The effect of bariatric surgery type on cardiac reverse remodelling.

INTRODUCTION: Bariatric surgery is effective in reversing adverse cardiac remodelling in obesity. However, it is unclear whether the three commonly performed operations; Roux-en-Y Gastric Bypass (RYGB), Laparoscopic Sleeve Gastrectomy (LSG) and Laparoscopic Adjustable Gastric Band (LAGB) are equal in their ability to reverse remodelling. METHODS: Fifty-eight patients underwent CMR to assess left ventricular mass (LVM), LV mass:volume ratio (LVMVR) and LV eccentricity index (LVei) before and after bariatric surgery (26 RYGB, 22 LSG and 10 LAGB), including 46 with short-term (median 251-273 days) and 43 with longer-term (median 983-1027 days) follow-up. Abdominal visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) were also assessed. RESULTS: All three procedures resulted in significant decreases in excess body weight (48-70%). Percentage change in VAT and EAT was significantly greater following RYGB and LSG compared to LAGB at both timepoints (VAT:RYGB -47% and -57%, LSG -47% and -54%, LAGB -31% and -25%; EAT:RYGB -13% and -14%, LSG -16% and -19%, LAGB -5% and -5%). Patients undergoing LAGB, whilst having reduced LVM (-1% and -4%), had a smaller decrease at both short (RYGB: -8%, p < 0.005; LSG: -11%, p < 0.0001) and long (RYGB: -12%, p = 0.009; LSG: -13%, p < 0.0001) term timepoints. There was a significant decrease in LVMVR at the long-term timepoint following both RYGB (-7%, p = 0.006) and LSG (-7%, p = 0.021), but not LAGB (-2%, p = 0.912). LVei appeared to decrease at the long-term timepoint in those undergoing RYGB (-3%, p = 0.063) and LSG (-4%, p = 0.015), but not in those undergoing LAGB (1%, p = 0.857). In all patients, the change in LVM correlated with change in VAT (r = 0.338, p = 0.0134), while the change in LVei correlated with change in EAT (r = 0.437, p = 0.001). CONCLUSIONS: RYGB and LSG appear to result in greater decreases in visceral adiposity, and greater reverse LV remodelling with larger reductions in LVM, concentric remodelling and pericardial restraint than LAGB.

Change in surface characteristics and permeability of human enamel after subjecting to radiation therapy.

Background: Radiation-related caries is a complex destructive lesion leading to uncompromising damage of enamel and dentin in patients suffering from head and neck cancer managed with radiotherapy. Aim: The purpose of this study was to evaluate the changes in the permeability of enamel and to assess the morphological and chemical changes of teeth surface subjected to 6 MV photon beam irradiation. Materials and Methods: For this in vitro study, coronal portion of 20 premolars were sectioned mesiodistally into halves and then grouped into two. Samples in group 1 (control) were not subjected to cycles of irradiation and those in group 2 (experimental) were subjected to a cumulative uniform radiation dose of 70 Gray fractioned in 35 fractions with 6 MV photons. The silver nitrate penetration method was used to assess the change in permeability of enamel. The variations in surface topography and mineral content were assessed using scanning electron microscopy with energy dispersive X-ray analysis. Dye penetration scores of surface texture changes were compared between the two groups utilizing the Chi-square test. The change in the elemental levels between enamel surfaces of the two groups was compared using an independent t-test. Results: The application of 6 MV photon radiation did not change enamel permeability and surface topography. However, a noteworthy reduction in the carbon content (P = 0.002) was observed in teeth subjected to irradiation. Conclusions: Though radiation exposure did not alter the enamel permeability and surface topography, it had caused significant chemical compositional changes. Carbon content was significantly reduced in irradiated enamel samples.

Correction: The Relative Contribution of Metabolic and Structural Abnormalities to Diastolic Dysfunction in Obesity.

This Article was originally published under a CC BY NC-ND 4.0 license, but has now been made available under a CC BY 4.0 license.

The relative contribution of metabolic and structural abnormalities to diastolic dysfunction in obesity.

