phenomenon, how that attachment is expressed may vary from culture-to-culture. This study explores possible explanations and implications for these variations.
Human-to-Animal Similarity and Participant Mood Influence Punishment Recommendations for Animal Abusers
Authors: Waerstad Jon , Hobbins Thea , Wirrel Joanne , Hunstone Mathew , Foy Emma , Allen Michael , Wikner Britt
Published: November 2002

Studies of observer responses to human-to-human abuse have found that both an observer's mood and the similarity of the victim to the observer affect the observer's desire to help the victim and punish the offender. The present study examined the extent to which similarity and mood also shape observer responses to human-to-animal abuse.We first manipulated participants' mood by giving non-contingent feedback on a hidden word task (positive, negative, or no feedback). Participants then read a scenario describing an instance of animal abuse (using four different specific kinds of animals and six general species categories). Results showed that participants in a better mood recommended harsher punishment for the offender.They also recommended harsher punishment for the abuse of animals more similar to humans. Similarity and mood interacted on fine recommendationsmdash;better mood accentuated the similarity effect. Empathy for an animal positively correlated with punishment recommendations for the offender. The study discusses directions for future research and theory development.
The Wild Side of Animal Domestication
Authors: Russell Nerissa
Published: November 2002

This paper examines not the process but the concept of nonhuman animal domestication. Domestication involves both biological and cultural components. Creating a category of domestic animals means constructing and crossing the boundaries between human and animal, culture and nature. The concept of domestication thus structures the thinking both of researchers in the present and of domesticators and herders in the past. Some have argued for abandoning the notion of domestication in favor of a continuum of human-nonhuman animal relationships. Although many human-animal relationships cannot be neatly pigeonholed as wild or domestic, this paper contends that the concept of domestication retains its utility.There is a critical distinction between animals as a resource and animals as property. Domestication itself had profound consequences for the societies and worldview of the domesticators and their descendents. In addition to the material effects of animal wealth, domestic animals provide both a rich source of metaphor and a model of domination that can be extended to humans.
Marxism and the Underdog
Authors: Perlo Katherine
Published: November 2002

Marxism has defined its key values in opposition to animals other than human in order to promote the interests of the most downtrodden human beings. Although it has characterized itself as a scientific historical and economic theory, sympathy for human suffering has provided its most powerful motivation as a political force. This capacity for sympathy, causing in modern times an extension of Marxist concerns beyond "class" in the original sense, is beginning to accommodate animals as are the theoretical concepts of alienation, surplus value, and historical materialism. Marxism's inconsistencies are being resolved in favor of the side that, for human as well as animal benefit, favors individual sentience and other pro-animal values. So, in a truly dialectical progression, the same quality of sympathy that at first caused Marxism to denigrate animals is now coming out in their support.
Nocturnal evolution of respiratory effort in obstructive sleep apnoea syndrome: influence on arousal threshold
Authors: Sforza E , Krieger J , Petiau C
Published: November 2002

It has been recently described that the overnight increase in maximal end-apnoeic oesophageal pressure (P(oes,max)), considered as an index of the arousal threshold to occlusion, mostly contributes to apnoea lengthening during the night. However, the rise in apnoea duration could also be caused by changes in hypoxaemia, chemosensitivity and upper airway resistance. To better define the relative contributions of each of these factors, we examined the recordings of nine patients. Before apnoea, the mean pulmonary resistance at peak inspiratory flow (RPIF) was computed. During apnoea, all swings in oesophageal pressure (P(oes)) were measured to define the P(oes,max), the increase from the minimum to the maximum (deltaP(oes)), the rate of increase in P(oes) (RP(oes)) and the P(oes) at the first occluded breath (P(oes,1)). A gradual and significant increase in apnoea duration (p=0.02), P(oes,max) (p=0.02) and deltaP(oes) (p=0.006) was present across the night without any changes in oxygen saturation, RPIF, and P(oes,1). The slope of increase in P(oes,max), apnoea duration and deltaP(oes) was correlated with the apnoea/hypopnoea index. We conclude that in obstructive sleep apnoea, the nocturnal rise in apnoea duration is attributable more to an increase in the arousal threshold related to apnoea recurrence than to changes in chemosensitivity and upper airway resistance.
Does arousal frequency predict daytime function?
Authors: Kingshott RN , Engleman HM , Deary IJ , Douglas NJ
Published: November 2002

