Systemic Inflammation in Young Adults Is Associated with Abnormal Lung Function in Middle Age

BACKGROUND:Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain. METHODOLOGY/PRINCIPAL FINDINGS:We evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P<0.001) and forced expiratory volume in 1 second (FEV(1)) (487 mL in quartile 4 vs. 446 mL in quartile 1, P<0.001) independent of cigarette smoking, body habitus, baseline lung function and demographic factors. Higher year 7 CRP was also associated with both greater loss of FVC (455 mL in quartile 4 vs. 390 mL in quartile 1, P<0.001) and FEV(1) (491 mL in quartile 4 vs. 442 mL in quartile 1, P = 0.001). Higher year 7 fibrinogen and CRP were associated with abnormal FVC at year 20 (odds ratio (OR) per standard deviation 1.51 (95% confidence interval (CI): 1.30-1.75) for fibrinogen and 1.35 (95% CI: 1.14-1.59) for CRP). Higher year 5 fibrinogen was additionally associated with abnormal FEV(1). A positive interaction was observed between pack-years cigarette smoking and year 7 CRP for the COPD endpoint, and among participants with greater than 10 pack-years of cigarette exposure, year 7 CRP was associated with greater odds of COPD at year 20 (OR per standard deviation 1.53 (95% CI: 1.08-2.16). CONCLUSION/SIGNIFICANCE:Systemic inflammation in young adults is associated with abnormal lung function in middle age. In particular, elevated CRP may identify vulnerability to COPD among individuals who smoke. TRIAL REGISTRATION:ClinicalTrials.gov NCT00005130

The Concise Guide to PHARMACOLOGY 2023/24:Transporters

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p

Genetic diversity of porcine group A rotavirus strains in the UK

Rotavirus is endemic in pig farms where it causes a loss in production. This study is the first to characterise porcine rotavirus circulating in UK pigs. Samples from diarrheic pigs with rotavirus enteritis obtained between 2010 and 2012 were genotyped in order to determine the diversity of group A rotavirus (GARV) in UK pigs. A wide range of rotavirus genotypes were identified in UK pigs: six G types (VP7); G2, G3, G4, G5, G9 and G11 and six P types (VP4); P[6], P[7], P[8], P[13], P[23], and P[32]. With the exception of a single P[8] isolate, there was less than 95% nucleotide identity between sequences from this study and any available rotavirus sequences. The G9 and P[6] genotypes are capable of infecting both humans and pigs, but showed no species cross-over within the UK as they were shown to be genetically distinct, which suggested zoonotic transmission is rare within the UK. We identified the P[8] genotype in one isolate, this genotype is almost exclusively found in humans. The P[8] was linked to a human Irish rotavirus isolate in the same year. The discovery of human genotype P[8] rotavirus in a UK pig confirms this common human genotype can infect pigs and also highlights the necessity of surveillance of porcine rotavirus genotypes to safeguard human as well as porcine health

Diversity of group A rotavirus on a UK pig farm

Group A rotaviruses (GARV) are a significant cause of enteritis in young pigs. The aim of this study was to extend our understanding of the molecular epidemiology of porcine GARV in the UK by investigating the genetic diversity of GARV on a conventional farrow-to-finish farm. Faecal samples were obtained from six batches of pigs in 2009 and 8 batches in 2010, when the pigs were 2, 3 (time point omitted in 2009), 4, 5, 6 and 8 weeks of age. Presence of rotavirus was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in 89% and 80% of samples from 2009 and 2010, respectively. A combination of multiplex PCRs and sequencing identified four VP7 genotypes (G2, G3, G4 and G5) and three VP4 genotypes (P[6], P[7] and P[32]) present in almost every combination over the 2 years. The predominant genotype combination was G5P[32] in 2009 and G4P[32] in 2010. Conservation among the P[32] sequences between 2009 and 2010 suggests that reassortment may have led to the different genotype combinations. There were significant changes in the predominant VP7 genotype prior to weaning at 4 weeks, and post weaning when pigs were moved to a different building. Phylogenetic analysis indicated that introduction of new viruses onto the farm was limited. Taken together, these findings suggest that genetically diverse GARV strains persist within the farm environment

The Concise Guide to PHARMACOLOGY 2023/24: Transporters.

Publication status: PublishedThe Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate