Associations between interpregnancy interval and preterm birth by previous preterm birth status in four high-income countries: a cohort study.

OBJECTIVE: To investigate the effect of interpregnancy interval (IPI) on preterm birth (PTB) according to whether the previous birth was preterm or term. DESIGN: Cohort study. SETTING: USA (California), Australia, Finland, Norway (1980-2017). POPULATION: Women who gave birth to first and second (n = 3 213 855) singleton livebirths. METHODS: Odds ratios (ORs) for PTB according to IPIs were modelled using logistic regression with prognostic score stratification for potential confounders. Within-site ORs were pooled by random effects meta-analysis. OUTCOME MEASURE: PTB (gestational age <37 weeks). RESULTS: Absolute risk of PTB for each IPI was 3-6% after a previous term birth and 17-22% after previous PTB. ORs for PTB differed between previous term and preterm births in all countries (P-for-interaction ≤ 0.001). For women with a previous term birth, pooled ORs were increased for IPI <6 months (OR 1.50, 95% CI 1.43-1.58); 6-11 months (OR 1.10, 95% CI 1.04-1.16); 24-59 months (OR 1.16, 95% CI 1.13-1.18); and ≥ 60 months (OR 1.72, 95%CI 1.60-1.86), compared with 18-23 months. For previous PTB, ORs were increased for <6 months (OR 1.30, 95% CI 1.18-1.42) and ≥60 months (OR 1.29, 95% CI 1.17-1.42), but were less than ORs among women with a previous term birth (P < 0.05). CONCLUSIONS: Associations between IPI and PTB are modified by whether or not the previous pregnancy was preterm. ORs for short and long IPIs were higher among women with a previous term birth than a previous PTB, which for short IPI is consistent with the maternal depletion hypothesis. Given the high risk of recurrence and assuming a causal association between IPI and PTB, IPI remains a potentially modifiable risk factor for women with previous PTB. TWEETABLE ABSTRACT: Short versus long interpregnancy intervals associated with higher ORs for preterm birth (PTB) after a previous PTB.

Interpregnancy interval and risk of perinatal death: a systematic review and meta-analysis.

BACKGROUND: Interpregnancy interval (IPI) <6 months is a potentially modifiable risk factor for adverse perinatal health outcomes. OBJECTIVE: This systematic review evaluated the international literature on the risk of perinatal death associated with IPI. SEARCH STRATEGY: Two independent reviewers screened titles and abstracts identified in MEDLINE, EMBASE and Scopus from inception to 4 April 2019 (Prospero Registration #CRD42018092792). SELECTION CRITERIA: Studies were included if they provided a description of IPI measurement and perinatal death, including stillbirth and neonatal death. DATA COLLECTION AND ANALYSIS: A narrative review was performed for all included studies. Random effects meta-analysis was used to compare unadjusted odds of perinatal death associated with IPI <6 months and IPI ≥6 months. Analyses were performed by outcome of the preceding pregnancy and study location. MAIN RESULTS: Of the 624 unique articles identified, 26 met the inclusion criteria. The pooled unadjusted odds ratio of perinatal death for IPI <6 months was 1.34 (95% CI 1.17-1.53) following a previous live birth, 0.85 (95% CI 0.73-0.99) following a previous miscarriage and 1.07 (95% CI 0.84-1.36) following a previous stillbirth compared with IPI ≥6 months. However, few high-income country studies reported an association after adjustment. Fewer studies evaluated the impact of long IPI on perinatal death and what evidence was available showed mixed results. CONCLUSIONS: Results suggest a possible association between short IPI and risk of perinatal death following a live birth, particularly in low- to middle-income countries. TWEETABLE ABSTRACT: Short IPI <6 months after a live birth was associated with greater risk of perinatal death than IPI ≥6 months.

Detection of Bacillus anthracis in animal tissues using InBios active anthrax detect rapid test lateral flow immunoassay.

