Respiratory health effects of diesel particulate matter

Particulate matter (PM) emissions involve a complex mixture of solid and liquid particles suspended in a gas, where it is noted that PM emissions from diesel engines are a major contributor to the ambient air pollution problem. Whilst epidemiological studies have shown a link between increased ambient PM emissions and respiratory morbidity and mortality, studies of this design are not able to identify the PM constituents responsible for driving adverse respiratory health effects. This review explores in detail the physico-chemical properties of diesel particulate matter (DPM), and identifies the constituents of this pollution source that are responsible for the development of respiratory disease. In particular, this review shows that the DPM surface area and adsorbed organic compounds play a significant role in manifesting chemical and cellular processes that if sustained can lead to the development of adverse respiratory health effects. The mechanisms of injury involved included: inflammation, innate and acquired immunity, and oxidative stress. Understanding the mechanisms of lung injury from DPM will enhance efforts to protect at-risk individuals from the harmful respiratory effects of air pollutants.

Delta opioid-receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats

Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

Antibiotics overuse in children with upper respiratory tract infections in Saudi Arabia : risk factors and potential interventions

Background: Antibiotics misuse is currently one of the major public health issues worldwide. This misuse can lead to the development of bacterial resistance, increasing the burden of chronic diseases, rising costs of health services, and the development of side effects. Several factors may influence this pattern of overuse. Objectives:This article will review the pertinent factors contributing to the overuse of antibiotics worldwide, and to assess the intervention strategies to limit this overuse. Methods: studies about antibiotics use in children were reviewed from several electronic databases, such as MEDLINE and Pubmed. Results: Factors contributing to the overuse of antibiotics could include psychosocial factors, such as behaviors and attitudes (e.g. self-medication, over-the-counter medication, or patients/parents pressure), and demographic factors, such as socio-economic status and education level. Several intervention strategies were reported to be effective in reducing the overuse of antibiotics, such as health education, doctor-patient communication, and policies change. Multifaceted interventions were found to be the most effective in reducing the antibiotics overuse.

Foot pain and functional limitation in healthy adults with hallux valgus : a cross-sectional study

Background Hallux valgus (HV) is a very common deformity of the first metatarsophalangeal joint that often requires surgical correction. However, the association between structural HV deformity and related foot pain and disability is unclear. Furthermore, no previous studies have investigated concerns about appearance and difficulty with footwear in a population with HV not seeking surgical correction. The aim of this cross-sectional study was to investigate foot pain, functional limitation, concern about appearance and difficulty with footwear in otherwise healthy adults with HV compared to controls. Methods Thirty volunteers with HV (radiographic HV angle >15 degrees) and 30 matched controls were recruited for this study (50 women, 10 men; mean age 44.4 years, range 20 to 76 years). Differences between groups were examined for self-reported foot pain and disability, satisfaction with appearance, footwear difficulty, and pressure-pain threshold at the first metatarsophalangeal joint. Functional measures included balance tests, walking performance, and hallux muscle strength (abduction and plantarflexion). Mean differences (MD) and 95% confidence intervals (CI) were calculated. Results All self-report measures showed that HV was associated with higher levels of foot pain and disability and significant concerns about appearance and footwear (p < 0.001). Lower pressure-pain threshold was measured at the medial first metatarsophalangeal joint in participants with HV (MD = -133.3 kPa, CI: -251.5 to -15.1). Participants with HV also showed reduced hallux plantarflexion strength (MD = -37.1 N, CI: -55.4 to -18.8) and abduction strength (MD = -9.8 N, CI: -15.6 to -4.0), and increased mediolateral sway when standing with both feet with eyes closed (MD = 0.34 cm, CI: 0.04 to 0.63). Conclusions These findings show that HV negatively impacts on self-reported foot pain and function, and concerns about foot appearance and footwear in otherwise healthy adults. There was also evidence of impaired hallux muscle strength and increased postural sway in HV subjects compared to controls, although general physical functioning and participation in physical activity were not adversely affected.

