The nasal mucosal late allergic reaction to grass pollen involves type 2 inflammation (IL-5 and IL-13), the inflammasome (IL-1ß), and complement.

Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1ß), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1ß and MIP-1ß/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1ß; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.

Robust Phonon-Plasmon Coupling in Quasifreestanding Graphene on Silicon Carbide.

Using inelastic electron scattering in combination with dielectric theory simulations on differently prepared graphene layers on silicon carbide, we demonstrate that the coupling between the 2D plasmon of graphene and the surface optical phonon of the substrate cannot be quenched by modification of the interface via intercalation. The intercalation rather provides additional modes like, e.g., the silicon-hydrogen stretch mode in the case of hydrogen intercalation or the silicon-oxygen vibrations for water intercalation that couple to the 2D plasmons of graphene. Furthermore, in the case of bilayer graphene with broken inversion symmetry due to charge imbalance between the layers, we observe a similar coupling of the 2D plasmon to an internal infrared-active mode, the LO phonon mode. The coupling of graphene plasmons to vibrational modes of the substrate surface and internal infrared active modes is envisioned to provide an excellent tool for tailoring the plasmon band structure of monolayer and bilayer graphene for plasmonic devices such as plasmon filters or plasmonic waveguides. The rigidity of the effect furthermore suggests that it may be of importance for other 2D materials as well.

IL-15 complexes induce NK- and T-cell responses independent of type I IFN signaling during rhinovirus infection.

Rhinoviruses are among the most common viruses to infect man, causing a range of serious respiratory diseases including exacerbations of asthma and COPD. Type I IFN and IL-15 are thought to be required for antiviral immunity; however, their function during rhinovirus infection in vivo is undefined. In RV-infected human volunteers, IL-15 protein expression in fluid from the nasal mucosa and in bronchial biopsies was increased. In mice, RV induced type I IFN-dependent expressions of IL-15 and IL-15Rα, which in turn were required for NK- and CD8(+) T-cell responses. Treatment with IL-15-IL-15Rα complexes (IL-15c) boosted RV-induced expression of IL-15, IL-15Rα, IFN-γ, CXCL9, and CXCL10 followed by recruitment of activated, IFN-γ-expressing NK, CD8(+), and CD4(+) T cells. Treating infected IFNAR1(-/-) mice with IL-15c similarly increased IL-15, IL-15Rα, IFN-γ, and CXCL9 (but not CXCL10) expression also followed by NK-, CD8(+)-, and CD4(+)-T-cell recruitment and activation. We have demonstrated that type I IFN-induced IFN-γ and cellular immunity to RV was mediated by IL-15 and IL-15Rα. Importantly, we also show that IL-15 could be induced via a type I IFN-independent mechanism by IL-15 complex treatment, which in turn was sufficient to drive IFN-γ expression and lymphocyte responses.

Una estrategia de intervención comunitaria en la prevención de los delitos sexuales en féminas / A strategy of community intervention to prevent sexual crimes on women

Se realizan un total de seis seminario-talleres sobre la frecuencia y características de los delitos sexuales en féminas en la provincia, en las zonas mayormente afectadas por el fenómeno (áreas de salud Raúl Sánchez y Hermanos Cruz) a los cuales asistieron 407 representantes de las comunidades elegidas y al término de cada sesión se aplicó a estos una encuesta anónima para recoger sus opiniones sobre el posible impacto del método en la preparación, para identificar situaciones relacionadas con la violencia sexual en féminas y también sobre sus posibles causas, destacándose la opinión popular de un 52,3 por ciento que los vinculan al alcoholismo y en otros porcientos, la falta de control de los padres para con los hijos, desajustes familiares e inadecuados vestuarios y horarios de salida de las jóvenes, entre otros, encontrando el método empleado, aceptación y apoyo entre los encuestados, que se consideran medianamente preparados para identificar y prevenir situaciones vulnerantes...(AU)

