Executive Summary: variation in susceptibility to ozone-induced health effects in rodent models of cardiometabolic disease

Abstract

Seven million premature deaths occur annually due to air pollution worldwide, of which ～80% are attributed to exacerbation of cardiovascular disease (CVD), necessitating greater attention to understanding the causes of susceptibility to air pollution in this sector of population. We used rat models of CVD with or without obesity and compared them to healthy strains to examine the risk factors of ozone-induced lung injury and inflammation. We examined functional, biochemical and molecular changes in several organs to evaluate how physiological factors as well as compensatory antioxidant reserves modulate processes by which ozone injury is influenced by underlying disease. In this study, we highlight key findings of this series of reports. We show that underlying cardiopulmonary insufficiency in genetically predisposed rats appears to increase the effective ozone dose; thus dosimetry is one factor contributing to exacerbated ozone effects. We further show that antioxidant reserve in airway lining fluid modulates ozone-induced damage such that strains with the least antioxidant reserve incur the greatest injury. And finally, we show that the inflammatory response to ozone is governed by a cluster of genes involved in regulating cytokine release, trafficking of inflammatory cells and processes related to cellular apoptosis and growth. All such processes are influenced not only by ozone dosimetry and the lung antioxidant milieu but also by the strain-specific genetic factors. In using a comprehensive systems biology research approach, our data reveal key risk factors for – and strategies to reduce risk of – air pollution mortality among those with CVD.     

Left ventricular gene expression profile of healthy and cardiovascular compromised rat models used in air pollution studies

Abstract

The link between pollutant exposure and cardiovascular disease (CVD) has prompted mechanistic research with animal models of CVD. We hypothesized that the cardiac gene expression patterns of healthy and genetically compromised, CVD-prone rat models, with or without metabolic impairment, will reveal underlying disease processes that facilitate understanding of the mechanisms of air pollution susceptibility differences. Left ventricular gene expression was examined using Affymetrix rat 230A-gene arrays in male, age-matched (12–14 weeks old) healthy Wistar Kyoto (WKY) and CV-compromised spontaneously hypertensive (SH), stroke-prone SH (SHSP), obese SH heart failure (SHHF) and obese insulin-resistant (JCR) rats. Principle component analysis separated strains in three clusters: (1) WKY, (2) JCR and (3) SH, SHSP and SHHF. Gene expression pattern in JCR differed from all other CVD strains. Both SHHF and JCR strains presented the most differentially expressed genes from WKY, but generally with opposing directional pattern suggesting that the CVD in these strains arise through different mechanisms. Hierarchical clustering of nuclear factor-kappaB target genes indicated varying degrees of, but similar directional changes, in SH, SHSP and SHHF relative to WKY rats, which may relate to the severity of their CVD. The JCR strain had less pronounced expressions of these genes suggesting milder cardiac disease. No unique expression pattern could be identified for genes implicated in stroke and heart failure in SHSP and SHHF rats, respectively. The data show that the CVD pathophysiological mechanisms differ in models with different genetic backgrounds, and therefore, the mechanisms by which air pollutants affect the cardiopulmonary system are likely to vary.     

The effects of air pollution and smoking on placental cadmium, zinc concentration and metallothionein expression

This study is designed to determine the placental zinc (Zn) and cadmium (Cd) levels in mothers who were smokers, mothers who were thought to be exposed to air pollution, and mothers who were non-smokers and to investigate the relationship between the expression of placental metallothionein (MT) binding these metals and blood progesterone level. Placental Zn and Cd levels were measured by atomic absorption spectrometry. Presence of placental MT was determined immunohistochemically. Placental changes were examined by light microscope after H&E and PAS staining. Immunohistochemical MT staining of syncytiotrophoblastic and villous interstitial cells were scored as positive or negative. Among the 92 mothers included in the study, 33 were smokers (Group I), 29 had been exposed to air pollution (Group II) and 30 were non-smoker rural residents who had never been exposed to air pollution (Group III). Mean off-spring birth weight of 3198.62+/-380.01 g and mean placenta weight of 561.38+/-111.55 g of Group II were lower when compared with those of other two groups. In Group I, mean placental Cd and Zn were 0.063+/-0.022 microg/g and 39.84+/-15.5 microg/g, respectively, being higher than in other groups. In Group II, mean placental Cd and Zn levels were higher than those of Group III. Blood progesterone levels of subjects in Group I (121 ng/ml) were the lowest of all groups. While the mean count of villi was the highest in Group III; the highest mean count of syncytial knots was in Group II. Thickening of vasculo-syncytial membrane was most prominent in Group I. Similarly, MT staining was positive and very dense in 72.7% (24/33) of cases in Group I (p相似文献   

Synergistic effects of exposure to concentrated ambient fine pollution particles and nitrogen dioxide in humans

Context: Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.