BACKGROUND: Obesity causes diastolic dysfunction, and is one of the leading causes of heart failure with preserved ejection fraction. Myocardial relaxation is determined by both active metabolic processes such as impaired energetic status and steatosis, as well as intrinsic myocardial remodelling. However, the relative contribution of each to diastolic dysfunction in obesity is currently unknown. METHODS: Eighty adult subjects (48 male) with no cardiovascular risk factors across a wide range of body mass indices (18.4-53.0 kg m-2) underwent magnetic resonance imaging for abdominal visceral fat, left ventricular geometry (LV mass:volume ratio) and diastolic function (peak diastolic strain rate), and magnetic resonance spectroscopy for PCr/ATP and myocardial triglyceride content. RESULTS: Increasing visceral obesity was related to diastolic dysfunction (peak diastolic strain rate, r=-0.46, P=0.001). Myocardial triglyceride content (ß=-0.2, P=0.008), PCr/ATP (ß=-0.22, P=0.04) and LV mass:volume ratio (ß=-0.61, P=0.04) all independently predicted peak diastolic strain rate (model R2 0.36, P<0.001). Moderated multiple regression confirmed the full mediating roles of PCr/ATP, myocardial triglyceride content and LV mass:volume ratio in the relationship between visceral fat and peak diastolic strain rate. Of the negative effect of visceral fat on diastolic function, 40% was explained by increased myocardial triglycerides, 39% by reduced PCr/ATP and 21% by LV concentric remodelling. CONCLUSIONS: Myocardial energetics and steatosis are more important in determining LV diastolic function than concentric hypertrophy, accounting for more of the negative effect of obesity on diastolic function than LV geometric remodelling. Targeting these metabolic processes is an attractive strategy to treat diastolic dysfunction in obesity.

The views of parents who experience intergenerational poverty on parenting and play: a qualitative analysis.

BACKGROUND: There is minimal literature on how parents experiencing intergenerational poverty view their role as parents and the value they place on children's play. The objective of this study was to examine how these parents view their parenting role and their beliefs about children's play. METHODS: Thirteen mothers of preschool-aged children who experienced intergenerational poverty were recruited to the study. Semi-structured interviews were conducted and were analysed using interpretive phenomenological analysis. RESULTS: Parents described their role as guiding their children to become 'good' people, to teach them skills and provide a routine within the home. There were two disconnections in the data including the view that whilst parenting was hard and lonely, it was also a private matter and participants preferred not to seek support. A second disconnection was in terms of their beliefs about play. Parents believed that whilst play was valuable to their child's development, it was not their role to play with children. However, if parents did play with their child, they noticed positive changes in their child's behaviour. CONCLUSION: The views of parents who experienced intergenerational poverty were similar to other reported findings in parenting studies. However, the current sample differed on not seeking help for support as well as not seeing their role as playing with their children, even though occasions of joining their child in play were associated with a positive change in their relationship with their child. This has implications for communicating about parenting issues with parents who have experienced intergenerational poverty.

When ignorance is bliss: weight perception, body mass index and quality of life in adolescents.

BACKGROUND/OBJECTIVES: Body weight is negatively associated with adolescent Health-Related Quality of Life (HRQoL). Despite this well-established relationship, some adolescents with obesity do not display the expected HRQoL decreases. This study hypothesised weight perception as a moderator of the association between weight status and adolescent HRQoL. SUBJECTS/METHODS: Subjects were secondary school students from an obesity prevention project in the Barwon South-West region of Victoria, Australia, entitled It's Your Move (N=3040). Measures included standardised body mass index (BMI-z; World Health Organization growth standards), weight perception and HRQoL, measured by the Paediatric Quality of Life Inventory. Linear regression and average marginal effect analyses were conducted on cross-sectional baseline data to determine the significance of any interaction between weight perception and measured weight status in shaping adolescent HRQoL. RESULTS: The BMI-z/perceived weight status interaction was significantly associated with adolescent HRQoL outcomes. Adolescents with BMI z-scores in the overweight/obesity range who perceived themselves as overweight had lower HRQoL than those who perceived themselves as 'about right.' Conversely, adolescents with BMI scores in the lower end of the normal range or in the thinness range who perceived themselves as underweight had lower HRQoL than those with 'about right' perceptions. CONCLUSIONS: This was the first study to report third-variable impacts of a body-perception variable on the relationship between adolescent weight status and HRQoL. Adolescents' weight perceptions significantly moderated the relationship between overweight/obesity and reduced HRQoL. Adolescents who were outside the normal weight range and misperceived their objectively measured weight status enjoyed a higher HRQoL than adolescents whose weight perception was concordant with their actual weight status. These findings suggest that practitioners may need to exercise caution when educating adolescents about their weight status, as such 'reality checks' may negatively impact on adolescent HRQoL. It is suggested that more research be conducted to examine this potential effect.