Patients with the sleep apnoea/hypopnoea syndrome (SAHS) have impaired daytime function with demonstrable sleepiness and impaired cognition. The hypothesis that brief arousals from sleep cause these daytime impairments was tested. One hundred and fifty patients with sleep disordered breathing were studied prospectively, comparing overnight polysomnography with daytime measures of objective sleepiness, psychological well-being and cognitive performance. Significant, but weak (r2<0.1), relationships were seen between several nocturnal measures (apnoea/hypopnoea index, arousals and desaturation variables) and daytime measures of quality of life, well-being, subjective sleepiness, symptoms and cognitive performance. The only significant relationship between nocturnal variables and objective sleepiness was a very weak correlation (r2<0.05) between the lowest oxygen saturation and mean maintenance of wakefulness test (MWT) result. The MWT was better correlated with daytime function than the multiple sleep latency test. This study shows a lack of strong relationships between conventional nocturnal measures and daytime function in patients with sleep disordered breathing.
Effect of low-dose acetazolamide on the ventilatory CO2 response during hypoxia in the anaesthetized cat
Authors: Wagenaar M , Teppema L , Berkenbosch A , Olievier C , Folgering H
Published: November 2002

Acetazolamide, a carbonic anhydrase inhibitor, is used in patients with chronic obstructive pulmonary diseases and central sleep apnoea syndrome and in the prevention and treatment of the symptoms of acute mountain sickness. In these patients, the drug increases minute ventilation (V'E), resulting in an improvement in arterial oxygen saturation. However, the mechanism by which it stimulates ventilation is still under debate. Since hypoxaemia is a frequently observed phenomenon in these patients, the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the ventilatory response to hypercapnia during hypoxaemia (arterial oxygen tension (Pa,O2)=6.8+/-0.8 kPa, mean+/-SD) was investigated in seven anaesthetized cats. The dynamic end-tidal forcing (DEF) technique was used, enabling the relative contributions of the peripheral and central chemoreflex loops to the ventilatory response to a step change in end-tidal carbon dioxide tension, (PET,CO2) to be separated. Acetazolamide reduced the CO2 sensitivities of the peripheral (Sp) and central (Sc) chemoreflex loops from 0.22+/-0.08 to 0.11+/-0.03 L x min(-1) x kPa(-1) (mean+/-SD) (p<0.01) and from 0.74+/-0.32 to 0.40+/-0.10 L x min(-1) x kPa(-1) (p<0.01), respectively. The apnoeic threshold B (x-intercept of the ventilatory CO2 response curve) decreased from 2.88+/-0.97 to 0.95+/-0.92 kPa (p<0.01). The net result was a stimulation of ventilation at PET,CO2 <5 kPa. The effect of acetazolamide is possibly due to a direct effect on the peripheral chemoreceptors as well as to an effect on the cerebral blood flow regulation. Possible clinical implications of these results are discussed.
Effects of negative pressure assisted ventilation on dyspnoeic sensation and breathing pattern
Authors: Nishino T , Isono S , Ide T
Published: November 2002

Although negative pressure assisted ventilation with an assist-control mode may have a potential therapeutic role in the treatment of severe dyspnoea, the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns have not been examined. We examined the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns produced by a combination of resistive loading and hypercapnia in nine healthy subjects breathing spontaneously. Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale. Negative pressure assisted ventilation caused a significant reduction in sensation of respiratory discomfort from a visual analogue scale score of 74 (55-91) (median (range)) before negative pressure assisted ventilation to 34 (15-53) during negative pressure assisted ventilation (p<0.01). During negative pressure assisted ventilation, there were significant changes in breathing patterns characterized by an increase in tidal volume and a decrease in respiratory frequency, while neither minute ventilation nor end-tidal carbon dioxide tension changed. Our results indicate that negative pressure assisted ventilation with the assist-control mode is effective in relief of dyspnoea and that negative pressure assisted ventilation influences the control of breathing to minimize respiratory discomfort.
Domiciliary liquid oxygen versus concentrator treatment in chronic hypoxaemia: a cost-utility analysis
Authors: Andersson A , Strom K , Brodin H , Alton M , Boman G , Jakobsson P , Lindberg A , Uddenfeldt M , Walter H , Levin LA
Published: November 2002