The Active Anthrax Detect (AAD) Rapid Test lateral flow immunoassay is a point-of-care assay that was under investigational use for detecting Bacillus anthracis capsular polypeptide (polyglutamic acid) in human blood, serum and plasma. Small sample volumes, rapid results and no refrigeration required allow for easy use in either the field or laboratory. Although the test was developed for use in suspect cases of human inhalation anthrax, its features also make it a potentially powerful tool for testing suspect animal cases. We tested animal tissue samples that were confirmed or ruled out for B. anthracis. The AAD Rapid Tests were also deployed in the field, testing animal carcasses during an anthrax outbreak in hippopotami (Hippopotamus amphibius) and Cape buffalo (Syncerus caffer) in Namibia. Evaluation of all samples showed a specificity of 82% and sensitivity of 98%. However, when the assay was used on specimens from only fresh carcasses (dead for <24 h), the specificity increased to 96%. The AAD Rapid Test is a rapid and simple screening assay, but confirmatory testing needs to be done, especially when the age of the sample (days animal has been deceased) is unknown. SIGNIFICANCE AND IMPACT OF THE STUDY: In countries where anthrax is endemic, many human outbreaks are often caused by epizootics. Earlier detection of infected animals may allow for identification of exposed people, early implementation of prevention and control methods, and ultimately lessen the number of people and animals affected. Detection of Bacillus anthracis in animal tissues using a simple, rapid and field-deployable method would allow for faster outbreak response. We evaluated a simple sample collection and processing method for use with the Active Anthrax Detect Rapid Test lateral flow immunoassay to screen dead animals for anthrax.

Analysis of Whole-Genome Sequences for the Prediction of Penicillin Resistance and ß-Lactamase Activity in Bacillus anthracis.

Penicillin (PEN) is a low-cost option for anthrax treatment, but naturally occurring resistance has been reported. ß-Lactamase expression (bla1, bla2) in Bacillus anthracis is regulated by a sigma factor (SigP) and its cognate anti-sigma factor (RsiP). Mutations leading to truncation of RsiP were previously described as a basis for PEN resistance. Here, we analyze whole-genome sequencing (WGS) data and compare the chromosomal sigP-bla1 regions from 374 B. anthracis strains to determine the frequency of mutations, identify mutations associated with PEN resistance, and evaluate the usefulness of WGS for predicting PEN resistance. Few (3.5%) strains contained at least 1 of 11 different mutations in sigP, rsiP, or bla1. Nine of these mutations have not been previously associated with PEN resistance. Four strains showed PEN resistance (PEN-R) by conventional broth microdilution, including 1 strain with a novel frameshift in rsiP. One strain that carries the same rsiP frameshift mutation as that found previously in a PEN-R strain showed a PEN-susceptible (PEN-S) phenotype and exhibited decreased bla1 and bla2 transcription. An unexpectedly small colony size, a reduced growth rate, and undetectable ß-lactamase activity levels (culture supernatant and cell lysate) were observed in this PEN-S strain. Sequence analysis revealed mutations in genes associated with growth defects that may contribute to this phenotype. While B. anthracis rsiP mutations cannot be exclusively used to predict resistance, four of the five strains with rsiP mutations were PEN-R. Therefore, the B. anthracis sigP-bla1 region is a useful locus for WGS-based PEN resistance prediction, but phenotypic testing remains essential. IMPORTANCE Determination of antimicrobial susceptibility of B. anthracis is essential for the appropriate distribution of antimicrobial agents for postexposure prophylaxis (PEP) and treatment of anthrax. Analysis of WGS data allows for the rapid detection of mutations in antimicrobial resistance (AMR) genes in an isolate, but the presence of a mutation in an AMR gene does not always accurately predict resistance. As mutations in the anti-sigma factor RsiP have been previously associated with high-level penicillin resistance in a limited number of strains, we investigated WGS assemblies from 374 strains to determine the frequency of mutations and performed functional antimicrobial susceptibility testing. Of the five strains that contained mutations in rsiP, only four were PEN-R by functional antimicrobial susceptibility testing. We conclude that while sequence analysis of this region is useful for AMR prediction in B. anthracis, genetic analysis should not be used exclusively and phenotypic susceptibility testing remains essential.

Evidence for the Existence of a CXCL17 Receptor Distinct from GPR35.

The chemokine CXCL17 is associated with the innate response in mucosal tissues but is poorly characterized. Similarly, the G protein-coupled receptor GPR35, expressed by monocytes and mast cells, has been implicated in the immune response, although its precise role is ill-defined. A recent manuscript reported that GPR35 was able to signal in response to CXCL17, which we set out to confirm in this study. GPR35 was readily expressed using transfection systems but failed to signal in response to CXCL17 in assays of ß-arrestin recruitment, inositol phosphate production, calcium flux, and receptor endocytosis. Similarly, in chemotaxis assays, GPR35 did not confirm sensitivity to a range of CXCL17 concentrations above that observed in the parental cell line. We subsequently employed a real time chemotaxis assay (TAXIScan) to investigate the migratory responses of human monocytes and the monocytic cell line THP-1 to a gradient of CXCL17. Freshly isolated human monocytes displayed no obvious migration to CXCL17. Resting THP-1 cells showed a trend toward directional migration along a CXCL17 gradient, which was significantly enhanced by overnight incubation with PGE2 However, pretreatment of PGE2-treated THP-1 cells with the well-characterized GPR35 antagonist ML145 did not significantly impair their migratory responses to CXCL17 gradient. CXCL17 was susceptible to cleavage with chymase, although this had little effect its ability to recruit THP-1 cells. We therefore conclude that GPR35 is unlikely to be a bona fide receptor for CXCL17 and that THP-1 cells express an as yet unidentified receptor for CXCL17.

Environmental hydro-refugia demonstrated by vegetation vigour in the Okavango Delta, Botswana.

Climate shifts at decadal scales can have environmental consequences, and therefore, identifying areas that act as environmental refugia is valuable in understanding future climate variability. Here we illustrate how, given appropriate geohydrology, a rift basin and its catchment can buffer vegetation response to climate signals on decadal time-scales, therefore exerting strong local environmental control. We use time-series data derived from Normalised Difference Vegetation Index (NDVI) residuals that record vegetation vigour, extracted from a decadal span of MODIS images, to demonstrate hydrogeological buffering. While this has been described previously it has never been demonstrated via remote sensing and results in relative stability in vegetation vigour inside the delta, compared to that outside. As such the Delta acts as a regional hydro-refugium. This provides insight, not only to the potential impact of future climate in the region, but also demonstrates why similar basins are attractive to fauna, including our ancestors, in regions like eastern Africa. Although vertebrate evolution operates on time scales longer than decades, the sensitivity of rift wetlands to climate change has been stressed by some authors, and this work demonstrates another example of the unique properties that such basins can afford, given the right hydrological conditions.

Children's palliative care now! Highlights from the second ICPCN conference on children's palliative care, 18-21 May 2016, Buenos Aires, Argentina.

The International Children's Palliative Care Network held its second international conference on children's palliative care in Buenos Aires, Argentina, from the 18th-21st May 2016. The theme of the conference was 'Children's Palliative Care…. Now!' emphasising the need for palliative care for children now, as the future will be too late for many of them. Six pre-conference workshops were held, addressing issues connected to pain assessment and management, adolescent palliative care, ethics and decision-making, developing programmes, the basics of children's palliative care, and hidden aspects of children's palliative care. The conference brought together 410 participants from 40 countries. Plenary, concurrent, and poster presentations covered issues around the status of children's palliative care, genetics, perinatal and neonatal palliative care, the impact of children's palliative care and the experiences of parents and volunteers, palliative care as a human right, education in children's palliative care, managing complex pain in children, spiritual care and when to initiate palliative care. The 'Big Debate' explored issues around decision-making and end of life care in children, and gave participants the opportunity to explore a sensitive and thought provoking topic. At the end of the conference, delegates were urged to sign the Commitment of Buenos Aires which called for governments to implement the WHA resolution and ensure access to palliative care for neonates, children and their families, and also commits us as palliative care providers to share all that we can and collaborate with each other to achieve the global vision of palliative care for all children who need it. The conference highlighted the ongoing issues in children's palliative care and participants were continually challenged to ensure that children can access palliative care NOW.

Anal heterosex among young people and implications for health promotion: a qualitative study in the UK.