Objectives: Determine if simultaneous exposure to PM and NO₂ results in synergistic interactions.

Materials and methods: Healthy young volunteers were exposed to clean air, nitrogen dioxide (NO₂, 0.5 ppm), concentrated fine particles from Chapel Hill air (PM_2.5CAPs, 89.5?±?10.7 µg/m³), or NO₂+PM_2.5CAPs for 2?h. Each subject performed intermittent exercise during the exposure. Parameters of heart rate variability (HRV), changes in repolarization, peripheral blood endpoints and lung function were measured before and 1 and 18?h after exposure. Bronchoalveolar lavage (BAL) was performed 18?h after exposure.

Results: NO₂ exposure alone increased cholesterol and HDL 18?h after exposure, decreased high frequency component of HRV one and 18?h after exposure, decreased QT variability index 1?h after exposure, and increased LDH in BAL fluid. The only significant change with PM_2.5CAPs was an increase in HDL 1?h after exposure, likely due to the low concentrations of PM_2.5CAPs in the exposure chamber. Exposure to both NO₂ and PM_2.5CAPs increased BAL α1-antitrypsin, mean t wave amplitude, the low frequency components of HRV and the LF/HF ratio. These changes were not observed following exposure to NO₂ or PM_2.5CAPs alone, suggesting possible interactions between the two pollutants.

Discussion and conclusions: NO₂ exposure may produce and enhance acute cardiovascular effects of PM_2.5CAPs. Assessment of health effects by ambient PM should consider its interactions with gaseous copollutants.     

Mulberry leaves and their potential effects against cardiometabolic risks: a review of chemical compositions,biological properties and clinical efficacy

Context: Cardiometabolic risks are regarded as the crucial factors associated with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an increased attention to medicinal plants in the current healthcare system, the effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have been consecutively considered in scientific research.

Objective: The present review compiles and summarizes the chemical compositions, biological properties and clinical efficacy of mulberry leaves that are related to the amelioration of cardiometabolic risks.

Methods: Published English literature from the PubMed, Science Direct and Google Scholar databases was searched by using ‘mulberry leaves’ ‘Morus spp.’, ‘hyperglycemia’, ‘hyperlipidemia’, ‘obesity’, ‘hypertension’, ‘oxidative stress’, ‘atherosclerosis’ and ‘cardiovascular diseases’ as the keywords. The relevant articles published over the past two decades were identified and reviewed.

Results: Mulberry leaves contain numerous chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the prominent functional compounds. Preclinical and clinical studies showed that mulberry leaves possessed various beneficial effects against cardiometabolic risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity, antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and cardioprotective effects.

Conclusions: Mulberry leaves could be a promising therapeutic option for modulating cardiometabolic risks. However, further investigations should be performed to substantiate the potential of mulberry leaves in practical uses.     

Fine particulate air pollution and hospital admissions for congestive heart failure: a case-crossover study in Taipei

Abstract

This study was undertaken to determine whether there was an association between fine particles (PM_2.5) levels and hospital admissions for congestive heart failure (CHF) in Taipei, Taiwan. Hospital admissions for CHF and ambient air pollution data for Taipei were obtained for the period 2006–2010. The relative risk of hospital admissions was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality and long-term time trends. For the single pollutant model (without adjustment for other pollutants), increased CHF admissions were significantly associated with PM_2.5 both on warm days (>23?°C) and cool days (<23?°C), with an interquartile range increase associated with a 13% (95% CI?=?9–17%) and 3% (95% CI?=?0–7%) increase in CHF admissions, respectively. In the two-pollutant models, PM_2.5 remained significant after the inclusion of SO₂ or O₃ both on warm and cool days. This study provides evidence that higher levels of PM_2.5 increase the risk of hospital admissions for CHF.     

Ambient air pollution,blood mitochondrial DNA copy number and telomere length in a panel of diabetes patients

Abstract

Context: Several previous studies proposed a link between particulate matter (PM) pollution and mitochondrial DNA copy number (MtDNAcn) and telomere length (TL). However, this evidence is quite limited and inconsistent, especially on how the particle size affects the associations and on whether there exists such an association with gaseous pollutants.