A series of six seminaries were performed in order to know the frequency and characteristics of sexual crimes, especially in women. The study was carried out in a population of 407 neighbors in Pinar del Río Province, belonging to a selected health area of Raúl Sánchez and Hermanos Cruz Teaching Polyclinic. At the end of each seminary an anonymous survey was applied to gathers their opinion to get a big effects of this technique to identify some sexual crimes and furthermore the main ethiology. A 52,3 poecent reported an opinion about alcoholism with approved-supported methods for the entire universe. They are mild prepared to identify and prevent vulnerable situations...(AU)

Una estrategia de intervención comunitaria en la prevención de los delitos sexuales en féminas / A strategy of community intervention to prevent sexual crimes on women

Se realizan un total de seis seminario-talleres sobre la frecuencia y características de los delitos sexuales en féminas en la provincia, en las zonas mayormente afectadas por el fenómeno (áreas de salud " Raúl Sánchez " y "Hermanos Cruz") a los cuales asistieron 407 representantes de las comunidades elegidas y al término de cada sesión se aplicó a estos una encuesta anónima para recoger sus opiniones sobre el posible impacto del método en la preparación, para identificar situaciones relacionadas con la violencia sexual en féminas y también sobre sus posibles causas, destacándose la opinión popular de un 52,3% que los vinculan al alcoholismo y en otros porcientos, la falta de control de los padres para con los hijos, desajustes familiares e inadecuados vestuarios y horarios de salida de las jóvenes, entre otros, encontrando el método empleado, aceptación y apoyo entre los encuestados, que se consideran medianamente preparados para identificar y prevenir situaciones vulnerantes.

A series of six seminaries were performed in order to know the frequency and characteristics of sexual crimes, especially in women. The study was carried out in a population of 407 neighbors in Pinar del Río Province, belonging to a selected health area of Raúl Sánchez and Hermanos Cruz Teaching Polyclinic. At the end of each seminary an anonymous survey was applied to gathers their opinion to get a big effects of this technique to identify some sexual crimes and furthermore the main ethiology. A 52.3 % reported an opinion about alcoholism with approved-supported methods for the entire universe. They are mild prepared to identify and prevent vulnerable situations.

COPD-related morbidity and mortality after smoking cessation: status of the evidence.

The evidence base for the benefit of quitting smoking as regards morbidity and mortality outcomes in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) is limited. The present article is a review of the existing literature. A systematic literature search in medical databases was performed until March 2006, and subsequently until September 1, 2007. The outcomes examined were COPD-related morbidity and mortality (including all-cause mortality) in COPD patients in connection with smoking cessation. A total of 21 and 27 published articles on morbidity and mortality, respectively, were identified and reviewed. For both outcomes, only a few of the studies included patients with severe COPD. Most of the studies reported a beneficial effect of smoking cessation compared with continued smoking, whereas a few found no improvement. Methodological problems, including small study sizes, poor data quality, possibility of reverse causality and incomplete ascertainment of cause of death, limit interpretation of some of the studies. The evidence as a whole supports the conclusion that, even in severe chronic obstructive pulmonary disease, smoking cessation slows the accelerated rate of lung function decline and improves survival compared with continued smoking.

Caracterización médico-legal de los delitos sexuales en Pinar del Río, 2003-2005 / Medical and legal characteristics of sex offenses in Pinar del Río, 2003-2005

Se encuestó una muestra de 399 víctimas de diferentes edades enviadas al departamento de Medicina legal de Pinar del Río en el trienio 2003 2005 por estarse instruyendo procedimiento penal a causa de algún delito realizado por intermedio de una conducta sexual impositiva que da lugar a la radicación del expediente. Se aplicó de modo directo una encuesta anónima, abierta, previamente elaborada y constitutiva de 9 preguntas, los resultados fueron tabulados por el método de los palotes y llevadas las variables a sábanas, agrupadas en tablas, arrojando la información que los municipios más afectados fueron Pinar del Río, San Cristóbal, consolación del Sur, San Juan y Sandino, siendo los grupos etáreos más vulnerantes las menores de 20 años. Las figuras delictivas que más se repiten son la violación y los abusos lascivos predominando en la relación víctima –victimario; los conocidos, vecinos , padrastros y familiares. En el modus operandi sobresalen el abuso de confianza, intimidación, violencia física y abuso de autoridad, siendo la casa de la víctima y alrededores, casa del victimario, centro de estudios o trabajo y cercanías, caminos, carreteras, lugares recreativos, los lugares mayormente escogidos por los ofensores...(AU)

