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1.
Wetlands (Wilmington) ; 43(8): 105, 2023.
Article in English | MEDLINE | ID: mdl-38037553

ABSTRACT

Wetlands cover a small portion of the world, but have disproportionate influence on global carbon (C) sequestration, carbon dioxide and methane emissions, and aquatic C fluxes. However, the underlying biogeochemical processes that affect wetland C pools and fluxes are complex and dynamic, making measurements of wetland C challenging. Over decades of research, many observational, experimental, and analytical approaches have been developed to understand and quantify pools and fluxes of wetland C. Sampling approaches range in their representation of wetland C from short to long timeframes and local to landscape spatial scales. This review summarizes common and cutting-edge methodological approaches for quantifying wetland C pools and fluxes. We first define each of the major C pools and fluxes and provide rationale for their importance to wetland C dynamics. For each approach, we clarify what component of wetland C is measured and its spatial and temporal representativeness and constraints. We describe practical considerations for each approach, such as where and when an approach is typically used, who can conduct the measurements (expertise, training requirements), and how approaches are conducted, including considerations on equipment complexity and costs. Finally, we review key covariates and ancillary measurements that enhance the interpretation of findings and facilitate model development. The protocols that we describe to measure soil, water, vegetation, and gases are also relevant for related disciplines such as ecology. Improved quality and consistency of data collection and reporting across studies will help reduce global uncertainties and develop management strategies to use wetlands as nature-based climate solutions. Supplementary Information: The online version contains supplementary material available at 10.1007/s13157-023-01722-2.

2.
Microbiol Spectr ; 9(2): e0094121, 2021 10 31.
Article in English | MEDLINE | ID: mdl-34468194

ABSTRACT

The entry of antibiotic resistance genes (ARGs) into aquatic systems has been documented for large municipal wastewater treatment plants (WWTPs), but there is less study of the impact of smaller plants that are situated on small rural rivers. We sampled water metagenomes for ARGs and taxa composition from the Kokosing River, a small rural river in Knox County, Ohio, which has been designated an Ohio State Scenic River for retention of natural character. Samples were obtained 1.0 km upstream, 120 m downstream, and 6.4 km downstream from the effluent release of the Mount Vernon WWTP. ARGs were identified in metagenomes using ShortBRED markers from the comprehensive antibiotic resistance database (CARD) screened against UniPROT. Through all seasons, the metagenome just downstream of the WWTP effluent showed a substantial elevation of at least 15 different ARGs, including 6 ARGs commonly associated with Acinetobacter baumannii, such as msrE, mphE (macrolide resistance), and tet(39) (tetracycline resistance). The ARGs most prevalent near the effluent pipe persisted 6.4 km downriver. Using metagenomic phylogenetic analysis (MetaPhlAn2) clade-specific marker genes, the taxa distribution near the effluent showed elevation of reads annotated as Acinetobacter species as well as gut-associated taxa, Bacteroides and Firmicutes. The ARG levels and taxa prevalence showed little dependence on seasonal chlorination of the effluent. Nitrogen and phosphorus were elevated near the effluent pipe but had no consistent correlation with ARG levels. We show that in a rural river microbiome, year-round wastewater effluent substantially elevates ARGs, including those associated with multidrug-resistant A. baumannii. IMPORTANCE Antibiotic resistance is a growing problem worldwide, with frequent transmission between pathogens and environmental organisms. Rural rivers can support high levels of recreational use by people unaware of inputs from treated wastewater, while wastewater treatment plants (WWTPs) can generate a small but significant portion of flow volume into a river surrounded by forest and agriculture. There is little information on the rural impacts of WWTP effluent on the delivery and transport of antibiotic resistance genes. In our study, the river water proximal to wastewater effluent shows evidence for the influx of multidrug-resistant Acinetobacter baumannii, an opportunistic pathogen of concern for hospitals but also widespread in natural environments. Our work highlights the importance of wastewater effluent in management of environmental antibiotic resistance, even in high quality, rural river systems.