Whether long-term oxygen therapy (LTOT) improves quality of life in chronic hypoxaemia has been questioned. LTOT with an oxygen concentrator (C/C) and gas cylinders for ambulation is considered cumbersome compared to mobile liquid oxygen equipment (L). The hypothesis for this study was that LTOT with liquid oxygen treatment (L) improves patients' health-related quality of life, but that it is also more expensive compared to concentrator (C/C) treatment. A prospective, randomized multicentre trial comparing C/C with L for LTOT was conducted during a six-month period. Fifty-one patients (29 on L and 22 on C/C) with chronic hypoxaemia, regularly active outside the home, participated in the study initially. Costs for oxygen were obtained from the pharmacies. Patient diaries and telephone contacts with members of the healthcare sector were used to estimate costs. Health-related quality of life was measured by the Sickness Impact Profile (SIP) and the EuroQol, instruments at the start and after 6 months. The average total cost per patient for group C/C for the six-month period was US$1,310, and for group L it was US$4,950. Health-related quality of life measured by the SIP instrument showed significant differences in favour of group L in the categories/dimensions of physical function, body care, ambulation, social interaction and total SIP score. In conclusion, liquid-oxygen treatment was more expensive compared to concentrator treatment. However, treatment effects showed that liquid oxygen had a better impact on quality of life.
Exhaled nitric oxide is not elevated in the inflammatory airways diseases of cystic fibrosis and bronchiectasis
Authors: Ho LP , Innes JA , Greening AP
Published: November 2002

Airways inflammation has been associated with increased nitric oxide (NO) in the exhaled breath. It was, therefore, questioned whether exhaled NO could act as an indicator of the severity of airways inflammation in the chronic suppurative lung diseases cystic fibrosis (CF) and bronchiectasis. NO levels in a single exhalation were measured using a chemiluminescence analyser. Thirty-six patients with CF and 16 with bronchiectasis were studied and compared with 22 normal subjects and 35 asthmatic patients. All subjects were nonsmokers and all measurements were made when patients were clinically stable. In addition, exhaled NO was measured in 10 CF patients at the time of onset of an acute infective exacerbation and followed for 7 days during the treatment of the exacerbation in eight of the 10 patients. No significant differences were found in NO levels in patients with CF or bronchiectasis compared with normals (median 4.0, 5.5 and 4.4 parts per billion (ppb), respectively), but all were lower than in asthma patients (10.4 ppb). The NO levels in the CF patients at time of exacerbation were not increased and did not change during treatment. These data show that nitric oxide levels in the exhaled breath of patients with chronic suppurative lung diseases, in contrast to asthma, are not elevated, despite the presence of substantial airways inflammation. Possible explanations include poor diffusion of nitric oxide across increased and viscous airway secretions, removal of nitric oxide by reaction with reactive oxygen species in the inflamed environment and failure of upregulation of epithelial inducible nitric oxide synthase in chronic suppurative conditions.
Relationships between nasal potential difference and respiratory function in adults with cystic fibrosis
Authors: Fajac I , Hubert D , Bienvenu T , Richaud-Thiriez B , Matran R , Kaplan JC , Dall'Ava-Santucci J , Dusser DJ
Published: November 2002

This study investigated the relations between nasal transepithelial electric potential difference (PD) and the phenotype and genotype of cystic fibrosis (CF) adult patients. Basal nasal PD was measured in 95 adult CF patients who were classified into three groups of nasal PD (expressed as absolute values) according to the 10th and the 90th percentiles (28.3 and 49.2 mV, respectively), which defined group 1 (nasal PD < or =28.3 mV), group 2 (nasal PD 28.3-49.2 mV) and group 3 (nasal PD > or =49.2 mV). Patients from group 1 had a higher forced vital capacity (FVC) than patients from groups 2 and 3 (76.5+/-22.4 versus 57.4+/-21.2 and 55.7+/-21.1% predicted, respectively, p<0.05) and a higher forced expiratory volume in one second (FEV1) (69.3+/-24.0 versus 42.5+/-22.4 and 42.2+/-21.4% pred, respectively, p<0.01). Among patients with severe mutations (deltaF508 homozygotes, or one deltaF508 mutation plus another "severe" mutation, or two "severe" mutations), patients from group 1 had a higher FVC, FEV1 and arterial oxygen tension than patients from groups 2 and 3 (p<0.05 for each comparison). The results show that in adult cystic fibrosis patients a normal basal nasal potential difference is related to milder respiratory disease, irrespective of the severity of the genotype.
In vitro-induced human airway hyperresponsiveness to bradykinin
Authors: Molimard M , Naline E , Boichot E , Devillier P , Lagente V , Begaud B , Advenier C
Published: November 2002