This study was conducted on different ages 399 victims, where a questionnaire was assessed. They were sent to Legal Medicine Departament of Pinar del Río, during triennium 2003-2005 due to a penal processing. A crime was comsummated in relation to impositive sexual mis conduct with proceeding files an anonymous, opening and direct questionnaire with 9 questions was analyzed. The data were statistically analyzed using palotes methods. All the variables were placed in a sheep and graphic. Pinar del Río, San Cristobal, Consolación Sur, San Juan and Sandino, were more affected. Patients of 20 years old and lees were more wounded violation and lascivious abuse were more frcuently with a big important to stepfather neighbor and relatives. In the operanting modus we consider abuse of confidence, intimidation and physical violence the perfect selected place by ofender are victim home and around, hear a school or job...(AU)

Caracterización medico legal de los delitos sexuales en Pinar del Río, 2003-2005 / Medical and legal characteristics of sex offenses in Pinar del Río, 2003-2005

Se encuestó una muestra de 399 víctimas de diferentes edades enviadas al departamento de Medicina legal de Pinar del Río en el trienio 2003-2005 por estarse instruyendo procedimiento penal a causa de algún delito realizado por intermedio de una conducta sexual impositiva que da lugar a la radicación del expediente. Se aplicó de modo directo una encuesta anónima, abierta, previamente elaborada y constitutiva de 9 preguntas, los resultados fueron tabulados por el método de los palotes y llevadas las variables a sábanas, agrupadas en tablas, arrojando la información que los municipios más afectados fueron Pinar del Río, San Cristóbal, consolación del Sur, San Juan y Sandino, siendo los grupos etáreos más vulnerantes las menores de 20 años. Las figuras delictivas que más se repiten son la violación y los abusos lascivos predominando en la relación víctima - victimario; los conocidos, vecinos, padrastros y familiares. En el modus operandi sobresalen el abuso de confianza, intimidación, violencia física y abuso de autoridad, siendo la casa de la víctima y alrededores, casa del victimario, centro de estudios o trabajo y cercanías, caminos, carreteras, lugares recreativos, los lugares mayormente escogidos por los ofensores.

This study was conducted on different ages 399 victims, where a questionnaire was assessed. They were sent to Legal Medicine Departament of Pinar del Río, during triennium 2003-2005 due to a penal processing. A crime was comsummated in relation to impositive sexual mis conduct with proceeding files an anonymous, opening and direct questionnaire with 9 questions was analyzed. The data were statistically analyzed using palotes methods. All the variables were placed in a sheep and graphic. Pinar del Río, San Cristobal, Consolación Sur, San Juan and Sandino, were more affected. Patients of 20 years old and lees were more wounded violation and lascivious abuse were more frcuently with a big important to stepfather neighbor and relatives. In the operanting modus we consider abuse of confidence, intimidation and physical violence the perfect selected place by ofender are victim home and around, hear a school or job.

Effects of a reversible beta-tryptase and trypsin inhibitor (RWJ-58643) on nasal allergic responses.

BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released during mast cell degranulation and tryptase/trypsin inhibitors are a novel potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES: This study was performed to assess the effects of RWJ-58643 on nasal symptoms, eosinophil influx, and cytokine and chemokine release following nasal allergen challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis (n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or matched placebo given 30 min before NAC in a double-blind, randomized crossover design. A single dose of 200 microg budesonide was studied in an open-label extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5 (30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug administration. Nasal lavage mediators were analysed using a sensitive multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg) caused a late eosinophilia and preceding increases in IL-5 compared with placebo. CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin inhibition has therapeutic potential in allergic inflammation, however, this property is dose responsive and higher doses are ineffective and may cause eosinophilia.

Variability of bronchial inflammation in chronic obstructive pulmonary disease: implications for study design.