Religious/Spiritual Well-being, personality and mental health: a review of results and conceptual issues.

The current paper provides background to the development of the Multidimensional Inventory for Religious/Spiritual Well-being and then summarises findings derived from its use with other measures of health and personality. There is substantial evidence for religiosity/spirituality being positively related to a variety of indicators of mental health, including subjective well-being and personality dimensions. Furthermore, religiosity/spirituality can play an important role in the process of recovering from mental illness as well as providing a protective function against addictive or suicidal behaviours. However, further research is needed to examine the mechanisms through which religiosity/spirituality have an impact on health-related conditions.

Seasonal necrophagous insect community assembly during vertebrate carrion decomposition.

Necrophagous invertebrates have been documented to be a predominant driver of vertebrate carrion decomposition; however, very little is understood about the assembly of these communities both within and among seasons. The objective of this study was to evaluate the seasonal differences in insect taxa composition, richness, and diversity on carrion over decomposition with the intention that such data will be useful for refining error estimates in forensic entomology. Sus scrofa (L.) carcasses (n = 3-6, depending on season) were placed in a forested habitat near Xenia, OH, during spring, summer, autumn, and winter. Taxon richness varied substantially among seasons but was generally lower (1-2 taxa) during early decomposition and increased (3-8 taxa) through intermediate stages of decomposition. Autumn and winter showed the highest richness during late decomposition. Overall, taxon richness was higher during active decay for all seasons. While invertebrate community composition was generally consistent among seasons, the relative abundance of five taxa significantly differed across seasons, demonstrating different source communities for colonization depending on the time of year. There were significantly distinct necrophagous insect communities for each stage of decomposition, and between summer and autumn and summer and winter, but the communities were similar between autumn and winter. Calliphoridae represented significant indicator taxa for summer and autumn but replaced by Coleoptera during winter. Here we demonstrated substantial variability in necrophagous communities and assembly on carrion over decomposition and among seasons. Recognizing this variation has important consequences for forensic entomology and future efforts to provide error rates for estimates of the postmortem interval using arthropod succession data as evidence during criminal investigations.

Changes in epicardial and visceral adipose tissue depots following bariatric surgery and their effect on cardiac geometry.

Introduction: Obesity affects cardiac geometry, causing both eccentric (due to increased cardiac output) and concentric (due to insulin resistance) remodelling. Following bariatric surgery, reversal of both processes should occur. Furthermore, epicardial adipose tissue loss following bariatric surgery may reduce pericardial restraint, allowing further chamber expansion. We investigated these changes in a serial imaging study of adipose depots and cardiac geometry following bariatric surgery. Methods: 62 patients underwent cardiac magnetic resonance (CMR) before and after bariatric surgery, including 36 with short-term (median 212 days), 37 medium-term (median 428 days) and 32 long-term (median 1030 days) follow-up. CMR was used to assess cardiac geometry (left atrial volume (LAV) and left ventricular end-diastolic volume (LVEDV)), LV mass (LVM) and LV eccentricity index (LVei - a marker of pericardial restraint). Abdominal visceral (VAT) and epicardial (EAT) adipose tissue were also measured. Results: Patients on average had lost 21kg (38.9% excess weight loss, EWL) at 212 days and 36kg (64.7% EWL) at 1030 days following bariatric surgery. Most VAT and EAT loss (43% and 14%, p<0.0001) occurred within the first 212 days, with non-significant reductions thereafter. In the short-term LVM (7.4%), LVEDV (8.6%) and LAV (13%) all decreased (all p<0.0001), with change in cardiac output correlated with LVEDV (r=0.35,p=0.03) and LAV change (r=0.37,p=0.03). Whereas LVM continued to decrease with time (12% decrease relative to baseline at 1030 days, p<0.0001), both LAV and LVEDV had returned to baseline by 1030 days. LV mass:volume ratio (a marker of concentric hypertrophy) reached its nadir at the longest timepoint (p<0.001). At baseline, LVei correlated with baseline EAT (r=0.37,p=0.0040), and decreased significantly from 1.09 at baseline to a low of 1.04 at 428 days (p<0.0001). Furthermore, change in EAT following bariatric surgery correlated with change in LVei (r=0.43,p=0.0007). Conclusions: Cardiac volumes show a biphasic response to weight loss, initially becoming smaller and then returning to pre-operative sizes by 1030 days. We propose this is due to an initial reversal of eccentric remodelling followed by reversal of concentric remodelling. Furthermore, we provide evidence for a role of EAT contributing to pericardial restraint, with EAT loss improving markers of pericardial restraint.

When entomological evidence crawls away: Phormia regina en masse larval dispersal.

In criminal and civil legal investigations the forensic entomologist usually assists in providing an estimate of the postmortem interval, which closely couples with the time or period of insect activity. A minimum period of insect activity is often interpreted and estimated by dipteran larval developmental age of the oldest specimens collected at a crime scene and/or autopsy. In entomological evidence protocols investigators are recommended to search a 2-10 m perimeter area for the oldest larvae that may have begun to disperse away from the body for burial and pupation. In this study, we described a case of a large aggregate (> 90% larvae) en masse postfeeding dispersal of blow fly larvae away from replicate swine carcasses serving as models of human decomposition. Larval dispersal was evaluated for a spring and a summer trial, with en masse characteristics only occurring during the latter. This en masse dispersal occurred in five out of six replicate carcasses and masses moved from 2 to 26 m away. These data and observations suggest the importance of performing searches > 10 m from human remains for entomological evidence at crime scenes. By missing the oldest larvae at a crime scene, interpretation of entomological evidence can be compromised and erroneous. Based on these data and observations we recommend the crime scene investigators and researchers consider increasing the search radius around crime scene remains to increase the likelihood that the oldest larvae have been collected for analysis.

Prenatal maternal mental health and fetal growth restriction: a systematic review.

Maternal mental disorders during pregnancy are associated with a range of adverse health outcomes for offspring. This systematic review examines studies reporting on the relationship between maternal depression, anxiety or stress during pregnancy and fetal growth measured during pregnancy using ultrasound biometry. A systematic search of PsycINFO, Medline, Scopus, Web of Science and Embase was conducted and 1575 records were identified, with nine studies meeting inclusion criteria gathering data from over 7000 participants. All studies measured depression, six examined anxiety and depression, and five examined all three exposures. The majority measured symptoms rather than clinically diagnosable disorder. Studies consistently reported significant associations between maternal mental health, particularly anxiety symptoms, and reduced fetal head growth. Other fetal growth parameters showed inconsistent findings. A number of studies suggest that cortisol dysregulation associated with maternal mental health may play a role in fetal growth restriction. However, heterogeneity in the timing of growth measurement, assessment measures used for mental health and inconsistencies in adjustment for confounders, limits the synthesis and interpretation of findings. Future studies should consider differences in the timing, intensity and duration of mental health symptoms over pregnancy and should employ diagnostic assessment of mental disorders. Fetal growth should be repeatedly measured and further work is needed to establish the biological mechanisms involved.

Body composition, tissue deposition, and lysine utilization for protein deposition of barrows and gilts fed crystalline or protein-bound lysine.

An experiment with 2 trials (28 d/trial) was conducted to determine body composition, tissue deposition, and utilization of Lys for protein deposition (PD) of barrows and gilts fed -Lys·HCl (CLys) or protein-bound Lys in soybean meal (SBM). Thirty-two growing pigs (16 barrows and 16 gilts; average initial BW of 18.6 kg) were used in each of 2 trials. Four pigs (2 barrows and 2 gilts) were euthanized at the start of each trial to determine initial body composition. The remaining pigs were euthanized at the end of the trials to determine empty-body composition and deposition rates of water, protein, fat, ash, and AA. Pigs were randomly allotted to 1 of 7 dietary treatments. There were 2 replications per treatment in each trial for a total of 4 replications. Dietary treatments consisted of a corn-SBM basal diet (0.48% Lys) and diets containing 0.56%, 0.65%, and 0.74% standardized ileal digestible (SID) Lys that were achieved by adding Lys to the basal diet from either SBM or CLys. Pigs fed the CLys-supplemented diets at 0.65% SID Lys had more ( < 0.05) body water (663 vs. 624 g/kg) and less ( < 0.01) body protein (153 vs. 160 g/kg) than pigs fed the SBM-supplemented diets. Body fat content decreased ( < 0.01) as the dietary Lys increased similarly for pigs fed Lys from SBM and pigs fed CLys. Gilts had greater ( = 0.05) body Lys content in body protein than barrows (7.68 vs. 7.52 g/100 g). Empty-body ash contents were not different between pigs fed CLys or SBM-supplemented diets. Water deposition and PD increased linearly ( < 0.01) with dietary Lys and were least ( < 0.01) in pigs fed the basal diet but were similar when comparing pigs fed CLys and SBM-supplemented diets at the same dietary Lys concentration. Lysine deposition showed a linear increase ( < 0.01) with dietary Lys but was not different between pigs fed the 2 Lys sources at the same concentration. Barrows and gilts did not differ in tissue deposition rates. Overall, empty-body contents and deposition rates of essential and nonessential AA were not different between pigs fed CLys and pigs fed SBM-bound Lys. The amount of SID Lys required for PD ranged between 0.09 and 0.13 g/g for both sources of Lys. The Lys deposition:SID Lys intake ratio was greater ( < 0.01) in gilts than barrows (0.62 vs. 0.56). Body composition, tissue deposition, and utilization of Lys for PD and Lys deposition were not different in pigs fed diets supplemented with -Lys·HCl with respect to protein-bound Lys in SBM.