The open window of susceptibility to infection after acute exercise in healthy young male elite athletes

The 'open window' theory is characterised by short term suppression of the immune system following an acute bout of endurance exercise. This window of opportunity may allow for an increase in susceptibility to upper respiratory illness (URI). Many studies have indicated a decrease in immune function in response to exercise. However, many studies do not indicate changes in immune function past 2 hours after the completion of exercise, consequently failing to determine whether these immune cells numbers, or importantly their function, return to resting levels before the start of another bout of exercise. Ten male 'A' grade cyclists (age 24.2 +/- 5.3 years; body mass 73.8 +/- 6.5 kg; VO(2peak) 65.9 +/- 7.1 mL.kg(-1).min(-1)) exercised for two hours at 90% of their second ventilatory threshold. Blood samples were collected pre-, immediately post-, 2 hours, 4 hours, 6 hours, 8 hours, and 24 hours post-exercise. Immune variables examined included total leukocyte counts, neutrophil function (oxidative burst and phagocytic function), lymphocyte subset counts (CD4(+), CD8(+), and CD16(+)/56(+)), natural killer cell activity (NKCA), and NK phenotypes (CD56(dim)CD16(+), and CD56(bright)CD16(-)). There was a significant increase in total lymphocyte numbers from pre-, to immediately post-exercise (p<0.01), followed by a significant decrease at 2 hours post-exercise (p<0.001). CD4(+) T-cell counts significantly increased from pre-exercise, to 4 hours post- (p<0.05), and 6 hours post-exercise (p<0.01). However, NK (CD16(+)/56(+)) cell numbers decreased significantly from pre-exercise to 4 h post-exercise (p<0.05), to 6 h post-exercise (p<0.05), and to 8 h post-exercise (p<0.01). In contrast, CD56(bright)CD16- NK cell counts significantly increased from pre-exercise to immediately post-exercise (p<0.01). Neutrophil oxidative burst activity did not significantly change in response to exercise, while neutrophil cell counts significantly increased from pre-exercise, to immediately post-exercise (p<0.05), and 2 hours post-exercise (p<0.01), and remained significantly above pre-exercise levels to 8 hours post-exercise (p<0.01). Neutrophil phagocytic function significantly decreased from 2 hours post-exercise, to 6 hours post- (p<0.05), and 24 hours post-exercise (p<0.05). Finally, eosinophil cell counts significantly increased from 2 hours post to 6 hours post- (p<0.05), and 8 hours post-exercise (p<0.05). This is the first study to show changes in immunological variables up to 8 hours post-exercise, including significant NK cell suppression, NK cell phenotype changes, a significant increase in total lymphocyte counts, and a significant increase in eosinophil cell counts all at 8 hours post-exercise. Suppression of total lymphocyte counts, NK cell counts and neutrophil phagocytic function following exercise may be important in the increased rate of URI in response to regular intense endurance training.

Probiotics, immunity and exercise : a review

Nutritional practices that promote good health and optimal athletic performance are of interest to athletes, coaches, exercise scientists and dietitians. Probiotic supplements modulate the intestinal microbial flora and offer promise as a practical means of enhancing gut and immune function. The intestinal microbial flora consists of diverse bacterial species that inhabit the gastrointestinal tract. These bacteria are integral to the ontogeny and regulation of the immune system, protection of the body from injection, and maintenance of intestinal homeostasis. The interaction of the gut microbial flora with intestinal epithelial cells and immune cells exerts beneficial effects on the upper respiratory tract, skin and uro-genital tract. The capacity for probiotics to modulate perturbations in immune function after exercise highlight their potential for use in individuals exposed to high degrees of physical and environment stress. Future studies are required to address issues of dose-response in various exercise settings, the magnitude of species-specific effects, mechanisms of action and clinical outcomes in terms of health and performance.

In vitro and in vivo studies on protease-activated receptor-2

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with â- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced â-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.