Subject(s)
Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Drug Resistance, Multiple, Bacterial/genetics , Wastewater/microbiology , Water Purification/methods , Anti-Bacterial Agents/pharmacology , Bacteroides/drug effects , Bacteroides/genetics , Firmicutes/drug effects , Firmicutes/genetics , Humans , Macrolides/pharmacology , Metagenome/genetics , Microbiota/drug effects , Microbiota/genetics , Ohio , Phylogeny , Rivers/microbiology , Tetracyclines/pharmacology
3.
Environ Monit Assess ; 191(Suppl 1): 322, 2019 Jun 20.
Article in English | MEDLINE | ID: mdl-31222469

ABSTRACT

In 2011, the US Environmental Protection Agency and its partners conducted the first National Wetland Condition Assessment at the continental-scale of the conterminous United States. A probability design for site selection was used to allow an unbiased assessment of wetland condition. We developed a vegetation multimetric index (VMMI) as a parsimonious biological indicator of ecological condition applicable to diverse wetland types at national and regional scales. Vegetation data (species presence and cover) were collected from 1138 sites that represented seven broad estuarine intertidal and inland wetland types. Using field collected data and plant species trait information, we developed 405 candidate metrics with potential for distinguishing least disturbed (reference) from most disturbed sites. Thirty-five of the metrics passed range, repeatability, and responsiveness screens and were considered as potential component metrics for the VMMI. A permutation approach was used to calculate thousands of randomly constructed potential national-scale VMMIs with 4, 6, 8, or 10 metrics. The best performing VMMI was identified based on limited redundancy among constituent metrics, sensitivity, repeatability, and precision. This final VMMI had four broadly applicable metrics (floristic quality index, relative importance of native species, richness of disturbance-tolerant species, and relative cover of native monocots). VMMI values and weights from the survey design for probability sites (n = 967) were used to estimate wetland area in good, fair, and poor condition, nationally and for each of 10 ecoregion by wetland type reporting groups. Strengths and limitations of the national VMMI for describing ecological condition are highlighted.


Subject(s)
Environmental Monitoring/methods , Plants/classification , Wetlands , Data Collection , Ecology , Environmental Biomarkers , Probability , United States , United States Environmental Protection Agency
4.
Ecosphere ; 8(10)2017 Oct.
Article in English | MEDLINE | ID: mdl-30237908

ABSTRACT

The use of models by ecologists and environmental managers, to inform environmental management and decision-making, has grown exponentially in the past 50 years. Due to logistical, economical, and theoretical benefits, model users frequently transfer preexisting models to new sites where data are scarce. Modelers have made significant progress in understanding how to improve model generalizability during model development. However, models are always imperfect representations of systems and are constrained by the contextual frameworks used during their development. Thus, model users need better ways to evaluate the possibility of unintentional misapplication when transferring models to new sites. We propose a method of describing a model's application niche for use during the model selection process. Using this method, model users synthesize information from databases, past studies, and/or past model transfers to create model performance curves and heat maps. We demonstrated this method using an empirical model developed to predict the ecological condition of plant communities in riverine wetlands of the Appalachian Highland physiographic region, U.S.A. We assessed this model's transferability and generalizability across (1) riverine wetlands in the contiguous U.S.A., (2) wetland types in the Appalachian Highland physiographic region, and (3) wetland types in the contiguous U.S.A. With this methodology and a discussion of its critical steps, we set the stage for further inquiries into the development of consistent and transparent practices for model selection when transferring a model.

5.
Nat Commun ; 7: 13835, 2016 12 13.
Article in English | MEDLINE | ID: mdl-27958272

ABSTRACT

Wetland soils contain some of the highest stores of soil carbon in the biosphere. However, there is little understanding of the quantity and distribution of carbon stored in our remaining wetlands or of the potential effects of human disturbance on these stocks. Here we use field data from the 2011 National Wetland Condition Assessment to provide unbiased estimates of soil carbon stocks for wetlands at regional and national scales. We find that wetlands in the conterminous United States store a total of 11.52 PgC, much of which is within soils deeper than 30 cm. Freshwater inland wetlands, in part due to their substantial areal extent, hold nearly ten-fold more carbon than tidal saltwater sites-indicating their importance in regional carbon storage. Our data suggest a possible relationship between carbon stocks and anthropogenic disturbance. These data highlight the need to protect wetlands to mitigate the risk of avoidable contributions to climate change.

6.
J Environ Qual ; 43(1): 409-17, 2014 Jan.
Article in English | MEDLINE | ID: mdl-25602575

ABSTRACT

We measured soil properties, carbon and nutrient (nitrogen, phosphorus) pools, ambient and potential denitrification, and phosphorus sorption index (PSI) in natural depressional wetlands and depressional wetlands restored through the U.S. Department of Agriculture (USDA) Wetland Reserve Program. We measured the same suite of variables in natural and USDA Conservation Reserve Program-restored riparian buffers and in agricultural fields adjacent to both systems to determine the degree to which ecosystem services are being provided through restoration in different hydrogeomorphic settings. Organic carbon and nutrient pools, PSI, and denitrification were greater in natural than in 5- to 10-yr-old restored depressional wetlands. In riparian soils, carbon and nutrient pools, PSI, and denitrification were comparable between restored and natural systems, suggesting that these services develop quickly after restoration. Restored depressional wetlands had lower soil organic C, N, and P relative to agricultural soils, whereas the opposite trend was observed in restored riparian soils. Four-year-old restored riparian buffers achieved equivalence to natural riparian buffers within 4 yr, whereas restored depressional wetlands took longer to provide these ecosystem services (i.e., PSI, denitrification, C storage) at levels comparable to natural wetlands. Restored depressional wetlands and riparian buffers provide ecosystem services lost through previous conversion to agriculture throughout the Midwest; however, the development of these services depends on hydrodynamics (pulsed versus nonpulsed), parent material, soil texture (sand, clay), and disturbance regime (prescribed fire) of the site. As restoration continues throughout the region, C sequestration and nutrient removal in these systems is expected to increase water quality at the local and regional levels.

7.
Environ Manage ; 44(2): 369-77, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19504150

ABSTRACT

We sampled 92 wetlands from four different basins in the United States to quantify observer repeatability in rapid wetland condition assessment using the Delaware Rapid Assessment Protocol (DERAP). In the Inland Bays basin of Delaware, 58 wetland sites were sampled by multiple observers with varying levels of experience (novice to expert) following a thorough training workshop. In the Nanticoke (Delaware/Maryland), Cuyahoga (Ohio), and John Day (Oregon) basins, 34 wetlands were sampled by two expert teams of observers with minimal protocol training. The variance in observer to observer scoring at each site was used to calculate pooled standard deviations (SD(pool)), coefficients of variation, and signal-to-noise ratios for each survey. The results showed that the experience level of the observer had little impact on the repeatability of the final rapid assessment score. Training, however, had a large impact on observer to observer repeatability. The SD(pool) in the Inland Bay survey with training (2.2 points out of a 0-30 score) was about half that observed in the other three basins where observers had minimal training (SD(pool) = 4.2 points). Using the results from the survey with training, we would expect that two sites assessed by different, trained observers who obtain DERAP scores differing by more than 4 points are highly likely to differ in ecological condition, and that sites with scores that differ by 2 or fewer points are within variability that can be attributed to observer differences.


Subject(s)
Environmental Monitoring/methods , Wetlands , Geography , Models, Theoretical , United States
8.
Br J Surg ; 91(6): 699-704, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15164437