New targets for anti-inflammatory drugs.

Inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, psoriasis and asthma, provide drug discoverers with a tremendous challenge. The precise causes of these diseases are not known, but our understanding of the molecular and cellular mechanisms associated with inflammatory diseases has increased dramatically. As a consequence, a wide array of gene targets have emerged that control cell influx and activation, inflammatory mediator release and activity, and tissue proliferation and degradation. Since multiple gene products have been identified at the sites of inflammation, there has been a surge of interest in identifying intracellular signaling targets, including transcription factors that control inflammatory gene expression and which are amenable to drug discovery.

Hydrogen production from switchgrass via an integrated pyrolysis-microbial electrolysis process.

A new approach to hydrogen production using an integrated pyrolysis-microbial electrolysis process is described. The aqueous stream generated during pyrolysis of switchgrass was used as a substrate for hydrogen production in a microbial electrolysis cell, achieving a maximum hydrogen production rate of 4.3 L H2/L anode-day at a loading of 10 g COD/L-anode-day. Hydrogen yields ranged from 50±3.2% to 76±0.5% while anode Coulombic efficiency ranged from 54±6.5% to 96±0.21%, respectively. Significant conversion of furfural, organic acids and phenolic molecules was observed under both batch and continuous conditions. The electrical and overall energy efficiency ranged from 149-175% and 48-63%, respectively. The results demonstrate the potential of the pyrolysis-microbial electrolysis process as a sustainable and efficient route for production of renewable hydrogen with significant implications for hydrocarbon production from biomass.

Clinical significance of carotid plaque hemorrhage.

We correlated the clinical and pathologic findings in 77 consecutive carotid plaques removed at endarterectomy to determine the clinical role of intraplaque hemorrhage. Intraplaque hemorrhages of various severity were seen in 86% of plaques. They were, for the most part, deeply located (63%) and infrequently connected with the lumen. They related closely to the severity of carotid stenosis, but bore no relationship to the timing of symptoms. Luminal thrombus was infrequently seen, and was always microscopic. Hemorrhage into carotid plaque appears to represent an index of the severity of the stenosis and plaque instability rather than to play a direct role in the pathogenesis of transient ischemic attacks or stroke.

The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases.

Neuropathologic confirmation is required to validate the NINCDS-ADRDA Work Group criteria for the clinical diagnosis of Alzheimer's disease (AD). Neuropathologic inclusion and exclusion criteria for AD, however, are not uniform. The purpose of this investigation was to examine the confirmation rate for the Work Group criteria against differing neuropathologic criteria for AD. The sample consisted of 57 cases, 22 of which had received a clinical diagnosis of AD. Nine neuropathologic criteria for AD were applied in a blind fashion to each of the 57 cases. Our results indicated that, depending on the neuropathologic criteria applied, the clinicopathologic agreement ranged from 64% to 86%. These findings demonstrate the need for universally accepted neuropathologic and clinical criteria for AD.

Middle interhemispheric variant of holoprosencephaly: a distinct cliniconeuroradiologic subtype.