Objective: We aimed to investigate the short-term associations of size-fractionated PM and gaseous pollutants with blood MtDNAcn and TL.

Methods: We conducted a longitudinal panel study involving 6 repeated measurements among 35 Type 2 diabetes patients in Shanghai, China from April to June 2013. We measured the real-time concentrations of size-fractionated PM (0.25–10?μm) and criteria gaseous pollutants. Blood MtDNAcn and TL were tested by a quantitative real-time PCR–based assay. Linear mixed-effect models were used to explore their short-term associations using multiple lag periods, after controlling for individual characteristics, time trends and weather conditions.

Results: In general, there were inverse but statistically non-significant associations between all pollutants and MtDNAcn. Coarse PM appeared to be more closely linked with MtDNAcn than smaller PM. The associations between various air pollutants and TL were generally positive but very weak. There were no clear lag patterns for these associations. The associations between air pollutants and MtDNAcn and TL were strengthened but still not significant among those who did not take statins regularly.

Conclusions: This study did not support short-term associations of PM or gaseous pollutants with blood MtDNAcn and TL in type 2 diabetes patients.     

The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: IV. Vascular effects of repeated inhalation exposure to a mixture of five inorganic gases

Abstract

An experiment was conducted to test the hypothesis that a mixture of five inorganic gases could reproduce certain central vascular effects of repeated inhalation exposure of apolipoprotein E-deficient mice to diesel or gasoline engine exhaust. The hypothesis resulted from preceding multiple additive regression tree (MART) analysis of a composition–concentration–response database of mice exposed by inhalation to the exhausts and other complex mixtures. The five gases were the predictors most important to MART models best fitting the vascular responses. Mice on high-fat diet were exposed 6?h/d, 7?d/week for 50 d to clean air or a mixture containing 30.6?ppm CO, 20.5?ppm NO, 1.4?ppm NO₂, 0.5?ppm SO₂, and 2.0?ppm NH₃ in air. The gas concentrations were below the maxima in the preceding studies but in the range of those in exhaust exposure levels that caused significant effects. Five indicators of stress and pro-atherosclerotic responses were measured in aortic tissue. The exposure increased all five response indicators, with the magnitude of effect and statistical significance varying among the indicators and depending on inclusion or exclusion of an apparent outlying control. With the outlier excluded, three responses approximated predicted values and two fell below predictions. The results generally supported evidence that the five gases drove the effects of exhaust, and thus supported the potential of the MART approach for identifying putative causal components of complex mixtures.     

The complexities of air pollution regulation: the need for an integrated research and regulatory perspective.

The Clean Air Act mandates the U.S. Environmental Protection Agency to periodically reassess existing and new science that underlie the regulation of major ambient pollutants -- particulate matter (PM) and tropospheric ozone being most notable. While toxic effects have been ascribed individually to these and other pollutants in the air, it is clear that mixtures of these contaminants have the potential to interact and thereby influence their overall toxic outcomes. It follows that a more comprehensive assessment of the potential health effects of the air pollution complex might better protect human health; however, traditional regulatory drivers and funding constraints have impeded progress to such a goal. Despite difficulties in empirically conducting studies of complex mixtures of air pollutants and acquiring relevant exposure data, there remains a need to develop integrated, interdisciplinary research and analytical strategies to provide more comprehensive (and relevant) assessments of associated health outcomes and risks. The research and assessment communities are endeavoring to dissect this complexity using varied approaches Here we present five interdisciplinary perspectives of this evolving line of thought among researchers and those who use such data in assessment: (1) analyses that coordinate air quality-health analyses utilizing representative polluted U.S. air sheds to apportion source and component-specific health risks; (2) novel approaches to characterize air quality in terms of emission sources and how emission reduction strategies might effectively impact pollutant levels; (3) insights from present-day studies of effects of single ambient pollutants in animal and controlled clinical toxicology studies and how these are evolving to address air pollution; (4) refinements in epidemiologic health assessments that take advantage of the complexities of existent air quality conditions; and (5) new approaches to integrative analyses to establish the criteria for regulation of PM and other criteria pollutants. As these examples illustrate, implementing multidisciplined and integrative strategies offer the promise of more realistic and relevant science, greater reductions in uncertainty, and improved overall air pollution assessment. The regulatory mandate may lag behind the science, but real gains both in public health benefit and the science to dissect complex problems will result.     