Lipopolysaccharide (LPS) and interleukin (IL)-1beta have been reported to induce airway hyperresponsiveness in several animal models. This study investigated the effect of LPS or IL-1beta on bradykinin-induced human isolated bronchi contraction. LPS (100 ng x mL(-1) for 3-6 h) and IL-1beta (3x10(-10) and 3x10(-9) M for 20 min to 3 h) time-dependently potentiated bradykinin-induced contraction. This contraction was abolished, as in control experiments, by indomethacin (10(-6) M) or by the thromboxane (Tx) receptor antagonist GR 32191 but not by the cyclo-oxygenase-2 inhibitor, CGP28238. In contrast, the Tx mimetic U46619-induced contraction of human bronchi was not enhanced IL-1beta pretreatment. In the presence of GR 32191 (10(-6) M), bradykinin induced a prostanoid dependent relaxation that was not significantly modified by IL-1beta pretreatment. Determination of prostanoids in the organ bath fluid showed that bradykinin induced TxB2, the stable metabolite of TxA2, and 6-keto prostaglandin F1alpha, the stable metabolite of PGI2, release. Only TxA2 release was potentiated by IL-1beta. Taken together our results suggest that interleukin-1beta (1-3 h)-induced potentiation of the effect of bradykinin is linked to an increased activity of thromboxane synthase and, in turn, to increased thromboxane synthesis.
Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs
Authors: Kanazawa H , Fujiwara H , Hirata K , Yoshikawa J
Published: November 2002

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.
Increased airway osmolarity inhibits the action of nitric oxide in the rabbit
Authors: Hogman M , Hjoberg J , Hedenstierna G
Published: November 2002

Inhalation of nitric oxide (NO) is known to dilate preconstricted airways. In asthmatics, there are large variations in the effect of NO on airway tone. One explanation of these variations may be different degrees of airway wall oedema. The effect of NO inhalation on methacholine (meth)-induced airway constriction was investigated in a rabbit model. Oedema and a change in osmolarity of the airways was achieved by hypertonic saline nebulization and hyperventilation with dry gas. There was an increase in resistance to meth at a concentration of 3 mg x mL(-1), of 86+/-14 cmH2O x L(-1) x s (mean+/-SEM) after oedema formation, compared with 46+/-16 cmH2O x L(-1) x s without oedema. Inhalation of 80 parts per million (ppm) NO failed to counter the increase in resistance due to meth, 92+/-14 cmH2O x L(-1) x s after hypertonic saline nebulization. After hyperventilation of dry gas, the increase in resistance due to meth at 1 mg x mL(-1) was 27+/-11 cmH2O x L(-1) x s with 80 ppm NO and 28+/- 5 cmH2O x L(-1) x s without NO. In conclusion, the relaxant effect of nitric oxide-inhalation on the airway smooth muscle can be blocked by an increase in the osmolarity of the airway surface liquid. The mechanism of this inhibition of nitric oxide remains to be established.
Effect of nitric oxide synthase inhibitor on allergen- and hyperventilation-induced bronchoconstriction in guinea-pigs
Authors: Nogami H , Umeno E , Kano S , Hirose T , Nishima S
Published: November 2002