OBJECTIVE: To explore expectations, experiences and circumstances of anal sex among young people. DESIGN: Qualitative, longitudinal study using individual and group interviews. PARTICIPANTS: 130 men and women aged 16-18 from diverse social backgrounds. SETTING: 3 contrasting sites in England (London, a northern industrial city, rural southwest). RESULTS: Anal heterosex often appeared to be painful, risky and coercive, particularly for women. Interviewees frequently cited pornography as the 'explanation' for anal sex, yet their accounts revealed a complex context with availability of pornography being only one element. Other key elements included competition between men; the claim that 'people must like it if they do it' (made alongside the seemingly contradictory expectation that it will be painful for women); and, crucially, normalisation of coercion and 'accidental' penetration. It seemed that men were expected to persuade or coerce reluctant partners. CONCLUSIONS: Young people's narratives normalised coercive, painful and unsafe anal heterosex. This study suggests an urgent need for harm reduction efforts targeting anal sex to help encourage discussion about mutuality and consent, reduce risky and painful techniques and challenge views that normalise coercion.

Evaluating social and behavioural impacts of English smoke-free legislation in different ethnic and age groups: implications for reducing smoking-related health inequalities.

OBJECTIVE: To explore social and behavioural impacts of English smoke-free legislation (SFL) in different ethnic groups. DESIGN: A longitudinal, qualitative panel study of smokers using in-depth interviews conducted before and after introduction of SFL. PARTICIPANTS: A purposive sample of 32 smokers selected from three ethnic groups in deprived London neighbourhoods with approximately equal numbers of younger and older, male and female respondents. RESULTS: SFL has had positive impacts with half smoking less and three quitting. Although there were no apparent differences in smoking and quitting behaviours between groups, there were notable differences in the social impacts of SFL. The greatest negative impacts were in smokers over 60 years, potentially increasing their social isolation, and on young Somali women whose smoking was driven more underground. In contrast, most other young adult smokers felt relatively unaffected by SFL, describing unexpected social benefits. Although there was high compliance, reports of illegal smoking were more frequent among young, ethnic minority smokers, with descriptions of venues involved suggesting they are ethnically distinct and well hidden. Half of respondents reported stopping smoking in their own homes after SFL, but almost all were Somali or Turkish. White respondents tended to report increases in home smoking. DISCUSSION: Although our study suggests that SFL can lead to reductions in tobacco consumption, it also shows that impacts vary by ethnicity, age and sex. This study highlights the importance of understanding the meaning of smoking in different social contexts so future tobacco control interventions can be developed to reduce health and social inequalities.

Spatial and temporal modelling for parasite transmission studies and risk assessment.

Spatial and temporal modelling of parasite transmission and risk assessment require relevant spatial information at appropriate spatial and temporal scales. There is now a large literature that demonstrates the utility of satellite remote sensing and spatial modelling within geographical information systems (GIS) and firmly establishes these technologies as the key tools for spatial epidemiology. This review outlines the strength of satellite remotely sensed data for spatial mapping of landscape characteristics in relation to disease reservoirs, host distributions and human disease. It is suggested that current satellite technology can fulfill the spatial mapping needs of disease transmission and risk modelling, but that temporal resolution, which is a function of the satellite data acquisition characteristics, may be a limitating factor for applications requiring information about landscape or ecosystem dynamics. The potential of the Modis sensor for spatial epidemiology is illustrated with reference to mapping spatial and temporal vegetation dynamics and small mammal parasite hosts on the Tibetan plateau. Future research directions and priorities for landscape epidemiology are considered.

Evaluation of two selective media for the isolation of Bacillus anthracis.