Oxidative damage to biological macromolecules in Prague bus drivers and garagemen: Impact of air pollution and genetic polymorphisms

DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2′-deoxyguanosine and 15-F_2t-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24 h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher levels of DNA instability and oxidative damage to biological macromolecules than the controls. The incidence of oxidized lesions in lymphocyte DNA, but not the urinary levels of 8-oxodG, correlated with exposure to benzene and triglycerides increased this damage. Oxidative damage to lipids and proteins was associated with exposure to cPAHs and the lipid peroxidation levels positively correlated with age and LDL cholesterol, and negatively with vitamin C. The carriers of at least one variant hOGG1 (Cys) allele tended to higher oxidative damage to lymphocyte DNA than those with the wild genotype, while XPD23 (Gln/Gln) homozygotes were more susceptible to the induction of DNA strand breaks. In contrast, GSTM1 null variant seemed to protect DNA integrity.     

Air pollution and emergency room visits for cardiac arrhythmia in a subtropical city: Taipei,Taiwan

This study was undertaken to determine whether there was an association between air pollutant levels and emergency room (ER) visits for cardiac arrhythmia in Taipei, Taiwan. ER visits for cardiac arrhythmia and ambient air pollution data for Taipei were obtained for the period 2000–2006. The relative risk of ER visits was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. In the single-pollutant model, on warm days (≥23°C), statistically significant positive associations were found for all pollutants except SO₂. On cool days (<23°C), all pollutants were also significantly associated with the number of ER visits for cardiac arrhythmia, except SO₂. For the two-pollutant model, results for O₃ and NO₂ remained statistically significant on both warm and cool days. This study provides evidence that higher levels of ambient air pollutants increase the risk of ER visits for cardiac arrhythmia.     

Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

Abstract

Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. However, cross-model organ pathologies and clinical manifestations are often not compared. We hypothesized that genetic CVD rat models will exhibit baseline pathologies and will thus express varied lung response to acute ozone exposure. Male 12–14-week-old healthy Wistar Kyoto (WKY), Wistar (WIS), and Sprague–Dawley (SD) rats and CVD-compromised spontaneously hypertensive (SH), fawn-hooded hypertensive (FHH), stroke-prone SH (SHSP), obese SH heart-failure (SHHF), obese diabetic JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0?ppm ozone for 4?h and clinical biomarkers, and lung, heart and kidney pathologies were compared immediately following (0–h) or 20-h later. Strain differences were observed between air-exposed CVD-prone and WKY rats in clinical biomarkers and in kidney and heart pathology. Serum cholesterol was higher in air-exposed obese SHHF and JCR compared to other air-exposed strains. Ozone did not produce lesions in the heart or kidney. CVD-prone and SD rats demonstrated glomerulopathy and kidney inflammation (WKY?=?WIS?=?SH?<?SD?=?SHSP?<?SHHF?<?JCR?=?FHH) regardless of ozone. Cardiac myofiber degeneration was evident in SH, SHHF, and JCR, while only JCR tends to have inflammation in coronaries. Lung pathology in air-exposed rats was minimal in all strains except JCR. Ozone induced variable alveolar histiocytosis and bronchiolar inflammation; JCR and SHHF were less affected. This study provides a comparative account of the clinical manifestations of disease and early-life organ pathologies in several rat models of CVD and their differential susceptibility to lung injury from air pollutant exposure.     

The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: I. Background,experimental strategy and critique

Abstract

The National Environmental Respiratory Center Program was initiated as an experiment to explore strategies for identifying the components of complex air pollution mixtures that cause health effects associated statistically with air pollution. A strategy involving multivariate analysis of a composition-concentration-response database was adopted. A novel database was created by exposing rodents daily for up to six months to one of four combustion-related mixtures and measuring respiratory, cardiovascular and general toxicological responses after one week or six months of exposure. The mixtures included multiple concentrations of diesel and gasoline engine exhaust, hardwood smoke and simulated downwind coal combustion emissions. After reporting the biological effects of each mixture and comparing effects among them, 47 significant effects were selected for multiple additive regression tree analysis to identify putative causal components. Although the four mixtures provided a database marginally sufficient for the analysis, the results suggested the putative causes of 19 significant effects with acceptable confidence. This article describes and critiques the Program and its strategy. The integrated results are presented in two accompanying papers, and mixture-specific results were presented in preceding papers, which are cited. The experiment demonstrated the potential utility of the general approach and identified certain cause–effect relationships for confirmatory studies. A follow-up study provided support for causation by the components implicated for one of those relationships. The advantages and disadvantages of the Program’s management and funding strategies are discussed.     