ABSTRACT

BACKGROUND: Breast cancer has been considered a more indolent disease in the elderly, who are less tolerant of aggressive therapy. This trial tested the hypothesis that tamoxifen without surgery would provide adequate control of breast cancer for the remainder of life in elderly women, thereby sparing them surgery. METHOD: Women aged over 70 years with operable, invasive breast cancer were randomized to receive either tamoxifen alone or surgery plus tamoxifen. Time to treatment failure (TTF), indicating initial primary treatment failure, was the primary endpoint. Overall mortality, and death from breast cancer were also compared between the two groups. RESULTS: Between 1984 and 1991, 455 patients were included in the trial. The analysis was based on a median follow-up of 12.7 years. The TTF was significantly shorter in the tamoxifen alone group: hazard ratio (HR) 4.41 (95 per cent confidence interval (c.i.) 3.31 to 5.88). Ninety-three (40.4 per cent) of 230 patients randomized to tamoxifen alone underwent surgery for the management of their disease. Both overall mortality and mortality from breast cancer were significantly increased in the tamoxifen alone group, although the survival curves did not diverge for the first 3 three years: HR 1.29 (95 per cent c.i. 1.04 to 1.59) and 1.68 (95 per cent c.i. 1.15 to 2.47) respectively. CONCLUSION: Omission of primary surgery in unselected elderly women with operable breast cancer who were fit for the procedure resulted in an increased rate of progression, therapeutic intervention and mortality.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Combined Modality Therapy/methods , Tamoxifen/therapeutic use , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Cause of Death , Combined Modality Therapy/mortality , Female , Follow-Up Studies , Humans , Neoplasm Recurrence, Local
9.
Ir Med J ; 94(10): 299-300, 302, 2001.
Article in English | MEDLINE | ID: mdl-11837627

ABSTRACT

A joint project between general practitioners and the South Eastern Health Board resulted in the establishment of a network of computerised practices collecting morbidity data in 1998 - 1999. Five practices established age sex registers for public and private patients. The International Classification of Primary Care 2 (ICPC-2) was used to define inclusion criteria for a range of illnesses relevant to primary care and public health. Problems arose in validating and extracting data in three practices. Disease prevalence for 17 illnesses was established for two practices only. The project clearly established the problems associated with morbidity data collection in general practice which include absence of a national patient registration system, absence of a national electronic messaging standard, difficulties extracting data from practice software systems and the need for a high level of dedicated staff and resources to implement such a project.


Subject(s)
Data Collection/methods , Family Practice/statistics & numerical data , Morbidity , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Data Collection/standards , Female , Forms and Records Control/standards , Humans , Ireland/epidemiology , Male , Middle Aged , Quality Control , Sex Distribution
10.
J Epidemiol Community Health ; 54(8): 581-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10890869

ABSTRACT

Atopic eczema is a chronic skin condition affecting between 5% and 20% of children aged up to 11 years at one time or other. Research suggests that prevalence is increasing and various environmental factors have been implicated in the aetiology. While often seen to be a minor problem, research suggests that it can cause considerable disruption to the lives of children and their carers and involves significant cost for the family and health care systems. The current consensus is that the majority of cases of atopic eczema are most appropriately managed within primary care. However, management of the condition is problematic because diagnosis is often difficult. Consultations tend to focus on the physical aspects of the problems neglecting the psychosocial, while treatment remains mainly palliative and can be as diverse as the condition itself. More appropriate and effective primary care management and support for children with atopic eczema and their carers will only be developed if health professionals become more aware of the social context of the disease and the impact on the lives of those affected. Public health responses focusing on primary prevention are also needed. This paper reviews a diverse literature on the epidemiology of the condition, the way in which it affects the lives of children and their carers and the factors that shape their help seeking decisions. The aim is to contribute to a more substantial knowledge base for public health and primary care developments and to point to areas for future research


Subject(s)
Dermatitis, Atopic/epidemiology , Health Policy , Patient Acceptance of Health Care/psychology , Child , Child, Preschool , Dermatitis, Atopic/etiology , Dermatitis, Atopic/prevention & control , Female , Humans , Male , Prevalence , Primary Health Care/organization & administration , Public Health Practice , Sleep Wake Disorders/etiology , Socioeconomic Factors , Stress, Psychological/etiology , United Kingdom/epidemiology
11.
Kidney Int ; 49(2): 477-80, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8821832