Inhaled particle counts on bicycle commute routes of low and high proximity to motorised traffic

Frequent exposure to ultrafine particles (UFP) is associated with detrimental effects on cardiopulmonary function and health. UFP dose and therefore the associated health risk are a factor of exposure frequency, duration, and magnitude of (therefore also proximity to) a UFP emission source. Bicycle commuters using on-road routes during peak traffic times are sharing a microenvironment with high levels of motorised traffic, a major UFP emission source. Inhaled particle counts were measured along popular pre-identified bicycle commute route alterations of low (LOW) and high (HIGH) motorised traffic to the same inner-city destination at peak commute traffic times. During commute, real-time particle number concentration (PNC; mostly in the UFP range) and particle diameter (PD), heart and respiratory rate, geographical location, and meteorological variables were measured. To determine inhaled particle counts, ventilation rate was calculated from heart-rate-ventilation associations, produced from periodic exercise testing. Total mean PNC of LOW (compared to HIGH) was reduced (1.56 x e4 ± 0.38 x e4 versus 3.06 x e4 ± 0.53 x e4 ppcc; p = 0.012). Total estimated ventilation rate did not vary significantly between LOW and HIGH (43 ± 5 versus 46 ± 9 L•min; p = 0.136); however, due to total mean PNC, accumulated inhaled particle counts were 48% lower in LOW, compared to HIGH (7.6 x e8 ± 1.5 x e8 versus 14.6 x e8 ± 1.8 x e8; p = 0.003). For bicycle commuting at peak morning commute times, inhaled particle counts and therefore cardiopulmonary health risk may be substantially reduced by decreasing exposure to motorised traffic, which should be considered by both bicycle commuters and urban planners.

Exercise for health : a randomized, controlled trial evaluating impact of a pragmatic, translational exercise intervention on quality of life, function and treatment-related side effects following breast cancer

Purpose Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Methods Outcomes included quality of life (QoL), function (fitness and upper-body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5-weeks PS], mid-intervention [6-months PS], post-intervention [12-months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n=67), Tel (n=67) and UC (n=60) groups. Results: There were significant (p<0.05) interaction effects on QoL, fitness and fatigue, with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side-effects between groups. Conclusion This translational intervention trial, delivered either face-to-face or over-the-telephone, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

Visual motion perception predicts driving hazard perception ability

PURPOSE: To examine the basis of previous findings of an association between indices of driving safety and visual motion sensitivity and to examine whether this association could be explained by low-level changes in visual function. METHODS: 36 visually normal participants (aged 19 – 80 years), completed a battery of standard vision tests including visual acuity, contrast sensitivity and automated visual fields. and two tests of motion perception including sensitivity for movement of a drifting Gabor stimulus, and sensitivity for displacement in a random-dot kinematogram (Dmin). Participants also completed a hazard perception test (HPT) which measured participants’ response times to hazards embedded in video recordings of real world driving which has been shown to be linked to crash risk. RESULTS: Dmin for the random-dot stimulus ranged from -0.88 to -0.12 log minutes of arc, and the minimum drift rate for the Gabor stimulus ranged from 0.01 to 0.35 cycles per second. Both measures of motion sensitivity significantly predicted response times on the HPT. In addition, while the relationship involving the HPT and motion sensitivity for the random-dot kinematogram was partially explained by the other visual function measures, the relationship with sensitivity for detection of the drifting Gabor stimulus remained significant even after controlling for these variables. CONCLUSION: These findings suggest that motion perception plays an important role in the visual perception of driving-relevant hazards independent of other areas of visual function and should be further explored as a predictive test of driving safety. Future research should explore the causes of reduced motion perception in order to develop better interventions to improve road safety.

Evaluation of screening tests for predicting older driver performance and safety assessed by an on-road test

A number of tests and test batteries are available for the prediction of older driver safety, but many of these have not been validated against standardized driving outcome measures. The aim of this study was to evaluate a series of previously described screening tests in terms of their ability to predict the potential for safe and unsafe driving. Participants included 79 community-dwelling older drivers (M=72.16 years, SD=5.46; range 65-88 years; 57 males and 22 females) who completed a previously validated multi-disciplinary driving assessment, a hazard perception test, a hazard change detection test and a battery of vision and cognitive tests. Participants also completed a standardized on-road driving assessment. The multi-disciplinary test battery had the highest predictive ability with a sensitivity of 80% and a specificity of 73%, followed by the hazard perception test which demonstrated a sensitivity of 75% and a specificity of 61%. These findings suggest that a relatively simple and practical battery of tests from a range of domains has the capacity to predict safe and unsafe driving in older adults.

Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand

Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.

Relationship among CFH and ARMS2 genotypes, macular pigment optical density, and neuroretinal function in persons without age-related macular degeneration

Purpose: To determine whether there is a difference in neuroretinal function and in macular pigment optical density between persons with high- and low-risk gene variants for age-related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare the results on neuroretinal function to patients with manifest early AMD. Methods and Participants: Neuroretinal function was assessed with the multifocal electroretinogram (mfERG) for 32 participants (22 healthy persons with no AMD and 10 early AMD patients). The 22 healthy participants with no AMD had high- or low-risk genotypes for either CFH (rs380390) and/or ARMS2 (rs10490924). Trough-to-peak response densities and peak-implicit times were analyzed in 5 concentric rings. Macular pigment optical densitometry was assessed by customized heterochromatic flicker photometry. Results: Trough-to-peak response densities for concentric rings 1 to 3 were, on average, significantly greater in participants with high-risk genotypes than in participants with low-risk genotypes and in persons with early AMD after correction for age and smoking (p<0.05). The group peak- implicit times for ring 1 were, on average, delayed in the patients with early AMD compared with the participants with high- or low-risk genotypes, although these differences were not significant. There was no significant correlation between genotypes and macular pigment optical density. Conclusion: Increased neuroretinal activity in persons who carry high-risk AMD genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Neuroretinal function in healthy persons genetically susceptible to AMD may be a useful additional early biomarker (in combination with genetics) before there is clinical manifestation.

Drugs and the respiratory system

17.1 Drugs for bronchial asthma and Chronic Obstructive Pulmonary Disease (COPD) 17.1.1 Introduction to asthma 17.1.2 Introduction to COPD 17.1.3 Drug delivery by inhalation 17.1.4 Drugs to treat 17.1.4.1 β2-adrenoceptor agonists 17.1.4.2 Muscarinic receptor antagonists 17.1.4.3 Leukotriene receptor antagonists 17.1.4.4 Theophylline 17.1.4.5 Oxygen for COPD 17.1.5 Drugs to prevent asthma 31.5.1 Glucocorticoids 31.5.2 Cromolyn sodium 17.1.6 Combination to treat and prevent asthma 17.1.7 Drug for allergic asthma – omalizumab 17.1.8 Emergency treatment of asthma 17.2. Expectorants, mucolytics, cough and oxygen 17.2.1 Introduction to expectorants and mucolytics 17.2.2 Expectorants 17.2.3 Mucolytics 17.2.4 Cough 17.2.5 Oxygen 17.3. Drugs for rhinitis and rhinorrea 17.3.1 Introduction 17.3.2 Histamine and H1-receptor antagonists 17.3.3 Sympathomimetic 17.3.4 Muscarinic receptor antagonists 17.3.4 Cromolyn sodium 17.3.5 Glucocorticoids

Insights into the role and function of L2, the minor capsid protein of papillomaviruses

Human papillomaviruses (HPV) are responsible for the most common human sexually transmitted viral infections, and high-risk types are responsible for causing cervical and other cancers. The minor capsid protein L2 of HPV plays important roles in virus entry into cells, localisation of viral components to the nucleus, in DNA binding, capsid formation and stability. It also elicits antibodies that are more cross-reactive between HPV types than does the major capsid protein L1, making it an attractive potential target for new-generation, more broadly protective subunit vaccines against HPV infections. However, its low abundance in natural capsids-12-72 molecules per 360 copies of L1-limits its immunogenicity. This review will explore the biological roles of the protein, and prospects for its use in new vaccines. © 2009 Springer-Verlag.