The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: II. Comparison of responses to diesel and gasoline engine exhausts,hardwood smoke and simulated downwind coal emissions

Abstract

The NERC Program conducted identically designed exposure–response studies of the respiratory and cardiovascular responses of rodents exposed by inhalation for up to 6 months to diesel and gasoline exhausts (DE, GE), wood smoke (WS) and simulated downwind coal emissions (CE). Concentrations of the four combustion-derived mixtures ranged from near upper bound plausible to common occupational and environmental hotspot levels. An “exposure effect” statistic was created to compare the strengths of exposure–response relationships and adjustments were made to minimize false positives among the large number of comparisons. All four exposures caused statistically significant effects. No exposure caused overt illness, neutrophilic lung inflammation, increased circulating micronuclei or histopathology of major organs visible by light microscopy. DE and GE caused the greatest lung cytotoxicity. WS elicited the most responses in lung lavage fluid. All exposures reduced oxidant production by unstimulated alveolar macrophages, but only GE suppressed stimulated macrophages. Only DE retarded clearance of bacteria from the lung. DE before antigen challenge suppressed responses of allergic mice. CE tended to amplify allergic responses regardless of exposure order. GE and DE induced oxidant stress and pro-atherosclerotic responses in aorta; WS and CE had no such effects. No overall ranking of toxicity was plausible. The ranking of exposures by number of significant responses varied among the response models, with each of the four causing the most responses for at least one model. Each exposure could also be deemed most or least toxic depending on the exposure metric used for comparison. The database is available for additional analyses.     

Nitric oxide as a metabolic regulator during exercise: effects of training in health and disease

1. Accumulating animal and human data suggest that nitric oxide (NO) is important for both coronary and peripheral haemodynamic control and metabolic regulation during performance of exercise. 2. While still controversial, NO of endothelial origin is thought to potentiate exercise-induced hyperaemia, both in the peripheral and coronary circulations. The mechanism of release may include both acetylcholine derived from the neuromuscular junction and vascular shear stress. 3. A splice variant of neuronal nitric oxide synthase (NOS), nNOSmicro, incorporating an extra 34 amino acids, is expressed in human skeletal muscle. In addition to being a potential modulator of blood flow, skeletal muscle-derived NO is an important regulator of muscle contraction and metabolism. In particular, recent human data indicate that NO modulates muscle glucose uptake during exercise, independently of blood flow. 4. Exercise training in healthy individuals promotes adaptations in the various NO systems, which can increase NO bioavailability through a variety of mechanisms, including increased NOS enzyme expression and activity. Such adaptations likely contribute to increased exercise capacity and protection from cardiovascular events. 5. Cardiovascular risk factors, including hypercholesterolaemia, hypertension, diabetes and smoking, as well as established disease, are associated with impairment of the various NO systems. Given that NO is an important signalling mechanism during exercise, such impairment may contribute to limitations in exercise capacity through inadequate coronary or peripheral blood delivery and via metabolic effects. 6. Exercise training in individuals with elevated cardiovascular risk or established disease can increase NO bioavailability and may represent an important mechanism by which exercise training provides benefit in the setting of secondary prevention.     