There is variability in the distribution of inflammatory cells in bronchial tissue in chronic obstructive pulmonary disease (COPD). Better strategies for biopsy sampling of the airway mucosa may improve the capacity to show a difference between study populations where variability in distribution exists. The current authors have examined sources of biological variability in the quantification of inflammatory cells in endobronchial biopsies using immunostained samples taken from 51 subjects with COPD, with a mean forced expiratory volume in one second of 1.71 L, 55% predicted. The distribution of variance contributed by different sources was similar for different inflammatory cell types. For CD8+ cells, a key inflammatory cell in COPD, the largest contribution to intra-subject variability (39%) was time (i.e. 10 weeks between biopsies of placebo-treated subjects), followed by airway generation (23%), biopsy (2.5%), zone (within section; 1.4%) and section (0.4%). Power calculations demonstrated that examining one section from one biopsy, from each of two airway generations, would require a sample size of 32 subjects per group to show a difference of one doubling or halving in CD8+ cells, compared with 47 subjects per group if only one airway generation was sampled. Therefore, biopsies from more than one airway generation should be examined in order to maximise statistical power to detect a difference between study groups.

Single dose topical corticosteroid inhibits IL-5 and IL-13 in nasal lavage following grass pollen challenge.

BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. OBJECTIVE: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.

Consumidores de alcohol estudiados por necropsia: Pinar del Río 2001-2003

Se estudiaron 65 necropsias realizadas en el Departamento de Medicina Legal de Pinar del Río, en casos en que el consumo del alcohol aparece presente y relacionado al momento de la muerte. Se determinó la relación de la causa del deceso con el alcohol y se encuentróque tres quintas partes de ellos mueren antes de llegar a la tercera edad, en su mayoría siendo aptos y en activa vinculación laboral, con grados variables de adicción y consumo, pero apareciendo que el alcohol es causa básica o contribuyente de muerte en el 63,2 por ciento de ellos y que en general en el grupo se pierden como promedio 19,5 años de vida respecto a la expectativa del momento con un mínimo de 36 años perdidos para la mitad del grupo, razón que justifica medidas que impongan un consumo responsable en todo lugar y circunstancias...(AU)

Consumidores de alcohol estudiados por necropsia. Pinar del Río 2001-2003 / Study by necropsy of alcohol addicts. Pinar del Rio 2001-2003

Se estudiaron 65 necropsias realizadas en el Departamento de Medicina Legal de Pinar del Río, en casos en que el consumo del alcohol aparece presente y relacionado al momento de la muerte. Se determinó la relación de la causa del deceso con el alcohol y se encontró que tres quintas partes de ellos mueren antes de llegar a la tercera edad, en su mayoría siendo aptos y en activa vinculación laboral, con grados variables de adicción y consumo, pero apareciendo que el alcohol es causa básica o contribuyente de muerte en el 63,2 % de ellos y que en general en el grupo se pierden como promedio 19,5 años de vida respecto a la expectativa del momento con un mínimo de 36 años perdidos para la mitad del grupo, razón que justifica medidas que impongan un consumo responsable en todo lugar y circunstancias.

Sixty five autopsies which were done at Forensic Medicine Department in Pinar del Rio were studied in cases where the alcohol abuse seems to be present and related to death. It?s determined the relationship between the cause of death and the alcohol abuse and it?s found that 3/5 of patients die before old age having most of them an active labouring link, but various grades of addiction and alcohol abuse, but it seems that alcohol is the basic or the contributing factor to death (63.2 %) and it also seems that 19.5 years are lost according to the current expectation of life with a minimal of 36 years lost, so it is necessary some measurements for a responsible alcohol behaviour towards alcohol abuse in every place and every moment.

Topical corticosteroid inhibits interleukin-4, -5 and -13 in nasal secretions following allergen challenge.