ABSTRACT

MHC Class II genes may contribute to susceptibility to IgA nephropathy (IgAN). We have previously identified a restriction fragment length polymorphism (RFLP) of the DQB1 region that associated with IgAN in British Caucasoids. However, another group, while demonstrating a DQB1 association, was unable to confirm our finding. MHC molecules are heterodimers consisting of an alpha and beta chain, and thus polymorphism of the DQA1 alpha chain may also be important to disease pathogenesis in IgAN. Therefore, we have determined DQA1 alleles and re-examined DQB1 alleles in British Caucasoids with IgAN using an approach that can differentiate between the common DQ alleles; we have also extended our studies to Caucasoid populations from Northern and Southern Europe, thereby addressing the possibility of variation in genetic susceptibility between populations. DNA was prepared from IgAN patients (British, N = 105; Italian, N = 71; Finnish, N = 48) and healthy controls (British, N = 111; Italian, N = 63; Finnish, N = 41). DQA1 alleles were identified by TaqI RFLP and Southern blotting; alleles that could not be fully resolved by Taq Southern blotting were identified by PCR-RFLP. DQB1 alleles were identified by polymerase chain reaction (PCR) based technique (PCR-RFLP). No consistent association of DQ alleles were found between the populations studied. In British patients a decreased frequency of DQB1*0201 was observed (P = 0.008), in Finnish patients a decreased frequency of DQB1*0602 was observed (P = 0.01), and in Italian patients no association between DQ markers and IgAn was found. These data demonstrate population variation in disease association, but no strong or consistent association in the DQ region.


Subject(s)
Glomerulonephritis, IGA/genetics , HLA-DQ Antigens/genetics , Polymorphism, Genetic , Alleles , Europe/epidemiology , Finland/epidemiology , Glomerulonephritis, IGA/epidemiology , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , Hematuria , Histocompatibility Testing , Humans , Italy/epidemiology , Prevalence , United Kingdom/epidemiology
12.
Diabetologia ; 38(10): 1223-9, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8690176

ABSTRACT

An association between insulin-dependent diabetes mellitus (IDDM) and polymorphisms of the insulin gene on chromosome 11p15 (INS) is a consistent finding in Europid populations. While one study suggested that the INS association is restricted to HLA-DR4-positive individuals, studies in other Europid populations have shown the disease-associated INS genotype to confer susceptibility independently of HLA-DR. We have investigated the role of INS in susceptibility to IDDM in Finland, which has the highest incidence of diabetes mellitus in the world, at two polymorphic restriction sites, 5' and 3' to the insulin gene. From the DiMe (Childhood Diabetes in Finland) Study we studied 154 diabetic children without regard to HLA-DR type; 108 DR4 positive/non-DR3 diabetic children; 39 DR3 positive/non-DR4 diabetic children; 30 DR4/DR3 positive diabetic children; 31 non-DR4/non-DR3 diabetic children; 96 matched DiMe control subjects and 86 other healthy, non-diabetic Finnish control subjects. We found an overall association between IDDM and INS in the high-risk Finnish population only with the 5' polymorphism and identified an INS haplotype negatively associated with IDDM in Finland. However, among diabetic subjects with a reduced HLA-associated susceptibility (non-DR4/non-DR3) both 3' and 5' INS loci showed an association with IDDM (p values 0.02 and 0.0002, respectively). Thus, in the Finnish population insulin gene-encoded susceptibility to IDDM exerts a maximum effect in those with reduced HLA-associated risk.


Subject(s)
Chromosomes, Human, Pair 11 , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , HLA-DR Antigens/genetics , Insulin/genetics , Polymorphism, Genetic , Adolescent , Child , Child, Preschool , Chromosome Mapping , Diabetes Mellitus, Type 1/epidemiology , Disease Susceptibility/immunology , Europe , Finland , Genetic Predisposition to Disease , Genotype , HLA-DR4 Antigen/genetics , Humans , Incidence , Infant , Reference Values , Risk Factors
13.
Diabetologia ; 37(9): 937-44, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7806025