To elucidate the role of endogenous nitric oxide (NO) in allergen- (AIB) and hyperventilation-induced bronchoconstriction (HIB), the effects of an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on AIB and HIB were studied in guinea-pigs. In the AIB group, 21 anaesthetized guinea-pigs, actively sensitized with 1% ovalbumin, were challenged with aerosolized 0.1% ovalbumin solution under mechanical ventilation. In the HIB group, 14 guinea-pigs were challenged with hyperventilation (tidal volume of 12 mL x kg(-1) at 150 breaths x min(-1) with 21% O2 and 5% CO2 dry gas) for 5 min. In both groups, lung resistance (RL) was measured using a pressure-volume-sensitive body plethysmograph, with or without L-NAME pretreatment (8 mg x kg(-1) i.v. followed by 2 mg x kg(-1) x min(-1) i.v.). The NO precursor, L-arginine was injected at a rate of 15 mg x kg(-1) x min(-1) after L-NAME injection (10 mg x kg(-1)) in the AIB group. The results were as follows. In the AIB group, the maximal RL change was significantly potentiated by pretreatment with L-NAME. This potentiating effect of L-NAME was reversed by L-arginine. In the HIB group, the pretreatment with L-NAME had no effect on increases in RL. These findings suggest that endogenous nitric oxide may play an important role in the modulation of allergen-, but not hyperventilation-induced bronchoconstriction in guinea-pigs.
Costs of asthma according to the degree of severity
Authors: Serra-Batlles J , Plaza V , Morejon E , Comella A , Brugues J
Published: November 2002

An increase in asthma-related morbidity and mortality has been reported recently, resulting in a substantial increase in the economic impact of this condition. Little information is available relating to the costs of asthma depending on the degree of severity of the disease. Total, direct and indirect costs generated by asthma patients who sought medical care for asthma control over a one-year period in a northern area of Spain were determined. Data were obtained from the patients themselves and severity of illness was classified into mild, moderate and severe according to the International Consensus Report on Diagnosis and Treatment of Asthma, 1992. The average total annual asthma-derived cost was estimated at US$2,879 per patient, with averages of US$1,336 in mildly asthmatic patients, US$2,407 in moderate asthma and US$6,393 in severe asthma. At all levels of severity, indirect costs were twice as high as direct costs, and at the same degree of severity, direct costs due to medication and hospitalization were higher among females than males. A minority of severe asthmatics incurred some 41% of the total costs. The cost of asthma was surprisingly high and varied substantially depending on the degree of severity of the disease. Further knowledge of the costs of asthma across various levels of severity will contribute to a better characterization of optimal intervention strategies for asthma care.
Comparative effects of anti-inflammatory corticosteroids in human bone-derived osteoblast-like cells
Authors: Namkung-Matthai H , Seale JP , Brown K , Mason RS
Published: November 2002

While effects of inhaled corticosteroids on serum markers of bone metabolism in normal and asthmatic subjects have been reported, there are little data on the direct effects of these corticosteroids on end-organs such as bone. The results presented here compare the effects of budesonide and its epimers (22S- and 22R-budesonide), fluticasone and dexamethasone on growth and differentiation of cultured human bone cells. Osteoblast-like cells were cultured from human foetal bone chips grown to confluence and used at first subculture. At concentrations of 10(-11)-10(-7) M each corticosteroid (CS) caused a dose-dependent decrease in [3H]thymidine incorporation into deoxyribonucleic acid (DNA), median effective concentration (EC50): fluticasone (0.06 nM) >22R (0.26 nM) >22S (0.4 nM) >budesonide (0.47 nM) >dexamethasone (1.5 nM). Each CS resulted in a dose-dependent increase in alkaline phosphatase activity, EC50: fluticasone (0.14 nM) >22R (0.2 nM)=22S (0.2 nM) >budesonide (0.4 nM) >dexamethasone (1.6 nM). The 1,25 dihydroxyvitamin D3 (1,25(OH)2D3)-stimulated osteocalcin production was decreased in the presence of each CS, EC50: fluticasone (0.02 nM) >22S (0.1 nM) >22R (0.2 nM) >budesonide (1.0 nM) >dexamethasone (1.8 nM). In human bone cells the potencies of fluticasone and budesonide in relation to dexamethasone are not dissimilar to those derived from human lymphocytes in vitro.
Selective phosphodiesterase inhibitors modulate the activity of alveolar macrophages from sensitized guinea-pigs
Authors: Germain N , Bertin B , Legendre A , Martin B , Lagente V , Payne A , Boichot E
Published: November 2002