AIMS: To evaluate two selective media, polymyxin, lysozyme, ethylenediaminetetraacetic acid, thallium acetate (PLET) agar and R&F Anthracis chromogenic agar (ChrA), for the isolation and selection of Bacillus anthracis. METHODS AND RESULTS: Sixteen genotypically diverse B. anthracis strains were sub-cultured onto PLET and ChrA to test the sensitivity (ability of B. anthracis to grow and produce expected colony morphology) of both media. Fourteen of the 16 B. anthracis strains produced the expected morphology on PLET (88% sensitive) while 13/16 produced the expected morphology on the ChrA medium (81% sensitive). Seventeen other Bacillus strains and 18 nonBacillus spp. strains were used to evaluate the media's selectivity (ability to inhibit non-B. anthracis growth). PLET inhibited growth of 14/35 strains (40% selective), including six Bacillus strains, while ChrA inhibited 3/35 (9% selective). In addition, we did not observe any differences between the recovered CFU on PLET or ChrA when plating extractions of spiked soil. CONCLUSIONS: Polymyxin, lysozyme, ethylenediaminetetraacetic acid, thallium acetate agar was more selective and sensitive than ChrA. SIGNIFICANCE AND IMPACT OF THE STUDY: Although both media are more expensive than sheep blood agar, for samples with high numbers of bacteria, they can be used to isolate B. anthracis with proper training and experience and with the knowledge that there are limitations to each media.

Crown Rot of Abies balsamea var. phanerolepis Caused by Phytophthora cactorum in Virginia.

In early July 2004, a severe crown rot of Canaan fir (Abies balsamea var. phanerolepis Fern.) was reported to the Virginia Cooperative Extension, Frederick County Office, and subsequently to the Virginia Tech Disease Clinic in Virginia Beach. One thousand five-year-old Canaan fir transplants (approximately 11 mm in caliper and 31 cm high) had been purchased from a tree nursery in Oregon and planted in the field in Frederick County, VA, in April of 2004. The field site had not been cultivated for 4 years after an apple orchard had been removed in 2000. By mid-May, needle browning had become serious, affecting the lower crown first. By August, transplants had suffered 40% mortality. Basal stems of affected plants were obviously discolored. Root and basal stem samples from several infected plants were then cultured on PARP-V8 agar on three different dates. Phytophthora sp. isolates were recovered from all stem samples but none from the roots. These isolates produced a large number of papillate sporangia that were caducous with short pedicels. Abundant oogonia with paragynous antheridia formed oospores directly on isolation plates within 7 days. The isolates were keyed as P. cactorum (2). This identification was confirmed using a single-strand-conformation polymorphism analysis of ribosomal DNA internal transcribed spacer (ITS)-1 (4). It appears that the source of inoculum was P. cactorum associated with the previous apple crop, since Canaan fir from the same transplant lot planted in a nearby field without a history of apples remained healthy. P. cactorum has been reported to cause root rot of noble fir (A. procera Rhedo), Pacific silver fir (A. amabilis (Dougl.) Forbes), and Shasta red fir (A. magnifica var. shastensis Lemm.) in the Pacific Northwest (3). It has also caused crown rot of Fraser fir (A. fraseri (Pursh) Poir.), noble fir, white fir (A. concolor (Gord. & Glend.) Lindl.), and balsam fir (A. balsamea (L.) Mill.) in Michigan (1). To our knowledge, this is the first report of P. cactorum attacking Canaan fir. Canaan fir currently is a recommended Christmas tree species for areas where Fraser fir does not do well due to root rot caused by Phytophthora cinnamomi. This study suggests that such a recommendation must be used with caution. Growing Canaan fir trees in P. cactorum-infested soil could result in devastating crop losses as reported in this note. References: (1) G. C. Adams, Jr. and A. Bielenin. Plant Dis. 72:79, 1988. (2) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St. Paul, MN, 1996. (3) P. B. Hamm and E. M. Hansen. Eur. J. For. Pathol. 12:167, 1982. (4) P. Kong et al. Fungal Genet. Biol. 39:238, 2003.

Effect of a complex environmental mixture from coal tar containing polycyclic aromatic hydrocarbons (PAH) on the tumor initiation, PAH-DNA binding and metabolic activation of carcinogenic PAH in mouse epidermis.