ABSTRACT

In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in the population and are not associated with IDDM. Comparison of the A2 and non-A2 haplotypes at the DNA level showed that they were identical at HLA-B, -DR, and -DQ loci. Evidence that class I alleles confer susceptibility to IDDM was obtained from the two HLA-C, -B, -DR and -DQ haplotypes most frequently found in IDDM patients in Finland. A24, A3 and A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw7, B8, DR3, DQ2 were all found to be associated with IDDM. In Finland these seven haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33% of diabetic haplotypes and 10.3% of non-diabetic haplotypes (p < 0.00001). The contribution of the class I region to IDDM susceptibility was also apparent in those IDDM patients lacking the disease-predisposing class II alleles. Significantly more non-DR3/non-DR4 IDDM patients (47 of 55) possessed two of the IDDM-associated HLA-A alleles compared to non-DR3/non-DR4 control subjects (40 of 58; p = 0.038). Moreover, IDDM patients confirmed by oligotyping as unable to form a 'diabetes-susceptibility' DQ heterodimer, tended to possess two diabetes-associated HLA-A alleles (12 of 13) compared to control subjects (12 of 20; p = 0.056).


Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , Genes, MHC Class I , HLA-A Antigens/genetics , Adolescent , Alleles , Base Sequence , Child , DNA Primers , Diabetes Mellitus, Type 1/epidemiology , Finland , Genetic Predisposition to Disease , HLA-B Antigens/genetics , HLA-C Antigens/genetics , HLA-DR Antigens/genetics , Humans , Molecular Sequence Data , Polymerase Chain Reaction/methods , Risk Factors
14.
Pharmacol Biochem Behav ; 33(1): 75-9, 1989 May.
Article in English | MEDLINE | ID: mdl-2780792

ABSTRACT

The intracerebroventricular (ICV) injection of the mast cell degranulator Compound 48/80 (2.5-2.0 micrograms/kg) produced a marked behavioral syndrome in normotensive rats. The behaviors included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, and a later phase of sedation. The highest doses (15 and 20 micrograms/kg) also produced catalepsy and episodes of "barrel rolling" (continuous rolling of 1-8 turns around the longitudinal axis). These behaviors were observed for approximately 15-30 min although the sedation and catalepsy were maintained for 90-120 min. A second ICV injection of the 10 micrograms/kg dose of Compound 48/80 given 2 hr after an initial injection of this dose, produced a much reduced response and the numbers of head and body shakes, and episodes of paw tremor and grooming were between 20-30% of those produced by the first injection. The reduced effect of the second injection indicates that the behavioral effects of Compound 48/80 may arise from the acute degranulation of mast cells rather than direct effects on neuronal populations or the cerebral vasculature.


Subject(s)
Behavior, Animal/drug effects , p-Methoxy-N-methylphenethylamine/pharmacology , Animals , Cytoplasmic Granules/drug effects , Female , Injections, Intraventricular , Mast Cells/drug effects , Rats , Rats, Inbred Strains , Time Factors , p-Methoxy-N-methylphenethylamine/administration & dosage
15.
Br J Pharmacol ; 94(4): 1115-22, 1988 Aug.
Article in English | MEDLINE | ID: mdl-3145088

ABSTRACT

1. The effects of REV 5901 on the platelet activating factor (Paf)-induced (a) bronchoconstriction, (b) contraction of lung parenchymal strips and (c) increased airways responsiveness to histamine, were assessed in the guinea-pig. REV 5901 is a 5-lipoxygenase inhibitor and competitive peptidoleukotriene antagonist which does not inhibit multiple forms of phosphodiesterase. 2. In urethane/pentobarbitone anaesthetized animals, REV 5901 (10 or 30 mg kg-1, i.v.) substantially inhibited the bronchoconstriction, measured as changes in airways resistance (RL) and dynamic lung compliance (Cdyn), induced by leukotriene D4 (2.5 micrograms kg-1, i.v.) but did not attenuate that induced by Paf (50 ng kg-1, i.v.). 3. Paf contracted the lung parenchymal strip in a concentration-dependent manner. REV 5901 (25 microM) neither altered the magnitude of the contractions nor the tissue sensitivity to Paf. The sustained contraction induced by Paf was not affected when REV 5901 was added after the response had reached a plateau. 4. Contractions of parenchymal strips to Paf (50 nM) were prevented by pretreatment with the competitive Paf antagonists, SRI 63441 and WEB 2086. Also WEB 2086, but not SRI 63441, reversed established Paf-induced contractions and relaxed parenchymal strips from intrinsic tone in the absence of Paf. 5. Paf (20 ng kg-1, i.v.) caused an acute increase in airways responsiveness to histamine (4-12 micrograms kg-1, i.v.) which was attenuated by REV 5901 at 10 mg kg-1, i.v. and abolished by 30 mg kg-1, i.v. 6. These data suggest that leukotrienes do not participate in Paf-induced bronchoconstriction or contraction of the lung parenchymal strip, but may play a role in the increased responsiveness of the airways to histamine observed after Paf challenge in the guinea-pig.


Subject(s)
Hydroxyquinolines/pharmacology , Lipoxygenase Inhibitors , Lung/drug effects , Platelet Activating Factor/pharmacology , Quinolines , SRS-A/pharmacology , Animals , Female , Guinea Pigs , Histamine/pharmacology , In Vitro Techniques , Lung Compliance/drug effects , Male
16.
Agents Actions ; 24(1-2): 8-19, 1988 Jun.
Article in English | MEDLINE | ID: mdl-2841832

ABSTRACT

Platelet activating factor (Paf, 0.02 micrograms/kg, i.v. bolus) caused an acute increase in airways responsiveness to histamine in anaesthetized guinea-pigs prepared for recording airways resistance (RL) and dynamic compliance (Cdyn). Aspirin pretreatment (10 mg/kg, i.v.) attenuated the return of airways responsiveness to prechallenge levels. Pretreatment with the combined cyclooxygenase/lipoxygenase inhibitors BW 755C (20 mg/kg, i.v.) and ETYA (20 mg/kg, i.v.), or with the putative cysteinyl-containing leukotriene antagonist FPL 55712 (0.25 mg/kg/min, i.v.), or a Paf antagonist SRI 63441 (2.5 mg/kg, i.v.), prevented Paf-induced increased airways responsiveness. Inhibitors of leukotriene synthesis, BW 755C and ETYA, or action, FPL 55712, had variable effects on Paf-induced bronchoconstriction. These data suggest that lipoxygenase metabolites, possibly leukotrienes, may mediate an acute increase in airways responsiveness to histamine after Paf exposure.


Subject(s)
Bronchi/drug effects , Histamine/pharmacology , Lipoxygenase/metabolism , Platelet Activating Factor/pharmacology , 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine , 5,8,11,14-Eicosatetraynoic Acid/pharmacology , Airway Resistance/drug effects , Animals , Aspirin/pharmacology , Bronchi/physiology , Chromones/pharmacology , Female , Guinea Pigs , Leukotriene B4/physiology , Lung Compliance/drug effects , Male , Pyrazoles/pharmacology , Quinolinium Compounds/pharmacology , SRS-A/physiology
17.
Agents Actions ; 24(1-2): 1-7, 1988 Jun.
Article in English | MEDLINE | ID: mdl-3136622

ABSTRACT

In anaesthetized guinea-pigs pretreated with propranolol (1 mg/kg, i.v.), platelet activating factor (Paf, 0.02 micrograms/kg, i.v.) caused an acute increase in airways response to histamine (0.5-3.0 micrograms/kg, i.v.) measured as intratracheal pressure. Treatment with the cyclooxygenase inhibitors, aspirin (10 mg/kg, i.v.) or indomethacin (5 mg/kg, i.v.), enhanced the magnitude and duration of this effect but a combined lipoxygenase/cyclooxygenase inhibitor, BW 755C (20 mg/kg, i.v.), prevented the increase in responsiveness. In aspirin treated animals, a putative lipoxygenase inhibitor NDGA (10 mg/kg, i.v.). or atropine methyl nitrate (1 mg/kg, i.v.) or bilateral vagotomy reduced the magnitude of Paf-induced increased histamine responses but did not prevent the effect. Bronchoconstriction induced by Paf was variably influenced by the drug treatments. These data suggest that Paf causes an acute increase in airways responsiveness to histamine in the guinea-pig through a mechanism that may, in part, be dependant on the release of lipoxygenase metabolites.