BACKGROUND: Cytokines and chemokines produced by allergen-reactive T-helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. OBJECTIVE: This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. METHODS: Patients with grass pollen seasonal-allergic rhinitis (n = 13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 microg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. RESULTS: Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL-4, IL-5, IL-6 and IL-13 responses in the filter paper taken in the late phase (P < 0.05 for IL-4 and IL-13, P < 0.01 for IL-5 and IL-6). Levels of chemokines (eotaxin, RANTES, MCP-1, MIP-1alpha, IL-8 and IP-10) were also reduced in the late phase (P < 0.01 at 8 h). However, levels of IL-2, IL-3, IL-7, IL-12 (p40 and p70), -15, TNF-alpha, IFN-gamma and GM-CSF were not affected. CONCLUSION: Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

Cough frequency in children with stable asthma: correlation with lung function, exhaled nitric oxide, and sputum eosinophil count.

BACKGROUND: A study was undertaken to assess the correlation between cough frequency in asthmatic children with lung function and two non-invasive markers of airway inflammation. METHODS: Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5-13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters. RESULTS: Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV1) and eNO were 88.5% (IQR 79.5-98) and 23.9 ppb (IQR 11.4-41.5), respectively. The median number of cough episodes was 14 (IQR 7.0-24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1-10.5), p<0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0-9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's r =0.781, p<0.001) but not with FEV1 or sputum eosinophil count (r =-0.270, p=0.157; r =0.173, p=0.508, respectively). CONCLUSIONS: Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.

Sputum T lymphocytes in asthma, COPD and healthy subjects have the phenotype of activated intraepithelial T cells (CD69+ CD103+).

BACKGROUND: T cells of intraepithelial phenotype have previously been detected in bronchoalveolar lavage (BAL) fluid in a range of lung diseases; these cells express the adhesion molecule alpha(E)beta(7) integrin, CD103, the ligand for epithelial cell E-cadherin. In subjects with asthma CD4+ lymphocytes are the predominant T cell subtype found in bronchial biopsy specimens and in BAL fluid, whereas CD8+ lymphocytes have been shown to predominate in subjects with chronic obstructive pulmonary disease (COPD). The aim of this study was to analyse the expression of CD103, activation markers (CD25 and CD69), and chemokine receptors (CXCR3, CCR5 and CCR3) on CD4+ and CD8+ lymphocytes from sputum and peripheral blood of subjects with asthma, COPD, and healthy controls. METHODS: T cell surface markers were assessed by immunofluorescence labelling and flow cytometry of gated lymphocytes among CD45+ leucocytes in sputum cell suspensions. RESULTS: Sputum lymphocytes expressed higher levels of CD103 and CD69 than blood lymphocytes in all subject groups, with CD103 expressed at higher levels on CD8+ than on CD4+ cells. There were no detectable differences in numbers of CD4+ and CD8+ T cells between subjects with asthma, COPD and controls. The percentage of sputum lymphocytes expressing CXCR3 was lower in subjects with asthma or COPD than in healthy controls; CCR3 was not detectable on sputum or blood lymphocytes. CONCLUSIONS: Sputum T lymphocytes are predominantly of activated intraepithelial phenotype (CD103+ CD69+), and normal numbers of CD4+ and CD8+ T cell populations are found in the sputum of patients with asthma and COPD.

Eotaxin receptor (CCR3) antagonism in asthma and allergic disease.

A range of low molecular weight chemicals have been developed to antagonise the eotaxin receptor, cysteine-cysteine chemokine receptor-3 (CCR3), with the aim of selectively inhibiting eosinophil recruitment into tissue sites. However, the results of recent clinical trials with monoclonal antibodies directed against interleukin-5 (IL-5) question the role of eosinophils in mediating the symptoms of asthma and allergic disease. For this reason, the plans for clinical development of certain CCR3 antagonists have been halted. However, eotaxin 1-3 and a variety of other chemokines interact with CCR3; and this receptor is expressed not only on eosinophils but also on basophils, mast cell subpopulations, activated Th2 cells, macrophages, and airway epithelial cells. Hence, CCR3 is closely associated with asthma and allergy and blockade of this receptor may have pronounced beneficial effects in these diseases. We consider the chemical structures of CCR3 antagonist molecules from a range of pharmaceutical companies, and present an early clinical development plan for a hypothetical CCR3 antagonist. CCR3 antagonists are likely to be safe and effective therapies for allergic diseases, and their clinical pharmacology can readily be defined within phase I/II studies in patients with allergy and asthma.