Human exposure to polycyclic aromatic hydrocarbons (PAH) occurs through complex mixtures such as coal tar. The effect of complex PAH mixtures on the activation of carcinogenic PAH to DNA-binding derivatives and carcinogenesis were investigated in mice treated topically with NIST (National Institute of Standards and Technology) Standard Reference Material 1597 (SRM), a complex mixture of PAH extracted from coal tar, and either additional benzo[a]pyrene (B[a]P) or dibenzo[a,l]pyrene (DB[a,l]P). In an initiation-promotion study using 12-O-tetradecanoylphorbol-13-acetate as the promoter for 25 weeks, the SRM and B[a]P co-treated mice had a similar incidence of papillomas per mouse compared with the group exposed to B[a]P alone as the initiator. PAH-DNA adduct analysis of epidermal DNA by 33P-post-labeling and reversed-phase high-performance liquid chromatography found the SRM co-treatment led to a significant decrease in the total level of DNA adducts and B[a]P-DNA adducts to less than that observed in mice treated with B[a]P alone at 6, 12 and 72 h exposure. After 24 and 48 h exposure, there was no significant difference in the levels of adducts between these groups. In the DB[a,l]P initiation-promotion study, the co-treated group had significantly fewer papillomas per mouse than mice treated with DB[a,l]P alone as initiator. Averaging over the times of exposure gave strong evidence that mice co-treated with SRM and DB[a,l]P had a significantly lower level of PAH-DNA adducts than mice treated with DB[a,l]P alone. Western immunoblots showed that both cytochrome P450 (CYP) 1A1 and 1B1 were induced by the SRM. These results are consistent with the hypothesis that two major factors determining the carcinogenic activity of PAH within a complex mixture are (i) the persistence of certain PAH-DNA adducts as well as total adduct levels, and (ii) the ability of the components present in the mixture to inhibit the activation of carcinogenic PAH by the induced CYP enzymes.

Persistence of a distinct Corynebacterium diphtheriae clonal group within two communities in the United States and Canada where diphtheria is endemic.

Molecular characterization of 53 U.S. and Canadian Corynebacterium diphtheriae isolates by multilocus enzyme electrophoresis, ribotyping, and random amplified polymorphic DNA showed that strains with distinct molecular subtypes have persisted in the United States and Canada for at least 25 years. These strains are endemic rather than imported from countries with current endemic or epidemic diphtheria.

Polarized infrared emissivity for a rough water surface.

The polarization state of infrared emission from water at large viewing angles is explained mathematically by a polarization-dependent emissivity. To provide polarized emissivity values for a wind-roughened water surface in a convenient format, this electronic paper provides interactive tables and plots of polarized water emissivity for the spectral range of 3-15 microm. The rough surface is modeled as a collection of specular facets with slopes given by a Gaussian distribution. The interactive electronic format provides a tutorial on emission polarization and it allows readers to copy the desired numbers and paste them into their electronic applications without the difficulty of transcribing numbers from printed tables.

Cranial vascular effects of zolmitriptan, a centrally active 5-HT1B/1D receptor partial agonist for the acute treatment of migraine.

The anti-migraine drug zolmitriptan is a novel 5-HT1B/1D receptor partial agonist which, unlike sumatriptan, has been shown to cross the intact blood-brain barrier. In this study we examined whether or not the ability to access the cerebro-vascular intima affects the way in which a centrally-active 5-HT1B/1D receptor agonist influences cranial haemodynamics. The effects of zolmitriptan on carotid arterial blood flow distribution were studied in anaesthetised cats using radiolabelled microspheres. Zolmitriptan (10-1000 microg kg(-1) i.v.) selectively reduced arteriovenous-anastomotic (AVA) conductance producing a maximum decrease of 92.5+/-2.3%. The drug also produced a modest reduction in extra-cerebral conductance (23.9+/-6.5% maximum reduction at 30 microg kg(-1), i.v.), but was without effect on cerebral conductance. Using laser doppler flowmetry in anaesthetised cats, zolmitriptan (1-30 microg kg(-1), i.v.) produced dose-dependent decreases in ear microvascular conductance (15+/-5 to 60+/-6%) which mirrored decreases in carotid arterial conductance (12+/-11 to 61+/-5%). By contrast, zolmitriptan at doses up to 1000 microg kg(-1) was without effect on cerebral microvascular conductance. Although zolmitriptan crosses the blood-brain barrier and can therefore access the cerebro-vascular intima, this study suggests that this property does not adversely affect cerebrovascular function.