BACKGROUND: The middle interhemispheric variant (MIH) is a subtype of holoprosencephaly (HPE) in which the posterior frontal and parietal areas lack midline separation, whereas more polar areas of the cerebrum are fully cleaved. While the neuroradiologic features of this subtype have been recently detailed, the clinical features are largely unknown. OBJECTIVE: To present the clinical manifestations of MIH and to compare them with classic subtypes (alobar, semilobar, and lobar) of HPE. METHODS: The authors evaluated 15 patients with MIH in a multicenter study. Neuroimaging and clinical data were collected and correlated. They compared the data with those of 68 patients who had classic HPE. RESULTS: The frequency of endocrinopathy in MIH (0%) was lower compared with the classic subtypes (72%) (p < 0.0001). This correlated with the lack of hypothalamic abnormalities. The percentage of patients with seizures (40%) did not significantly differ from classic HPE. Spasticity was the most common motor abnormality, seen in 86% of MIH patients, similar to other subtypes. The frequency of choreoathetosis in MIH (0%) was lower than that for semilobar HPE (41%) (p < 0.0039). This correlated with the lack of caudate and lentiform nuclei abnormalities. Developmental functions, including mobility, upper-extremity function, and language, of the MIH group were similar to the least severe classic type, lobar HPE. CONCLUSION: MIH is a recognizable variant of HPE with differing clinical prognosis. Similar to the lobar subtype by functional measures, MIH differs from classic HPE by the absence of endocrine dysfunction and choreoathetosis.

Synthesis of [[(naphthalenylmethoxy)- and [[(quinolinylmethoxy)phenyl]amino]oxoalkanoic acid esters. A novel series of leukotriene D4 antagonists and 5-lipoxygenase inhibitors.

A series of novel [[(naphthalenylmethoxy)- and [[(quinolinylmethoxy)phenyl]amino]oxoalkanoic acid esters have been prepared. These compounds were tested as inhibitors of rat polymorphonuclear leukocyte (PMN) 5-lipoxygenase (LO) in vitro and as inhibitors of ovalbumin (OA) and leukotriene D4 (LTD4) induced bronchospasm in the guinea pig (GP) in vivo. Many naphthalenyl compounds were potent inhibitors of 5-LO, and several quinolinyl compounds were potent inhibitors of LTD4-mediated bronchospasms in the GP. The most potent naphthalenyl compound, 4-[[3-(2-naphthalenylmethoxy)phenyl]hydroxyamino]-4-oxobutanoic acid, methyl ester (6v), had an IC50 of 0.6 microM in the 5-LO assay. The most potent compound in vivo, 4-[[3-(2-quinolinylmethoxy)phenyl]hydroxyamino]-4-oxobutanoic acid, methyl ester (6e), had ED50's of 3.3 mg/kg and 27.4 mg/kg (intraduodenally) against LTD4- and OA-induced bronchospasm, respectively. When tested as an antagonist of LTD4-induced contraction of isolated GP tracheal spiral strips, 6e was shown to be a competitive inhibitor with a pKB value of 5.33.

Synthesis and antiallergic activity of a novel series of 5-lipoxygenase inhibitors.

A series of novel substituted [[(phenoxymethyl)phenyl]amino]oxoalkanoic acid esters have been synthesized. These compounds were tested in vitro for their ability to inhibit the synthesis of 5-hydroxyeicosatetraenoic acid and leukotriene (LT) B4 from rat polymorphonuclear leukocytes (PMN) and in vivo as inhibitors ovalbumin- (OA) and LTD4-induced bronchospasm in the guinea pig. Compounds 5-12 and 25 had IC50's between 1 and 5.6 microM in the rat PMN 5-lipoxygenase assay. Compounds 1, 3, and 16 inhibited OA-induced bronchoconstriction (61%, 64%, and 57%, respectively), but only 1 showed activity against LTD4-induced bronchoconstriction. When tested against LTD4-induced contraction of isolated guinea pig tracheal spiral strips, 1 was a competitive inhibitor with a pKB of 4.94.

Antiinflammatory effects of some copper complexes.

Copper complexes of a range of ligands have been prepared and evaluated for antiinflammatory activity and irritancy after oral, subcutaneous, and local administration in rats and guinea pigs. The antiinflammatory activities were found to depend on the species used and the route of administration. When nonantiinflammatory ligands were used, the response was generally dose dependent. With D-penicillamine and when the ligands were themselves antiinflammatory in animal models of inflammation--as was the case with flufenamic acid, levamisole, aspirin, L-histidine, and 2-amino-2-thiazoline--differences in antiinflammatory activity were observed between the copper complexes and the free ligands. In some cases, the copper complexes were the more effective. There was a weak correlation between local (subplantar) irritation and the dose of copper but, for four compounds studied in more detail, the response in the local subplantar test and degree of antiinflammatory activity were not related, suggesting that the action of copper is not solely by a counterirritant mechanism. No obvious differences between the activities of copper(I) and copper(II) compounds were observed, suggesting that a common metabolite may be involved in the antiinflammatory action of copper.