The aim of this study was to investigate the effects of selective phosphodiesterase (PDE)3 and PDE4 inhibitors on arachidonate release by alveolar macrophages from sensitized and challenged guinea-pigs. Guinea-pigs were sensitized and challenged with ovalbumin administered by aerosol. Bronchoalveolar lavage was performed 48 h later and the PDE and cyclic adenosine monophosphate (cAMP) contents of or the arachidonate release from alveolar macrophages, stimulated in vitro with N-formyl-Met-Leu-Phe (fMLP), were evaluated. PDE3 and PDE4 activities were detected in preparations of macrophage lysate from sensitized challenged and sensitized control animals. Oral pretreatment, prior to antigen challenge in sensitized guinea-pigs, with rolipram or Ro 20-1724 (PDE4 inhibitors) but not milrinone (PDE3 inhibitor) significantly reduced the arachidonate release from alveolar macrophages. In vitro incubation of alveolar macrophages from challenged guinea-pigs with Ro 20-1724 or the cAMP analogue dibutyryl cAMP (db-cAMP) but not milrinone or the cyclic guanosine monophosphate (cGMP) analogue 8-bromo-cGMP (8-br-cGMP) significantly reduced arachidonate release. Incubation of the cells with a combination of milrinone plus rolipram or Ro 20-1724 elicited a marked and significant reduction in arachidonate release by alveolar macrophages stimulated with fMLP. In conclusion, these data show that phosphodiesterase-4 isoenzyme may regulate the release of inflammatory mediators such as arachidonate from macrophages through an increase in intracellular cyclic adenosine monophosphate. This suggests that phosphodiesterase-4 inhibitors have potential in the treatment of inflammatory disorders of the lung.
Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer
Authors: Thorsson L , Edsbacker S
Published: November 2002

The absolute systemic availability and pulmonary deposition of budesonide inhaled from a pressurized metered-dose inhaler (pMDI) attached to a Nebuhaler spacer was determined in 15 healthy subjects. The study was of an open cross-over design. Each subject randomly received three single doses of budesonide on separate days: 0.5 mg given intravenously and 1.0 mg (0.2 mg x 5) by inhalation from a pMDI with a Nebuhaler, with or without concomitant oral charcoal intake to prevent gastrointestinal absorption. Charcoal intake did not significantly affect the systemic availability or deposition of budesonide. The systemic availability was 36+/-14% (metered dose, mean+/-SD) with charcoal and 35+/-10% without. The pulmonary deposition was 36+/-14% with charcoal and 34+/-11% without. Erroneous administration, in which the canister was shaken only before the first of the five actuations, halved the systemic availability. In conclusion, the pulmonary deposition of budesonide from a pressurized metered-dose inhaler with Nebuhaler is high under optimum conditions. The small discrepancy between the systemic availability and pulmonary deposition indicates that the contribution from deposition in the oropharynx and subsequent absorption from the gastrointestinal tract is negligible. The marked reduction in the systemic availability of budesonide with the unshaken canisters confirms that the performance of a pressurized metered-dose inhaler is very much dependent on proper handling.
Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone
Authors: Leach CL , Davidson PJ , Boudreau RJ
Published: November 2002

Hydrofluoroalkane-134a (HFA) beclomethasone dipropionate (BDP) was formulated in a metered-dose inhaler (MDI) to deliver a particle size of 1.1 microm compared with 35 microns for currently marketed chlorofluorocarbon (CFC)-BDP products. Two phase I single-dose human deposition studies were conducted using technetium 99m-radiolabelled BDP in a press-and-breathe actuator without an add-on spacer. A healthy volunteer study (n=6) showed that 55-60% of the HFA-BDP ex-actuator dose was deposited in the lungs, with 29-30% deposited in the oropharynx. CFC-BDP deposition was 4-7% in the lungs and 90-94% in the oropharynx. The pattern of deposition within the lung showed that HFA-BDP was spread diffusely throughout the lung airways, whereas CFC-BDP was confined to the central airways with little, if any, peripheral airway deposition. A second study with asthmatics (n=16) confirmed that 56% of the HFA-BDP dose was deposited in the airways, with 33% in the oropharynx. In conclusion, hydrofluoroalkane-134a-beclomethasone dipropionate deposition was much greater in the airways than chlorofluorocarbon-beclomethasone dipropionate, with a concomitant reduction in oropharyngeal deposition. The increased lung deposition efficiency of the hydrofluoroalkane propellant has led to a reduction in the amount of beclomethasone dipropionate needed to achieve a similar efficacy. The penetration of the hydrofluoroalkane to the small airways may provide asthma treatment not afforded by conventional chlorofluorocarbons.