Subject(s)
Bronchi/drug effects , Histamine/pharmacology , Lipoxygenase/metabolism , Platelet Activating Factor/pharmacology , 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine , Animals , Aspirin/pharmacology , Atropine Derivatives/pharmacology , Bronchi/physiology , Female , Guinea Pigs , Indomethacin/pharmacology , Male , Masoprocol/pharmacology , Pyrazoles/pharmacology , Vagotomy
18.
Neuropharmacology ; 27(5): 537-40, 1988 May.
Article in English | MEDLINE | ID: mdl-2839794

ABSTRACT

The effects of successive injections of the alpha-adrenoceptor agonist clonidine (25, 50 and 100 ug/kg given at hourly intervals) on the body temperature of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, previously treated for 48 hr with slow release emulsions (subcutaneous) containing either morphine (morphine SR, 100 mg/kg), naloxone (naloxone SR, 80 mg/kg) or no drug (vehicle SR), were examined. The successive injections of clonidine produced dose-dependent falls in body temperature which were quantitatively similar in the vehicle-treated WKY and spontaneously hypertensive rats. The hypothermic effects of clonidine in the morphine-dependent WKY and spontaneously hypertensive rats, and in the naloxone-treated WKY and spontaneously hypertensive rats, were not different to those of the respective vehicle-treated controls. These results suggest that endogenous mu-receptor opioid peptides do not have a major involvement in the hypothermic actions of clonidine, in either normotensive or spontaneously hypertensive rats.


Subject(s)
Body Temperature/drug effects , Clonidine/pharmacology , Narcotics/pharmacology , Receptors, Opioid/metabolism , Animals , Clonidine/administration & dosage , Female , Injections, Intraperitoneal , Morphine/pharmacology , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Receptors, Opioid, mu
19.
Agents Actions Suppl ; 23: 195-200, 1988.
Article in English | MEDLINE | ID: mdl-3140616

ABSTRACT

Inhibitors of platelet activating factor (PAF) and leukotriene synthesis or action are of interest as potential anti-asthmatic drugs. The present study outlines evidence suggesting an interaction between PAF and lipoxygenase products mediating increased airways responsiveness to histamine in vivo.


Subject(s)
Lipoxygenase/metabolism , Platelet Activating Factor/pharmacology , Respiratory System/drug effects , Animals , Asthma/drug therapy , Guinea Pigs , Histamine/pharmacology , In Vitro Techniques , Leukotriene Antagonists , Leukotrienes/biosynthesis , Platelet Activating Factor/antagonists & inhibitors , Platelet Activating Factor/physiology
20.
Neuropharmacology ; 26(8): 1167-71, 1987 Aug.
Article in English | MEDLINE | ID: mdl-3658120

ABSTRACT

The effect of varying the ratio of extraction volume to tissue weight (EVR) on the apparent concentration of histamine (HA) in the hypothalamus of the rat was examined. Increasing the weight of tissue (by pooling 1, 2 or 3 hypothalami), in a constant extraction volume, resulted in progressive decreases in apparent concentration of histamine in the hypothalamus. These concentrations were 642, 450 and 282 ng/g, respectively. Morphine (10 mg/kg, i.p.) significantly reduced the concentration of histamine in the hypothalamus. Expressed as percentages of the saline-control values (obtained for the extraction volume to tissue weight of 35.7, 57.2 and 118.4 ml/g), treatment with morphine resulted in 24, 17 and 11% reductions in the concentration of histamine in the hypothalamus, respectively. However, expressed in terms of ng/g, the reductions in histamine induced by morphine were 68, 75 and 69 ng/g, respectively. It is concluded that morphine may consistently affect a single pool of histamine. The possibility that de novo histamine is formed in the homogenate during the extraction process is discussed.


Subject(s)
Histamine/analysis , Hypothalamus/analysis , Morphine/pharmacology , Animals , Chromatography, Gel , Female , Hypothalamus/drug effects , Morphine/administration & dosage , Rats , Rats, Inbred Strains , Spectrophotometry , Time Factors
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