安徽地区汉族心血管疾病患者SLCO1B1与ApoE基因多态性分布及其在他汀类药物临床个体化应用中的意义

目的:探讨脂质及药物代谢相关基因SLCO1B1和ApoE的基因多态性在安徽地区汉族心血管疾病患者中的分布,以评估他汀类药物个体化用药的效益/风险比。方法:利用PCR-荧光探针法技术检测2019年1月至2020年8月合肥市第二人民医院736例心血管疾病患者外周血基因组中SLCO1B1基因的rs2306283(388A>G)和rs4149056(521T>C)位点和ApoE基因的rs429358(388T>C)和rs7412(526C>T)位点的基因多态性分布特点,并与已报道的中国其他地区汉族心血管疾病患者的数据进行比较,分析不同地区间的基因型分布差异。结果:检测到安徽地区汉族心血管疾病患者中SLCO1B1基因型有6种,分别为*1a/*1a型(6.11%)、*1a/*1b型(29.08%)、*1b/*1b型(44.57%)、*1a/*15型(4.08%)、*1b/*15型(15.49%)、*15/*15型(0.68%),未检测到*1a/*5型、*5/*5型和*5/*15型;ApoE基因有6种表型,分别为E2/E2型(0.41%)、E2/E3型(11.96%)、E2/E4型(1.09%)、E3/E3型(67.66%)、E3/E4型(17.93%)、E4/E4型(0.95%)。两种基因的基因多态性频率分布满足Hardy-Weinberg遗传平衡,具有群体代表性。本研究人群中携带SLCO1B1正常肌病风险型的比例最高,约占79.76%;SLCO1B1中度肌病风险型和高度肌病风险型的人群比例较低,分别为19.57%和0.68%。ApoE大众类基因型比例最高,约占68.75%;ApoE保护类基因型及风险类基因型的人群比例分别为12.37%和18.88%。不同性别间SLCO1B1和ApoE基因表型患者差异无统计学意义。与华南地区心血管疾病患者相比,安徽地区ApoE基因多态性分布差异有统计学意义(P<0.05)。结论:安徽地区736例心血管疾病患者SLCO1B1和ApoE基因型分别以他汀药物剂量耐受性较高的正常肌病风险型和对他汀药物敏感的大众类基因型为主,服用他汀类药物诱发肌病的风险较低,降脂疗效较好;且两种基因的多态性分布均不受性别的影响,但ApoE基因多态性分布特征可能在地域上存在差异。因此,检测SLCO1B1和APOE基因多态性对于临床评估效益/风险比有重要的指导意义。     

The indane diastereoisomers,PH2 and PH5: divergence between their effects in delayed‐type hypersensitivity models and a model of colitis

Objectives

Compounds PH2 and PH5 are distereoisomers of novel indane compounds, synthesised as analogues of secondary metabolites of the fern, Onychium. In this study, we compare their effects on a variety of inflammatory models.

Methods

In an effort to extend our knowledge of their anti‐inflammatory profile, we have investigated their activity in two models of delayed‐type hypersensitivity (DTH); the methylated bovine serum albumin model (mBSA) and the oxazolone contact hypersensitivity (CHS) model, on IL2 release from Jurkat cells and in the dextran sulphate sodium (DSS) murine model of inflammatory bowel disease.

Key findings

Both diastereoisomers are equipotent in reducing paw swelling in the mBSA model and in inhibiting interleukin (IL) 2 release from Jurkat cells. They are equally ineffective in the oxazolone contact hypersensitivity model (CHS). Only the diastereoisomer, PH5, protects against DSS‐induced colitis and of its two enantiomers, only the S,S‐enantiomer, PH22, possesses this activity. PH2 is ineffective in the DSS model.

Conclusions

The results suggest that the beneficial effect of PH5, and its enantiomer PH22, in the DSS model is a consequence of an action on a target specific to the colitis model. The implications of such data suggest an unknown target in this disease model that may be exploited to therapeutic advantage.

     

Illicit drugs and the media: models of media effects for use in drug policy research

Issues. Illicit drugs are never far from the media gaze and although identified almost a decade ago as ‘a new battleground’ for the alcohol and other drug (AOD) field there has been limited research examining the role of the news media and its effects on audiences and policy. Approach. This paper draws together media theories from communication literature to examine media functions. We illustrate how each function is relevant for media and drugs research by drawing upon the existing literature examining Australian media coverage during the late 1990s of escalating heroin‐related problems and proposed solutions. Key Findings. Media can influence audiences in four key ways: by setting the agenda and defining public interest; framing issues through selection and salience; indirectly shaping individual and community attitudes towards risk; and feeding into political debate and decision making. Each has relevance for the AOD field. For example, media coverage of the escalating heroin‐related problems in Australia played a strong role in generating interest in heroin overdoses, framing public discourse in terms of a health and/or criminal issue and affecting political decisions. Implications and Conclusion. Media coverage in relation to illicit drugs can have multifarious effects. Incorporating media communication theories into future research and actions is critical to facilitate understanding of the short‐ and long‐term impacts of media coverage on illicit drugs and the avenues by which the AOD field can mitigate or inform future media debates on illicit drugs.[Lancaster K, Hughes CE, Spicer B, Matthew‐Simmons F, Dillon P. Illicit drugs and the media: Models of media effects for use in drug policy research. Drug Alcohol Rev 2011;30:397–402]