Vascular 5-HT1-like receptors mediating vasoconstriction and vasodilatation: their characterization and distribution in the intact canine cardiovascular system.

1. In anaesthetized dogs, intra-left atrial administration of 5-hydroxytryptamine (5-HT) and selected tryptamine analogues (5-carboxamidotryptamine, 5-CT; 5-methyl tryptamine, 5-MT; alpha-methyl 5-hydroxytryptamine, alpha-HT; sumatriptan, Sum) in the presence of ketanserin and MDL72222 (5-HT2 and 5-HT3 receptor antagonists, respectively), produced dose-related changes in carotid, coronary and renal vascular conductance mediated by vascular 5-HT1-like receptors. 2. In the carotid vascular bed, 5-HT, 5-MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-HT = Sum > 5-MT > alpha-HT. By contrast in this vascular bed, 5-CT was a potent vasodilator. 3. In the coronary vascular bed, 5-HT, 5-CT, 5-MT and alpha-HT were vasodilators with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > 5-MT > alpha-HT. In this vascular bed, Sum was without effect. 4. In the renal vascular bed, 5-HT, 5-CT, 5-MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > Sum > 5-MT > alpha-HT. 5. The coronary (and carotid) vasodilator responses to 5-CT were antagonized by the 5-HT1-like receptor antagonists, spiperone (1 mg kg-1) and methiothepin (0.1 mg kg-1), whereas the renal vasoconstrictor responses to this tryptamine analogue were antagonized only by methiothepin. 6. It is concluded from these studies that agonist finger-printing in vivo, using tryptamine analogues,identifies and confirms the functional presence of at least two pharmacologically distinct subtypes of the 5-HT1-like receptor in the intact canine cardiovascular system. These two subtypes are located on the vascular smooth muscle and mediate direct vasoconstriction and vasodilatation responses in vivo.7. In addition, these studies confirm that the distribution of these subtypes within the major vascular beds, shows a marked heterogeneity. The carotid vascular responses to the tryptamine analogue sindicate the presence of both the vasodilator and the vasoconstrictor subtypes. The coronary vascular responses to these analogues are, however, consistent with presence of the vasodilator subtype, only. By contrast, the renal vascular responses to these analogues indicates only the presence of the vasoconstrictor subtype.

Selective 5-lipoxygenase inhibitor BW A4C does not influence progression of tissue injury in a canine model of regional myocardial ischaemia and reperfusion.

The effects of BW A4C, a selective arachidonate 5-lipoxygenase (5-LO) inhibitor, on the progression of myocardial tissue injury were examined in anaesthetised, open-chest beagle dogs subjected to 90-min occlusion of the left anterior descending coronary artery (LAD) followed by 120-min reperfusion. Regional myocardial blood flow (RMBF, microspheres), segment shortening (sonomicrometry), and infarct size (tetrazolium stain) as an index of tissue injury were measured. Control animals (group 1, n = 11) received an infusion of vehicle [50% vol/vol glycofurol and distilled water, 47 ml at 12 ml h-1, intravenously (i.v.)] beginning 15 min before ischaemia and continuing until the end of reperfusion. Treated animals received either 10 (group 2, n = 11) or 50 micrograms kg-1 min-1 (group 3, n = 5) BW A4C i.v. in the same period. The infarct/risk zone ratio (I/R) in group 1 (24.1 +/- 6.0%) was not significantly different from that of group 2 (28.0 +/- 8.4%) or group 3 (46.1 +/- 6.7%). The close inverse relationship observed in controls between I/R ratio and collateral flow was not altered by either dose of BW A4C. Segment shortening during ischaemia (-0.2 +/- 2.7, -2.4 +/- 1.7, and -1.5 +/- 1.7%) and reperfusion (4.9 +/- 2.8, 1.0 +/- 1.8, and -1.0 +/- 1.9%) and during an isoprenaline infusion to unmask stunned myocardium (14.7 +/- 3.0, 14.7 +/- 2.6, and 7.4 +/- 1.7%) were not significantly different between groups 1, 2, and 3.(ABSTRACT TRUNCATED AT 250 WORDS)